Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of drug-drug interactions: concepts and approaches

1. A priori knowledge of the enzyme inhibitory potential of new drug entities and the drug-metabolizing enzymes involved can be used in support of important decisions on the future progress of a drug in clinical development. 2. Important advances in the knowledge of human drug-metabolizing enzymes have largely fuelled the integration of in vitro drug metabolism and clinical drug interaction studies for use in drug development programmes. 3. The likelihood of correctly predicting in vivo drug-drug interactions appears highly dependent on selecting the correct enzyme inhibition model for use in deriving the inhibitor constant (Ki) and correctly determining the available concentration of inhibitor at the active site of the enzyme(s) of interest. 4. The uncertainty and inaccuracy of predicting the extent and duration of in vivo drug interactions currently stems from a lack of definitive models by which to assess likely substrate and inhibitor concentrations at the active site of metabolism. Additional issues contributing to the uncertainty of predicting drug interactions include assumptions of the contribution of presystemic drug extraction and the effect of inhibitors on the processes involved. 5. This review considers the practical aspects of in vitro enzyme inhibition studies and the use of in vitro-in vivo correlation approaches described in the literature to predict in vivo drug-drug interactions.
Short‐term carbon cycling responses of a mature eucalypt woodland to gradual stepwise enrichment of atmospheric CO2 concentration

Projections of future climate are highly sensitive to uncertainties regarding carbon (C) uptake and storage by terrestrial ecosystems. The Eucalyptus Free‐Air CO2 Enrichment (EucFACE) experiment was established to study the effects of elevated atmospheric CO2 concentrations (eCO2) on a native mature eucalypt woodland with low fertility soils in southeast Australia. In contrast to other FACE experiments, the concentration of CO2 at EucFACE was increased gradually in steps above ambient (+0, 30, 60, 90, 120, and 150 ppm CO2 above ambient of ~400 ppm), with each step lasting approximately 5 weeks. This provided a unique opportunity to study the short‐term (weeks to months) response of C cycle flux components to eCO2 across a range of CO2 concentrations in an intact ecosystem. Soil CO2 efflux (i.e., soil respiration or Rsoil) increased in response to initial enrichment (e.g., +30 and +60 ppm CO2) but did not continue to increase as the CO2 enrichment was stepped up to higher concentrations. Light‐saturated photosynthesis of canopy leaves (Asat) also showed similar stimulation by elevated CO2 at +60 ppm as at +150 ppm CO2. The lack of significant effects of eCO2 on soil moisture, microbial biomass, or activity suggests that the increase in Rsoil likely reflected increased root and rhizosphere respiration rather than increased microbial decomposition of soil organic matter. This rapid increase in Rsoil suggests that under eCO2, additional photosynthate was produced, transported belowground, and respired. The consequences of this increased belowground activity and whether it is sustained through time in mature ecosystems under eCO2 are a priority for future research.
Near-real-time stereo matching method using temporal and spatial propagation of reliable disparity

Abstract. A stereo approach to resolve the occlusion problem in stereo video sequence is introduced. We define a measure to evaluate the reliability of an initial disparity in combination with a left-right consistency check. An initial matching cost volume is computed with an absolute difference-census measure. In the spatial propagation stage, the outlier with a low reliability value is replaced/updated with the reliable disparity information in the support region. Because previous methods establish correspondence on a per-frame basis, they cannot obtain temporally coherent disparity results over a stereo sequence. In order to overcome the occlusion problem in a dynamic situation, we employ the modified codebook with color, disparity, reliability, array of the matching cost, and final access time in a temporal propagation procedure. Experimental results show that the proposed algorithm with general-purpose computing on graphics processing units (GPGPU) provides better performance when applied to disparity maps of real-time indoor/outdoor scenes.
Factors affecting initial placement of accounting Ph.Ds

