Miracle-dz/UniFAR-FTUs huggingface dataset:
Alternative Hfq‐sRNA interaction modes dictate alternative mRNA recognition

Many bacteria use small RNAs (sRNAs) and the RNA chaperone Hfq to regulate mRNA stability and translation. Hfq, a ring‐shaped homohexamer, has multiple faces that can bind both sRNAs and their mRNA targets. We find that Hfq has at least two distinct ways in which it interacts with sRNAs; these different binding properties have strong effects on the stability of the sRNA in vivo and the sequence requirements of regulated mRNAs. Class I sRNAs depend on proximal and rim Hfq sites for stability and turn over rapidly. Class II sRNAs are more stable and depend on the proximal and distal Hfq sites for stabilization. Using deletions and chimeras, we find that while Class I sRNAs regulate mRNA targets with previously defined ARN repeats, Class II sRNAs regulate mRNAs carrying UA‐rich rim‐binding sites. We discuss how these different binding modes may correlate with different roles in the cell, with Class I sRNAs acting as emergency responders and Class II sRNAs acting as silencers.
Sustainable diets for the future: Can we contribute to reducing greenhouse gas emissions by eating a healthy diet?

BACKGROUND Food systems account for 18-20% of UK annual greenhouse gas emissions (GHGEs). Recommendations for improving food choices to reduce GHGEs must be balanced against dietary requirements for health. OBJECTIVE We assessed whether a reduction in GHGEs can be achieved while meeting dietary requirements for health. DESIGN A database was created that linked nutrient composition and GHGE data for 82 food groups. Linear programming was used iteratively to produce a diet that met the dietary requirements of an adult woman (19-50 y old) while minimizing GHGEs. Acceptability constraints were added to the model to include foods commonly consumed in the United Kingdom in sensible quantities. A sample menu was created to ensure that the quantities and types of food generated from the model could be combined into a realistic 7-d diet. Reductions in GHGEs of the diets were set against 1990 emission values. RESULTS The first model, without any acceptability constraints, produced a 90% reduction in GHGEs but included only 7 food items, all in unrealistic quantities. The addition of acceptability constraints gave a more realistic diet with 52 foods but reduced GHGEs by a lesser amount of 36%. This diet included meat products but in smaller amounts than in the current diet. The retail cost of the diet was comparable to the average UK expenditure on food. CONCLUSION A sustainable diet that meets dietary requirements for health with lower GHGEs can be achieved without eliminating meat or dairy products or increasing the cost to the consumer.
Female-specific flightless phenotype for mosquito control

Dengue and dengue hemorrhagic fever are increasing public health problems with an estimated 50–100 million new infections each year. Aedes aegypti is the major vector of dengue viruses in its range and control of this mosquito would reduce significantly human morbidity and mortality. Present mosquito control methods are not sufficiently effective and new approaches are needed urgently. A “sterile-male-release” strategy based on the release of mosquitoes carrying a conditional dominant lethal gene is an attractive new control methodology. Transgenic strains of Aedes aegypti were engineered to have a repressible female-specific flightless phenotype using either two separate transgenes or a single transgene, based on the use of a female-specific indirect flight muscle promoter from the Aedes aegypti Actin-4 gene. These strains eliminate the need for sterilization by irradiation, permit male-only release (“genetic sexing”), and enable the release of eggs instead of adults. Furthermore, these strains are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy.
Grandparents’ age and the risk of Down's syndrome in Norway

Background. High maternal age is a well‐recognized risk factor for Down's syndrome. There are also several studies of a possible effect of paternal age, but no consistent evidence of an association is found. Less is known about any effects of the age of grandparents. Objective. To assess whether maternal or paternal grandparents’ age is associated with the risk of Down's syndrome. Methods. We used logistic regression analyses with data from the Medical Birth Registry of Norway, adjusting for possible confounding factors. Results. We found no evidence of an association with the risk of Down's syndrome either for a maternal grandmother's age (odds ratio 0.9, 95% confidence interval 0.6–1.5 per 10‐year increase in grandmother's age) or for any of the other grandparents’ age. Conclusions. High maternal age remains the only well‐established age‐related risk factor for Down's syndrome. There is little evidence that the increased risk represented by older mothers is passed on to offspring of her non‐affected daughters.
Synergistic Inhibition of Breast Cancer Cell Growth by an Epigenome-Targeting Drug and a Tyrosine Kinase Inhibitor.

