Miracle-dz/UniFAR-FTUs huggingface dataset:
Transmembrane Residues Together with the Amino Terminus Limit the Response of the Parathyroid Hormone (PTH) 2 Receptor to PTH-related Peptide*

The mechanisms of ligand binding and receptor activation for G-protein-coupled receptors in the secretin/parathyroid hormone (PTH) receptor subfamily are not understood. The PTH1 receptor (PTH1R) signals in response to both PTH and parathyroid hormone-related peptide (PTHrP), whereas the PTH2 receptor (PTH2R) responds only to PTH, not to PTHrP. To locate PTHrP discriminatory domains in the PTH2R, we generated PTH1R/PTH2R chimeras in which the extracellular amino-terminal domains were exchanged. Production of cAMP in response to 1 μm PTHrP or PTH was identical in cells expressing the PTH1R with the PTH2R amino terminus and in cells expressing the PTH2R with the PTH1R amino terminus. The ability of the chimeric receptor with the PTH2R amino terminus to respond fully to PTHrP showed that the body of the PTH2R must contain sites that limit the response to PTHrP. Mutations to PTH1R sequence were therefore made in each of the seven transmembrane domains of the PTH2R. Mutations in transmembrane domains 3 and 7 resulted in receptors able to respond to PTHrP. Thus, residues in more than one domain form a barrier or filter, allowing the receptor to discriminate between different ligands.
ATP2B1 gene Silencing Increases Insulin Sensitivity through Facilitating Akt Activation via the Ca2+/calmodulin Signaling Pathway and Ca2+-associated eNOS Activation in Endothelial Cells

Endothelial cell insulin resistance may be partially responsible for the higher risk of atherosclerosis and cardiovascular disease in populations with insulin resistance and type 2 diabetes mellitus (T2DM). A genome-wide association study revealed a significant association between the ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) gene and T2DM in two community-based cohorts from the Korea Association Resource Project. However, little is known about the implication of the ATP2B1 gene on T2DM. In the present study, we investigated the role of the ATP2B1 gene in endothelial cell insulin sensitivity. ATP2B1 gene silencing resulted in enhanced intracellular calcium concentrations and increased insulin-induced Akt activation compared to that in the negative siRNA-transfected HUVECs (Human Umbilical Vein Endothelial Cells). The elevated insulin sensitivity mediated by ATP2B1 gene silencing was Ca2+/calmodulin-dependent, as verified by administration of the calcium chelator BAPTA-AM or the calmodulin-specific antagonist W7. Moreover, higher levels of phosphorylation of eNOS (Ser1177) were observed in ATP2B1-silenced HUVECs. In addition to BAPTA-AM and W7, L-NAME, an eNOS antagonist, abolished insulin-induced Akt phosphorylation at Ser473 in both si-Neg and si-ATP2B1-transfected endothelial cells. These results indicate that the enhanced insulin sensitivity in ATP2B1-silenced endothelial cells is alternatively dependent on an increase in intracellular Ca2+ and the subsequent activation of the Ca2+/calmodulin/eNOS/Akt signaling pathway. In summary, ATP2B1 gene silencing increased insulin sensitivity in endothelial cells by directly modulating the Ca2+/calmodulin signaling pathway and via the Ca2+/calmodulin/eNOS/Akt signaling pathway alternatively.
Predicting large fetuses at birth: do multiple ultrasound examinations and longitudinal statistical modelling improve prediction?