The perceived prestige of the doctoral degree granting institution traditionally has had a major effect on job opportunities available to a new accounting Ph.D. However, given recent shortages of accounting academics, the role of program prestige may have changed. It is possible that individual factors also may now play a role in the initial placement decision. This study examines the effects of both doctoral program prestige and individual factors on the initial placement decision. While our results indicate that doctoral program prestige still largely dictates the initial placement decision, several other factors are found to be important. New graduates initially placed at higher level institutions report faculty involvement during the application process as well as significant research support by the hiring institution. New faculty placing lower than expected report the mix of teaching and research as well as the quality of life as being significant factors in their employment decision.
Tourism and The Employment Growth : The Albanian case

Tourism is a service sector which has shown a big development throughout the world. The tourism's contribution in the country's economy cannot be calculated exactly because tourism is a mixture of sectors, it embodies a great number of small service sectors. However, in this survey there are theoretical and empirical studies, which once again show that tourism has a positive effect on employment. This study aims to determine the relationship between tourism and the Employment in Albania during the period 1999-2012. Time series have quarterly data and their study is done using the Engle Granger test, Johansen Co- integration and the correction of error. The empiric results show that tourism has had a positive effect on employment, and the co-integration test has demonstrated that there is a strong relationship between the two variables in long run period.
The psychological impact of test results following diagnostic coronary CT angiography.

OBJECTIVE Coronary computed tomography (CT) angiography is an advanced cardiac imaging test commonly used for diagnosing early signs of ischemic heart disease. Despite its importance in cardiology, little is known about its psychological effect on patients. The present study sought to examine these effects in relation to illness perceptions, cardiac health behavior intentions, and subsequent health behaviors. METHODS Forty-five nonacute cardiac patients who were referred for diagnostic coronary CT angiography completed questionnaires prior to testing and following the receipt of test results, at which point illness perceptions and intentions to take cardiac medication, as well as diet and exercise intentions were measured. Exercise and dietary behaviors were measured at follow-up 6 weeks later. Changes on these variables were then compared between patients diagnosed with normal arteries and patients diagnosed with diseased arteries. RESULTS Compared to positive-testing patients, patients with normal test results reported significant changes toward more positive illness perceptions following testing, with improvements in emotional effect of illness, illness concern, consequences, and personal control of illness. The illness perception of treatment control was seen as more important among positive-testing patients, whereas both groups reported increases in illness coherence. Health behavior intentions (cardiac medication intentions and exercise intentions) increased for positive-testing patients only, as did physical activity at follow-up. CONCLUSIONS Diagnosis-dependent psychological effects can be detected following coronary CT angiography. These effects have important implications for patient health and health care in diagnostic contexts, and the results from this study can be used to guide further research in this area.
β-Arrestin-mediated Signaling Regulates Protein Synthesis*

Seven transmembrane receptors (7TMRs) exert strong regulatory influences on virtually all physiological processes. Although it is historically assumed that heterotrimeric G proteins mediate these actions, there is a newer appreciation that β-arrestins, originally thought only to desensitize G protein signaling, also serve as independent receptor signal transducers. Recently, we found that activation of ERK1/2 by the angiotensin receptor occurs via both of these distinct pathways. In this work, we explore the physiological consequences of β-arrestin ERK1/2 signaling and delineate a pathway that regulates mRNA translation and protein synthesis via Mnk1, a protein that both physically interacts with and is activated by β-arrestins. We show that β-arrestin-dependent activation of ERK1/2, Mnk1, and eIF4E are responsible for increasing translation rates in both human embryonic kidney 293 and rat vascular smooth muscle cells. This novel demonstration that β-arrestins regulate protein synthesis reveals that the spectrum of β-arrestin-mediated signaling events is broader than previously imagined.
What is the Role of Innovation in Productivity Growth in Central and Eastern European Countries?

