Miracle-dz/UniFAR-FTUs huggingface dataset:
Sorafenib and Sunitinib, Two Anticancer Drugs, Inhibit CYP3A4-Mediated and Activate CY3A5-Mediated Midazolam 1′-Hydroxylation

Sorafenib and sunitinib are novel small-molecule molecularly targeted anticancer drugs that inhibit multiple tyrosine kinases. These medicines have shown survival benefits in advanced renal cell carcinomas as well as in advanced hepatocellular carcinomas and gastrointestinal stromal tumors, respectively. The effects of sorafenib and sunitinib on midazolam 1′-hydroxylation catalyzed by human CYP3A4 or CYP3A5 were investigated. Sorafenib and sunitinib inhibited metabolic reactions catalyzed by recombinant CYP3A4. Midazolam hydroxylation was also inhibited in human liver microsomes harboring the CYP3A5*3/*3 genotype (poor CYP3A5 expressor). In contrast, midazolam 1′-hydroxylation catalyzed by recombinant CYP3A5 was enhanced by the coexistence of sorafenib or sunitinib in a concentration-dependent manner, with saturation occurring at approximately 10 μM. Midazolam hydroxylation was also enhanced in human liver microsomal samples harboring the CYP3A5*1/*1 genotype (extensive CYP3A5 expressor). Sorafenib N-oxidation and sunitinib N-deethylation, the primary routes of metabolism, were predominantly catalyzed by CYP3A4 but not by CYP3A5. The preincubation period of sorafenib and sunitinib before the midazolam addition in the reaction mixture did not affect the enhancement of CYP3A5-catalyzed midazolam hydroxylation, indicating that the enhancement was caused by parent sorafenib and sunitinib. Docking studies with a CYP3A5 homology model based on the structure of CYP3A4 revealed that midazolam closely docked to the heme of CYP3A5 compared with sorafenib or sunitinib, suggesting that these anticancer drugs act as enhancers, not as substrates. Our results thus showed that sorafenib and sunitinib activated midazolam 1′-hydroxylation by CYP3A5 but inhibited that by CYP3A4. Unexpected drug interactions involving sorafenib and sunitinib might occur via heterotropic cooperativity of CYP3A5.
Stress, depression, workplace and social supports and burnout in intellectual disability support staff.

BACKGROUND Staff providing support to people with intellectual disabilities are exposed to stressful work environments which may put them at an increased risk of burnout. A small prior literature has examined predictors of burnout in disability support staff, but there is little consensus. In this study, we examined direct and indirect associations between work stressors (i.e. challenging client behaviour), staff emotional response to the behaviour (i.e. perceived stress, anxiety, depression), social and organisational support resources, and staff burnout. METHODS A short survey examined client behaviour, staff psychological stress, anxiety, depression, social support (number, satisfaction), organisational support and burnout in 80 disability support staff in a community setting. RESULTS Burnout levels were similar to or slightly lower than normed values for human services staff. Cross-sectional regression analyses indicated that depression symptoms and organisational support were related to worse emotional exhaustion and depersonalisation, whereas less social support was related to less personal accomplishment. Social support satisfaction (but not social support number or organisational support) moderated between high psychological stress to less emotional exhaustion. CONCLUSIONS Taken together, these results suggest that depression symptoms and low organisational support were frequently concurrent with burnout symptoms. Furthermore, worker's personal and organisational supports may have helped bolster their sense of personal accomplishment, and buffered against the potential for emotional exhaustion.
Conformational Analysis of Dynorphin A (1–13) Using Hydrogen—Deuterium Exchange and Tandem Mass Spectrometry

Trifluoroethanol (TFE)-induced conformational changes in dynorphin A (1-13) were investigated using charge-state distribution (CSD) and hydrogen–deuterium exchange (HDX), combined with electrospray ionization (ESI) mass spectrometry (MS). Individual amino acids involved in secondary structural elements were identified by collision-induced dissociation-tandem mass spectrometry (MS/MS). It was observed that dynorphin A (1-13) largely exists in an unfolded conformation and a folded structure in increasing concentrations of TFE. In 50% TFE, it forms an α-helix that encompasses residues 1-9 and remains flexible from residues 10 to 13.
Interactive shading of 2.5D models

