Miracle-dz/UniFAR-FTUs huggingface dataset:
What is (synthetic) life? basic concepts of life in synthetic biology

One of the central aims of synthetic biology (SB) is to better understand the mechanisms of life by trying to develop and synthesize new forms and perhaps modes of life. While the question of what is life has occupied mankind for centuries, there is a lack of empirical research examining the basic concepts of life scientists within SB themselves refer to and build on. In order to gain insights into these fundamental concepts, we conducted a qualitative interview study with scientists working in the field of SB. The aim was to gain a better understanding of the underlying understandings, principles, and characteristics of (synthetic) life on the one hand, and the entangled consequences for the conducted experiments and studies as well as the pursued scientific approaches. We identified four primarily underlying basic concepts of life which serve as a fundamental framework for current and further scientific research within SB and have implications for research questions, approaches and aims as well as for the evaluation of scientific results.
Development on Infected Citrus over Generations Increases Vector Infection by ‘Candidatus Liberibacter Asiaticus in Diaphorina citri’

‘Candidatus Liberibacter asiaticus’ (CLas) is a major causal agent of citrus Huanglongbing (HLB), which is transmitted by Asian citrus psyllid (ACP), Diaphorina citri, causing severe losses in various regions of the world. Vector efficiency is higher when acquisition occurs by ACP immature stages and over longer feeding periods. In this context, our goal was to evaluate the progression of CLas population and infection rate over four ACP generations that continuously developed on infected citrus plants. We showed that the frequency of CLas-positive adult samples increased from 42% in the parental generation to 100% in the fourth generation developing on CLas-infected citrus. The bacterial population in the vector also increased over generations. This information reinforces the importance of HLB management strategies, such as vector control and eradication of diseased citrus trees, to avoid the development of CLas-infected ACP generations with higher bacterial loads and, likely, a higher probability of spreading the pathogen in citrus orchards.
Obesity, clinical, and genetic predictors for glycemic progression in Chinese patients with type 2 diabetes: A cohort study using the Hong Kong Diabetes Register and Hong Kong Diabetes Biobank

Background Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. Methods and findings In 1995–2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1–9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8–13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3–49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03–1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06–1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10−8) but not glycemic progression (HR: 1.01 [95% CI 0.96–1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. Conclusions Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.
Diplopia developed by cervical traction after cervical spine surgery

Diplopia is a rare complication of spine surgery. The abducens nerve is one of the cranial nerves most commonly related to diplopia caused by traction injury. We report a case of a 71-year-old woman who presented with diplopia developing from abducens nerve palsy after C1–C2 fixation and fusion due to atlantoaxial subluxation with cord compression. As soon as we discovered the symptoms, we suspected excessive traction by the instrument and subsequently performed reoperation. Subsequently, the patient’s symptoms improved. In other reported cases we reviewed, most were transient. However, we thought that our rapid response also helped the patient’s fast recovery in this case. The mechanisms by which postoperative diplopia develops vary and, thus, remain unclear. We should pay attention to the fact that the condition is sometimes an indicator of an underlying, life-threatening condition. Therefore, all patients with postoperative diplopia should undergo thorough ophthalmological and neurological evaluations as well as careful observation by a multidisciplinary team.
Dynamic switch migration with noncooperative game towards control plane scalability in SDN

As software‐defined networking (SDN) is a logically centralized technology, the control plane scalability in SDN is increasingly important with the network scale increasing. Load balancing and maximizing resource utilization are very critical to the control plane in SDN, while switch migration is an effective approach to achieve these two performance metrics. However, switch migration is NP‐hard problem because it belongs to the problem of combinatorial optimization. To avoid the NP‐hard problem, we propose a switch migration scheme by adopting noncooperative game to improve the control plane scalability in SDN. First, we design a novel load balancing monitoring scheme to detect the load imbalance between controllers and trigger migrating switches. Then, we use noncooperative game among controllers to decide switch migration to get the maximizing overall profits. Last, we prove that our proposed approach can get Pareto optimality. Extensive simulations prove that our method is able to achieve a more scalable control plane with load balancing and maximizing resource utilization.
Exome Sequencing Reveals a Phenotype Modifying Variant in ZNF528 in Primary Osteoporosis With a COL1A2 Deletion