The paper uses company level data from the Eurostat's Community Innovation Survey 2008 and applies CDM model in order to estimate the links between RD R&D intensity is an important factor of product innovation in the observed CEE countries and product innovation leads to higher productivity in Bulgaria and Romania, while process innovation leads to higher productivity in Bulgaria, but not in Romania.
Preferred gait and walk–run transition speeds in ostriches measured using GPS-IMU sensors

ABSTRACT The ostrich (Struthio camelus) is widely appreciated as a fast and agile bipedal athlete, and is a useful comparative bipedal model for human locomotion. Here, we used GPS-IMU sensors to measure naturally selected gait dynamics of ostriches roaming freely over a wide range of speeds in an open field and developed a quantitative method for distinguishing walking and running using accelerometry. We compared freely selected gait–speed distributions with previous laboratory measures of gait dynamics and energetics. We also measured the walk–run and run–walk transition speeds and compared them with those reported for humans. We found that ostriches prefer to walk remarkably slowly, with a narrow walking speed distribution consistent with minimizing cost of transport (CoT) according to a rigid-legged walking model. The dimensionless speeds of the walk–run and run–walk transitions are slower than those observed in humans. Unlike humans, ostriches transition to a run well below the mechanical limit necessitating an aerial phase, as predicted by a compass-gait walking model. When running, ostriches use a broad speed distribution, consistent with previous observations that ostriches are relatively economical runners and have a flat curve for CoT against speed. In contrast, horses exhibit U-shaped curves for CoT against speed, with a narrow speed range within each gait for minimizing CoT. Overall, the gait dynamics of ostriches moving freely over natural terrain are consistent with previous lab-based measures of locomotion. Nonetheless, ostriches, like humans, exhibit a gait-transition hysteresis that is not explained by steady-state locomotor dynamics and energetics. Further study is required to understand the dynamics of gait transitions. Highlighted Article: Ostriches moving freely overground prefer to walk very slowly and run over a broad range of speeds, with gait transitions at slower relative speeds than humans.
Novelty stress induces phospho‐acetylation of histone H3 in rat dentate gyrus granule neurons through coincident signalling via the N‐methyl‐d‐aspartate receptor and the glucocorticoid receptor: relevance for c‐fos induction

The hippocampus plays an important role in novelty detection, stress‐related adaptation and learning and memory. However, it is unknown whether the response to novelty in the hippocampus involves induction of chromatin remodelling events known to be associated with transcriptional regulation. Here, we examined whether exposure to a novel environment, a mild psychological stressor, would affect the number of phospho‐acetylated histone H3‐positive [P(Ser10)‐Ac(Lys14)‐H3+] neurons in the rat hippocampus. We show that: (i) the stressful situation induced a marked increase in the number of P(Ser10)‐Ac(Lys14)‐H3+ neurons, specifically in the dentate gyrus; (ii) the stress‐induced rise in P(Ser10)‐Ac(Lys14)‐H3+ neurons occurred in the dentate gyrus throughout the rostro‐caudal axis of the hippocampus, but they were exclusively located in the middle and superficial aspects of the granular cell layer of the upper blade of the dentate gyrus; (iii) antagonism of NMDA or glucocorticoid receptors, but not antagonism of mineralocorticoid receptors or inhibition of nitric oxide synthesis, attenuated the stress‐induced response; (iv) combined blockade of NMDA and glucocorticoid receptors ablated the stress‐induced histone modification response; (v) moreover, this combined blockade also abolished the induction of the P(Ser10)‐Ac(Lys14)‐H3‐associated gene product c‐fos after stress; (vi) administration of corticosterone to unstressed rats did not affect histone H3 phospho‐acetylation. Thus, novelty stress induces chromatin remodelling and c‐fos induction in mature dentate neurons through concurrent signalling via the NMDA receptor and the glucocorticoid receptor.
Hirudin in acute myocardial infarction. Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial.