Advances in computer-assisted methods for designing and animating 2D artistic models have incorporated depth and orientation cues such as shading and lighting effects. These features improve the visual perception of the models while increasing the artists' flexibility to achieve distinctive design styles. An advance that has gained particular attention in the last years is the 2.5D modeling, which simulates 3D rotations from a set of 2D vector arts. This creates not only the perception of animated 3D orientation, but also automates the process of inbetweening. However, previous 2.5D modeling techniques do not allow the use of interactive shading effects. In this work, we tackle the problem of providing interactive 3D shading effects to 2.5D modeling. Our technique relies on the graphics pipeline to infer relief and to simulate the 3D rotation of the shading effects inside the 2D models in real-time. We demonstrate the application on Phong, Gooch and cel shadings, as well as environment mapping, fur simulation, animated texture mapping, and (object-space and screen-space) texture hatchings.
NS3 helicase from dengue virus specifically recognizes viral RNA sequence to ensure optimal replication

Abstract The protein–RNA interactions within the flavivirus replication complex (RC) are not fully understood. Our structure of dengue virus NS3 adenosine triphosphatase (ATPase)/helicase bound to the conserved 5′ genomic RNA 5′-AGUUGUUAGUCU-3′ reveals that D290 and R538 make specific interactions with G2 and G5 bases respectively. We show that single-stranded 12-mer RNA stimulates ATPase activity of NS3, however the presence of G2 and G5 leads to significantly higher activation. D290 is adjacent to the DEXH motif found in SF2 helicases like NS3 and interacts with R387, forming a molecular switch that activates the ATPase site upon RNA binding. Our structure guided mutagenesis revealed that disruption of D290–R387 interaction increases basal ATPase activity presumably as a result of higher conformational flexibility of the ATPase active site. Mutational studies also showed R538 plays a critical role in RNA interactions affecting translocation of viral RNA through dynamic interactions with bases at positions 4 and 5 of the ssRNA. Restriction of backbone flexibility around R538 through mutation of G540 to proline abolishes virus replication, indicating conformational flexibility around residue R538 is necessary for RNA translocation. The functionally critical sequence-specific contacts in NS3 RNA binding groove in subdomain III reveals potentially novel allosteric anti-viral drug targets.
A Buoyancy-Vorticity Wave Interaction Approach to Stratified Shear Flow

Motivated by the success of potential vorticity (PV) thinking for Rossby waves and related shear flow phenomena, this work develops a buoyancy–vorticity formulation of gravity waves in stratified shear flow, for which the nonlocality enters in the same way as it does for barotropic/baroclinic shear flows. This formulation provides a time integration scheme that is analogous to the time integration of the quasigeostrophic equations with two, rather than one, prognostic equations, and a diagnostic equation for streamfunction through a vorticity inversion. The invertibility of vorticity allows the development of a gravity wave kernel view, which provides a mechanistic rationalization of many aspects of the linear dynamics of stratified shear flow. The resulting kernel formulation is similar to the Rossby-based one obtained for barotropic and baroclinic instability; however, since there are two independent variables—vorticity and buoyancy—there are also two independent kernels at each level. Though having two kernels complicates the picture, the kernels are constructed so that they do not interact with each other at a given level.
An investigational testbed design for next generation internet protocol mobility

Internet Protocol version 6 (IPv6) is presently gaining demand in almost every region of the world. In near future, IPv6 would be the key area of research and expansion in the internet protocol standards. IPv6 was built with the aim of improving the mobility and communications among these devices. Mobile IPv6 is becoming a highly demanding research area under which a lot of investigations are yet to be carried on in forth-coming days. But the experimentation in developing a real-time testbed setup with mobile nodes communicating in a complete IPv6 environment is very less. Hence, this paper addresses the designing and deployment of a real-time testbed setup that establishes the communication among the entities of an IPv6 environment and discusses the various network connection scenarios. The requirements for the testbed are discussed and heterogeneous networks are established for connectivity in IPv6 based mobile networks with the relevant configuration details of mobile nodes and agents in the network.
The Keele curriculum model: A contemporary framework for designing an inter-professional technology enhanced nursing curriculum

