Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering Escherichia coli for Glutarate Production as the C5 Platform Backbone

Glutarate is an important C5 linear-chain dicarboxylic acid, which is widely used in polyesters and polyamides such as nylon-4,5 and nylon-5,5 in the chemical industry. Glutarate is currently produced from the feedstocks derived from petroleum, specifically by oxidation of a mixture of cyclohexanone and cyclohexanol catalyzed by nitric acid. However, the chemical synthesis results in high pollution and dramatic greenhouse gas emission. Thus, the biological production of glutarate directly from the substrate is of great importance. Although there have been reports using Corynebacterium glutamicum to produce glutarate, it has serious limitations due to the limited lysine supply and long fermentation time. To solve this problem, a novel synthetic pathway was constructed in this study, and the highest glutarate titer was reported in Escherichia coli using a short fermentation time without lysine addition, making bio-based glutarate production much more feasible. ABSTRACT Glutarate is a linear-chain dicarboxylic acid with wide applications in the production of polyesters and polyamides such as nylon-4,5 and nylon-5,5. Previous studies focused on the biological production of glutarate from lysine with low yields and titers. Here, we report on glutarate production by Escherichia coli using a five-step reverse adipate degradation pathway (RADP) identified in Thermobifida fusca. By expressing the enzymes of RADP, the glutarate was detected by strain Bgl146 in shaken flasks. After fermentation optimization, the titer of glutarate by Bgl146 was increased to 4.7 ± 0.2 mM in shaken flasks. We further eliminated pathways for the major metabolites competing for carbon flux by CRISPR/Cas9 (ΔarcA, ΔldhA, ΔatoB, and ΔpflB). Moreover, the final strain Bgl4146 produced 36.5 ± 0.3 mM glutarate by fed-batch fermentation. These results constitute the highest glutarate titer reported in E. coli. IMPORTANCE Glutarate is an important C5 linear-chain dicarboxylic acid, which is widely used in polyesters and polyamides such as nylon-4,5 and nylon-5,5 in the chemical industry. Glutarate is currently produced from the feedstocks derived from petroleum, specifically by oxidation of a mixture of cyclohexanone and cyclohexanol catalyzed by nitric acid. However, the chemical synthesis results in high pollution and dramatic greenhouse gas emission. Thus, the biological production of glutarate directly from the substrate is of great importance. Although there have been reports using Corynebacterium glutamicum to produce glutarate, it has serious limitations due to the limited lysine supply and long fermentation time. To solve this problem, a novel synthetic pathway was constructed in this study, and the highest glutarate titer was reported in Escherichia coli using a short fermentation time without lysine addition, making bio-based glutarate production much more feasible.
Robotic technologies for solar‐powered UAVs: Fully autonomous updraft‐aware aerial sensing for multiday search‐and‐rescue missions

Large‐scale aerial sensing missions can greatly benefit from the perpetual endurance capability provided by high‐performance low‐altitude solar‐powered unmanned aerial vehicles (UAVs). However, today these UAVs suffer from small payload capacity, low energetic margins, and high operational complexity. To tackle these problems, this paper presents four individual technical contributions and integrates them into an existing solar‐powered UAV system: First, a lightweight and power‐efficient day/night‐capable sensing system is discussed. Second, means to optimize the UAV platform to the specific payload and to thereby achieve sufficient energetic margins for day/night flight with payload are presented. Third, existing autonomous launch and landing functionality is extended for solar‐powered UAVs. Fourth, as a main contribution an extended Kalman filter (EKF)‐based autonomous thermal updraft tracking framework is developed. Its novelty is that it allows the end‐to‐end integration of the thermal‐induced roll moment into the estimation process. It is assessed against unscented Kalman filter and particle filter methods in simulation and implemented on the aircraft's low‐power autopilot. The complete system is verified during a 26 h search‐and‐rescue aerial sensing mock‐up mission that represents the first‐ever fully autonomous perpetual endurance flight of a small solar‐powered UAV with a day/night‐capable sensing payload. It also represents the first time that solar‐electric propulsion and autonomous thermal updraft tracking are combined in flight. In contrast to previous work that has focused on the energetic feasibility of perpetual flight, the individual technical contributions of this paper are considered core functionality to guarantee ease‐of‐use, effectivity, and reliability in future multiday aerial sensing operations with small solar‐powered UAVs.
Beclin-1-Dependent Autophagy Protects the Heart During Sepsis

