Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Assay of Gi/o-Linked G Protein-Coupled Receptor Coupling to Potassium Channels Provides New Insights into the Pharmacology of the Group III Metabotropic Glutamate Receptors

The group III metabotropic glutamate receptors (mGluRs) represent a family of presynaptically expressed G-protein-coupled receptors (GPCRs) with enormous therapeutic potential; however, robust cellular assays to study their function have been difficult to develop. We present here a new assay, compatible with traditional high-throughput screening platforms, to detect activity of pharmacological ligands interacting with Gi/o-coupled GPCRs, including the group III mGluRs 4, 7, and 8. The assay takes advantage of the ability of the Gβγ subunits of Gi and Go heterotrimers to interact with G-protein regulated inwardly rectifying potassium channels (GIRKs), and we show here that we are able to detect the activity of multiple types of pharmacophores including agonists, antagonists, and allosteric modulators of several distinct GPCRs. Using GIRK-mediated thallium flux, we perform a side-by-side comparison of the activity of a number of commercially available compounds, some of which have not been extensively evaluated because of the previous lack of robust assays at each of the three major group III mGluRs. It is noteworthy that several compounds previously considered to be general group III mGluR antagonists have very weak activity using this assay, suggesting the possibility that these compounds may not effectively inhibit these receptors in native systems. We anticipate that the GIRK-mediated thallium flux strategy will provide a novel tool to advance the study of Gi/o-coupled GPCR biology and promote ligand discovery and characterization.
The redshift distribution of FIRST radio sources at 1 mJy

We present spectra for a sample of radio sources from the FIRST survey, and use them to define the form of the redshift distribution of radio sources at mJy levels. We targeted 365 sources and obtained 46 redshifts (13 per cent of the sample). We find that our sample is complete in redshift measurement to R∼18.6, corresponding to z∼0.2. Galaxies were assigned spectral types based on emission-line strengths. Early-type galaxies represent the largest subset (45 per cent) of the sample and have redshifts 0.15≲z≲0.5; late-type galaxies make up 15 per cent of the sample and have redshifts 0.05≲z≲0.2; starbursting galaxies are a small fraction (∼6 per cent), and are very nearby (z≲0.05). Some 9 per cent of the population have Seyfert 1/quasar-type spectra, all at z≳0.8, and 4 per cent are Seyfert 2 type galaxies at intermediate redshifts (z∼0.2). Using our measurements and data from the Phoenix survey (Hopkins et al.), we obtain an estimate for N(z) at S1.4 GHz≥1 mJy and compare this with model predictions. At variance with previous conclusions, we find that the population of starbursting objects makes up ≲5 per cent of the radio population at S∼1 mJy.
Evaluating alternative, diverse cropping systems that include canola, wheat, and red clover in Iowa

iii CHAPTER 1. GENERAL INTRODUCTION . 1 Dissertation organization . 5 References . 7 CHAPTER 2. COMPARING CORN FOLLOWING RED CLOVER GREEN MANURE WITH CORN FOLLOWING SOYBEAN . 12 Abstract . 12 Introduction . 13 Materials and Methods . 15 Results . 20 Discussion . 25 References . 32 CHAPTER 3. COOL-SEASON CROPPING SEQUENCES FEATURING CANOLA AND WHEAT . 42 Abstract . 42 Introduction . 43 Materials and Methods . 45 Results and Discussion . 49 Conclusion . 55 References . 56 CHAPTER 4. AGRONOMIC, ECONOMIC, AND VEGETATIVE GROUNDCOVER PERFORMANCE OF ALTERNATIVE CROPPING SYSTEMS IN IOWA . 68 Abstract . 68 Introduction . 69 Materials and Methods . 72 Results and Discussion . 79 Summary . 88 References . 91 CHAPTER 5. GENERAL CONCLUSION . 108 ACKNOWLEDGEMENTS . 111
Reverse (Convex) Conchal Bowl: Report of Eight Cases and Its Correction by Modified Conchoplasty Technique

Many different congenital malformations of the external ear are encountered in otology and plastic surgery practice. However, there has been only one report in the literature of reverse (convex) conchal deformity in otherwise normal ears. Eight such cases were encountered in the combined otology and plastic surgery practice at the authors’ institution. The condition was bilateral in two patients and unilateral in six patients; these patients had no other otological abnormalities. Two patients sought surgical correction. Modified conchoplasty, done by excising and replacing the conchal cartilage in reverse fashion, is presented. Controversies surrounding the embryogenesis of concha are also addressed.
Autonomous Software

Industrial-strength software is reaching a level of inherent complexity which tends to make an effective development, deployment and administration impossible. This has led to a rapidly growing interest in the notion of autonomous software, that is, software which takes over, and encapsulates, action choice and responsibility from its users and operators so that it can handle its complexity on its own. A key condition for the broad acceptance of autonomous software is the availability of a clear notion of autonomy as a software property upon which precise specification schemes for autonomous software systems can be build. There are diverse approaches available in computer science that are useful in this respect. This chapter describes a generic autonomy specification framework which gives an integrated view of these approaches and of the state of the art in specifying autonomy as a software property.
Energy, current, and success in defibrillation and cardioversion: clinical studies using an automated impedance-based method of energy adjustment.

