Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of KC 399, a novel ATP-sensitive K+ channel opener, on electrical and mechanical responses in dog tracheal smooth muscle.

The effects were observed of a newly synthesized bronchodilator, KC 339 [N-(2-cyanoethyl)-2,2-bis-fluoromethyl-6-nitro-2H-1-benzopyran-4- carbothioamide], on the electrical and mechanical properties of dog tracheal smooth muscle tissues and on accumulation of second messengers. KC 399 hyperpolarized the membrane in a concentration-dependent manner, the minimum concentration required to produce hyperpolarization being 1 nM and the maximum hyperpolarization occurring with 10 nM. The hyperpolarization was still observed in low K+ solution (< 1.2 mM), but not in high K+ solution (> 20 nM). Similarly, KC 399 inhibited the contraction evoked by less than 30 mM K+, but not by higher concentrations of K+ (> 30 mM). KC 399 (10 nM) suppressed the depolarization and membrane potential oscillation induced by carbachol (< 300 nM). In muscle tissues precontracted with 100 nM carbachol, KC 399 caused a concentration-dependent relaxation. The IC50 value for KC 399 was 4.2 nM (pIC50: 8.38 +/- 0.09, n = 7) and the maximum inhibition induced by 100 nM KC 399 was 96.1 +/- 0.7% (n = 7). KC 399 inhibited more effectively the tonic response of the contraction than the initial phasic response induced by carbachol. The relaxation and hyperpolarization induced by KC 399 were antagonized by glibenclamide and in part by charybdotoxin due to depolarization of the membrane. Carbachol increased the amount of d-myo-inositol-1,4,5-trisphosphate (InsP3), the maximal value occurring 10 sec after application. (ABSTRACT TRUNCATED AT 250 WORDS)
Reclassify controls at your own risk.

A key aspect of epidemiologic research is the correct measurement of exposures and poor health outcomes. When considering a binary disease, cases are generally confirmed using medical records or other trustworthy information. In contrast, controls’ nondiseased status is often based on self-report or simply the lack of evidence to the contrary. For example, genetic epidemiologic association studies commonly use convenience or unscreened controls who are assumed unaffected even though their actual disease status has not been assessed. Depending on the prevalence of disease in the source population of controls, some proportion may actually be cases. This disease misclassification or absence of knowledge about controls’ disease status can result in reduced power and information bias, thus threatening the internal validity of the findings. Ioannidis and colleagues propose to address this issue by reclassifying controls as cases if they have a high probability of disease, as estimated from prediction models of known genetic or environmental risk factors. If the prediction models have high sensitivity and specificity—and the prevalence of disease misclassification among controls is relatively high (>20%)—simulations show that this approach can improve the power to detect novel risk factors. Nonetheless, no clear improvement is seen when applying this method to a seemingly ideal study of progression to advanced age-related macular degeneration. This reclassification of controls should generally be avoided because it may actually increase bias and reduce precision. For reclassification, one must turn the estimated probabilities of disease into 100% certainty by selecting a cutoff for the predicted values above which controls are assumed affected. The probabilities will usually have a smooth distribution, and so the choice of cutoff is subjective and the ensuing results will be sensitive to this choice. For example, even in the absence of disease-classification errors but in the presence of a strong predictor, some controls will have a high probability of being a case; reclassifying them as cases based on the predicted values will bias inference from subsequent analyses. Is there an alternative to the approach suggested by Ioannidis et al? Instead of a deterministic, all-or-none reclassification of controls, there are more appropriate ways to incorporate into one’s analysis prior knowledge of uncertainty in disease status. Ioannidis et al touch on this in their discussion and note that they “presented a simple dichotomous correction, the equivalent of a diagnostic test evaluation. ” If it is reasonable to assign controls their probabilities of disease, the outcomes will now range from 0 to 1 (for the controls), with a large mass at 1 (for cases). To analyze such data, one can use a model from the ordinal logistic family: continuation ratio models (usual or reversed contrasting 1 vs. <1) or the cumulative odds model. Another possibility is to use an outcome-mixture model for
Corporate Social Responsibility (CSR) and Sustainability in Asian Luxury Hotels: Policies, Practices and Standards