Background: Cardiac dysfunction is a major component of sepsis-induced multiorgan failure in critical care units. Changes in cardiac autophagy and its role during sepsis pathogenesis have not been clearly defined. Targeted autophagy-based therapeutic approaches for sepsis are not yet developed. Methods: Beclin-1-dependent autophagy in the heart during sepsis and the potential therapeutic benefit of targeting this pathway were investigated in a mouse model of lipopolysaccharide (LPS)-induced sepsis. Results: LPS induced a dose-dependent increase in autophagy at low doses, followed by a decline that was in conjunction with mammalian target of rapamycin activation at high doses. Cardiac-specific overexpression of Beclin-1 promoted autophagy, suppressed mammalian target of rapamycin signaling, improved cardiac function, and alleviated inflammation and fibrosis after LPS challenge. Haplosufficiency for beclin 1 resulted in opposite effects. Beclin-1 also protected mitochondria, reduced the release of mitochondrial danger-associated molecular patterns, and promoted mitophagy via PTEN-induced putative kinase 1-Parkin but not adaptor proteins in response to LPS. Injection of a cell-permeable Tat-Beclin-1 peptide to activate autophagy improved cardiac function, attenuated inflammation, and rescued the phenotypes caused by beclin 1 deficiency in LPS-challenged mice. Conclusions: These results suggest that Beclin-1 protects the heart during sepsis and that the targeted induction of Beclin-1 signaling may have important therapeutic potential.
Positron emission tomography-based assessment of metabolic gradient and other prognostic features in sarcoma

Abstract. Intratumoral heterogeneity biomarkers derived from positron emission tomography (PET) imaging with fluorodeoxyglucose (FDG) are of interest for a number of cancers, including sarcoma. A range of radiomic texture variables, adapted from general methodologies for image analysis, has shown promise in the setting. In the context of sarcoma, our group introduced an alternative model-based approach to the measurement of heterogeneity. In this approach, the heterogeneity of a tumor is characterized by the extent to which the 3-D FDG uptake pattern deviates from a simple elliptically contoured structure. By using a nonparametric analysis of the uptake profile obtained from this spatial model, a variable assessing the metabolic gradient of the tumor is developed. The work explores the prognostic potential of this new variable in the context of FDG-PET imaging of sarcoma. A mature clinical series involving 197 patients, 88 of whom have complete time-to-death information, is used. Texture variables based on the imaging data are also evaluated in this series and a range of appropriate machine learning methodologies are then used to explore the complementary prognostic roles for structure and texture variables. We conclude that both texture-based and model-based variables can be combined to achieve enhanced prognostic assessments of outcome for patients with sarcoma based on FDG-PET imaging information.
A Systematic Review and Meta-Analysis of Human Milk Feeding and Morbidity in Very Low Birth Weight Infants

This systematic review and meta-analysis synthesised the post-1990 literature examining the effect of human milk on morbidity, specifically necrotising enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD) and neurodevelopment in infants born ≤28 weeks’ gestation and/or publications with reported infant mean birth weight of ≤1500 g. Online databases including Medline, PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled Trials were searched, and comparisons were grouped as follows: exclusive human milk (EHM) versus exclusive preterm formula (EPTF), any human milk (HM) versus EPTF, higher versus lower dose HM, and unpasteurised versus pasteurised HM. Experimental and observational studies were pooled separately in meta-analyses. Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings. Forty-nine studies (with 56 reports) were included, of which 44 could be included in meta-analyses. HM provided a clear protective effect against NEC, with an approximate 4% reduction in incidence. HM also provided a possible reduction in LOS, severe ROP and severe NEC. Particularly for NEC, any volume of HM is better than EPTF, and the higher the dose the greater the protection. Evidence regarding pasteurisation is inconclusive, but it appears to have no effect on some outcomes. Improving the intake of mother’s own milk (MOM) and/or donor HM results in small improvements in morbidity in this population.
Bilateral Electrodermal Activity in the Active–Alert Hypnotic Induction