This paper outlines a curriculum model for contemporary programme design for the purpose of embedding educational innovation and technology within an inter-professional nursing curriculum. It has been developed from work within the School of Nursing and Midwifery at Keele University during the re-write of both the nursing and midwifery curriculum. The Nursing and Midwifery Council (NMC) require approval of all recordable programmes every five years and as such the school took this review as an opportunity to explore the curriculum model currently in use and develop an approach that would facilitate the professional requirements of the programme alongside the embedding of innovative learning and teaching methodologies. The model springs from extensive application of contemporary pedagogy underpinning adult learning, and forces consideration of cognitive alignment within a multi-modal delivery framework [1]. The model builds upon the early work of Fowler and Mayes [2] and later work of Bird [3] who explored the antecedents and underpinning theory for success within online learning experiences. This model has greater reach; having strategic fit for acontemporary “technology enhanced learning” application within further and higher education [4], whilst ensuring the achievement of given professional standards [5].
Impact of a physical activity program on plasma concentrations of adiponectin, leptin and ghrelin in overweight and obese schoolchildren: A randomized controlled trial

Introduction: Child obesity has important consequences on the child’s health and is related to the risk of developing chronic diseases. That brings up the need for research assessing the impact of obesity-and overweight-reduction programs with close attention to methodology aspects and precise indicators of the impact of such programs. Goal: Assessing the impact of a physical activity program on the plasma concentrations of adiponectin, leptin, and ghrelin in overweight and obese schoolchildren. Methods: Randomized controlled trial, double-blind, with 6-to 9-year-old overweight and obese school-children. A sample of 79 schoolchildren randomly distributed into control and intervention groups was subjected to a physical activity program. The levels of adiponectin, leptin, ghrelin, body mass index, body fat percentage, anthropometry, lipid profile and glycemia were evaluated. The program’s impact was assessed through multivariate linear regression models. Result: When comparing the groups, a significant difference was found for adiponectin, which shows an increase in the proportion of subjects with higher adiponectin concentrations for the intervention group and a reduction in body mass index and body fat percentage. Conclusion: The impact of the intervention program was positive in increasing adiponectin levels associated with a reduction in body mass index and body fat percentage.
Ensemble Methods for the NTCIR-13 NAILS Task

The QUT team participated in the NTCIR-13 Neurally Augmented Image Labeling Strategies (NAILS) task, this report describes our approach to solving the problem of developing machine learning models for classifying EEG data from an RSVP image search task. We explore the use of commonly used successful methodologies from the P300 Speller Paradigm, in particular the use of ensembles of support vector machines, and evaluate whether these methods still apply to the potentially more complex image search task.
Sexual Disclosures: Connections to Relational Satisfaction and Closeness

This study examines sexual communication by describing the content of sexual disclosures within marital relationships and assessing the association between sexual disclosures and relational outcomes, specifically relational satisfaction and closeness. A survey administered to 293 married individuals (58% female) who had an average age of 40 years (range = 20–73), 13.7 years of marriage (range = 1 month to 54 years), and who reported high levels of relational satisfaction assessed the relation between the content of sexual disclosures and satisfaction and closeness. While sexual disclosures are made infrequently, positive affect and sexual preferences are disclosed more than negative topics and disclosing sexual information is positively related to relationship satisfaction, rρ(280) =. 26, p <. 001; and closeness, rs(280) =. 475, p <. 01. Therapists can use these findings to show clients the positive relation between revealing sexual information and relationship satisfaction and closeness, as reported by individuals experiencing relationship satisfaction.
Inflammation and free radicals in tumor development and progression

Abstract Inflammation is thought to be one of the major contributors to carcinogenesis. Accumulated studies in this field revealed that free radicals produced by inflammatory cells not only cause direct damage to DNA but also exert indirect effects such as de-regulation of cell proliferation and apoptosis, stimulation of angiogenesis, and modification of gene/protein expressions and protein activities, all of which are a critical step toward carcinogenesis. Free radicals have also been reported to act as both initiator and promoter of carcinogenic process. Recent evidence shows that free radicals convert benign tumors to more malignant ones (i.e. tumor progression) leading to the final stage of carcinogenesis. This article reviews the current findings linking inflammation and cancer, and shed light on inflammatory cell-derived free radicals as major endogenous reactive substances for tumor development and progression.
Dysphoria: self-devaluative and affective components in recovered depressed patients and never depressed controls