BACKGROUND Epigenome-targeting drugs, for example, histone decetylases (HDACs) inhibitors, have been recently shown to induce apoptosis in a variety of cancer cells, which could potentially be used as anticancer therapy. Tyrosine kinase inhibitors (TKIs) have been widely used in clinical trials of various cancers. HDAC inhibitor vorinostat, TKIs dasatinib have been tested in pivotal phase 2 clinical trials in patients with breast cancer. The combination treatment of vorinostat with dasatinib is expected to have synergistic effect on inhibiting breast cancer cell growth. MATERIALS AND METHODS Antiproliferation effects of the combined drugs on MCF-7 cells were designed according to Chou-Talalay method and analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell-cycle perturbation and cell apoptosis induction of the combination drugs were examined by Flow cytometry. The generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and the expression of Bcl-2 were determined by Western blot. RESULTS Our results revealed that the combination treatment had synergistic effects on anti-MCF7 cells, enhanced G2/M cell arrest, the generation of ROS, the loss of mitochondrial membrane potential, and cell apoptosis in MCF-7 cells in synergy. Moreover, the combination treatment decreased Bcl-2 expression. CONCLUSION Our results demonstrated that the combination of vorinostat with dasatinib exerted synergistic anticancer effects on MCF-7 cells by inducing cell cycle arrest, ROS production, and apoptosis through the mitochondria-mediated intrinsic pathway.
The 5′ region of the MSH2 gene involved in hereditary non‐polyposis colorectal cancer contains a high density of recombinogenic sequences

MSH2 rearrangements are involved in approximately 10% of hereditary non‐polyposis colorectal cancer (HNPCC) families, and in most of the rearrangements, exon 1 is deleted. We scanned by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF) 200 kb of genomic sequences upstream of the MSH2 transcription initiation site in 21 HNPCC families with exon 1 deletions. This QMPSF scan revealed 12 distinct 5′ breakpoints located up to 200 kb upstream of the MSH2 transcription initiation site. Sequencing analysis of the rearranged allele in 17 families revealed that most of the deletions (15/17) resulted from homologous Alu‐mediated recombination. QMPSF and sequencing analysis in these 21 families led us to detect the presence of 20 distinct 5′ breakpoints. In 14 out of 15 Alu‐mediated recombinations, we found, either within the identical region in which the recombination had probably occurred or in its vicinity, the 26‐bp Alu core sequence containing the recombinogenic Chi‐like motif. Compared to the equivalent regions of other human genes, the MSH2 upstream region was found to contain a high density of Alu repeats (30% within 228 kb and 43% within 50 kb), most of which belong to the old Alu S subfamilies. In conclusion, this study demonstrates the heterogeneity of the breakpoints within the MSH2 upstream region and reveals the remarkable density of recombinogenic Alu sequences in this region. Hum Mutat 26(3), 255–261, 2005. © 2005 Wiley‐Liss, Inc.
Wavelet compression for signal integrity analysis

Signal integrity (SI) analysis heavily relies on simulations. To support various interfaces and an increasing number of topologies, extensive simulations have been run over years. Such SI analysis is time and resource intensive, generating a huge amount of data. Can the existing big data set be exploited to ease our simulation and analysis efforts? In this work, we utilize wavelet techniques to compress one channel response (tens of thousands of data points) into only a small set of coefficients. There are many potential applications, if the reconstruction accuracy is maintained. One such application is to construct a Neural Net model of those coefficients over physical design parameters, such that the channel impulse response for any physical design can be obtained without any circuit simulation. This application, along with several others will be discussed in this paper. Moreover, wavelet-based techniques will be compared to more traditional compression techniques.
Solvent-shared pairs of densely charged ions induce intense but short-range supra-additive slowdown of water rotation.

The question "Can ions exert supra-additive effects on water dynamics? " has had several opposing answers from both simulation and experiment. We address this ongoing controversy by investigating water reorientation in aqueous solutions of two salts with large (magnesium sulfate) and small (cesium chloride) effects on water dynamics using molecular dynamics simulations and classical, polarizable models. The salt models are reparameterized to reproduce properties of both dilute and concentrated solutions. We demonstrate that water rotation in concentrated MgSO4 solutions is unexpectedly slow, in agreement with experiment, and that the slowdown is supra-additive: the observed slowdown is larger than that predicted by assuming that the resultant of the extra forces induced by the ions on the rotating water molecules tilts the free energy landscape associated with water rotation. Supra-additive slow down is very intense but short-range, and is strongly ion-specific: in contrast to the long-range picture initially proposed based on experiment, we find that intense supra-additivity is limited to water molecules directly bridging two ions in solvent-shared ion pair configuration; in contrast to a non-ion-specific origin to supra-additive effects proposed from simulations, we find that the magnitude of supra-additive slowdown strongly depends on the identity of the cations and anions. Supra-additive slowdown of water dynamics requires long-lived solvent-shared ion pairs; long-lived ion pairs should be typical for salts of multivalent ions. We discuss the origin of the apparent disagreement between the various studies on this topic and show that the short-range cooperative slowdown scenario proposed here resolves the existing controversy.
Parallelizing Fully Homomorphic Encryption