Predicting large fetuses at birth has long been a challenge in obstetric practice. We examined whether ultrasound examinations at multiple times during pregnancy improve the accuracy of prediction using repeated, longitudinal statistical modelling, and whether adding maternal characteristics improves the accuracy of prediction. We used data from a previous study conducted in Norway and Sweden from 1986 to 1989 in which each pregnant woman had four ultrasound examinations at around 17, 25, 33 and 37 weeks of gestation. At birth, infant size was classified as large-for-gestational age (LGA, >90th centile) and macrosomia (>4000 g) or not. We used a longitudinal random effects model with quadratic fixed and random effects to predict term LGA and macrosomia at birth. Receiver-operator curves and mean-squared error were used to measure accuracy of the prediction. Ultrasound examination around 37 weeks had the best accuracy in predicting LGA and macrosomia at birth. Adding multiple ultrasound examinations at earlier gestations did not improve the accuracy. Adjusting for maternal characteristics had limited impact on the accuracy of prediction. Thus, a single ultrasound examination at late gestation close to birth is the simplest method currently available to predict LGA and macrosomia.
Long-Term Care of the Liver Allograft Recipient

As outcomes after liver transplant surgery continue to improve, management of the long-term consequences of the procedure and the associated immunosuppression become increasingly important. Liver allograft recipients have, compared with age and sex-matched controls, increased risk for cardiovascular and cerebrovascular events and death, for bone disease, and for some cancers. Early recognition and treatment of modifiable risk factors, especially of hypertension (present in up to 77% recipients), diabetes (in up to 22%), obesity (up to 40%), renal impairment (in up to 50%), and hyperlipidemia (in up to 66%) are necessary to maintain prolonged and healthy survival. Early recognition of de novo cancers (which occur in up to 26% recipients) indicates the need for additional monitoring for skin cancer and lymphoproliferative disorders, as well as cancers of the lung, colon, and upper gastrointestinal track. Early recognition of bone disease and appropriate intervention will allow introduction of strategies to reduce bone fracture. In this article, we review the evidence for the extent and treatment of these modifiable conditions in the allograft recipient.
Specific inactivation of yeast hexokinase induced by xylose in the presence of a phosphoryl donor substrate.

Yeast hexokinase can be inactivated by xylose in the presence of MgATP. The effect is highly specific for xylose. The nucleotide and divalent metal specificities are similar to those of the hexokinase reaction. The dissociation constants, as deduced from the effect of the concentration of the inactivating agents on the rate of inactivation, are about 0.2 mM for MgATP and about 10 mM for xylose. These values are similar to the Michaelis constant and Ki value for these compounds as substrate and competitive inhibitor, respectively, in the hexokinase reaction. Sugars capable of binding at the sugar substrate subsite protect against xylose-induced inactivation with efficiencies closely related to their respective Ks or Ki values. The dissociation constant of glucose, as deduced from its protective effect, is about 0.04 mM. When resting yeast is incubated aerobically with 0.1 M xylose and 1% ethanol, a marked loss of hexokinase activity takes place. Among the possible mechanisms of this irreversible inactivation there is evidence against the involvement of phosphorylation or glycosylation of the protein as well as of a change in its degree of polymerization.
Climate change and invasion by intracontinental range-expanding exotic plants: the role of biotic interactions.

BACKGROUND AND AIMS In this Botanical Briefing we describe how the interactions between plants and their biotic environment can change during range-expansion within a continent and how this may influence plant invasiveness. SCOPE We address how mechanisms explaining intercontinental plant invasions by exotics (such as release from enemies) may also apply to climate-warming-induced range-expanding exotics within the same continent. We focus on above-ground and below-ground interactions of plants, enemies and symbionts, on plant defences, and on nutrient cycling. CONCLUSIONS Range-expansion by plants may result in above-ground and below-ground enemy release. This enemy release can be due to the higher dispersal capacity of plants than of natural enemies. Moreover, lower-latitudinal plants can have higher defence levels than plants from temperate regions, making them better defended against herbivory. In a world that contains fewer enemies, exotic plants will experience less selection pressure to maintain high levels of defensive secondary metabolites. Range-expanders potentially affect ecosystem processes, such as nutrient cycling. These features are quite comparable with what is known of intercontinental invasive exotic plants. However, intracontinental range-expanding plants will have ongoing gene-flow between the newly established populations and the populations in the native range. This is a major difference from intercontinental invasive exotic plants, which become more severely disconnected from their source populations.
Making it personal: web users and algorithmic personalisation