We studied a family with severe primary osteoporosis carrying a heterozygous p.Arg8Phefs*14 deletion in COL1A2, leading to haploinsufficiency. Three affected individuals carried the mutation and presented nearly identical spinal fractures but lacked other typical features of either osteogenesis imperfecta or Ehlers‐Danlos syndrome. Although mutations leading to haploinsufficiency in COL1A2 are rare, mutations in COL1A1 that lead to less protein typically result in a milder phenotype. We hypothesized that other genetic factors may contribute to the severe phenotype in this family. We performed whole‐exome sequencing in five family members and identified in all three affected individuals a rare nonsense variant (c.1282C > T/p.Arg428*, rs150257846) in ZNF528. We studied the effect of the variant using qPCR and Western blot and its subcellular localization with immunofluorescence. Our results indicate production of a truncated ZNF528 protein that locates in the cell nucleus as per the wild‐type protein. ChIP and RNA sequencing analyses on ZNF528 and ZNF528‐c.1282C > T indicated that ZNF528 binding sites are linked to pathways and genes regulating bone morphology. Compared with the wild type, ZNF528‐c.1282C > T showed a global shift in genomic binding profile and pathway enrichment, possibly contributing to the pathophysiology of primary osteoporosis. We identified five putative target genes for ZNF528 and showed that the expression of these genes is altered in patient cells. In conclusion, the variant leads to expression of truncated ZNF528 and a global change of its genomic occupancy, which in turn may lead to altered expression of target genes. ZNF528 is a novel candidate gene for bone disorders and may function as a transcriptional regulator in pathways affecting bone morphology and contribute to the phenotype of primary osteoporosis in this family together with the COL1A2 deletion. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
A mechanism for hunchback promoters to readout morphogenetic positional information in less than a minute

Cell fate decisions in the fly embryo are rapid: hunchback genes decide in minutes whether nuclei follow the anterior/posterior developmental blueprint by reading out positional information in the Bicoid morphogen. This developmental system is a prototype of regulatory decision processes that combine speed and accuracy. Traditional arguments based on fixed-time sampling of Bicoid concentration indicate that an accurate readout is impossible within the experimental times. This raises the general issue of how speed-accuracy tradeoffs are achieved. Here, we compare fixed-time to on-the-fly decisions, based on comparing the likelihoods of anterior/posterior locations. We found that these more efficient schemes complete reliable cell fate decisions within the short embryological timescales. We discuss the influence of promoter architectures on decision times and error rates, present concrete examples that rapidly readout the morphogen, and predictions for new experiments. Lastly, we suggest a simple mechanism for RNA production and degradation that approximates the log-likelihood function.
Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial

Abstract Background We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. Clinical Trials Registration NCT01898338.
Surveillance for Invasive Salmonella Disease in Bamako, Mali, From 2002 to 2018

Abstract Background Salmonella enterica bloodstream infections are an important cause of childhood morbidity and mortality, including in Mali. We report 17 years of surveillance for nontyphoidal and typhoidal S. enterica infections among inpatients and outpatients at l’Hôpital Gabriel Touré, the main source of pediatric tertiary care in Bamako, Mali. Methods Between June 2002 and December 2018, a blood culture was collected from 54 748 children aged ≤15 years with fever and/or suspected invasive bacterial infection who provided consent (38 152 inpatients, 16 596 outpatients). Bacterial pathogens were identified using standard microbiological techniques and serovars of S. enterica were determined by PCR and/or agglutination with antisera. Results Nontyphoidal Salmonella (NTS) was identified in 671 enrolled inpatients (1.8% of all enrolled inpatients, 13.8% of enrolled inpatients with a positive culture). S. Enteritidis, the most common NTS serovar, accounted for 38.5% of all NTS isolates (n = 258), followed by S. Typhimurium (31.7%, n = 213). The median (SD) age of children with a culture positive for NTS was 1.8 (3) years. Overall case fatality was 20.9%. An additional 138 inpatients (0.4%) had a positive culture for typhoidal Salmonella. NTS was identified in 11 outpatients (0.07%), while typhoidal Salmonella was found in 49 outpatients (0.3%). The annual incidence of invasive NTS disease decreased over the study period, but case fatality remained high. Conclusions Although incidence decreased, NTS remained a major cause of invasive bacterial infection and mortality among hospitalized children in Bamako, while typhoidal Salmonella was uncommon. Because 87% of NTS belonged to only 4 serovars, a multivalent vaccine may be an effective strategy to reduce the burden and mortality of invasive NTS.
The Optimal Location of Ground-Based GNSS Augmentation Transceivers

