Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic conformational changes of extracellular S5–P linkers in the hERG channel

The hERG channel has an unusually long ‘S5–P linker’ (residues 571–613) that lines the outer mouth of the pore. Previously, we have shown that residues along this S5–P linker are critical for the fast‐inactivation process and K+ selectivity of the hERG channel. Here we used several approaches to probe the structure of this S5–P linker and its interactions with other domains of the hERG channel. Circular dichroism and NMR analysis of a synthetic hERG S5–P linker peptide suggested that this linker is quite dynamic: its central region (positions 583–593) can be unstructured or helical, depending on whether it is immersed in an aqueous phase or in contact with a hydrophobic environment. Cysteine introduced into positions 583–597 of the S5–P linker can form intersubunit disulphide bonds, and at least four of them (at 584, 585, 588 and 589) can form disulphide bonds with counterparts from neighbouring subunits. We propose that the four S5–P linkers in a hERG channel can engage in dynamic conformational changes during channel gating, and interactions between S5–P linkers from neighbouring subunits contribute importantly to channel inactivation.
Predictors of partial remission in older patients treated for major depression: the role of comorbid dysthymia.

OBJECTIVE The authors studied demographic, clinical, social, and perceived health and well-being factors as predictors of partial remission in older patients treated for major depressive disorder (MDD). METHODS The sample included 186 patients who met DSM-IV criteria for MDD and underwent naturalistic treatment. Remission status was determined by Montgomery-Asberg Depression Rating Scale score. Ordinal logistic-regression was used to model the relationship between predictors and remission on an ordinal scale. RESULTS A total of 26.9% patients were in partial remission (score: 7-15), and 25.8% were not in remission (score: 16-60) 1 year after the index evaluation. In bivariate analyses, the odds of partial/no remission were significantly increased for those with comorbid MDD and dysthymia and for those with higher baseline depression scores, and decreased for those with higher perceived social support. Other factors potentially associated with outcome included number of mobility/IADL limitations, perceived stress, self-perceived health, life dissatisfaction, and heart trouble. Controlling for these potential confounders, comorbid MDD and dysthymia significantly predicted outcome. The effect of mobility/IADL limitations differed for those with comorbid dysthymia. CONCLUSIONS Among older adults treated for MDD, factors predicting partial remission appear to be similar to those predicting no remission. Patients with comorbid MDD and dysthymia are at increased risk for poor outcome, and predictors may vary by dysthymia status.
The chicken or the egg? Adaptation to desiccation and salinity tolerance in a lineage of water beetles

Transitions from fresh to saline habitats are restricted to a handful of insect lineages, as the colonization of saline waters requires specialized mechanisms to deal with osmotic stress. Previous studies have suggested that tolerance to salinity and desiccation could be mechanistically and evolutionarily linked, but the temporal sequence of these adaptations is not well established for individual lineages. We combined molecular, physiological and ecological data to explore the evolution of desiccation resistance, hyporegulation ability (i.e., the ability to osmoregulate in hyperosmotic media) and habitat transitions in the water beetle genus Enochrus subgenus Lumetus (Hydrophilidae). We tested whether enhanced desiccation resistance evolved before increases in hyporegulation ability or vice versa, or whether the two mechanisms evolved in parallel. The most recent ancestor of Lumetus was inferred to have high desiccation resistance and moderate hyporegulation ability. There were repeated shifts between habitats with differing levels of salinity in the radiation of the group, those to the most saline habitats generally occurring more rapidly than those to less saline ones. Significant and accelerated changes in hyporegulation ability evolved in parallel with smaller and more progressive increases in desiccation resistance across the phylogeny, associated with the colonization of meso‐ and hypersaline waters during global aridification events. All species with high hyporegulation ability were also desiccation‐resistant, but not vice versa. Overall, results are consistent with the hypothesis that desiccation resistance mechanisms evolved first and provided the physiological basis for the development of hyporegulation ability, allowing these insects to colonize and diversify across meso‐ and hypersaline habitats.
[Periarthritis humeroscapularis (PHS). Indications, technique and outcome of radiotherapy].

BACKGROUND Radiation treatment for patients with acute or subacute tendonitis or bursitis of the shoulder once commonplace has been mostly supplanted by antiinflammatory drug treatment. PATIENTS AND METHODS 106 patients with clinically evident disease of PHS were treated between January 1987 and May 1991. 73/106 patients had a continuous follow-up. 16/73 patients showed typical symptoms on both shoulders: therefore a total of 89 shoulders were examined in this investigation. A daily dose of 0.5 Gy was given for 3 times a week and a total dose of 3.0 Gy. After 8 weeks a second treatment course was performed. In follow-up the subjective (pain) and objective (limitation of abduction) symptoms were classified in 3 grade scales. RESULTS A marked pain reduction and an improved mobility (abduction of at least 20 degrees more than before radiation) could be observed in 72/89 shoulders (81%). 44/89 shoulders (49%) showed an excellent response and were completely free of pain and impairment of motion. CONCLUSION Radiotherapy of acute or subacute Periarthritis humeroscapularis is a very effective treatment if radiation starts within the first year of symptoms and if it is supported by physiotherapy.
The Effect of Tax Incentive for Dividend Income on Corporate Payout Policy