This thesis investigates how web users negotiate and engage with contemporary algorithmic personalisation practices; that is, practices which seek to infer (via data tracking mechanisms and other algorithmic means) a user’s habits, preferences or identity categorisations in order to ‘make personal’ some component of that user’s web experience. Drawing on thirty-six semi-structured interviews, I employ a qualitative methodology that seeks to bridge the gap between critical theorisations of algorithmic personalisation and the negotiations of web users themselves who encounter algorithmic personalisation in everyday life. To do this I focus on three sites of investigation. I first examine privacy tool Ghostery and the ways in which Ghostery users’ negotiate their positions as data-tracked subjects, especially in relation to privacy, knowledge and their sense of self. I then investigate Facebook’s autoposting apps as examples of algorithmic personalisation that act on the user’s behalf, and draw on the accounts of Facebook app users to explore themes such as identity performance, autonomous control and algorithmic governance. Finally I examine users’ engagement with the ‘predictive powers’ (Google Now, 2014) of the personalisation app Google Now, specifically in regards to notions of user trust, expectation and speculation. My critical enquiries produced a number of themes that tie this thesis together. Central were: the epistemic uncertainties that emerged as trust and anxiety in participant responses; the implications for a performative understanding of selfhood when algorithmic personalisation intervenes in user self-articulation; the (asymmetrical) data-for-services exchange which web users must negotiate with commercial data trackers; and the struggle for autonomy between user and system that algorithmic personalisation creates. The thesis also argues that algorithmic personalisation demands that web users’ identities be constituted as both a stable and fixable ‘single identity’, but also as recursively reworkable, dividualised and endlessly expressable entities.
JOURNAL CLUB: Scatter Radiation Dose From Digital Screening Mammography Measured in a Representative Patient Population.

OBJECTIVE The purpose of this study was to quantify the amount of scatter radiation received at the skin surface overlying the thyroid gland, salivary gland, lens of the eye, sternum, and uterus during a routine screening digital mammographic examination measured in a representative patient population. SUBJECTS AND METHODS The subjects were 207 women without symptoms with varied body mass indexes who underwent annual screening mammography while wearing six optically stimulated luminescence dosimeters placed at the bridge of the nose, right submandibular gland, right and left thyroid lobes, mid sternum, and 2 cm caudal to the umbilicus to assess scatter radiation dose to the skin. RESULTS The average scatter radiation doses at the skin surface during digital screening mammography in the representative population of women were as follows: overlying the right lobe of the thyroid, 0.24 mGy; left lobe of the thyroid, 0.25 mGy; salivary gland, 0.2 mGy; bridge of the nose, 0.025 mGy; sternum, 0.87 mGy; and umbilicus, 0.011 mGy. The scatter radiation doses at the umbilicus and the bridge of the nose were too low to measure with statistical confidence. Scatter radiation dose increased with increasing body mass index and increasing breast compression thickness. CONCLUSION Scatter radiation dose at the skin overlying organs of interest is a small fraction of the entrance skin dose to the breast. The low levels of scatter radiation measured do not support delaying clinically indicated mammography during early pregnancy.
BIOINFORMATICS APPLICATIONS

Summary: R/DWD is an extensible package for classiﬁcation. It is built based on a recently developed powerful classiﬁcation method called distance weighted discrimination (DWD). DWD is related to, and has been shown to be superior to, the support vector machine in situations that are fundamental to bioinformatics, such as very high dimensional data. DWD has proven to be very useful for several fundamental bioinformatics tasks, including classiﬁcation, data visualization and removal of biases, such as batch effects. Earlier DWD implementations, however, relied on Matlab, which is not free and requires a license. The major contribution of the R/DWD package is an implementation that is completely in R and thus can be used without any requirements for licensing or software purchase. In addition, R/DWD also provides efﬁcient solvers for second-order-cone-programming and quadratic programming. Availability and implementation: The package is freely available from cran.r-project.org.
The relationship of macular pigment optical density to serum lutein in retinitis pigmentosa.