Modern Global Navigation Satellite Systems (GNSS) allow for positioning with accuracies ranging from tens of meters to single millimeters depending on user requirements and available equipment. A major disadvantage of these systems is their unavailability or limited availability when the sky is obstructed. One solution is to use additional range measurements from ground-based nodes located in the vicinity of the receiver. The highest accuracy of distance measurement can be achieved using ultra wide band (UWB) or ZigBee phase shift measurement. The position of the additional transmitter must be carefully selected in order to obtain the optimal improvement in the dilution of precision (DOP), which reflects the improvement in the geometry of solution. The presented case study depicts a method for selecting the optimal location of a ground-based ranging source. It is based on a search of a minimum DOP value as a transmitter location function. The parameters of objective function are the elevation and azimuth of the transceiver. The solution was based on a limited-memory Broyden–Fletcher–Goldfarb–Shanno with Box constraints (L-BFGS-B) method and a numerical optimization algorithm for parameter value estimation. The presented approach allows for the selection of the optimal location of a ground-based source of ranging signals in GNSS processing from a geometry of solution point of view. This can be useful at the design stage of an augmentation network of ground-based transceivers. This article presents a theoretical basis and a case study presenting the selection of the optimal location of a ground-based ranging source.
Neuroparsin: a new energetic neurohormone in the African locust

The effects of neuroparsins on hemolymph trehalose and lipid levels and on total glycogen content were analyzed in Locusta migratoria. Saline and methanol extracts of the two lobes of the corpora cardiaca were assayed. Neuroparsins (A and B) were demonstrated to be hypertrehalosemic and hyperlipemic proteins of the neural lobe. Both of these metabolic activities of neuroparsins were somewhat less potent than those of adipokinetic hormone (AKH). Neuroparsin activity could be distinguished from AKH by blockage with an antiserum specific to neuroparsin. The hypertrehalosemic response induced by neuroparsins, in contrast to that of AKH, appeared to occur without a decrease of total glycogen content. The differential modes of action of AKH and neuroparsins could contribute to the fine modulation of carbohydrate metabolism in Locusta migratoria.
Biological Activity of Humulus lupulus (L.) Essential Oil and Its Main Components against Sitophilus granarius (L.)

Besides its use in the brewing industry, hop cones appear as a powerful source of biologically active compounds, already checked for their putative anticancer, antimicrobial, and other bioactivities. Conversely, hop use in pest control remains to date under-investigated. Therefore, the biological activity of hop essential oil (EO) and its main constituents was investigated here against Sitophilus granarius. Adult contact toxicity was found 24 h after treatment with hop EO (LD50/LD90 13.30/40.23 µg/adult), and its three most abundant components, α-humulene, β-myrcene, and β-caryophyllene (LD50/LD90 41.87/73.51, 75.91/126.05, and 138.51/241.27 µg/adult, respectively); negligible variations at 48 h, except for α-humulene (LD50/LD90 26.83/49.49 µg/adult), were found. The fumigant toxicity of the EO and terpenes was also checked: in the absence of wheat grains, β-myrcene showed the highest inhalation toxicity (LC50/LC90 72.78/116.92 mg/L air), whereas α-humulene, β-caryophyllene, and the EO induced similar values (LC50/LC90 about 130/200 mg/L air); with the exception for EO, the wheat presence increased (30–50%) LC50/LC90 values. Moreover, EO and terpenes were perceived by insect antennae and elicited repellent activity. Only β-caryophyllene showed an anticholinesterase effect, this suggesting that different mechanisms of action should be responsible for hop EO toxicity. Therefore, hop EO appears suitable for developing control means against this pest.
Combined metabolome and transcriptome analysis reveals key components of complete desiccation tolerance in an anhydrobiotic insect