The tourism and hospitality industry claims to embrace the concept of corporate social responsibility (CSR) but it seems unclear how and if companies integrate CSR activities into the core business and how they demonstrate real impacts and positive changes. The purpose of this research is to understand how Asian luxury hotels communicate about their CSR policies, practices and standards. It gives insights of best practices of CSR from luxury hotel groups that operate predominantly in Asia. The findings reveal that CSR is a blurry subject and there is a lack of an overall accepted definition and guidelines. The reporting of CSR activities by the Asian luxury hotels includes various overall activities, many of which are normal business practices. Many of these hotel groups are adopting international standards and most of them underline the importance of the environment and society. The study concludes that the motivation for CSR is oriented towards sustaining the basis for their operations. The outcome of the research suggests that further studies should analyze different hotel segments, such as local hotels or small-medium size hotels, in one particular country or comparing between various countries.
Follow up studies in rheumatoid arthritis

Do we really need follow up studies of randomised clinical trials in RA? In rheumatology we have been told for years that the results of randomised controlled trials may not be extrapolated to the long term, and that a gain in the beginning may not necessarily mean a gain in what we solemnly call the “final outcome”. In almost every review on disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA), long term efficacy and long term toxicity are always considered. The importance of long term data is repeatedly stated, without, however, explaining what information is really necessary. And regulatory authorities nowadays require long term studies before approving drugs which claim, for example, to preserve function. Probably as a consequence of this, we are now facing an increasing number of published follow up reports of clinical trials—for example, references 1–6a.1–6a The conclusion is always that some drug is still as effective and as toxic as its comparator, x years after the start of the trial, or that drug A “maintains its efficacy or its superiority over drug B” over time. A large number of arguments are mentioned by different authors to justify follow up studies. These arguments—more or less valid—include doubts about long term clinical efficacy, effects on radiological progression and function, long term toxicity, “drug survival time”, cost effectiveness, and quality of life. Intuitively, follow ups of randomised controlled trials (RCTs) enjoy a greater respect than observational studies, because patients were allocated to groups by chance, and most authors assume they can make an appropriate between-group comparison at the end. The questions to be asked in this editorial are:
MEANTIME, the NewsReader Multilingual Event and Time Corpus

In this paper, we present the NewsReader MEANTIME corpus, a semantically annotated corpus of Wikinews articles. The corpus consists of 480 news articles, i.e. 120 English news articles and their translations in Spanish, Italian, and Dutch. MEANTIME contains annotations at different levels. The document-level annotation includes markables (e.g. entity mentions, event mentions, time expressions, and numerical expressions), relations between markables (modeling, for example, temporal information and semantic role labeling), and entity and event intra-document coreference. The corpus-level annotation includes entity and event cross-document coreference. Semantic annotation on the English section was performed manually; for the annotation in Italian, Spanish, and (partially) Dutch, a procedure was devised to automatically project the annotations on the English texts onto the translated texts, based on the manual alignment of the annotated elements; this enabled us not only to speed up the annotation process but also provided cross-lingual coreference. The English section of the corpus was extended with timeline annotations for the SemEval 2015 TimeLine shared task. The “First CLIN Dutch Shared Task” at CLIN26 was based on the Dutch section, while the EVALITA 2016 FactA (Event Factuality Annotation) shared task, based on the Italian section, is currently being organized.
Age-Specific Incidence Rates of In situ Breast Carcinomas by Histologic Type, 1980 to 2001

