Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Fentanyl-Like Opioids and Hydromorphone on Human 5-HT3A Receptors

BACKGROUND: 5-HT3 receptors are involved in various physiologic functions, including the modulation of emesis. 5-HT3 antagonists are clinically widely used as potent antiemetics. Emesis is also a side effect of opioid analgesics. Intriguingly, the natural opioid morphine shows specific interactions with human 5-HT3 receptors at clinically relevant concentrations. In the present study, we investigated whether this is a general effect of opioids, even when they are structurally diverse. Therefore, another morphine (phenanthrene-type) derivative, hydromorphone, and fentanyl including its (4-anilinopiperidine-type) derivatives were tested. METHODS: Whole-cell patches from human embryonic kidney-293 cells, stably transfected with the human 5-HT3A receptor cDNA, were used to determine the opioid effects on the 5-HT (3 &mgr;M)-induced currents using the patch clamp technique (voltage-clamp). RESULTS: None of the fentanyl derivatives affected currents through the 5-HT3A receptor (3 &mgr;M 5-HT) significantly in the clinically relevant nanomolar concentration range (IC50 values >30 &mgr;M). In contrast, hydromorphone was considerably more potent (IC50 = 5.3 &mgr;M), slowing the current activation- and desensitization-kinetics significantly (at 3 &mgr;M by a factor of 1.9 and 2.4, respectively), similar to morphine. At concentrations much higher than clinically relevant, but within the range predicted from Meyer-Overton correlations for nonspecific interactions, the fentanyl derivatives all showed at least a tendency to suppress current amplitudes, but they had diverse effects on the activation- and desensitization-kinetics of 5-HT3A receptors. CONCLUSIONS: Only morphine and hydromorphone, but not the fentanyl derivatives, reduced 5-HT-induced current amplitudes and slowed current kinetics near clinically relevant concentrations. The high potencies of morphine and hydromorphone, when compared to their lipophilicities, suggest a specific interaction with 5-HT3A receptors. In contrast, the effects of fentanyl-type opioids appear to be of unspecific nature. Because the rank order of opioid potencies for human 5-HT3A receptors is opposite of that for opioid receptors, the site involved is structurally different from opioid receptor binding sites. In agreement with recent data on different phenols, a phenolic OH-group (which morphine and hydromorphone possess) may contribute to specific interactions of morphine and hydromorphone with the 5-HT3A receptor. Future clinical studies could test whether corresponding differences in emetogenicity between different classes of opioids will be found.
Toward more intuitive brain–computer interfacing: classification of binary covert intentions using functional near-infrared spectroscopy

Abstract. In traditional brain–computer interface (BCI) studies, binary communication systems have generally been implemented using two mental tasks arbitrarily assigned to “yes” or “no” intentions (e.g., mental arithmetic calculation for “yes”). A recent pilot study performed with one paralyzed patient showed the possibility of a more intuitive paradigm for binary BCI communications, in which the patient’s internal yes/no intentions were directly decoded from functional near-infrared spectroscopy (fNIRS). We investigated whether such an “fNIRS-based direct intention decoding” paradigm can be reliably used for practical BCI communications. Eight healthy subjects participated in this study, and each participant was administered 70 disjunctive questions. Brain hemodynamic responses were recorded using a multichannel fNIRS device, while the participants were internally expressing “yes” or “no” intentions to each question. Different feature types, feature numbers, and time window sizes were tested to investigate optimal conditions for classifying the internal binary intentions. About 75% of the answers were correctly classified when the individual best feature set was employed (75.89% ±1.39 and 74.08% ±2.87 for oxygenated and deoxygenated hemoglobin responses, respectively), which was significantly higher than a random chance level (68.57% for p<0.001). The kurtosis feature showed the highest mean classification accuracy among all feature types. The grand-averaged hemodynamic responses showed that wide brain regions are associated with the processing of binary implicit intentions. Our experimental results demonstrated that direct decoding of internal binary intention has the potential to be used for implementing more intuitive and user-friendly communication systems for patients with motor disabilities.
Managerial Ability and Bank‐Loan Pricing

This paper examines the impact of borrowers’ managerial ability on lenders’ bank-loan pricing and the channels through which managerial ability affects bank-loan pricing. Using a large sample of U.S. bank loans, we provide evidence that higher managerial ability is associated with lower bank-loan prices. This effect is stronger in firms with high information risk, suggesting that an important channel for managerial ability to affect bank-loan pricing is through improved financial disclosure to mitigate information asymmetry. The relation is also stronger for firms with weak business fundamentals, implying that another channel is through improved business performance. Of these two mechanisms, path analysis suggests that the business-fundamentals mechanism is the more important channel through which managerial ability affects bank-loan pricing.
Amendments to IAS 16 and IAS 41: Are There Any Differences between Plant and Animal from a Financial Reporting Point of View?

