Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonsense suppression by near-cognate tRNAs employs alternative base pairing at codon positions 1 and 3

Significance Readthrough-promoting drugs cause amino acid insertion at premature termination codons (PTCs), and thus have broad potential as a therapeutic approach to inherited disorders attributable to nonsense mutations. Because the mechanism involved in the insertion of near-cognate tRNAs at nonsense codons is unknown, we have identified the yeast translation errors ensuing from nonsense suppression occurring either inherently or enhanced by drugs or mutations that compromise termination fidelity. Our analyses of the products of nonsense suppression provide insights into the rules that govern readthrough at PTCs and delineate specific nonstandard Watson–Crick codon/anticodon base pairings critical to this process. These results should enable predictions of the likelihood of obtaining functional full-length readthrough products, and thus better clinical outcomes, with therapeutic nonsense suppression. Premature termination codons (PTCs) in an mRNA ORF inactivate gene function by causing production of a truncated protein and destabilization of the mRNA. Readthrough of a PTC allows ribosomal A-site insertion of a near-cognate tRNA, leading to synthesis of a full-length protein from otherwise defective mRNA. To understand the mechanism of such nonsense suppression, we developed a yeast system that allows purification and sequence analysis of full-length readthrough products arising as a consequence of endogenous readthrough or the compromised termination fidelity attributable to the loss of Upf (up-frameshift) factors, defective release factors, or the presence of the aminoglycoside gentamicin. Unlike classical “wobble” models, our analyses showed that three of four possible near-cognate tRNAs could mispair at position 1 or 3 of nonsense codons and that, irrespective of whether readthrough is endogenous or induced, the same sets of amino acids are inserted. We identified the insertion of Gln, Tyr, and Lys at UAA and UAG, whereas Trp, Arg, and Cys were inserted at UGA, and the frequency of insertion of individual amino acids was distinct for specific nonsense codons and readthrough-inducing agents. Our analysis suggests that the use of genetic or chemical means to increase readthrough does not promote novel or alternative mispairing events; rather, readthrough effectors cause quantitative enhancement of endogenous mistranslation events. Knowledge of the amino acids incorporated during readthrough not only elucidates the decoding process but also may allow predictions of the functionality of readthrough protein products.
Mirtazapine, a Noradrenergic and Specific Serotonergic Antidepressant, Attenuates Morphine Dependence and Withdrawal in Sprague-Dawley Rats

The effects of mirtazapine, a noradrenergic and specific serotonergic antidepressant, on morphine withdrawal and morphine conditioned place preference (CPP) were investigated in rats. Our results showed that some morphine withdrawal signs, including teeth chattering, grooming, chewing, and escape attendance, were attenuated by single pretreatments with 3, 10, or 30 mg/kg mirtazapine. Wet-dog shakes, rearing, and grooming were inhibited by daily pretreatment with 1, 3, or 10 mg/kg mirtazapine. The expression of morphine-induced CPP was significantly blocked by mirtazapine (10 or 30 mg/kg, i.p.), while chronic treatment with mirtazapine (1 or 10 mg/kg, i.p. once, daily, for six consecutive days) significantly attenuated the acquisition of morphine CPP. Our results demonstrated that mirtazapine attenuates morphine withdrawal and morphine-induced CPP in rats and suggest that mirtazapine may have therapeutic potential in the treatment of opiate dependence.
Career Wage Profiles and the Minimum Wage

A model of on-the-job training in the presence of a minimum wage is presented. This predicts that the minimum wage will have a negative effect on a worker's subsequent wage growth when the labour market is competitive but a U-shaped effect when it is not competitive. This prediction is then tested using data from the Annual Survey of Hours and Earnings in the United Kingdom. Workers who were affected by the minimum wage before age 22 are found to have significantly lower wage growth later in life than others, but only if they worked on jobs that were not covered by a collective labour agreement. Evidence suggests that this difference in wage growth reflects differences in productivity between workers. The results reconcile previous theoretical predictions by Becker and Acemoglu and Pischke.
Paroxetine versus clomipramine in adolescents with severe major depression: a double-blind, randomized, multicenter trial.