Incidence rates of ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) have increased rapidly over the past several decades largely due to the increased use of mammography. However, recent data from 1987 to 1999 indicate that invasive ductal carcinoma incidence rates have remained essentially constant, whereas rates of invasive lobular carcinoma have increased 65%, with greater increases observed among postmenopausal women. Data on recent trends in DCIS and LCIS incidence rates, particularly age-specific trends, are lacking. We evaluated trends in the incidence rates of DCIS overall, noncomedo DCIS, comedo DCIS, and LCIS using data from nine Surveillance, Epidemiology, and End Results cancer registries. DCIS incidence rates increased 7.2-fold [95% confidence interval (95% CI), 6.8-7.7] from 1980 to 2001, 1.8-fold (95% CI, 1.7-1.9) over the past 10 years (1992-2001), and 1.1-fold (95% CI, 1.0-1.2) over the past 5 years (1997-2001). The magnitudes of these increases were highest among women ages ≥50 years. Furthermore, over the past 10- and 5-year periods, rates of noncomedo DCIS have generally increased across all age groups, whereas rates of comedo DCIS held constant or decreased. LCIS incidence rates increased 2.6-fold (95% CI, 2.3-2.9) from 1980 to 2001, 1.3-fold (95% CI, 1.2-1.5) over the past 10 years, and 1.1-fold (95% CI, 1.0-1.3) over the past 5 years. Similar to invasive lobular carcinoma, but unlike invasive ductal carcinoma, incidence rates of both DCIS and LCIS continue to increase in the United States primarily among older women. These trends present important public health and clinical challenges.
Rapid six‐degree‐of‐freedom motion detection using prerotated baseline spherical navigator echoes

A new spherical navigator echo (SNAV) registration technique is presented. This technique starts by collecting a set of SNAV templates at a reference position. These templates are acquired by rotating the gradient system to result in rotation angles that uniformly cover a predefined range of rotation. The rotation angles between an unknown physically transformed position and the reference position are subsequently determined by finding the template with the lowest sum of squared differences with SNAV at the transformed position. Translations are calculated from the phase differences between the best‐match SNAV template and the SNAV acquired at the transformed position. In comparison with the conventional SNAV registration technique, the proposed technique is noniterative, robust, and can detect 3‐dimensional rigid body motion in less than 50 msec. The technique was verified with phantom and in vivo experiments, which demonstrated subdegree rotational and submillimeter translational accuracy over a range of simultaneous ±20° and ±10° mm of motion. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.
Advances in the development of vaccines against Neisseria meningitidis.

Developments during the past decade have renewed hopes for solving this seemingly intractable problem. Knowledge of the meningococcal genome has led to the identification of novel antigens that have been incorporated into the NMB vaccines now being studied in clinical trials. However, it remains unclear whether these vaccines will provide sufficient immunogenicity in infants as well as wide-ranging coverage. This review highlights the evolution of meningococcal vaccines in general and discusses strategies being used to overcome the barriers to developing vaccines against NMB. Epidemiology of N. meningitidis Infection Meningococcal disease is a global health problem. The World Health Organization estimates that there are 1.2 million cases of invasive meningococcal disease and 135,000 related deaths annually. 3 Although the disease occurs sporadically in industrialized countries, with an incidence of 0.35 cases per 100,000 population in the United States and of 1.01 per 100,000 in Europe (ranging from 0.25 to 4.4 per 100,000 in Italy and Malta, respectively), 4 the major disease burden is in the nonindustrialized countries. A recent epidemic in Nigeria resulted in 4164 cases and 171 deaths in 1 week alone. 5 The meningococcus is pathogenic only in humans. It colonizes the nasopharynx asymptomatically in up to 40% of the adult population but occasionally causes invasive disease. When the infection is classified according to the polysaccharide capsule surrounding the bacterium, only six capsular groups (A, B, C, W-135, X, and Y) are associated with invasive disease. 6 The epidemiology of disease caused by these groups varies: group A is responsible for large epidemics in Africa, in which the incidence approaches 1000 cases per 100,000 population (and may involve environmental factors), whereas groups B and C cause disease predominantly in industrialized and newly industrialized countries. 2,6 Recently, groups W-135 and X (predominantly in Africa) and group Y (in the United States and other countries) have emerged as important disease-causing isolates.
MEIOSIS: A PROSTAGLANDIN RESPONSE THAT IS NOT INHIBITED BY ASPIRIN