The aim of the paper is the evaluation of appropriateness of different ways for the measurement and reporting of different groups of biological assets. There are two possible ways of their measurement – cost and fair value. The substance of all kinds of biological assets differs significantly, especially for plants and animals. The single way for measurement of all kinds of biological assets is not satisfactory. The most significant difference is observable between bearer plants and biological assets in the form of living animals. The authors took into account a majority of factors influencing quality of individual ways of measurement, and evaluated the application of the above‑mentioned methods for representatives of both kinds of biological assets (apple orchard and dairy cows). The results of the study proved that the historical cost is the suitable way of bearer plants measurement, while the fair value measurement is more suitable for measurement of living animals.
Antitumoral Property of Ethanolic Extract of Propolis in Mice-Bearing Ehrlich Carcinoma, as Compared to Bleomycin

Antitum oral effect of ethanolic extract of propolis (EEP) was demonstrated in mature mice-bearing Ehrlich carcinoma. Survival rate after EEP treatment was compared to that of bleomycin, given alone or in combination every two days for 36 days and follow ed up for 14 additional days. The survival rate at 50 days was 55% after EEP and 40% after bleomycin, while all the mice-treated with EEP + bleomycin combination demonstrated shorter survival than the controls. It is concluded that while the in vivo activity of bleomycin is reduced in the presence of cytochrome-C-reductase inhibitors (like some of the EEP components are), the antitumoral property of EEP in the tumored animal model studied is significant and lasting.
Stimulation of Skin and Wound Fibroblast Migration by Mesenchymal Stem Cells Derived from Normal Donors and Chronic Wound Patients

Chronic wounds continue to be a major cause of morbidity for patients and an economic burden on the health care system. Novel therapeutic approaches to improved wound healing will need, however, to address cellular changes induced by a number of systemic comorbidities seen in chronic wound patients, such as diabetes, chronic renal failure, and arterial or venous insufficiency. These effects likely include impaired inflammatory cell migration, reduced growth factor production, and poor tissue remodeling. The multifunctional properties of bone marrow‐derived mesenchymal stem cells (MSCs), including their ability to differentiate into various cell types and capacity to secrete factors important in accelerating healing of cutaneous wounds, have made MSCs a promising agent for tissue repair and regeneration. In this study we have used an in vitro scratch assay procedure incorporating labeled MSCs and fibroblasts derived from normal donors and chronic wound patients in order to characterize the induction of mobilization when these cells are mixed. A modified Boyden chamber assay was also used to examine the effect of soluble factors on fibroblast migration. These studies suggest that MSCs play a role in skin wound closure by affecting dermal fibroblast migration in a dose‐dependent manner. Deficiencies were noted, however, in chronic wound patient fibroblasts and MSCs as compared with those derived from normal donors. These findings provide a foundation to develop therapies targeted specifically to the use of bone marrow‐derived MSCs in wound healing and may provide insight into why some wounds do not heal.
Annual species abundance in a tidal freshwater marsh: Germination and survival across an elevational gradient

Annual species contribute significantly to the standing biomass of tidal freshwater marshes, but they tend to be distributed unevenly along the elevation gradient, with higher surface elevations supporting greater densities of annual species. We explored the generation of this pattern by evaluating how different life history stages of annual species are related to elevation and to each other. In 2006, we counted seedlings emerging from the seed bank under optimal greenhouse conditions, as well as seedlings and mature stems of annual species in 38 plots located at different elevations in a tidal freshwater marsh near Alexandria, Virginia, USA. Annual species seedling and mature stem density increased with elevation of the marsh surface, but seed density did not change with elevation. Seeds of annual species germinated in saturated rather than flooded conditions (4.50 ±0.54 versus 1.66 ±0.26 species/ greenhouse container ±SE). Germination and survival from seedling to mature stem affected density of annual species across an elevational gradient, but the relative importance of either process differed by species. Amaranthus cannabinus was common and frequent in the seed bank (68% of all plots), and seed density increased with elevation, but seedlings and mature stems were infrequent at any elevation (21% and 5%, respectively), suggesting that germination is limiting its recruitment to standing vegetation. In contrast, Bidens laevis was uncommon in the seed bank (18% of all plots), but was frequently observed as seedlings and mature stems (55% and 34%, respectively). We therefore conclude that B. laevis recruitment was limited by its ephemeral seed bank. Impatiens capensis density did not appear to be limited by germination or survival to maturity as density of the species was high at all life history stages. Rather, its strong positive relationship with elevation at all life stages shows that I. capensis is limited by water inundation, particularly in spring when seeds require oxygen to germinate. Overall, we show that annual species increase in density at higher elevations in a tidal freshwater marsh, but that recruitment of each species may be limited by different intrinsic and extrinsic processes.
Successful treatment of severe dysrhythmias in infants with respiratory syncytial virus infections: two cases and a literature review.