As cloud computing has grown increasingly prevalent, the privacy of data on the cloud becomes an issue. Encryption is an effective way to enforce data privacy. However most of existing encryption schemes require data to be decrypted for computations where data becomes vulnerable for data intrusion. Homomorphic encryption is an encryption scheme which allows for computations on encrypted data and obtains an encrypted result which decrypted produces the same result of computations on the original data. Homomorphic encryption makes it possible to process data in an open computing environment such as cloud while enforcing data privacy. Data can be outsourced to a third party who offers computing services without risking data privacy. However, homomorphic encryption suffers the performance of computations. This paper presents a method to improve the performance of the scheme in a cloud environment.
Validation of a high throughput flow cytometric in vitro micronucleus assay including assessment of metabolic activation in TK6 cells

Genotoxicity is an unacceptable property for new drug candidates and we employ three screening assays during the drug discovery process to identify genotoxicity early and optimize chemical series. One of these methods is the flow cytometric in vitro micronucleus assay for which protocol optimizations have been described recently. Here, we report further validation of the assay in TK6 cells including assessment of metabolic activation. We first optimized assay conditions to allow for testing with and without metabolic activation in parallel in a 96‐well plate format. Then, we tested a set of 48 compounds carefully selected to contain known in vivo genotoxins, nongenotoxins and drugs. Avoidance of irrelevant positives, a known issue with mammalian cell‐based genotoxicity assays, is important to prevent early deselection of potentially promising compounds. Therefore, we enriched the validation set with compounds that were previously reported to produce irrelevant positive results in mammalian cell‐based genotoxicity assays. The resulting dataset was used to set the relevant cut‐off values for scoring a compound positive or negative, such that we obtained an optimal balance of high sensitivity (88%) and high specificity (87%). Finally, we tested an additional set of 16 drugs to further probe assay performance and 14 of them were classified correctly. To our knowledge, the present study is the most comprehensive validation of the in vitro flow cytometric micronucleus assay and the first to report parallel assessment with metabolic activation in reasonable throughput. The assay allows for rapidly screening novel compounds for genotoxicity and is therefore well‐suited for use in early drug discovery projects. Environ. Mol. Mutagen. 55:704–718, 2014. © 2014 Wiley Periodicals, Inc.
Relationship between oxytocin release and amplitude of oxytocin cell neurosecretory bursts during suckling in the rat.

Plasma concentrations of oxytocin and vasopressin were measured in relationship to oxytocin cell firing during suckling in urethane-anaesthetized rats. Preliminary experiments showed that plasma concentrations of oxytocin and vasopressin, which were increased immediately after anaesthesia, reverted to basal concentrations 3 h later. Moreover, it was found that exogenous oxytocin had entirely disappeared 5 min after i.v. bolus injections of known doses of oxytocin. Suckling did not modify the basal plasma concentration of oxytocin (14.6 +/- 2.9 compared with 14.6 +/- 1.5 pmol/l before suckling) except during a brief period immediately after neurosecretory bursts on oxytocin cells (37.8 +/- 5.2 pmol/l; P less than 0.001, n = 11). The plasma concentration of oxytocin did not differ significantly from the basal concentration 1.5 min later. The plasma concentration of vasopressin never varied. After two neurosecretory bursts of similar amplitude (total number of spikes during the burst) recorded on the same oxytocin cell, the variations in plasma concentration of oxytocin were also similar. When, for a given cell, the amplitude of neurosecretory bursts increased or decreased, the amount of oxytocin released changed in the same way. These data demonstrate (1) that suckling induces pulsatile release of oxytocin without vasopressin, and (2) a direct relationship between the amounts of oxytocin released and the amplitude of oxytocin cell neurosecretory bursts which argue in favour of simultaneous increases or decreases in the neurosecretory burst amplitudes on all oxytocin cells.
Lung function parameters improve prediction of VO2peak in an elderly population: The Generation 100 study

Peak oxygen uptake (VO2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO2peak, spirometry, and a gas diffusion test. Prediction models for VO2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p<0.001). FEV1, diffusing capacity of the lungs for carbon monoxide and hemoglobin concentration substantially improved the accuracy of VO2peak prediction when added to an established model in an elderly population.
Animal traction and household economies in Neolithic Europe