OBJECTIVE To date, two randomized, double-blind trials of serotonin reuptake inhibitors (SRIs) have shown that antidepressant drugs are effective in treating adolescent depression. In contrast, tricyclic antidepressants (TCAs) are not superior to placebo. This has led to a serotonin hypothesis in this age group. This study explores this hypothesis and compares paroxetine, a specific SRI, with clomipramine, a TCA with SRI activity. METHOD One hundred twenty-one adolescents (aged 12-20 years) with major depression were enrolled and randomized (stratified for age) to 20 or 40 mg of paroxetine or 75 mg or 150 mg of clomipramine for 8 weeks. Primary outcome measurements were the Clinical Global Impression (CGI) scale and the Montgomery and Asberg Depression Rating Scale (MADRS). RESULTS Of the 121 patients, 58 received clomipramine and 63 paroxetine. Based on intent-to-treat analysis, both agents had similar efficacy, with no effect of age; 48.3% and 58.2% of the subjects receiving clomipramine and 65.1% and 59.3% of those receiving paroxetine were rated responders on the MADRS and CGI scales, respectively. Study withdrawals were frequent in both groups (41% and 31%, respectively), but side effects were significantly more frequent with clomipramine (69% versus 49.2%, respectively; p = .027). CONCLUSION Paroxetine and clomipramine exhibit similar efficacy in adolescent depression. These data support the serotonin hypothesis but do not confirm it in the absence of a placebo arm. Given the adverse event profile of clomipramine, specific SRIs should be preferred. However, more placebo-controlled studies are needed to establish definitively the efficacy of SRIs in this age group.
Major grass pollen allergen Lol p 1 binds to diesel exhaust particles: implications for asthma and air pollution

Background Grass pollen allergens are known to be present in the atmosphere in a range of particle sizes from whole pollen grains (approx. 20 to 55 μim in diameter) to smaller size fractions < 2.5 μ (fine particles, PM2.5). These latter particles are within the respirable range and include allergen‐containing starch granules released from within the grains into the atmosphere when grass pollen ruptures in rainfall and are associated with epidemics of thunderstorm asthma during the grass pollen season. The question arises whether grass pollen allergens can interact with other sources of fine particles, particularly those present during episodes of air pollution.
Comparative analysis of switching performance of transistors in SOS process for RF applications

Silicon-on-sapphire (SOS) technology is gaining rapid ground in RF applications due to its inherent low parasitic capacitance and the availability of high Q passive components. In this paper, performance of different transistors in SOS technology for switching applications has been verified. Quality factor, OFF performance, and harmonic distortion of all N-types transistors have been simulated and a comparative analysis is provided. Based on this analysis it can be concluded that for the same W/L ratio, NL and IN transistors in the FC process give higher quality factor and also higher Con over Coff, while in the GC process, IN devices perform best.
Improving oral hygiene in the long-term care of the elderly--a RCT.

BACKGROUND Oral hygiene and health of the institutionalized elderly are frequently described as inadequate. OBJECTIVES This randomized and single-blinded (outcome evaluation) study compared three types of intervention for improving oral hygiene with a control. The purpose was to investigate whether there were any significant differences between the intervention and control groups. METHODS One hundred and six participants living in long-term care homes in South-West Germany were recruited and randomly divided into four groups-three therapy groups and one control group. For all three therapy groups, teeth and dentures were cleaned professionally and individual instruction was given. One of these groups was also re-instructed and remotivated by a dentist (n = 27). One also received help from, and was remotivation by, staff educated in dental hygiene (n = 26). The third therapy group was not remotivated after professional cleaning of teeth and dentures (n = 26). For the control group, there was no intervention (n = 23). The main target clinical data were mean plaque (plaque-control record, O'Leary), gingival bleeding (Ainamo/Bay), and denture hygiene indices. For assessment of the difference between being in an intervention group and in a control group, mixed-model analysis for repeated measurements was performed for each main target variable. In addition, target clinical data were evaluated in long-term follow-up after 3 years. RESULTS Compared with controls, denture hygiene, plaque, and gingival bleeding indices were significantly lower in the intervention groups over a twelve-week period (mixed model for repeated measurements; P < 0.023). Estimates of effects between control and each treatment group were comparable among the three therapy groups; however, even though two of the groups received further help and instruction. Long-term follow-up showed that all indices were significantly worse than at the last study recall (P < 0.001). CONCLUSIONS Professional cleaning of teeth and dentures, with individual instruction, can be recommended to improve oral hygiene. However, the effect decreases over time and renewal of the intervention is necessary.
Prostaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets

Of the known prostanoid receptors, human eosinophils express the prostaglandin D2 (PGD2) receptors DP1 [also D-type prostanoid (DP)] and DP2 (also chemoattractant receptor homologous molecule, expressed on Th2 cells), the prostaglandin E2 receptors EP2 and EP4, and the prostacyclin (PGI2) receptor IP. Prostanoids can bind to either one or multiple receptors, characteristically have a short half-life in vivo, and are quickly degraded into metabolites with altered affinity and specificity for a given receptor subtype. Prostanoid receptors signal mainly through G proteins and naturally activate signal transduction pathways according to the G protein subtype that they preferentially interact with. This can lead to the activation of sometimes opposing signaling pathways. In addition, prostanoid signaling is often cell-type specific and also the combination of expressed receptors can influence the outcome of the prostanoid impulse. Accordingly, it is assumed that eosinophils and their (patho-)physiological functions are governed by a sensitive prostanoid signaling network. In this review, we specifically focus on the functions of PGD2, PGE2, and PGI2 and their receptors on eosinophils. We discuss their significance in allergic and non-allergic diseases and summarize potential targets for drug intervention.
Influence of pellet diameter and length on the quality of pellets and performance, nutrient utilisation and digestive tract development of broilers fed on wheat-based diets