OBJECTIVES To describe severe myocardial manifestations in two infants with respiratory syncytial virus infection and to review published literature reporting cardiac involvement in patients with respiratory syncytial virus disease. DESIGN Case report and literature review. SETTING Tertiary care pediatric intensive care unit (ICU). PATIENTS Two infants admitted to the pediatric ICU for dysrhythmias and severe myocardial dysfunction and infected with respiratory syncytial virus. INTERVENTIONS Conventional cardiovascular, antidysrhythmic, and respiratory support, as well as extracorporeal membrane oxygenation and high-frequency oscillatory ventilation. MEASUREMENTS AND MAIN RESULTS Both patients had respiratory syncytial virus infections and clinical evidence of severe myocarditis, with dysrhythmias, cardiomegaly, and cardiogenic shock. Both infants survived their hospitalizations. To our knowledge, these two patients are the first reported cases of myocarditis in infants with respiratory syncytial virus infection. CONCLUSIONS Severe myocardial dysfunction and dysrhythmias may accompany respiratory syncytial virus infection in some infants and may be reversible with aggressive supportive therapy.
DOES GENDER MAKES ANY DIFFERENCE IN LIVELIHOODS DIVERSIFICATION? EVIDENCE FROM NORTHERN GHANA

The fact that rural livelihood portfolios is expanding and diversifying beyond agriculture is not contested. However, very little is known on gender dimension of rural livelihoods diversification and whether gender makes any difference in rural dwellers construction of livelihood portfolios. This paper therefore presents findings of analysis of data obtained from USAID sponsored Feed The Future population baseline survey conducted in 2012 in their Northern Ghana Zone of Influence, with the view of examining gender dimension of livelihoods diversification among the 13,580 respondents who were 15 years or older. Results of the analysis revealed significant gender differentiation in number of livelihood activities engaged in by men and women. The results established that livelihoods diversification is common across gender in Northern Ghana, but men are more likely to engage in more livelihood activities than women. Significantly more men than women were found to have been engaged in paid wage labour within the last 12 months, with women dominating the non-farm self-employed livelihood enterprises. This paper therefore recommends that, measures aim at women economic empowerment, should target providing training and financial support to enable women improve their non-farm livelihood enterprises.
Factors Influencing Equity Return Correlations between China’s Pairs of A- and B-Share Markets: Effect of QFII’s Implementation

This paper was intended to examine factors influencing the correlations between A- and B-shares of individual firms, and explore the effects of Qualified Foreign Institutional Investor’s (QFII) implementation on correlations. The empirical results show that interest rate differential, relative turnover rate, relative return volatility, and market sentiment had impacts on correlation both before and after the QFII’s implementation. After its implementation, correlations became more sensitive to premium, relative turnover rate and market sentiment. Furthermore, the estimated constant term for overall market correlation became more negative (raw values from -0.3413 to -0.8815), indicating an increasing correlation between A- and B-shares’ returns. The policy implications are that much benefit of diversification into emerging markets such as paired A-and B-shares can be accomplished, together with taking several influential factors into account.
Is smoking associated with favourable outcome in tPA‐treated stroke patients?

Smoking has been associated with improved outcome in thrombolysed patients with myocardial infarction and higher recanalization rates in stroke patients treated with tissue plasminogen activator (tPA). We hypothesized a positive association between smoking and favourable outcome in stroke patients treated with tPA and no such association in acute stroke patients not treated with tPA, suggesting a beneficial effect of smoking on thrombolysis with tPA.
Developments in France regarding the mandatory rotation of auditors: Do they enhance auditors’ independence?

Mandatory rotation of auditors or of audit firms has been the subject of extensive debate among academics, professionals, and regulators, especially since the financial crisis of the 2000s. Does rotation enhance auditors’ independence and audit quality? The research evidence on the impact of mandatory audit firm rotation on audit quality and auditor independence is inconclusive. This article offers a historical approach to understanding the implementation of mandatory rotation, based on the French case. The auditing profession in France is strongly regulated, with four main provisions designed to reinforce auditors’ independence: prohibitions on a priori and a posteriori incompatibilities, a 6-year audit tenure, a ban on non-audit services, and the use of joint audit. The rotation of auditors was merely an additional and non-compulsory tool. However, in 2014, the European Commission decided to implement the mandatory rotation of audit firms despite the opposition of the French accounting profession and regulators. Does this suggest that the French model was ineffective? It probably does not. In this specific context of France, a mandatory rotation of audit firms would seem unlikely to enhance audit quality.
Subthalamic Nucleus Deep Brain Stimulation Employs trkB Signaling for Neuroprotection and Functional Restoration