Sang-Yeob Lee* and Woo-Hyung Hong** In 2014, the Korean government introduced a temporary tax reform that provides tax incentives for dividend income to the shareholders of high dividend-yielding companies for a three-year. Considering the tax reform as an exogenous economic shock to the Korean economy, we sought to analyze and verify its impact on the corporate payout policies of listed companies. Our empirical results confirm that the reform contributes to statistically significant, but not dramatic, increases in corporate payout as well as in the amount of cash dividends. We also find that those companies with high proportion of major shareholders are more likely to satisfy the qualifying requirements of high dividend-yielding firms. This, in turn, attests to the important role of major shareholders’ ownership on determining corporate payout policy.
Monte-Carlo stability analysis of microwave amplifiers

Pole-zero identification is being increasingly used as a method to analyze the stability of microwave circuits. However, in its current form, the stability analysis through pole-zero identification relies on a quality assessment that is based on visual inspection. This implies a manual approach that limits in practice the handling of a large amount of data as in the case of a yield or sensitivity analysis. Here, an automated methodology based on pole-zero identification is applied to the stability evaluation in the context of a Monte-Carlo analysis. The methodology is based on an algorithm that prevents the adverse effects due to undermodeling and overmodeling on the stability criteria. The approach is illustrated through its application to two in-home built amplifier prototypes: a medium power band L FET amplifier exhibiting a low frequency oscillation and a SiGe HBT reconfigurable amplifier for Wifi/Wimax applications that shows an undesired frequency division for some particular input drive conditions.
Macroeconomic conditions and capital structure: evidence from publicly listed companies in the U.K.

This research investigates whether and to what extent macroeconomic variables, namely, business cycle, financial market risk, credit supply and stock market performance, affect capital structure of publicly listed U.K. firms. Specifically, by using fixed effects, random effects, tobit, and GLS regression models and GMM methods (SGMM and DGMM), this research tests if the macroeconomic variables affect capital structure in a manner that is consistent with the pecking order, trade-off and market timing theories. Without considering the effect of 2008 financial crisis, I find that, first, the results from static models and dynamic models of capital structures indicate that leverage is negatively associated with the business cycle. This is consistent with the prediction of pecking order theory. Second, the results from static models report that leverage is positively associated with credit supply which is consistent with either prediction of pecking order or trade-off theories. However, the dynamic models’ results show that leverage is negatively associated with credit supply which is consistent with prediction of market timing theory. Third, the results from static models report that leverage is negatively associated with financial market risk which is consistent with the predictions of trade-off theory. However, leverage is associated significantly and positively with financial market risk based on the dynamic model results which is consistent with the predictions of pecking order theory. Fourth, the results from static models report that leverage is positively associated with stock market performance which is consistent with predictions of pecking order theory. However, the dynamic models’ results show that stock market performance does not have an explanatory power on capital structure. Moreover, considering the effect of 2008 financial crisis, I find that, the results are the same and consistent with both the static and dynamic results with the exception of financial market risk’s result which is only consistent with the static model’s results. The above results are robust to the stated estimation strategies and indicate that macroeconomic condition has explanatory power on capital structure. In addition, this research, despite the strong empirical evidence supporting effect of macroeconomic conditions on capital structure does not have overwhelming evidence in support of any of the three stated theories. Furthermore, the empirical findings indicate that the effect of macroeconomic condition was more balanced after the crisis, suggesting that during crises due to the uncertain level of financial market risk, the effect is undetermined, and a trade-off rises for economic policy. Therefore, this research contributes to the literature, by using the four chosen macroeconomic variables, static and dynamic estimation strategies and U.K. data and by establishing the hypotheses to predict how the four stated macroeconomic variables affect capital structure under the pecking order, trade-off and market timing theories.
Protein kinase involved in lung injury susceptibility: Evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment

Acute lung injury (ALI) associated with sepsis and iatrogenic ventilator-induced lung injury resulting from mechanical ventilation are major medical problems with an unmet need for small molecule therapeutics. Prevailing hypotheses identify endothelial cell (EC) layer dysfunction as a cardinal event in the pathophysiology, with intracellular protein kinases as critical mediators of normal physiology and possible targets for drug discovery. The 210,000 molecular weight myosin light chain kinase (MLCK210, also called EC MLCK because of its abundance in EC) is hypothesized to be important for EC barrier function and might be a potential therapeutic target. To test these hypotheses directly, we made a selective MLCK210 knockout mouse that retains production of MLCK108 (also called smooth-muscle MLCK) from the same gene. The MLCK210 knockout mice are less susceptible to ALI induced by i.p. injection of the endotoxin lipopolysaccharide and show enhanced survival during subsequent mechanical ventilation. Using a complementary chemical biology approach, we developed a new class of small-molecule MLCK inhibitor based on the pharmacologically privileged aminopyridazine and found that a single i.p. injection of the inhibitor protected WT mice against ALI and death from mechanical ventilation complications. These convergent results from two independent approaches demonstrate a pivotal in vivo role for MLCK in susceptibility to lung injury and validate MLCK as a potential drug discovery target for lung injury.
Analgesia in newborns: a case-control study of the efficacy of nutritive and non-nutritive sucking stimuli.

PURPOSE To verify the nutritive and non-nutritive stimuli efficacy in the newborn's response to pain during venipuncture. METHODS The main sample was composed of 64 newborns that were randomly divided into three groups. The first group (n=20) received nutritive sucking stimulus that was performed through maternal breastfeeding. The second group (n=21) received non-nutritive sucking stimulus that was performed through the introduction of the researcher little finger in the newborn's oral cavity. The third group or control group (n=23) did not receive any analgesia stimulus. The newborns were evaluated using the Neonatal Infant Pain Scale, and the responses to painful stimuli were compared. RESULTS The nutritive as well as non-nutritive suction methods provided a comforting effect, resulting in lower pain response scores (p<0.05). There was no difference between the analgesia provided by both methods (p>0.05). CONCLUSION The nutritive and the non-nutritive sucking stimuli proved to be efficacious tools in relieving pain among newborns.
Intrafamilial variability in fragile X–associated tremor/ataxia syndrome

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a progressive adult‐onset tremor/ataxia syndrome caused by premutations in the FMR1 gene. In cranial MRI, the most characteristic findings are bilateral T2 hyperintense lesions within the middle cerebellar peduncles. Here we present a sibpair of two affected brothers presenting with very different symptoms (typical FXTAS versus essential tremor‐like), disease progression, and MRI findings, illustrating broad intrafamilial variability of FXTAS. Also, their family history suggests further evidence of possible manifestation of FXTAS in women. © 2005 Movement Disorder Society
In Search of an Effective Trade Policy for the Film Industry: Lessons from Korea

This article explores which trade-related policies are effective – that is both economically and culturally sound – to promote the film industry that has recently been highlighted more due to its prominent political, economic and cultural dimensions. By examining the trade-related policies of nine major countries for their film industries over the last forty years, several important findings are extracted which contribute towards a more pragmatic debate on ‘trade and culture’. First, regulatory barriers such as import or screen quotas should be avoided at all costs since they do not protect the domestic film industry. Second, tax relief schemes are unreliable because they tend to offer excessive support to attract foreign film producers. Third, as a choice to be considered, subsidies should be kept reasonable in size and focus on consistent goals. Fourth, well-designed trade agreements can contribute greatly to enhance film policies. Finally, once combined, these results explain to a large extent the remarkable success of the Korean film industry over the last two decades, which can be a good bench marker for countries that want to enhance their film industry and to promote their culture.
Introducing the Palliative Performance Scale to clinicians: the Grampian experience

Objectives The Palliative Performance Scale (PPS) was introduced across NHS Grampian. Our aim was to determine how practical and useful the PPS was for clinicians looking after palliative patients in a variety of settings. Methods A prospective audit approach was used in primary, secondary and nursing home care settings who. Demographic and assessment data were gathered for 3 months; feedback was gathered at the end of the data collection phase. Patient follow-up status was determined at 12 months. Results Fifteen clinical sites participated and feedback was obtained from all clinical areas (n=30). Most respondents found the PPS easy to use and that it helped recognise disease progression in cancer patients, but not in patients with dementia/frailty. Assessment data were gathered on 666 patients. Sixty per cent had a malignant diagnosis and 62.5% of the sample died within 12 months. Lower PPS scores at initial assessment indicated poorer prognosis. Median survival figures differed from previously published data. Falling PPS scores increased the risk of death compared with patients whose PPS scores remained static or improved. Conclusion Clinicians found the PPS to be a quick, useful way of assessing and reviewing functional changes in palliative patients. However, it may not identify the subtle changes in individuals with advanced dementia. The survival figures confirm that caution is needed in generalising survival data across different settings and populations. Further work is needed to examine changing functional status in patients with non-malignant diseases or dementia/frailty.
Academic Integrity in Canada: An Annotated Bibliography.