Most archaeological interest in the story of European social evolution has looked to the grand picture, as the bands combine and climb at last to achieve states and empires. What about the structure of European Neolithic as it was experienced at home, when the OX, the pig, the sheep and the goat came to live in the domestic unit of the single household?
Stability of Procainamide Injection in Clear Glass Vials and Polyvinyl Chloride Bags

Objectives: The objective of this study was to evaluate the chemical stability of procainamide hydrochloride, 100 mg/mL, when repackaged in clear glass vials or diluted to 3 mg/mL with normal saline and packaged in polyvinyl chloride (PVC) bags when stored at either 23°C and exposed to light (ETL) or 5°C and protected from light (PFL). Methods: Solutions were assayed using a stability-indicating high-performance liquid chromatography method. Samples (5 mL) were collected from triplicate containers on days 0, 7, 14, 21, 28, 56, 91, and 193. Color/clarity and pH changes were also monitored at each time interval. Results: During the study, all samples remained clear and there was only a slight pH change. The color of the solutions stored at 23°C intensified but did not correlate with a significant decrease in concentration, while solutions stored at 5°C remained unchanged. Solutions repackaged in glass vials were stable for 193 days when stored at 23ºC and ETL or 5ºC and PFL. When further diluted to 3 mg/mL with normal saline and packaged in PVC bags, procainamide was also stable for 193 days at either 23ºC and ETL or 5°C and PFL. Conclusions: The stability of procainamide, 100 mg/mL, repackaged in clear glass vials was 193 days when stored at either 23ºC and ETL or 5ºC or PFL. If diluted further to 3 mg/mL with normal saline and packaged in PVC bags, the drug was also stable for 193 days at either 23ºC and ETL or 5°C and PFL.
Italian Intersociety Recommendations on pain management in the emergency setting (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC).

BACKGRAUND Pain is the primary reason for admission to the Emergency Department (ED). However, the management of pain in this setting is often inadequate because of opiophagia, fear of excessive sedation, and fear of compromising an adequate clinical assessment. METHODS An intersociety consensus conference was held in 2010 on the assessment and treatment of pain in the emergency setting. This report is the Italian Intersociety recommendations on pain management in the emergency department setting. RESULTS The list of level A recommendations includes: 1) use of IV acetaminophen for opioid sparing properties and reduction of opioid related adverse events; 2) ketamine-midazolam combination preferred over fentanyl-midazolam fentanyl-propofol in pediatric patients; 3) boluses of ketamine IV (particularly in the population under the age of 2 years and over the age of 13) can lead to impairment of the upper airways, including the onset of laryngospasm, requiring specific expertise and skills for administration; 4) the use of ketamine increases the potential risk of psychomotor agitation, which can happen in up to 30% of adult patients (this peculiar side effect can be significantly reduced by concomitant systemic use of benzodiazepines); 5) for shoulder dislocations and fractures of the upper limbs, the performance of brachial plexus block reduces the time spent in ED compared to sedation; 6) pain relief and the use of opioids in patients with acute abdominal pain do not increase the risk of error in the diagnostic and therapeutic pathway in adults; 7) in newborns, the administration of sucrose reduces behavioural responses to blood sampling from a heel puncture; 8) in newborns, breastfeeding or formula feeding during the procedure reduces the measures of distress; 9) in pediatric patients, non-pharmacological techniques such as distraction, hypnosis and cognitive-behavioural interventions reduce procedural pain caused by the use of needles; 10) in pediatric patients, preventive application of eutectic mixtures of prilocaine and lidocaine allows arterial and venous samples to be taken in optimum conditions; 11) in pediatric patients, the combination of hypnotics (midazolam) and N2O is effective for procedural pain, but may be accompanied by loss of consciousness. CONCLUSION The diagnostic-therapeutic pathway of pain management in emergency should be implemented, through further interdisciplinary trials, in order to improve the EBM level of specific guidelines.
IoT based air pollution monitoring and predictor system on Beagle bone black

Urban air pollution rate has grown to alarming state across the India. Most of the cities are facing issue of poor air quality which fails to meet standards of air for good health. It is indeed necessary to develop an air pollution measurement and prediction system for a smart city. This proposed work acquires carbon dioxide and carbon monoxide level in the air along with Global Positioning System (GPS) location by using pollution detection sensor and uploads into Azure cloud services. Low cost embedded Beagle bone board along with gas sensors are used for data acquisition. Microsoft's Azure Machine learning service is used to predict the pollution metrics with the help of previous data. Processed data is fetched and represented by Power BI tool. Calibrated gas sensor data is fetched from sensors and successfully uploaded into cloud. Data stored in cloud is utilized by different cloud services to make the data meaningful. Proposed system is implemented and useful to monitor and reduce the pollution in a smart city by avoiding the pollution causes.