Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphosyntax, Prosody, and Linking Elements: The Auditory Processing of German Nominal Compounds

The morphosyntactic decomposition of German compound words and a proposed function of linking elements were examined during auditory processing using event-related brain potentials. In Experiment 1, the syntactic gender agreement was manipulated between a determiner and the initial compound constituent (the nonhead constituent), and between a determiner and the last constituent (head). Although only the head is (morpho)syntactically relevant in German, both constituents elicited a left-anterior negativity if its gender was incongruent. This strongly suggests that compounds are morphosyntactically decomposed. Experiment 2 tested the function of those linking elements which are homophonous to plural morphemes. It has been previously suggested that these indicate the number of nonhead constituents. The number agreement was manipulated for both constituents analogous to Experiment 1. Number-incongruent heads, but not nonhead constituents, elicited an N400 and a subsequent broad negativity, suggesting that linking elements are not processed as plural morphemes. Experiment 3 showed that prosodic cues (duration and fundamental frequency) are employed to differentiate between compounds and single nouns and, thereby, betwen linking elements and plural morphemes. Number-incongruent words elicited a broad negativity if they were produced with a single noun prosody; the same words elicited no event-related potential effect if produced with a compound prosody. A dual-route model can account for the influence of prosody on morphosyntactic processing.
The U-Turn in Government Facilitation: How Dutch Water Authorities Facilitate Nongovernmental Initiatives

Public authorities in infrastructure, aiming to facilitate societal initiatives, explore new forms of collaboration with nongovernmental actors. A comparative case study of two Dutch initiatives is conducted: energy generation at a public dam and the realization of a nature reserve. It is analyzed how and why the authorities’ strategy regarding their nongovernmental partners changes over time. Authorities’ strategy change is modeled on two axes: governmental investments and governmental influence, and a differentiation is made between limited facilitation, invitational facilitation, partnering, and Design, Build, Finance, Maintain, and Operate. A U-turn-shaped pattern in authorities’ strategy is found: Authorities move from partnering to limited facilitation and subsequently revert to invitational facilitation. Institutional factors, process factors, and initiative characteristics are identified that explain the strategy changes. It is concluded that government facilitation is a dynamic, interactive process and that authorities adapt their strategy to the initiative at hand and are pragmatic in their approach.
Relationship between Milk and Calcium Intake and Lipid Metabolism in Female Patients with Type 2 Diabetes

Purpose This study was conducted to determine the association between intake of milk and dairy products as well as calcium and biomarkers related to lipid metabolism in Korean female patients with type 2 diabetes. Materials and Methods A cohort of 509 female subjects (mean age: 59.0 years; range: 35-80 years) was recruited from Huh's Diabetes Clinic in Seoul between 2005 and 2010. Dietary intake was assessed using a validated food-frequency questionnaire. Subjects were divided into three groups on the basis of their daily intake of milk and dairy products [<50 g/day (0<50 g/day), 50-200 g/day, and >200 g/day (>200-1201 g/day)] and then further divided into two groups according to their daily calcium intake: below and above the estimated average requirement (EAR). Results After adjustment for age, body mass index, energy intake, exercise, use of nutritional supplements and cholesterol medication, the level of serum high-density lipoprotein (HDL)-cholesterol was significantly higher in subjects with milk and dairy products consumption of >200 g/day than in subjects in the other two groups. Those subjects with a milk and dairy products consumption of >200 g/day had significantly higher levels of apolipoprotein A-1 and a significantly lower atherogenic index than the other two groups. Patients with a calcium intake above the EAR exhibited a significantly greater serum HDL-cholesterol level than those with a calcium intake below the EAR. Conclusion Milk and dairy products, good sources of calcium, play a positive role in lipid profiles in female patients with type 2 diabetes.
Successful Prediction of Substrate-binding Pocket in SLC17 Transporter Sialin*