5 Executive Summary . 6 Introduction . 9 Background and Definitions . 9 Origins and Purpose of This Report . 9 Methodology . 10 Intended Audience . 10 Research Questions . 10 Inclusion and Exclusion Criteria . 10 Typology of Evidence . 12 Search Method . 12 I. Attitudes, Behaviours and Perceptions . 14 II. Academic Integrity in Professional Programs . 21 Education/Pre-service Teaching Programs . 21 Pharmacy Programs . 25 III. Understanding and Supporting International Students . 27 IV. Pedagogical Implications: Instruction and Prevention . 29 V. Focus on Technology . 36 VI. Institutional considerations: Policy, law and case management . 40 VII. Methodological Considerations: Plagiarism Research . 46 Conclusions . 47 References . 48 Academic Integrity in Canada: An Annotated Bibliography Eaton, Crossman, & Edino, 2019 | UNIVERSITY OF CALGARY 4 A Message from the Researchers We are grateful to the Werklund School of Education who provided funding for this project through a Research Development Grant (2017-2018). Further, we are grateful to the librarians at the University of Calgary who assisted us in locating and providing us with copies of materials listed in the institutional research databases, but were not easily accessible. The librarians tracked down and provided us with copies of these sources through the institutional document delivery service and we offer our gratitude for their efforts. Finally, we owe a debt of gratitude to those who provided feedback on this work. Sarah Elaine Eaton, Ph.D., Principal Investigator Katherine (Katie) Crossman, Ph.D., Research Associate Rachael Edino, Ph.D. Candidate, Research Assistant
The phantom of technological unemployment

Nowadays there are many gloomy prophecies provided by both technologists and economists about the detrimental effects of the so-called Fourth Industrial Revolution on aggregate employment and its composition. These prophecies imply that in the near future we will face Robocalypse — a massive replacement of people by machines alongside an explosion in joblessness. This paper provides theoretical, empirical and historical evidence that the phenomenon of technological unemployment is a phantom. The most general results can be summarized as follows: in the long run, reduction in labor demand under the impact of new technologies is merely a theoretical possibility that has never before been realized in practice; at the level of individual firms, there is a strong positive relationship between innovations and employment growth; at the sectoral level, technological changes cause a multidirectional employment response, since different industries are at different stages of the life cycle; at the macro level, technological progress acts as a positive or neutral, but not a negative factor; a surge in technological unemployment, even in the short-term, seems a remote prospect since in coming decades the pace of technological change is unlikely to be fast enough by historical standards; the impact of new technologies on labor supply may be a more serious problem than their impact on labor demand; technological changes seem to have a much greater effect on the composition of employment than on its level.
A Prospective Study of Physical Activity and Breast Cancer Incidence in African-American Women

Background: Physical activity has been associated with reduced risk of breast cancer. Evidence on the association in African Americans is limited. Methods: With prospective data from the Black Women's Health Study, we assessed vigorous exercise and walking in relation to incidence of invasive breast cancer overall (n = 1,364), estrogen receptor–positive (ER+, n = 688) cancer, and estrogen receptor–negative (ER−, n = 405) cancer, based on 307,672 person-years of follow-up of 44,708 African-American women ages 30 years or older at enrollment. Cox proportional hazards models estimated incidence rate ratios (IRR) and 95% confidence intervals (CI). Results: Vigorous exercise at baseline was inversely associated with overall breast cancer incidence (Ptrend = 0.05): the IRR for ≥7 h/wk relative to <1 h/wk was 0.74 (95% CI, 0.57–0.96). The association did not differ by ER status. Brisk walking for ≥7 h/wk was associated with a reduction similar to that for vigorous exercise. Vigorous exercise at the age of 30 years, 21 years, or in high school was not associated with breast cancer incidence. Sitting for long periods at work or watching TV was not significantly associated with breast cancer incidence. Conclusion: High levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African-American women. Impact: These results provide informative data on a potential modifiable risk factor, exercise, for breast cancer in African-American women. Cancer Epidemiol Biomarkers Prev; 23(11); 2522–31. ©2014 AACR.
The gut flora is required for the control of intestinal infection by poly(I:C) administration in neonates

We found that immunostimulation of the intestinal immune system of neonatal mice by poly(I:C) injection decreased intestinal infection by the parasite Cryptosporidium parvum. We showed that the presence of dendritic cells and the cooperation of mutually dependent cytokines, such as IL-12p40, and type I and type II IFNs, were involved in the mechanism of protection induced by poly(I:C). This protection is dependent not only on TLR3-TRIF signaling, but also on the activation of the TLR5-MyD88 pathway by gut microbiota. These results raise the possibility that flagellated intestinal commensal bacteria may, in the presence of natural or synthetic agonists of TLR3, provide synergy between the TRIF and MyD88 signaling pathways, thereby favoring the development of mucosal defenses. In this addendum, we summarize these recent findings and discuss their implications for neonatal infections and immunomodulatory strategies.