The purposes of this study were two. First, we wanted to evaluate in patients a technique for automated adjustment of selected energy for defibrillation or cardioversion based on transthoracic impedance. Second, we wanted to define the relationship of peak current and shock success in various arrhythmias. Applying a previously validated method of predicting transthoracic impedance in advance of any shock, we modified defibrillators to automatically double the operator-selected energy if the predicted impedance exceeded 70 omega. Success rates of shocks given for ventricular and atrial arrhythmias from these modified energy-adjusting defibrillators were compared with success rates for shocks given from standard defibrillators. We prospectively collected data on 347 patients who received a total of 1009 shocks. Low-energy (100 J) shocks given to high-impedance (greater than or equal to 70 omega) patients had a poor success rate; in such high-impedance patients significant improvement in shock success rate was achieved by the energy-adjusting defibrillators. For example, when 100 J shocks were selected for high-impedance patients in ventricular fibrillation the energy-adjusting defibrillators achieved a shock success rate of 75%, whereas standard defibrillators achieved a shock success rate of only 36% (p less than .01). Similar improvements were seen for ventricular tachycardia and atrial fibrillation. Thus, automated energy adjustment based on transthoracic impedance is a beneficial approach to defibrillation and cardioversion. For ventricular fibrillation, atrial fibrillation, and atrial flutter there was a clear relationship between peak current and shock success. (ABSTRACT TRUNCATED AT 250 WORDS)
Adverse Drug Events: Database Construction and in Silico Prediction

Adverse drug events (ADEs) are the harms associated with uses of given medications at normal dosages, which are crucial for a drug to be approved in clinical use or continue to stay on the market. Many ADEs are not identified in trials until the drug is approved for clinical use, which results in adverse morbidity and mortality. To date, millions of ADEs have been reported around the world. Methods to avoid or reduce ADEs are an important issue for drug discovery and development. Here, we reported a comprehensive database of adverse drug events (namely MetaADEDB), which included more than 520,000 drug-ADE associations among 3059 unique compounds (including 1330 drugs) and 13,200 ADE items by data integration and text mining. All compounds and ADEs were annotated with the most commonly used concepts defined in Medical Subject Headings (MeSH). Meanwhile, a computational method, namely the phenotypic network inference model (PNIM), was developed for prediction of potential ADEs based on the database. The area under the receive operating characteristic curve (AUC) is more than 0.9 by 10-fold cross validation, while the AUC value was 0.912 for an external validation set extracted from the US-FDA Adverse Events Reporting System, which indicated that the prediction capability of the method was reliable. MetaADEDB is accessible free of charge at http://www.lmmd. org/online_services/metaadedb/. The database and the method provide us a useful tool to search for known side effects or predict potential side effects for a given drug or compound.
Activation of antibacterial autophagy by NADPH oxidases

Autophagy plays an important role in immunity to microbial pathogens. The autophagy system can target bacteria in phagosomes, promoting phagosome maturation and preventing pathogen escape into the cytosol. Recently, Toll-like receptor (TLR) signaling from phagosomes was found to initiate their targeting by the autophagy system, but the mechanism by which TLR signaling activates autophagy is unclear. Here we show that autophagy targeting of phagosomes is not exclusive to those containing TLR ligands. Engagement of either TLRs or the Fcγ receptors (FcγRs) during phagocytosis induced recruitment of the autophagy protein LC3 to phagosomes with similar kinetics. Both receptors are known to activate the NOX2 NADPH oxidase, which plays a central role in microbial killing by phagocytes through the generation of reactive oxygen species (ROS). We found that NOX2-generated ROS are necessary for LC3 recruitment to phagosomes. Antibacterial autophagy in human epithelial cells, which do not express NOX2, was also dependent on ROS generation. These data reveal a coupling of oxidative and nonoxidative killing activities of the NOX2 NADPH oxidase in phagocytes through autophagy. Furthermore, our results suggest a general role for members of the NOX family in regulating autophagy.
Differentiating Interpersonal Correlates of Depressive Symptoms and Social Anxiety in Adolescence: Implications for Models of Comorbidity