1. The influence of pellet diameter and length on the quality of pellets and performance, nutrient utilisation and digestive tract development of broilers given wheat-based diets was examined from 10 to 42 d of age. The experimental design was a 2 × 2 factorial arrangement of treatments evaluating two pellet diameters (3 and 4.76 mm) and two pellet lengths (3 and 6 mm). From 0 to 9 d of age, all birds were offered a common starter diet pelleted with a 3-mm diameter die and 3-mm length. Broiler grower (d 10 to 21) and finisher (d 22 to 42) diets, based on wheat, were formulated and then subjected to the 4 different treatments. 2. In grower diets, increasing pellet diameter and pellet length reduced the gelatinised starch (GS) content of the diets. In finisher diets, GS content of 3-mm diameter pellets did not change with increasing pellet length but decreased in 4.76-mm diameter pellets. 3. In grower and finisher diets, increments in intact pellet weight, pellet durability index and pellet hardness with increasing pellet length were greater in 3-mm diameter pellets than those with 4.76-mm diameter. 4. Increasing pellet length from 3 to 6 mm increased apparent metabolisable energy values. Neither the interaction nor main effects were significant for the ileal digestibility of nitrogen and starch. 5. During the grower period (d 10 to 21), birds given pellets of 6-mm length had greater body-weight gain than those given 3-mm length pellets. Feeding 6-mm length pellets decreased feed per body-weight gain compared to 3-mm length pellets. During the finisher (d 22 to 42) and whole grow-out (d 10 to 42) periods, while different pellet lengths had no effect on feed per body-weight gain values at 3-mm pellet diameter, increasing the pellet length decreased feed per body-weight gain at 4.76-mm pellet diameter. 6. Increasing pellet diameter and pellet length reduced the relative length of duodenum. Birds given 3-mm diameter pellets had heavier proventriculus compared to those given 4.76-mm diameter pellets. 7. Overall, the data suggest that increasing the pellet length from 3 to 6 mm improved the body-weight gain and feed per body-weight gain during the grower period (d 10 to 21). While the positive effect on body-weight gain disappeared as the birds grew older, improvements in feed per body-weight gain were maintained over the finisher and whole grow-out periods only in 4.76-mm diameter pellets. Small diameter die holes and longer pellet lengths may be considered as potential manipulations to manufacture high-quality pellets under low conditioning temperatures.
Status Concern and Relative Deprivation in China: Measures, Empirical Evidence and Economic and Policy Implications

Status concern and feelings of relative deprivation affect individual behaviour and well-being. Traditional norms and the alarming inequality in China have made relative deprivation increasingly intense for the Chinese population. This article reviews empirical literature on China that attempts to test the relative deprivation hypothesis, and also reviews the origins and pathways of relative deprivation, compares its economic measures in the literature and summarises the scientific findings. Drawing from solid empirical evidence, the author discusses the important policy implications on redistribution, official regulations and grassroots sanctions, and relative poverty alleviation.
Studies on Nitrogen-Fixing Blue-Green Algae. I. Growth and Nitrogen Fixation by Anabaena Cylindrica Lemm.

Myrothecium verrucaria. The Quartermaster General Laboratories, Research Report, Microbiology Series No. 11: 1-50. 1948. 5. MANDELS, G. R. and NORTON, A. B. The invertase of Myrothecium vecrXtrcaria-its location, synthesis and secretion. The Quartermaster General Laboratories, Research Report, Microbiology Series No. 12: 1-35. 1949. 6. MANDELS, G. R. Metabolism of sucrose and related oligosaccharides by spores of the fungus Myrothecium verrucaria. Plant Physiol. 29: 18-26. 1954. 7. MILLER, G. L. and MILLER, E. E. Determination of nitrogen in biological materials-improved Kjeldahl-Nessler method. Anal. Chem. 20: 481-488. 1948.
Nitric oxide impairs normoxic degradation of HIF-1alpha by inhibition of prolyl hydroxylases.