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most common neurosurgical treatment for Parkinson's disease motor symptoms. In preclinical models, STN DBS provides neuroprotection for substantia nigra (SN) dopamine neurons and increases BDNF in the nigrostriatal system and primary motor cortex. However, whether BDNF signaling in the SN participates in the neuroprotective effects of DBS remains unknown. We demonstrate that STN DBS in male rats activates signaling downstream of tropomyosin receptor kinase type B (trkB), namely, phosphorylation of Akt and ribosomal protein S6, in SN neurons. Long-term trkB blockade abolished STN DBS-mediated neuroprotection of SN neurons following progressive 6-hydroxydopamine lesion and was associated with decreased phosphorylated ribosomal protein S6 immunoreactivity. Acute trkB blockade in rats with stable nigrostriatal denervation attenuated the forelimb akinesia improvement normally induced by STN DBS. These results suggest that STN DBS increases BDNF-trkB signaling to contribute to the neuroprotective and symptomatic efficacy of STN DBS. SIGNIFICANCE STATEMENT Subthalamic nucleus deep brain stimulation (STN DBS) is increasingly used in mid- to late-stage Parkinson's disease (PD) but with an incomplete knowledge of its molecular mechanisms. STN DBS is neuroprotective against neurotoxicants in animal models and increases BDNF. This study is the first to show that BDNF signaling through the cognate tropomyosin receptor kinase type B (trkB) receptor occurs in substantia nigra pars compacta neurons and is required for neuroprotection. In addition, blockade of trkB unexpectedly reduced the functional benefit of STN DBS on a short timescale that is inconsistent with canonical trkB signaling pathways, suggesting a noncanonical role for trkB in STN DBS-mediated behavioral effects. Together, these data implicate trkB signaling in the symptomatic efficacy and disease-modifying potential of STN DBS.
Essays on Commodity Price Shocks, Bank Risk and Market Volatility Forecasting

My dissertation has three main chapters. Chapter 2 develops a structural dynamic factor model that estimates the effects of commodity price shocks on the Canadian macroeconomy, bank lending and bank risk. Unlike most literature treating commodity price changes as exogenous, I identify global structural shocks driving real commodity prices and find that global demand and commodity market–specific shocks are crucial. These two shocks are shown to have quite different implications for bank lending and risk, which confirms the importance of disentangling shocks driving commodity price changes. I also discover that on average, the total loan growth and the noninterest income ratio of large Canadian banks are more responsive to the above two commodity price shocks than those of small Canadian banks. Chapter 3, coauthored with Tian Xie, studies how to better forecast the daily market volatility (VIX) index. We propose utilizing the ordinary least square post– least absolute shrinkage and selection operator (OLS post–Lasso) from Belloni and Chernozhukov (2013) to select the predictors and estimate the coefficients for a heterogeneous autoregressive (HAR) model (Corsi, 2009). In an out–of–sample analysis with the VIX data, our proposed OLS post–Lasso HAR (OLHAR) model generates a different combination of predictors from those ex ante imposed by the standard HAR model. Moreover, the OLHAR model shows its dominance over the standard
Extinction of cued fear memory involves a distinct form of depotentiation at cortical input synapses onto the lateral amygdala

The amygdala is known to be a critical storage site of conditioned fear memory. Among the two major pathways to the lateral amygdala (LA), the cortical pathway is known to display a presynaptic long‐term potentiation which is occluded with fear conditioning. Here we show that fear extinction results in a net depression of conditioning‐induced potentiation at cortical input synapses onto the LA (C‐LA synapses). Fear conditioning induced a significant potentiation of excitatory postsynaptic currents at C‐LA synapses compared with naïve and unpaired controls, whereas extinction apparently reversed this potentiation. Paired‐pulse low‐frequency stimulation (pp‐LFS) induced synaptic depression in the C‐LA pathway of fear‐conditioned rats, but not in naïve or unpaired controls, indicating that the pp‐LFS‐induced depression is specific to associative learning‐induced changes (pp‐LFS‐induced depotentiationex vivo). Importantly, extinction occluded pp‐LFS‐induced depotentiationex vivo, suggesting that extinction shares some mechanisms with the depotentiation. pp‐LFS‐induced depotentiationex vivo required NMDA receptor (NMDAR) activity, consistent with a previous finding that blockade of amygdala NMDARs impaired fear extinction. In addition, pp‐LFS‐induced depotentiationex vivo required activity of group II metabotropic glutamate receptors (mGluRs), known to be present at presynaptic terminals, but not AMPAR internalization, consistent with a presynaptic mechanism for pp‐LFS‐induced depotentiationex vivo. This result is in contrast with another form of ex vivo depotentiation in the thalamic pathway that requires both group I mGluR activity and AMPAR internalization. We thus suggest that extinction of conditioned fear involves a distinct form of depotentiation at C‐LA synapses, which depends upon both NMDARs and group II mGluRs.