Research on psychosocial correlates of depression and social anxiety often has not accounted for their comorbidity. Differentiating correlates of depression and social anxiety may inform the development of comorbidity models. Building on research linking both disorders to interpersonal dysfunction, this study examined interpersonal correlates of depressive symptoms and social anxiety in nonreferred early adolescent (M age = 13.46) girls (n = 83), controlling for comorbid symptoms. Although both showed significant bivariate correlations with peer and family variables, partial correlations revealed that social anxiety (controlling for depressive symptoms) was more strongly related to peer variables (e.g., social competence and trust and communication in friendships), whereas depressive symptoms (controlling for social anxiety) were more strongly related to family variables (e.g., lower trust and greater alienation and conflict). Comorbid girls showed heightened peer and family alienation compared to purely dysphoric or anxious girls. Implications for casual models of comorbidity and for understanding poorer outcomes associated with comorbidity and discussed.
Influence of the home environment on diet quality and weight status of adolescents : a social ecological framework

This cross-sectional study assessed the association of psychological, social, and environmental factors in the home environment with diet quality and Body Mass Index-for Age percentile (BMI-for-Age percentile) in a sample of 103 mother-adolescent dyads. Adolescents in the lowest home environment tertile had poorer diet quality, with lower compliance for total fruit, whole fruit, total vegetable, empty calories, and overall diet quality. Availability of healthy foods (p=0.00), healthy eating attitude (p=0.01), and accessibility to unhealthy foods (p=0.04) in the home were the strongest predictors of diet quality; whereas self-efficacy (p=0.02) and availability of healthy foods (p=0.02) emerged as significant predictors of BMI-for-Age percentile. These results highlight the role of the home environment in determination of diet quality and BMI of adolescents.
Studies of the relationship between Schistosoma and their intermediate hosts. III. The genus Biomphalaria and Schistosoma mansoni from Egypt, Kenya, Sudan, Uganda, West Indies (St. Lucia) and Zaire (two different strains: Katanga and Kinshasa)

ABSTRACT The compatibility between strains of Schistosoma mansoni from Egypt, Kenya, Sudan, Uganda, the West Indies, and Zaire (two strains which came from Katanga and from Kinshasa), and various species and strains of Biomphalaria, i.e., Biomphalaria pfeifferi, B. alexandrina, B. glabrata and B. camerunensis was investigated. Data as mortality, rate of infection of the surviving snails, duration of infection, cercarial production per day per positive snail, etc., were observed. The main emphasis was placed on determining the total cercarial production per 100 exposed snails for each snail population. It was possible to infect all the tested populations of B. pfeifferi with the various strains of S. mansoni, but the observation as e.g. TCP/100 exposed snails varied greatly according to the population of snail and the strain of S. mansoni. The results for the remaining species of Biomphalaria varied greatly, depending on the combination, e.g. B. alexandrina was only susceptible to the local S. mansoni from Egypt. The highest TCP/100 exposed snails was more than 1 million for the strains of S. mansoni from Egypt, Kenya and the West Indies in B. alexandrina, B. pfeifferi and B. glabrata, respectively. The next group, with a TCP/100 exposed snails on 7 – 800 000 consists of S. mansoni from Sudan, Uganda and Zaire (Katanga) all in B. pfeifferi. The last tested strain of S. mansoni, Zaire (Kinshasa) yielded a cercarial production on 500 000 per 100 exposed snails in B. pfeifferi and B. camerunensis. The shortest prepatent period, 19 days, was observed for S. mansoni from Kinshasa, Zaire, in B. camerunensis, and the longest prepatent period, 25 days, was found for strains from Egypt and from the West Indies in B. alexandrina and B. glabrata, respectively. In general, a very long duration of infection, lasting up to 200 days, was observed.
Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact

Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation-induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α-smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor-β1 (TGF-β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme-linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography-mass spectrometry analysis. The deposition of collagen I and α-SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF-β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1-regulated TGF-β1/Smad signaling was involved in silica inhalation-induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling.
A Variable 0.58-2.44 Hz Quasi-periodic Oscillation in the Eclipsingand Dipping Low-Mass X-Ray Binary EXO 0748–676

We report the discovery of a quasi-periodic oscillation (QPO) in data obtained with the Rossi X-Ray Timing Explorer of the dipping and eclipsing low-mass X-ray binary EXO 0748-676. The QPO had a frequency between 0.58 and 2.44 Hz changing on timescales of a few days and an rms amplitude between 8% and 12%, and it was detected in the persistent emission during dips and during type I X-ray bursts. During one observation, when the count rate was a factor of 2-3 higher than otherwise, the QPO was not detected. The strength of the QPO did not significantly depend on photon energy and is consistent with being the same in the persistent emission, both during and outside the dips and during type I X-ray bursts. Frequency shifts were observed during three of the four X-ray bursts. We argue that the QPO is produced by the same mechanism as the QPO recently found by Jonker et al. in 4U 1323-62. Although the exact mechanism is not clear, it is most likely related to the high inclination of both systems. An orbiting structure in the accretion disk that modulates the radiation from the central source seems the most promising mechanism.
The effects of prenatal maternal stress on children's cognitive development: Project Ice Storm