Hypoxia inducible factor-1 (HIF-1) is the master regulator of metabolic adaptation to hypoxia. It is appreciated that HIF-1alpha accumulation is achieved under normoxic conditions by e.g., nitric oxide. We determined molecular mechanisms of HIF-1alpha accumulation under the impact of S-nitrosoglutathione (GSNO). In human embryonic kidney cells GSNO provoked nuclear accumulation of HIF-1alpha. This appeared unrelated to gene transcription and protein translation, thus pointing to inhibition of HIF-1alpha degradation. Indeed, GSNO as well as the hypoxia mimic CoCl2 decreased ubiquitination of HIF-1alpha and GSNO-induced HIF-1alpha failed to coimmunoprecipitate with pVHL (von Hippel Lindau protein). Considering that HIF-1alpha-pVHL interactions require prolyl hydroxylation of HIF-1alpha, we went on to demonstrate inhibition of HIF-1alpha prolyl hydroxylases (PHDs) by GSNO. In vitro HIF-1alpha-pVHL interactions revealed that GSNO dose-dependently inhibits PHD activity but not the interaction of a synthetic peptide resembling the hydroxylated oxygen-dependent degradation domain of HIF-1alpha with pVHL. We conclude that GSNO-attenuated prolyl hydroxylase activity accounts for HIF-1alpha accumulation under conditions of NO formation during normoxia and that PHD activity is subject to regulation by NO.
Dynamic Specification in Econometric Estimation

The use of dvnamlc specIfIcatIOn wIth an error COl' rectlOn mechanIsm (ECM) In slngle·equatlOn and multlequatlOn macroeconomIc forecasting models hah become WIdespread over the last decade In a single· equatIOn context the recent work of Hendrv (4 5) on aggregate consumptIOn and monel' demand has been very I nfluentlal I The foundatIOns of th,s research rest heavily on the earher wage-pnce work of Sargan (8) In a multlequatlOn context all the malOI Umted KIngdom macroeconomIc models Includlll;! the London Business School and the Bank of England. have adopted dynamIc spec;flcatlOn and the ECM III many of theIr slllgle equatIons In the Umted States, the Federal Reserve Board's multlcountry model also makes ex· tenslve use of th,s techmque
Determinants of health care seeking for childhood illnesses in Nairobi slums

The practice of appropriate health seeking has a great potential to reduce the occurrence of severe and life‐threatening child illnesses. We assessed the influence of socio‐demographic, economic and disease‐related factors in health care seeking for child illnesses among slum dwellers of Nairobi, Kenya. A survey round of the Nairobi Urban Demographic Surveillance System (NUDSS) generated information on 2‐week child morbidity, illness symptoms, perceived illness severity and use of modern health services. During this round of data collection, interviewers visited a total of 15 174 households, where 3015 children younger than 5 years lived. Of the 999 (33.1%) children who were reported to have been sick, medical care of some sort was sought for 604 (60.5%). Lack of finances (49.6%) and a perception that the illness was not serious (28.1%) were the main reasons given for failure to seek health care outside the home. Health care seeking was most common for sick children in the youngest age group (0–11 months). Caretakers sought medical care more frequently for diarrhoea symptoms than for coughing and even more so when the diarrhoea was associated with fever. Perception of illness severity was strongly associated with health care seeking. Household income was significantly associated with health care seeking up to certain threshold levels, above which its effects stabilized. Improving caretaker skills to recognize danger signs in child illnesses may enhance health‐seeking behaviour. Integrated Management of Child Illnesses (IMCI) programmes must be accessible free of charge to the urban poor in order to increase health care seeking and bring about improvements in child survival.
On Energy-Efficient Edge Caching in Heterogeneous Networks

In this paper, we study the problem of content placement for caching at the wireless edge with the goal to maximize the energy efficiency (EE) of heterogeneous wireless networks. In particular, we consider the minimization of two fundamental metrics: the expected backhaul rate and the energy consumption. We derive both metrics in closed-form expressions, and we solve the minimization problem as a convex optimization for each, highlighting the existence of a tradeoff between the two metrics. Further, we show the advantage of encoding the data using maximum-distance separable (MDS) codes over the alternative concept of file fragmentation, with respect to both backhaul rate and energy consumption. Then, we thoroughly study the performance of the optimal MDS-encoded caching scheme in terms of overall energy consumption for an important heterogeneous network scenario. We compare our optimal strategy to several other sub-optimal caching strategies, including the caching scheme, minimizing the backhaul rate, and we analyze the effects of the system parameters on the overall performance. Our analysis can be generalized to any network topology and to any small-cell base station capability. Our results show that the optimal placement of MDS-encoded content in caches at the wireless edge increases significantly the overall EE of the heterogeneous network. This demonstrates the importance of the edge caching strategy for energy-efficient network designs.
Follow What I Do, and Also What I Say: Monetary Policy Impact on Brazil’s Financial Markets

We find that futures rates increase (decrease) after both an increase in the reference interest rate and a hawkish (dovish) communication by the BCB. Moreover, BCB words create more noise, since they increase volatility of futures rates. Our analysis reveals that BCB communication has increased its effectiveness after the 2008 crisis, while deeds became less relevant.