Abstract Shifts in hemispheric dominance were previously proposed to play a role in hypnosis. Participants (N = 32) were exposed to an active–alert hypnosis induction and a music-control condition while electrodermal activity was registered bilaterally, providing information on alterations in hemispheric dominance. The results suggest that highly hypnotizable participants show a shift to right-sided and low hypnotizable participants demonstrated a shift to left-sided electrodermal dominance in response to the induction, whereas no change in laterality is present in the control condition. Additionally, the authors found that self-reported hypnosis experiences were also associated with a shift in laterality. These results underline the importance of the shift to right hemispheric activity in hypnosis and underscore the importance of hemispheric changes in shaping subjective experience.
The Technology Revolution at the Limits of Detection

In 1980 Sydney Brenner proclaimed “progress in science depends on new techniques, new discoveries, and new ideas, probably in that order”, but this was not a novel concept. For decades people have understood the biosciences are not merely hypothesis-led but are driven as much by technological developments. New tools and technologies are essential in advancing modern biology, allowing lines of investigation that otherwise remain inaccessible.
Incorporation of Levodopa into Biopolymer Coatings Based on Carboxylated Carbon Nanotubes for pH-Dependent Sustained Release Drug Delivery

Four drug delivery systems were formulated by non-covalent functionalization of carboxylated single walled carbon nanotubes using biocompatible polymers as coating agent (i.e., Tween 20, Tween 80, chitosan or polyethylene glycol) for the delivery of levodopa, a drug used in Parkinson’s disease. The chemical interaction between the coating agent and carbon nanotubes-levodopa conjugate was confirmed by Fourier transform infrared (FTIR) and Raman studies. The drug release profiles were revealed to be dependent upon the type of applied coating material and this could be further adjusted to a desired rate to meet different biomedical conditions. In vitro drug release experiments measured using UV-Vis spectrometry demonstrated that the coated conjugates yielded a more prolonged and sustained release pattern compared to the uncoated conjugate. Cytotoxicity of the formulated conjugates was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using normal mouse embryonic fibroblast 3T3 cell line. Compared to the non-coated conjugate, the MTT data indicated that the coating procedure improved the biocompatibility of all systems by 34–41% when the concentration used exceeded 100 μg/mL. In conclusion, the comprehensive results of this study suggest that carbon nanotubes-based drug carrier coated with a suitable biomaterial may possibly be a potential nanoparticle system that could facilitate drug delivery to the brain with tunable physicochemical properties.
From e-Health to i-Health: Prospective Reflexions on the Use of Intelligent Systems in Mental Health Care

Depressive disorders cover a set of disabling problems, often chronic or recurrent. They are characterized by a high level of psychiatric and somatic comorbidities and represent an important public health problem. To date, therapeutic solutions remain unsatisfactory. For some researchers, this is a sign of decisive paradigmatic failure due to the way in which disorders are conceptualized. They hypothesize that the symptoms of a categorical disorder, or of different comorbid disorders, can be interwoven in chains of interdependencies on different elements, of which it would be possible to act independently and synergistically to influence the functioning of the symptom system, rather than limiting oneself to targeting a hypothetical single underlying cause. New connected technologies make it possible to invent new observation and intervention tools allowing better phenotypic characterization of disorders and their evolution, that fit particularly well into this new “symptoms network” paradigm. Synergies are possible and desirable between these technological and epistemological innovations and can possibly help to solve some of the difficult problems people with mental disorders face in their everyday life, as we will show through a fictional case study exploring the possibilities of connected technologies in mental disorders in the near future.
A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer

Background Niclosamide, an FDA-approved anti-helminthic drug, has activity in preclinical models of castration-resistant prostate cancer (CRPC). Potential mechanisms of action include degrading constitutively active androgen receptor splice variants (AR-Vs) or inhibiting other drug-resistance pathways (e.g., Wnt-signaling). Published pharmacokinetics data suggests that niclosamide has poor oral bioavailability, potentially limiting its use as a cancer drug. Therefore, we launched a Phase I study testing oral niclosamide in combination with enzalutamide, for longer and at higher doses than those used to treat helminthic infections. Methods We conducted a Phase I dose-escalation study testing oral niclosamide plus standard-dose enzalutamide in men with metastatic CRPC previously treated with abiraterone. Niclosamide was given three-times-daily (TID) at the following dose-levels: 500, 1000 or 1500mg. The primary objective was to assess safety. Secondary objectives, included measuring AR-V expression from circulating tumor cells (CTCs) using the AdnaTest assay, evaluating PSA changes and determining niclosamide’s pharmacokinetic profile. Results 20 patients screened and 5 enrolled after passing all screening procedures. 13(65%) patients had detectable CTCs, but only one was AR-V+. There were no dose-limiting toxicities (DLTs) in 3 patients on the 500mg TID cohort; however, both (N = 2) subjects on the 1000mg TID cohort experienced DLTs (prolonged grade 3 nausea, vomiting, diarrhea; and colitis). The maximum plasma concentration ranged from 35.7–82 ng/mL and was not consistently above the minimum effective concentration in preclinical studies. There were no PSA declines in any enrolled subject. Because plasma concentrations at the maximum tolerated dose (500mg TID) were not consistently above the expected therapeutic threshold, the Data Safety Monitoring Board closed the study for futility. Conclusions Oral niclosamide could not be escalated above 500mg TID, and plasma concentrations were not consistently above the threshold shown to inhibit growth in CRPC models. Oral niclosamide is not a viable compound for repurposing as a CRPC treatment. Clinical trial registry Clinicaltrials.gov: NCT02532114
PSO-MPC control of artificial pancreas

PSO tuning of Model Predictive Control (MPC) implemented in Artificial Pancreas is presented in this paper. The objective function of PSO-based MPC is defined using closed loop information to perform a minimal computation time which is achieved by a small number of iterations and a reduced population size. The controller implementation in a test platform approved by the FDA shows an acceleration in reference tracking with a reduction of overshoot and a complete avoidance of hypoglycemia.
An Information-Theoretic Analysis for Thompson Sampling with Many Actions

Information-theoretic Bayesian regret bounds of Russo and Van Roy capture the dependence of regret on prior uncertainty. However, this dependence is through entropy, which can become arbitrarily large as the number of actions increases. We establish new bounds that depend instead on a notion of rate-distortion. Among other things, this allows us to recover through information-theoretic arguments a near-optimal bound for the linear bandit. We also offer a bound for the logistic bandit that dramatically improves on the best previously available, though this bound depends on an information-theoretic statistic that we have only been able to quantify via computation.
Composite Antenna for Ultrawide Bandwidth Applications: Exploring Conceptual Design Strategies and Analysis

In the recent era of wireless communication, ultrawide bandwidth (UWB) technology is in high demand because of its wide application in short-range and high-speed data communication. In 2002, the frequency spectrum for UWB systems was decided by the U.S. Federal Communication Commission to be between 3.1 and 10.7 GHz [1]. Three types of radiators support UWB in commercial appliances: 1) microstrip, 2) slot, and 3) dielectric resonator antennas (DRA). Microstrip and slot antennas are compact in size, but they suffer from low-gain characteristics. This drawback can be overcome by DRA, but at the expense of size [2], [3].
Towards an autonomic Bayesian fault diagnosis service for SDN environments based on a big data infrastructure

Software Defined Networks (SDN) are gaining momentum as a solution for current and future networking issues. Its programmability and centralised control enables a more dynamic management of the network. But this feature introduces the cost of a potential increase in failures, since every modification introduced on the control plane is a new possibility for failures to appear and cause a decrement of the quality for the offered service. Following a classical approach, this kind of problems could be solved increasing the number of high skilled human operators, which would dramatically increase network operation cost. Our approach is to apply Machine Learning and Data Analysis for monitoring and diagnosis SDN networks with the goal of automating these tasks. In this paper, we present an architecture for a self-diagnosis service which is deployed on top of a SDN management platform. In addition, a prototype of the proposed service with different diagnosis models for SDN networks has been developed. The evaluation shows encouraging results which will be explored in future works.
Associations between psychometrically assessed life history strategy and daily behavior: data from the Electronically Activated Recorder (EAR)