BACKGROUND The TIMI 9 trial evaluated whether the direct antithrombin hirudin is more effective than an indirect-acting antithrombin, heparin, as adjunctive therapy for thrombolysis in myocardial infarction. METHODS AND RESULTS Patients (n = 3002) with acute myocardial infarction were treated with aspirin and either accelerated-dose tissue plasminogen activator (TPA) or streptokinase. They were randomized within 12 hours of symptoms to receive either intravenous heparin (5000 U bolus followed by infusion of 1000 U/h) or hirudin (0.1 mg/kg bolus followed by infusion of 0.1 mg/ kg per hour). The infusions of both antithrombins were titrated to a target activated partial thromboplastin time (aPTT) of 55 to 85 seconds and were administered for 96 hours. Patients randomized to hirudin were significantly more likely to have an aPTT measurement in the target range (P < .0001). The primary end point (death, recurrent nonfatal myocardial infarction, or development of severe congestive heart failure or cardiogenic shock by 30 days) occurred in 11.9% of the 1491 patients in the heparin group and 12.9% of the 1511 patients in the hirudin group (P = NS). Subgroup analyses did not reveal any profile of patients who benefited more from one of the antithrombins. The rate of major hemorrhage was similar in the heparin (5.3%) and hirudin (4.6%) groups; intracranial hemorrhage occurred in 0.9% of the heparin and 0.4% of the hirudin patients. CONCLUSIONS Heparin and hirudin have an equal effect as adjunctive therapy to TPA and streptokinase in preventing unsatisfactory outcome in patients with acute myocardial infarction. Similar rates of major bleeding were observed for patients in the heparin and hirudin groups.
The Restorative Environment: Nature and Human Experience

Early human beings were a part of nature. Over the millennia the gulf between humanity and the natural environment has steadily widened. Now, however, there is growing concern that this gulf has become toogreat, that we have strayed too far for our own good. This shift is due, at least in part, to a change in circumstances. Increasingly, people are confronted by pressures that are inexorably changing their lives. Although these pressures are by no means new, their steady increase and their cumulative impact are leading to increasingly unfortunate consequences. Many of the pressures people face today are the results of three interacting forces: advances in technology, the knowledge explosion, and the increasing world population. Since these trends are more likely to get worse than better, they provide a useful working hypcithesis as to what the pressures facing future populations might look like. Although these trends each have distinct manifestations, they also have some common consequences. In particular, they all contribute to the experience of mental fatigue, which can lead people to be less tolerant, less effective, and less healthy. Natural environments can play a central role in reducing these unfortunate effects. The thrust of my argument can summarized in terms of three basic themes:
Chemical composition and larvicidal activities of the essential oil of Zanthoxylum armatum DC (Rutaceae) against three mosquito vectors.

BACKGROUND & OBJECTIVES In view of the recently increased interest in developing plant origin insecticides as an alternative to chemical insecticide, this study was undertaken to assess the larvicidal potential of the essential oil from the seeds of Zanthoxylum armatum DC [syn. Z. alatum Roxb] (Rutaceae) against three medically important species of mosquito vectors, Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. METHODS Essential oil was hydro distilled in the laboratory from the seeds obtained from the market and the chemical constituents of the oil were determined using GC/GC-MS. Bioefficacy of the essential oil was evaluated under laboratory conditions using III instar mosquito larvae. RESULTS Among the three mosquito species tested, Cx. quinquefasciatus was the most sensitive (LC50 = 49 ppm) followed by Ae. aegypti (LC50 = 54 ppm) and An. stephensi (LC50 = 58 ppm). GC-MS analysis of the oil revealed at least 28 compounds, consisting mainly of oxygenated monoterpenes (75%) and monoterpenes (22%). Linalool though constituted a major part (57%), failed to produce any appreciable mortality when tested alone. INTERPRETATION & CONCLUSION From the results it can be concluded that the larvae of the three mosquito species were susceptible to the essential oil composition. Such findings would be useful in promoting research aiming at the development of new agent for mosquito control based on bioactive chemical compounds from indigenous plant sources as an alternative to chemical larvicides.
Thermographically measured normal skin temperature asymmetry in the human male