Significance Anhydrobiosis is a reversible ametabolic state that occurs in response to severe desiccation. The largest anhydrobiotic animal known is the larva of the African chironomid Polypedilum vanderplanki. Here, we investigated how the metabolism of larvae changes during the desiccation–rehydration cycle and how simple biochemical processes determine viability of the chironomid. Major findings suggest that, in addition to its known anhydroprotectant role, trehalose acts as a major source of energy for rehydration. Citrate and adenosine monophosphate, accumulated in the dry state, allow rapid resumption of metabolism during the recovery phase. Finally, metabolic waste is stored as stable or nontoxic compounds such as allantoin, xanthurenic acid, or ophthalmic acid that may also act as antioxidants. Some organisms have evolved a survival strategy to withstand severe dehydration in an ametabolic state, called anhydrobiosis. The only known example of anhydrobiosis among insects is observed in larvae of the chironomid Polypedilum vanderplanki. Recent studies have led to a better understanding of the molecular mechanisms underlying anhydrobiosis and the action of specific protective proteins. However, gene regulation alone cannot explain the rapid biochemical reactions and independent metabolic changes that are expected to sustain anhydrobiosis. For this reason, we conducted a comprehensive comparative metabolome–transcriptome analysis in the larvae. We showed that anhydrobiotic larvae adopt a unique metabolic strategy to cope with complete desiccation and, in particular, to allow recovery after rehydration. We argue that trehalose, previously known for its anhydroprotective properties, plays additional vital roles, providing both the principal source of energy and also the restoration of antioxidant potential via the pentose phosphate pathway during the early stages of rehydration. Thus, larval viability might be directly dependent on the total amount of carbohydrate (glycogen and trehalose). Furthermore, in the anhydrobiotic state, energy is stored as accumulated citrate and adenosine monophosphate, allowing rapid reactivation of the citric acid cycle and mitochondrial activity immediately after rehydration, before glycolysis is fully functional. Other specific adaptations to desiccation include potential antioxidants (e.g., ophthalmic acid) and measures to avoid the accumulation of toxic waste metabolites by converting these to stable and inert counterparts (e.g., xanthurenic acid and allantoin). Finally, we confirmed that these metabolic adaptations correlate with unique organization and expression of the corresponding enzyme genes.
Main Factors Influencing Whole Grain Consumption in Children and Adults—A Narrative Review

Despite their recognized health benefits, intakes of whole grains (WG) are below recommended levels in almost all countries worldwide. This observation highlights the need to increase WG consumption by understanding factors influencing this consumption and how they could be favorably impacted. This review focused on facilitators of and barriers to WG consumption and how to improve the effectiveness of programs aiming at increasing WG consumption. The main methods to facilitate WG intakes in both adults and children seem to be to (i) increase the availability and the variety of foods containing WG, (ii) improve their sensory appeal, (iii) reduce their purchase cost, (iv) use a familiarization period to introduce them to consumers (with a gradual increase in consumed amounts and repeated exposure), and (v) improve communication and labeling to enhance consumers’ ability to identify products with WG. These strategies may be used to improve the effectiveness of programs aiming at promoting WG consumption, with a further emphasis on the need to apply them over a long period of time, and potentially to include tasting sessions of new foods containing WG. Finally, these strategies should involve broad partnerships between multiple stakeholders at the regulatory, institutional and industrial levels.
An analysis of energy use and input costs for maize production in Turkey.

The purpose of this study was to determine energy equivalents of inputs and output in maize production in Bursa province. The data in this study were collected from maize farms in Bursa province, Karacabey district. Questionnaires were administered through face-to-face interview in 2011 July, 2011. The results of the study show that fertilizers have the highest rate of energy equivalency of all the inputs used in maize production at 51.47%. The energy equivalent rate of electricity is 20.30% and the energy equivalent rate of fuel is 23.29%. The energy equivalent rates for human power, machinery, chemicals and water for irrigation were determined to be low in maize production. According to the output/input ratio calculated, the energy ratio is 0.76 in maize production in the research area. This ratio implies that the inputs used in maize production have not been used effectively. Ineffective use of these resources also causes environmental problems.