Antidromic stimulation of the sensory nerve to the rabbit eye produces pupillary meiosis, supposedly by release of prostaglandins into the aqueous humour. The analogy between this phenomenon and neurogenic inflammation is drawn. It is shown that aspirin and indomethacin, known blockers of prostaglandin synthesis and release, fail to block the meiosis thus produced.
Stress-Induced GSK3 Regulates the Redox Stress Response by Phosphorylating Glucose-6-Phosphate Dehydrogenase in Arabidopsis[C][W][OA]

A change in reactive oxygen species levels is a fundamental phenomenon in response to stress. This study provides mechanistic insight into how the stress-activated glycogen synthase kinase 3 ASKα regulates the activity of G6PD6 and is thus critical for the cellular response to salinity stress. Diverse stresses such as high salt conditions cause an increase in reactive oxygen species (ROS), necessitating a redox stress response. However, little is known about the signaling pathways that regulate the antioxidant system to counteract oxidative stress. Here, we show that a Glycogen Synthase Kinase3 from Arabidopsis thaliana (ASKα) regulates stress tolerance by activating Glc-6-phosphate dehydrogenase (G6PD), which is essential for maintaining the cellular redox balance. Loss of stress-activated ASKα leads to reduced G6PD activity, elevated levels of ROS, and enhanced sensitivity to salt stress. Conversely, plants overexpressing ASKα have increased G6PD activity and low levels of ROS in response to stress and are more tolerant to salt stress. ASKα stimulates the activity of a specific cytosolic G6PD isoform by phosphorylating the evolutionarily conserved Thr-467, which is implicated in cosubstrate binding. Our results reveal a novel mechanism of G6PD adaptive regulation that is critical for the cellular stress response.
A study of subband structure and transport of two-dimensional holes in strained-Si p-MOSFETs using full-band modeling

The quantum confinement of the two-dimensional (2D) hole gas in the inversion layer of strained-Si p-MOSFETs is investigated theoretically. The hole mobility enhancement was found to originate from the suppressed inter-band scattering due to subband splitting and the reduced effective mass in the lowest subband with strain.
Prospective Study of Serum 25-hydroxy Vitamin D and Tooth Loss

Vitamin D deficiency and oral diseases (periodontitis, caries, and tooth loss) are highly prevalent in Germany. Previous studies suggested that vitamin D might be a modifiable and protective factor for periodontitis, caries, and tooth loss. However, prospective studies investigating such associations are limited. We explored the association between the concentration of serum 25-hydroxy vitamin D (25OHD) and incidence of tooth loss, progression of clinical attachment loss (CAL) ≥ 3 mm, and progression of restorative and caries status in a population-based longitudinal study. We analyzed data from 1,904 participants from the Study of Health in Pomerania with a five-year follow-up. Generalized estimating equation models were applied to evaluate tooth-specific associations between serum 25OHD and incidence of tooth loss, progression of CAL ≥ 3 mm, and progression of restorative and caries status. Age, sex, education, smoking status, alcohol drinking, waist circumference, dental visit frequency, reasons of dental visit, vitamin D or calcium supplements, and season of blood draw were considered as confounders. Serum 25OHD was inversely associated with incidence of tooth loss. A significant dose-response relationship (p = .0022) was observed across the quintiles of serum 25OHD. After adjusting for multiple confounders, each 10-µg/L increase of serum 25OHD was associated with a 13% decreased risk of tooth loss (risk ratio: 0.87; 95% confidence interval: 0.79, 0.96). The association was attenuated for changes of CAL ≥ 3 mm when adjusting for multiple confounders. No significant association was found between serum 25OHD and caries progression. Vitamin D might be a protective factor for tooth loss. The effect might partially be mediated by its effect on periodontitis.
Impact of the Village Model: Results of a National Survey