Background: Sialin is a clinically relevant lysosomal sialic acid exporter related to vesicular glutamate transporters and other SLC17 transporters. Results: Using synthetic sialic acid analogues, homology modeling, site-directed mutagenesis, and virtual screening, we built and validated a three-dimensional model of sialin. Conclusion: The three-dimensional model successfully predicts small molecule binding to sialin. Significance: The model will help identifying pharmacological tools targeted to SLC17 transporters. Secondary active transporters from the SLC17 protein family are required for excitatory and purinergic synaptic transmission, sialic acid metabolism, and renal function, and several members are associated with inherited neurological or metabolic diseases. However, molecular tools to investigate their function or correct their genetic defects are limited or absent. Using structure-activity, homology modeling, molecular docking, and mutagenesis studies, we have located the substrate-binding site of sialin (SLC17A5), a lysosomal sialic acid exporter also recently implicated in exocytotic release of aspartate. Human sialin is defective in two inherited sialic acid storage diseases and is responsible for metabolic incorporation of the dietary nonhuman sialic acid N-glycolylneuraminic acid. We built cytosol-open and lumen-open three-dimensional models of sialin based on weak, but significant, sequence similarity with the glycerol-3-phosphate and fucose permeases from Escherichia coli, respectively. Molecular docking of 31 synthetic sialic acid analogues to both models was consistent with inhibition studies. Narrowing the sialic acid-binding site in the cytosol-open state by two phenylalanine to tyrosine mutations abrogated recognition of the most active analogue without impairing neuraminic acid transport. Moreover, a pilot virtual high-throughput screening of the cytosol-open model could identify a pseudopeptide competitive inhibitor showing >100-fold higher affinity than the natural substrate. This validated model of human sialin and sialin-guided models of other SLC17 transporters should pave the way for the identification of inhibitors, glycoengineering tools, pharmacological chaperones, and fluorescent false neurotransmitters targeted to these proteins.
23Na‐NMR detects hypoxic injury in intact kidney: Increases in sodium inhibited by DMSO and DMTU

Hypoxic injury in the isolated perfused rat kidney (IPRK) was monitored using 23Na‐NMR in the presence or absence of 1.5 and 15 mM dimethylthiourea (DMTU) or 15 mM dimethylsulphoxide (DMSO) before and after inducing hypoxia. Hypoxia induced a prompt exponential increase in total renal 23Na+, renal vascular resistance, and sodium excretion and decreased inulin clearance and adenine nucleotides and reduced glutathione concentrations. Lipid peroxide metabolites were unaltered. The increase in 23Na+ was significantly reduced (P < 0.001) by both DMTU and DMSO although hypoxic perturbations of function and biochemical parameters were not. Posthypoxic increases in renal 23Na+ include approximately 10% from the intratubular compartment, but principally reflect the intracellular and interstitial compartments. The results demonstrate that 23Na‐NMR is a sensitive indicator of hypoxic renal injury in intact kidney and suggest that DMTU and1 DMSO protect against hypoxic injury by a mechanism independent of free radical‐binding.
Electroencephalographic sleep and natural killer activity in depressed patients and control subjects.

&NA; Insomnia is associated with a reduction of natural killer (NK) activity in depression independent of the severity of other depressive symptoms. This study extends these findings by exploring the relationship between objective electroencephalographic (EEG) assessment of sleep and values of NK activity in depressed patients (n = 23) and in control subjects (n = 17). The sleep EEG parameters total sleep time, sleep efficiency, and duration of nonREM sleep were each positively correlated with NK activity in the depressed patients and in the control subjects, demonstrating similar relationships between the amount of sleep and NK activity in the separate groups. These observations support the hypothesis that sleep measures are associated with NK cytotoxicity, independent of the effects of severity of depressive symptoms or the presence of a mood disorder.
Liver, Brain, and Heart Metallothionein Induction by Stress

To date, stress has been reported to induce metallothionein (MT) synthesis in the liver only. In the present experiment, the effects of food and water deprivation alone or of immobilization stress plus food and water deprivation on liver, brain, and heart MT have been studied in adult male rats. Liver and brain MT levels were increased by immobilization stress as soon as 6 h after the onset of stress. Eighteen hours of immobilization, which is accompanied by food and water deprivation, further increased liver and brain MT levels and significantly increased heart MT content. A specific effect of immobilization was evident in all three tissues, because the effect of food and water deprivation alone was significantly lower than that of immobilization plus starvation. Changes in MT apparently were not related to changes in cytosolic Zn.
Effect of 1-Minute Fluoride Treatment on Potential Virulence and Viability of a Cariogenic Biofilm

Fluoride is a well-studied and widely used agent for the prevention of dental caries. Although dental caries is strongly related to cariogenic biofilms, the effect of brief fluoride treatment on the virulence properties of biofilms has not been well studied. This study evaluated the effect of a 1-min fluoride treatment on the virulence properties and viability of cariogenic biofilms, using a Streptococcus mutans biofilm model. For this study, 46-hour-old S. mutans biofilms were formed on saliva-coated hydroxyapatite discs and were treated with fluoride (0, 30, 300, 1,000, and 2,000 ppm F-) for 1 min. Viability and changes in acidogenicity, aciduricity and extracellular polysaccharide (EPS) formation of the biofilms were analyzed using biochemical and microbiological methods (pH drop, H+ permeability, acid killing, and bacterial colony-forming unit assays). Laser scanning confocal fluorescence microscopy study was also performed. After the 1-min fluoride treatment, acidogenicity, aciduricity, and EPS formation of 46-hour-old S. mutans biofilms were significantly reduced when treated with concentrations ≥300 ppm F-. The antivirulence activities of the 1-min fluoride treatment increased in a concentration-dependent pattern. However, the 1-min fluoride treatments did not affect viability, biovolume, and microcolony appearance of biofilm bacteria, even at high concentrations. These results suggest that the brief treatment with fluoride at concentrations ≥300 ppm F- is an effective measure for controlling cariogenic biofilms.
Orthotopic heart transplantation in a transgenic pig-to-primate model.