The detection of thermal asymmetry may lead to the diagnosis of significant disease states, especially those of a neoplastic or vascular nature. Estimates of acceptable thermal asymmetry have been made; thermal asymmetry has not previously been quantified in normal subjects. In 10 normal male volunteers, ages 17–38, thermal difference between symmetric areas of the chest, abdomen, and back never exceeded 1°C. Statistical treatment of these data suggests that thermal differences in excess of this in the male are abnormal.
What consumers don't know about genetically modified food, and how that affects beliefs

In the debates surrounding biotechnology and genetically modified (GM) food, data from consumer polls are often presented as evidence for precaution and labeling. But how much do consumers actually know about the issue? New data collected from a nationwide U.S. survey reveal low levels of knowledge and numerous misperceptions about GM food. Nearly equal numbers of consumers prefer mandatory labeling of foods containing DNA as do those preferring mandatory labeling of GM foods. When given the option, the majority of consumers prefer that decisions about GM food be taken out of their hands and be made by experts. After answering a list of questions testing objective knowledge of GM food, subjective, self‐reported knowledge declines somewhat, and beliefs about GM food safety increase slightly. Results suggest that consumers think they know more than they actually do about GM food, and queries about GM facts cause respondents to reassess how much they know. The findings question the usefulness of results from opinion polls as a motivation for creating public policy surrounding GM food. —McFadden, B. R. , Lusk, J. L. What consumers don't know about genetically modified food, and how that affects beliefs. FASEB J. 30, 3091–3096 (2016). www.fasebj. org
The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus

Despite improvements in awareness and treatment of type II diabetes mellitus (TIIDM), this disease remains a major source of morbidity and mortality worldwide, and prevalence continues to rise. Oxidative damage caused by free radicals has long been known to contribute to the pathogenesis and progression of TIIDM and its complications. Only recently, however, has the role of the Nrf2/Keap1/ARE master antioxidant pathway in diabetic dysfunction begun to be elucidated. There is accumulating evidence that this pathway is implicated in diabetic damage to the pancreas, heart, and skin, among other cell types and tissues. Animal studies and clinical trials have shown promising results suggesting that activation of this pathway can delay or reverse some of these impairments in TIIDM. In this review, we outline the role of oxidative damage and the Nrf2/Keap1/ARE pathway in TIIDM, focusing on current and future efforts to utilize this relationship as a therapeutic target for prevention, prognosis, and treatment of TIID.
Assessment of the soft tissue thickness at the lower anterior face in adult patients with different skeletal vertical patterns using cone-beam computed tomography.

OBJECTIVE To evaluate and compare the soft tissue thickness values at the lower anterior face among adult patients with different vertical growth patterns using cone-beam computed tomography. MATERIAL AND METHODS The study sample consisted of 105 adult patients (54 women and 51 men) with a normal sagittal skeletal pattern divided into three groups according to the vertical growth pattern: high-angle (women/men, 22/13; mean age, 24.54 ± 4.45 years), low-angle (women/men, 14/21; mean age, 24.62 ± 5.08 years), and normal-angle (women/men, 18/17; mean age, 24.22 ± 5.40 years) groups. The soft tissue thickness measurements at the lower anterior face in each group were done and analyzed using the one-way analysis of variance and Tukey tests. RESULTS Soft tissue thickness values were the lowest in the high-angle group for both women and men. For women, the thickness values at the labrale superius, labrale inferius, and pogonion were found to be statistically significantly smaller in the high-angle group (11.49 ± 1.05 mm, 12.70 ± 1.92 mm, and 11.64 ± 2.65 mm, respectively) compared with the values in the normal-angle group (13.31 ± 2.01 mm, 15.08 ± 1.94 mm, and 14.69 ± 3.08 mm, respectively) (P < .05, P < .05, and P < .01, respectively). For men, however, no statistically significant differences were found among the vertical growth patterns (P > .05). CONCLUSION Women had statistically significantly thinner thickness at the labrale superius, labrale inferius, and pogonion in the high-angle group compared with the normal-angle group.