PURPOSE To determine whether macular pigment optical density (MPOD) is related to serum lutein or serum zeaxanthin in patients with retinitis pigmentosa. METHODS The authors measured MPOD with heterochromatic flicker photometry, serum lutein and serum zeaxanthin by high performance liquid chromatography, and central foveal retinal thickness by optical coherence tomography (OCT) in 176 patients (age range, 18-68 years) with typical forms of retinitis pigmentosa; 37 (21%) of these patients had cystoid macular edema (CME) by OCT. The authors performed multiple regression analysis with MPOD as the dependent variable and with log(e) serum lutein and log(e) serum zeaxanthin as independent variables adjusting for age, sex, iris color, central foveal retinal thickness, and, in some analyses, serum total cholesterol. RESULTS MPOD increased with increasing serum lutein (P = 0.0017) and decreased with increasing serum total cholesterol (P = 0.0025) but was unrelated to serum zeaxanthin. MPOD was higher in patients with brown irides than in patients with lighter irides (P = 0.014) and was nonmonotonically related to central foveal retinal thickness (P < 0.0001), being lower in eyes with more photoreceptor cell loss and in eyes with moderate to marked CME. CONCLUSIONS MPOD is independently related to serum lutein, serum total cholesterol, iris color, and central foveal retinal thickness in patients with retinitis pigmentosa.
From preferences to policies in coalition governments—Unpacking policy making in European higher education

This article focuses on the role of political parties for policy making, and it traces the development from party preferences over coalition positions to policy proposals. The main argument is that parties with more similar preferences agree on more encompassing sets of policies, and that if a coalition formulates a policy in its agreement the chances for a policy proposal are higher. However, the need to negotiate the coalition agreement with other parties mediates the influence of partisan preferences. The article is based on a qualitative content analysis of documents as well as expert interviews from three West European countries and focuses on higher education policy. The results show preferences of governing parties influence policy proposals also in situations of coalition government. Furthermore, coalition agreements are found to be central documents in policy making as they limit veto capacities and indicate where substantial policy change is likely.
Assessment of channel propagation conditions for FDD LTE transmissions in the spanish high-speed railways

Railway and telecommunication companies have showed a great interest in deploying broadband mobile wireless networks in high-speed trains with the aim of supporting both provisioning of passenger services and automatic train control and signaling. This motivates the study of broadband wireless communications between a base-station transmitter and a mobile receiver whose antennas are placed on the top a high-speed train carriage. In this work, propagation measurements in a commercial high-speed line in Spain were carried out by employing standard-compliant Long Term Evolution (LTE) signals. The Signal-to-Noise Ratio (SNR) values along the commercial line were measured and parameters characterizing the channel, such as the Power Delay Profile (PDP), were estimated. Finally, the bounds of the unconstrained capacity were also derived from different train velocities up to 200 km/h.
Research on Overlapping Individuals in MOEAs: Causation, Probability for Quantity and Influence on Assessment

The existence of overlapping individuals in the evolution population means that the MOEAs do a redundant work of searching the overlapping region in the searching space, which weakens the ability of the MOEAs to exploit new feasible regions. Hence the running efficiency of the algorithm turns to be lower. This paper focused on the overlapping individuals in MOEAs. We probed into the causation why overlapping individuals come into being and then gave a probability analysis of the quantity with the statistical results supported. We also managed to find the influence that the overlapping individuals have on the assessment of the algorithm. The experiments illustrated that MOEAs with overlapping individuals removed gained solution sets with better diversity than that obtained by the original ones. The famous NSGA-II was taken as the example MOEA and the conclusion can be extended to other MOEAs.
How well does charge reparametrisation account for solvent screening in molecular mechanics calculations? The example of myosin