ABSTRACT Villages are a relatively new, consumer-directed model that brings together older adults in a community who have a mutual interest in aging in place. These membership organizations provide social and civic engagement opportunities, volunteer provided support services, and referral to vetted community providers to achieve their primary goals of promoting independence and preventing undesired relocations. This cross sectional survey of 1,753 active Village members from 28 Villages across the US measured members’ perceived impacts in the areas of social connection, civic engagement, service access, health and well-being, and ability to age in place. Results showed that involvement in the Village was a key factor associated with greater perceived impacts. Over half of members perceive that the Village has improved their sense of connection to others and their feeling that they have someone to count on. Though younger members in better health were more likely to perceive impacts in social connections, results suggest older women, living alone with some disability may be the most likely to experience improved health, quality of life, and mobility. The implications for social work practice are discussed.
Identification of Human UMP/CMP Kinase 1 as Doxorubicin Binding Target Using Protein Microarray

Doxorubicin (DOX) is a leading anthracycline drug with exceptional efficacy; however, little is known about the molecular mechanisms of its side effects, which include heart muscle damage, noncancerous cell death, and drug resistance. A total of 17,950 human proteins expressed in HEK293 cells were screened and yielded 14 hits. Competitive and binding experiments further verified the binding of DOX to UMP/CMP kinase 1 (CMPK1), and microscale thermophoresis showed that DOX binds to CMPK1 with a Kd of 1216 nM. In addition, we observed that the binding of DOX to CMPK1 activated the phosphorylation of CMP, dCMP, and UMP. A significant activation was observed at the concentration of 30 µM DOX and reached plateau at the concentration of DOX 30 µM, 150 µM, and 100 µM, respectively. DOX would add up stimulation of CMPK1 by DTT and overcome inhibition of CMPK1 by NaF, EDTA. In summary, we showed that DOX might bind to the nonactive site of CMPK1 and regulate its activity with magnesium.
Induction problems , indirect positive evidence , and Universal Grammar : Anaphoric one revisited

One motivation for Universal Grammar (UG) comes from the existence of induction problems in language acquisition, and their solutions. Previous induction problem characterizations have typically not recognized that INDIRECT POSITIVE evidence may be both available and useful, in addition to other types of evidence. As a case study, we investigate whether a probabilistic learner utilizing indirect positive evidence can solve the induction problem traditionally associated with English anaphoric one. Though full adult knowledge of the representation and interpretation of anaphoric one is extensive, recent experimental work with young children has provided an empirical basis to focus on that accords with the original characterization of this induction problem. In particular, given a specific anaphoric one context, an adult interpretation appears to be generated by toddlers, based on their preferential looking behavior. We find that our modeled learner, given realistic input, can reproduce this toddler anaphoric one behavior, which was thought to indicate the induction problem had been solved by this age. However, we find this behavior can be generated even when a non-adult representation underlies it. This suggests that the previous characterization of this anaphoric one induction problem may need revision, as the link between observable behavior and underlying knowledge is not straightforward. Nonetheless, at least some aspects of the adult representation are in place, and the question remains as to how even that level of knowledge is attained so early in development. We discuss the nature of the learning biases that can generate child behavior, and how this impacts the larger debate about the motivation for UG and its contents.
Effects of inhaled beclomethasone compared to systemic dexamethasone on lung inflammation in preterm infants at risk of chronic lung disease

The purpose of this study was to compare the effects of daily inhaled beclomethasone (3 × 500 μg) started on day 3 of life, with that of systemic dexamethasone (0.5 mg/kg/day) started between days 11–13 on clinical variables, lung inflammation, and pulmonary microvascular permeability in preterm infants at risk for chronic lung disease (CLD). Following administration of surfactant, preterm neonates with RDS and a birth weight of less than 1,200 g were included in this comparative observational pilot study when still mechanically ventilated and with an oxygen requirement on the third day of life. The patients (gestational age 26.1 ± 0.9 weeks, birth weight 826 ± 140 g, mean ± SD) were alternately allocated to prophylactic treatment with inhaled beclomethasone (n = 7), or to early systemic dexamethasone therapy after day 10 of life, if clinically indicated (n = 9). Pulmonary inflammation and lung permeability were assessed by analyzing the levels of interleukin‐8, elastase α1 proteinase inhibitor, free elastase activity, and albumin in tracheal aspirates on days 10 and 14 of life. The secretory component of IgA served as reference protein.