Life history theory has generated cogent, well-supported hypotheses about individual differences in human biodemographic traits (e.g., age at sexual maturity) and psychometric traits (e.g., conscientiousness), but little is known about how variation in life history strategy (LHS) is manifest in quotidian human behavior. Here I test predicted associations between the self-report Arizona Life History Battery and frequencies of 12 behaviors observed over 72 h in 91 US college students using the Electronically Activated Recorder (EAR), a method of gathering periodic brief audio recordings as participants go about their daily lives. Bayesian multi-level aggregated binomial regression analysis found no strong associations between ALHB scores and behavior frequencies. One behavior, presence at amusement venues (bars, concerts, sports events) was weakly positively associated with ALHB-assessed slow LHS, contrary to prediction. These results may represent a challenge to the ALHB’s validity. However, it remains possible that situational influences on behavior, which were not measured in the present study, moderate the relationships between psychometrically-assessed LHS and quotidian behavior.
The effectiveness of sustainable serial casting for clubfoot deformity in a low resource setting

Aims Our aim was to assess the effectiveness of the Malawi Clubfoot Programme and comment on such health care strategies in developing countries. Methods Medical records of 1069 children attending 29 clinics within Malawi were identified between 2007 and 2013. Due to incomplete recording, only 596 patients had adequate data which could be further analysed. Results The mean age of presentation was 103 days (range 0–8 years) with a sex distribution of M1.76:F1. The mean Pirani score at presentation was 4.55 and on completion of casting was 1.39. A correlation was identified between the number of castings and the initial Pirani score (positive coefficient 0.2626 p<0.0001), the final casting score (negative coefficient -0.1441 p<0.0006) and the change in Pirani score (positive coefficient 0.3200 (p<0.0001)). The number of patients attending the clinics increased per year and the average number of castings was reduced from 6 to 5 between 2008 and 2012. There was also moderate correlation between the number of years the programme had been re-instated and the average change in Pirani score between in each casting (R score 0.36) Conclusion Serial casting performed by paramedical personnel within an established self- sustained national programme can effectively treat CTEV in low resource countries.
A Dual Repeat Cis-Element Determines Expression of GERANYL DIPHOSPHATE SYNTHASE for Monoterpene Production in Phalaenopsis Orchids

Phalaenopsis bellina is a scented orchid emitting large amount of monoterpenes. GERANYL DIPHOSPHATE SYNTHASE (PbGDPS) is the key enzyme for monoterpene biosynthesis, and shows concomitant expression with the emission of monoterpenes during flower development in P. bellina. Here, we identified a dual repeat cis-element in the GDPS promoter that is critical for monoterpene biosynthesis in Phalaenopsis orchids. A strong correlation between the dual repeat and the monoterpene production was revealed by examination of the GDPS promoter fragments over 12 Phalaenopsis species. Serial-deletion of the 2-kb GDPS promoter fragments demonstrated that the integrity of the dual repeat was crucial for its promoter activities. By screening the Arabidopsis transcription factors (TFs) cDNA library using yeast one-hybrid assay, AtbZIP18, a member of group I of bZIP TFs, was identified to be able to bind the dual repeat. We then identified PbbZIP4 in the transcriptome of P. bellina, showing 83% identity in the DNA binding region with that of AtbZIP18, and the expression level of PbbZIP4 was higher in the scented orchids. In addition, PbbZIP4 transactivated the GDPS promoter fragment containing the dual repeat in dual luciferase assay. Furthermore, transient ectopic expression of PbbZIP4 induced a 10-fold production of monoterpenoids in the scentless orchid. In conclusion, these results indicate that the dual repeat is a real TF-bound cis-element significant for GDPS gene expression, and thus subsequent monoterpene biosynthesis in the scented Phalaenopsis orchids.