BACKGROUND Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients. METHODS Orthotopic xenogeneic heart transplantation was performed using piglets, transgenic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids. RESULTS Five grafts failed within 18 hr without any histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically normal xenograft, because of pancytopenia. CONCLUSIONS The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.
High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris.

IMPORTANCE Isotretinoin is the most effective treatment for acne. The ideal dosing regimen is unknown. OBJECTIVE To determine the rates of relapse of acne vulgaris and retrial of isotretinoin after high cumulative-dose treatment and the changes to the adverse effect profile. DESIGN, SETTING, AND PARTICIPANTS A prospective, observational, intervention study was conducted from August 1, 2008, to August 31, 2010, in a single academic tertiary care center with multiple providers. A total of 180 patients with acne resistant to other treatments were enrolled. Of these, 116 participated in the 12-month follow-up survey, for a response rate of 64.4%. EXPOSURE Patients received isotretinoin, with dosing based on the providers' judgment. Patients were divided into 2 groups on the basis of cumulative dosing (<220 mg/kg and ≥ 220 mg/kg). MAIN OUTCOMES AND MEASURES Relapse (treatment with a prescription topical or oral acne medication after a course of isotretinoin) or retrial (retreatment with isotretinoin) at 12-month follow-up and adverse effects experienced during and after 12 months of treatment. RESULTS The mean age of the participants was 19.3 years, 51.9% were female, and 74.1% were white. At 12 months' follow-up, 97.4% of the patients reported that their acne was improved. Overall, acne in 32.7% of patients in the study relapsed at 12 months, and 1.72% of the patients required a retrial. In the lower-dose treatment group (<220 mg/kg), the relapse rate was 47.4% (95% CI, 32.3%-63.0%) compared with 26.9% (95% CI, 18.3%-37.8%) in the high-dose group (P = .03). Almost 100% of the patients in both treatment groups developed cheilitis and xerosis during treatment. Retinoid dermatitis was significantly more common in the high-dose treatment group (53.8% vs 31.6%; P = .02). None of the other adverse effects was significantly different between the 2 groups. CONCLUSIONS AND RELEVANCE The dosing regimen used in the present study is considerably higher than that used in previous studies of isotretinoin. At 1 year after completion of isotretinoin treatment, we found that patients receiving 220 mg/kg or more had a significantly decreased risk of relapse. Rash was the only adverse effect that was significantly more common in the high-dose group during treatment. This study suggests that significantly higher doses of isotretinoin are effective for treating acne and decreasing relapse rates without increasing adverse effects.
Safety and efficacy of saphenectomy in elderly patients.

AIM The aim of this study is to evaluate safety and efficacy of saphenactomy in elderly patients. PATIENTS AND METHODS A total of 358 patients with varicose veins of the lower limbs treated between January 2001 and December 2011. 213 of these were patients under 65 years old and 145 patients were over this age. We have evaluated short- and long-term complications to compare the results among young and elderly patients. RESULTS Postoperative complications that occurred were: infection, haematoma, nerve injury (paresthesia and pain) and deep vein thrombosis. Although a trend towards better results was observed among the young patients, no significant differences were shown in our experience. CONCLUSION Elective saphenectomy has a good outcome also in the elderly patients. The slightly higher rate of complications that occurred in older patients is not significant and does not support advising against the use of this surgical approach in the elderly. So in our opinion saphenectomy is quite safe and feasible also in patients over 65 years.
Differentiating Intraocular Glucocorticoids