There exists considerable research on the effects of prenatal maternal stress on offspring. Animal studies, using random assignment to experimental and control groups, demonstrate the noxious effects of prenatal maternal stress on physical, behavioural and cognitive development. The generalizability of these results to humans is problematic given that cognitive attributions moderate reactions to stressors. In humans, researchers have relied upon maternal anxiety or exposure to life events as proxies for the stressors used with animals. Yet, the associations between maternal anxiety or potentially non-independent life events and problems in infants are confounded by genetic transmission of temperament from mother to child. We summarize the literature on prenatal maternal stress and infant cognitive development, leading to the conclusion that the human literature lacks the ability to separate the effects of the objective exposure to a stressor and the mother's subjective reaction. We then describe our prospective Project Ice Storm in which we are following 150 children who were exposed in utero to a natural disaster. We demonstrate significant effects of the objective severity of exposure on cognitive and language development at age two years with important moderating effects of the timing during pregnancy. The implications of our findings are discussed.
Analysis of low flow indices under varying climatic conditions in Poland

Changes in low flow indices under future climates are estimated for eight catchments in Poland. A simulation approach is used to derive daily flows under changing climatic conditions, following RCP 4.5 and RCP 8.5 emission scenarios. The HBV rainfall–runoff model is used to simulate low flows. The model is calibrated and validated using streamflow observations from periods 1971–2000 and 2001–2010. Two objective functions are used for calibration: Nash–Sutcliffe and log transformed Nash–Sutcliffe. Finally, the models are run using the bias-corrected precipitation and temperature data simulated by GCM/RCM models for the periods 2021–2050 and 2071–2100. We estimate low flow indices for the simulated time series, including annual minima of 7-day mean river flows and number, severity and duration of low flow events. We quantify the biases of low flow indices by N-way analysis of variance (ANOVA) analysis and Tukey test. Results indicate a large effect of climate models, as well as objective functions, on the low flow indices obtained. A comparison of indices from the two future periods with the reference period 1971–2000 confirms the trends obtained in previous studies, in the form of a projected decrease in the frequency and intensity of low flow events.
Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

Statins for Prevention of Atrial Fibrillation. Background: Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti‐inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation (NCT00252967).
THE ONSET OF ELECTRICAL COMMUNICATION BETWEEN CELLS IN THE DEVELOPING STARFISH EMBRYO

In many adult tissues electrical measurements have shown the cells to be joined by regions of low electrical resistance, indicating that there is relatively free movement of small ions between them. Similar junctions have been identified electrically in some embryonic tissues (see Ito and Hori, 1966; Potter, Furshpan, and Lennox, 1966 ; Sheridan, 1968; for reviews, see Loewenstein, 1966; and Furshpan and Potter, 1968) . In the newt Triturus pyrrhogaster (Ito and Hori, 1966) electrical coupling is found between the two cells resulting from the first cleavage, and thereafter between all blastomeres . It also occurs between all cells in early cleavage stages of the teleost fish Fundulus (Bennett and Trinkaus, 1968) . However, in the echinoderms Asterias (starfish) and Echinarachnius (sand dollar) no junctions of low resistance are found between the first two blastomeres (Ashman, Kanno, and Loewenstein, 1964, and Loewenstein, 1966) . It is of interest, therefore, to determine if and when electrical coupling does arise between the cells of echinoderm embryos, and whether the appearance of this coupling can be correlated with their developmental properties. The results of our electrical measurements on eggs of Asterias forbesi are the subject of this paper . They show that the daughter cells of the first cleavage are not coupled electrically . Ashman et al . (op . cit.) have reported the same result previously, although in their experiments the eggs were treated with urea to soften the fertilization membrane. It has been suggested (Ito and Loewenstein, 1969) that such treatment may have altered the coupling pattern present in the Asterias egg. Our studies show this not to be the case . In addition, our studies show that there is no significant electrical communication between blastomeres after the second, third, or fourth cleavages . However, after the fifth cleavage (i .e ., at the 32-cell stage), the passage of ion currents between blastomeres occurs, indicating that junctions of low resistance are established by this stage . These findings correlate well with the observations of Wolpert and Mercer (1963) on embryos of Psammechinus miliaris, a sea urchin. Their electronmicrographs illustrate the formation of septate desmosomes between cells first occurring at the early blastula stage of this embryo . Septate desmosomes are strongly implicated as the means of electrical communication between cells in other systems (Loewenstein, 1966) .