The rate constant of an enzyme-catalysed reaction is one of the major target properties to understand protein function. Atomic-detail computer simulations can in principle be used to estimate rate constants from the energy profile along the reaction coordinate. For such simulations, molecular mechanics is combined with a quantum description of the reaction process. In molecular mechanics calculations, the electrostatic field is represented by the Coulomb potential of partial atomic charges which have been parametrised for small building blocks in vacuum and transferred to the macromolecule. In aqueous solution, however, the electrostatic interactions are affected by the solvent polarization. While this can be described by numerically solving the Poisson-Boltzmann equation, it is computationally expensive. A simple approximation to this is to optimally reproduce the electrostatic potential in solution by reparametrising the partial atomic charges in such a way that a simple Coulomb potential can still be used. Such a procedure would allow to perform fast calculations of reaction processes in proteins while accounting for the solvent screening effect. Here, this method is tested on myosin, a motor protein that is both an enzyme and exists in very different conformations.
Monozygotic boys with fragile X syndrome

Monozygotic twin boys with fragile X syndrome underwent thorough genetic, psychiatric, neurological, and language evaluations at 10 years of age. They both demonstrated physical features, speech and language difficulties, social problems, and attentional deficits that characterize the behavioural phenotype of fragile X syndrome. Despite identical genetic constitutions, there were important developmental and behavioural heterogeneities. Twin A showed less social interaction and symbolic play and more speech and language dysfunction than twin B. Twin A also had significantly larger caudate volumes. It is suggested that the Xq27.3 anomaly may not be sufficient to account for all the behavioural phenotypic and neuroanatomical features of fragile X syndrome.
Using Human Patient Simulation to Prepare Student Pharmacists to Manage Medical Emergencies in an Ambulatory Setting

Objective. To implement a simulation-based educational experience focused on medical emergencies in an ambulatory pharmacy setting. Design. Second-year student pharmacists were assigned randomly to groups and played the role of pharmacists in a community pharmacy setting in which a simulated patient experienced 1 of 5 emergency scenarios: medication-related allergic reaction, acute asthma attack, hypoglycemia, myocardial infarction, and stroke. The students were expected to use patient assessment techniques to determine which emergency the simulated patient was experiencing and the appropriate intervention. Following each simulation, a debriefing session was conducted. Assessment. Eighty-two student pharmacists completed the simulation activity. Ninety-three percent of student groups correctly identified the emergency. A post-activity survey instrument was administered, and 83% of responders indicated this activity was effective or very effective. Conclusion. Simulation of emergencies seen in an ambulatory pharmacy setting allowed students to assert knowledge, practice communication skills, apply assessment techniques, and work as a team in a low-risk environment.
General practitioners’ perceptions of introducing near-patient testing for common infections into routine primary care: A qualitative study

Objective. Near-patient tests are promoted for guiding management of common infections in primary care with a view to enhancing the effectiveness of prescribing decisions and containing antimicrobial resistance. Changes in clinical practice should be based on appraisals of the factors that might influence change, viewed from the perspective of those expected to implement the change. We therefore explored the views of general practitioners concerning the possible introduction of near-patient tests for managing common infections. Design. Qualitative semi-structured interview study. Interviews were recorded and analysed using thematic content analysis. Setting. General practices in south-east Wales, UK. Subjects. A total of 26 general practitioners (GPs) from high fluroquinolone antibiotics prescribing practices and 14 GPs from practices that prescribed fluroquinolones close to the south-east Wales mean. Results. There was strong enthusiasm for a hypothetical near-patient, finger-prick blood tests that could distinguish viral from bacterial infections. Many GPs emphasized that such tests would be valuable in “selling” decisions not to prescribe antibiotics to patients. Concerns included limited additional useful information to guide prescribing above clinical diagnosis alone, that patients might deteriorate even if the tests correctly identified a viral aetiology, and that GPs would need to be convinced by research evidence supporting uptake. Several indicated that tests would be useful only for a limited number of patients and they were concerned by time pressures, apparatus maintenance and quality control, cost, and possible objections from patients, especially children. Conclusions. Despite GP enthusiasm for the concept of a rapid test to distinguish viral from bacterial infection, strategies to promote uptake would be enhanced if concerns were addressed regarding the importance and feasibility of such tests in daily practice.