Background: Natural corticosteroids (e.g. hydrocortisone) and synthetic selective glucocorticoid (GC) agonists have been used by ophthalmologists for decades to treat various forms of ocular inflammation. More recently, increased clinical use of locally delivered GC has shown significant benefit for the treatment of multiple retinal indications including macular edema associated with uveitis, retinal vascular occlusions and diabetes. Our current understanding of the clinical utility of specific intraocular GC far surpasses our knowledge of their biologic and pharmacologic activities in the eye. Objective: To present an update on GC receptor (GR) biology in general and as it applies to the eye, and discuss the pharmacokinetics, delivery and pharmacology of the commonly used intraocular GC dexamethasone (DEX), triamcinolone acetonide (TA) and fluocinolone acetonide (FA). Results: DEX, TA and FA are structurally similar but significantly differentiated by their aqueous and lipid solubility, delivery system requirements, pharmacokinetics and interactions with functional GR. Culture of human trabecular meshwork cells and full transcriptome microarray analysis reveals that DEX, TA and FA generate unique gene transactivation and repression profiles as well as potentially distinct biologic responses that are not only steroid structure dependent, but also dose and time dependent. Finally, DEX and FA markedly protect photoreceptors from degenerating in animal models of excessive light and retinitis pigmentosa, respectively. Conclusion: It is tempting to speculate that the unique pharmacokinetic and pharmacologic profiles of the commonly used intraocular steroids and novel future drugs may reveal significant differences in their therapeutic value in patients with macular edema or other inflammatory disease, in their ocular adverse side effect profile, and their ability to normalize glial and neuronal function in diseased retina.
Novel aryl β-aminocarbonyl derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase: binding mode revised by docking and GRIND2-based 3D-QSAR procedures

Trypanothione reductase has long been investigated as a promising target for chemotherapeutic intervention in Chagas disease, since it is an enzyme of a unique metabolic pathway that is exclusively present in the pathogen but not in the human host, which has the analog Glutathione reductase. In spite of the present data-set includes a small number of compounds, a combined use of flexible docking, pharmacophore perception, ligand binding site prediction, and Grid-Independent Descriptors GRIND2-based 3D-Quantitative Structure-Activity Relationships (QSAR) procedures allowed us to rationalize the different biological activities of a series of 11 aryl β-aminocarbonyl derivatives, which are inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR). Three QSAR models were built and validated using different alignments, which are based on docking with the TcTR crystal structure, pharmacophore, and molecular interaction fields. The high statistical significance of the models thus obtained assures the robustness of this second generation of GRIND descriptors here used, which were able to detect the most important residues of such enzyme for binding the aryl β-aminocarbonyl derivatives, besides to rationalize distances among them. Finally, a revised binding mode has been proposed for our inhibitors and independently supported by the different methodologies here used, allowing further optimization of the lead compounds with such combined structure- and ligand-based approaches in the fight against the Chagas disease.
Do globalisation and adoption of IFRS by banks in Africa lead to less earnings management?

Purpose This paper aims to analyse the implications of globalisation and the adoption of international standards (International Financial Reporting Standards [IFRS]) for accounting information quality. Design/methodology/approach This paper uses a sample of 329 banks across 29 countries leading up to and beyond the implementation of IFRS to test for related hypotheses. Findings First, banks’ financial statements are prepared on the basis of international standards as national economies are integrated when social norms are diffused. Building on these results, the second test suggests that the relatively high-quality earnings among banks in Africa during the period is attributable to the adoption of and interaction of IFRS with globalisation and the strategy of banks to diversify within and across interest and non-interest income. Originality/value The authors investigate how globalisation and the adoption of IFRS affect accounting information quality.
Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1‐ and Rad53‐dependent checkpoint in budding yeast

We studied the response of nucleotide excision repair (NER)‐defective rad14Δ cells to UV irradiation in G1 followed by release into the cell cycle. Only a subset of checkpoint proteins appears to mediate cell cycle arrest and regulate the timely activation of replication origins in the presence of unrepaired UV‐induced lesions. In fact, Mec1 and Rad53, but not Rad9 and the Rad24 group of checkpoint proteins, are required to delay cell cycle progression in rad14Δ cells after UV damage in G1. Consistently, Mec1‐dependent Rad53 phosphorylation after UV irradiation takes place in rad14Δ cells also in the absence of Rad9, Rad17, Rad24, Mec3 and Ddc1, and correlates with entry into S phase. Two‐dimensional gel analysis indicates that late replication origins are not fired in rad14Δ cells UV‐irradiated in G1 and released into the cell cycle, which instead initiate DNA replication from early origins and accumulate replication and recombination intermediates. Progression through S phase of UV‐treated NER‐deficient mec1 and rad53 mutants correlates with late origin firing, suggesting that unregulated DNA replication in the presence of irreparable UV‐induced lesions might result from a failure to prevent initiation at late origins.
Budesonide and formoterol combination for the treatment of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world. Current guidelines recommend the addition of inhaled steroids to bronchodilators, which are central to the symptomatic management of COPD in patients with severe disease. Budesonide/formoterol is a combination inhaled steroid and long-acting bronchodilator delivered by a dry-powder inhaler, approved for use in COPD. Two large, randomised, double-blind, 12-month studies found that combination budesonide/formoterol is more effective than either component alone in addressing many important aspects of the disease, such as pulmonary function, symptoms, use of relief medication, health-related quality of life and exacerbation in patients suffering from severe COPD. This review discusses the pharmacological and clinical properties of the drug.