Background. The Interacting Cognitive Subsystems analysis of cognitive vulnerability to depression predicts that subjective experiences of dysphoria in recovered depressed patients will be qualitatively different from those of controls. This study tested this prediction using a new instrument, the Depressed States Checklist. Methods. Twenty-three recovered recurrently depressed patients and 54 never depressed controls rated the affective and self-devaluative components of a dysphoric experience. Results. Groups reported similar levels of affective component but recovered depressed patients reported higher self-devaluative dysphoric experience. At zero affective component of dysphoria neither group reported any self-devaluative feelings. With increasing affective component of dysphoria, the self-devaluative component increased significantly more in recovered patients than in controls. The ratio of self-devaluative to affective components of dysphoria significantly differentiated recovered depressed patients from controls. Conclusions. As predicted, dysphoria in recovered depressed patients is qualitatively different from controls in ways that increase vulnerability to major depression. The Depressed States Checklist is a new, brief, measure of cognitive vulnerability to depression that may be particularly useful in large, prospective, epidemiological studies.
Workshop on Haptic Interaction Design for Musical Applications Using Physical Models

A workshop for NIME 2013 is proposed on haptic interaction design for musical applications. The focus lies primarily on using physical models for programming haptic force feedback. During the workshop, participants will program the FireFader haptic device using the Synth-A-Modeler physical modeling framework, which combines elements from digital waveguide, mass-interaction, and modal synthesis. The source code for Synth-A-Modeler will be officially released to the open-source community at the NIME 2013 conference.
A CMOS Image Sensor With In-Pixel Two-Stage Charge Transfer for Fluorescence Lifetime Imaging

A CMOS image sensor for time-resolved fluorescence lifetime imaging with subnanosecond time resolution is presented. In order to analyze the fluorescence lifetime, the proposed CMOS image sensor has two charge transfer stages using a pinned photodiode structure in which the first charge transfer stage is for the time-resolved sifting of fluorescence in all the pixels simultaneously and the second charge transfer stage is for reading the signals in each pixel sequentially with correlated double sampling operation. A 0.18-mum CMOS image sensor technology with a pinned photodiode process option is used for the implementation of a 256 times 256 CMOS image sensor. The decaying images and lifetimes of fura-2 solutions having different concentrations are successfully measured with a 250-ps time step using the CMOS image sensor and ultraviolet laser diode as a light source.
Antitumor Effects and Acute Oral Toxicity Studies of a Plant Extract Mixture Containing Rhus verniciflua and Some Other Herbs

A novel antitumor agent was developed from six kinds of herbs containing Rhus verniciflua (Rv-PEM01). The components were traditionally established for each formula for traditional medicine. The formula was designed to affect antitumor effect as well as maintain host immune functions. First, we investigated the antiproliferative activities of Rv-PEM01 on human and canine tumor cell lines in vitro, and on antitumor effects using BALB/cAJcl-nu/nu mice in vivo. Acute oral toxicity of Rv-PEM01 was also investigated in vivo in ddY mice. Rv-PEM01 exhibited antiproliferative activities against PC-3 (IC50: 0.328 ± 0.081 mg/ml), A549 (IC50: 0.520 ± 0.070 mg/ml), D-17 (IC50: 0.124 ± 0.037 mg/ml) and MRC-5 (IC50: 0.505 ± 0.058 mg/ml) cells. Luteolin 7-β-D-glucopyranoside and apigenin 7-β-D-glucopyranoside were identified as the main active compounds in Rv-PEM01 by HPLC analysis. The single dose toxicity study of Rv-PEM01 did not result in any deaths or abnor-malities in daily behavior, body weight gain, or anatomical observations at necropsy. Thus, so we could not calculate the 50% lethal dose (LD50) in mice, but it would be higher than 5.0 g/kg. Treat- ment with Rv-PEM01 at a dose of 2.5 g/kg tended to show antitumor activities on mice bearing Colon26 tumors compared with the control group. It was concluded that the formula was a safe antitumor agent with no side effects on mouse physiological function as judged by survival and organ weight.
Selective Protein Hyperpolarization in Cell Lysates Using Targeted Dynamic Nuclear Polarization.

Nuclear magnetic resonance (NMR) spectroscopy has the intrinsic capabilities to investigate proteins in native environments. In general, however, NMR relies on non-natural protein purity and concentration to increase the desired signal over the background. We here report on the efficient and specific hyperpolarization of low amounts of a target protein in a large isotope-labeled background by combining dynamic nuclear polarization (DNP) and the selectivity of protein interactions. Using a biradical-labeled ligand, we were able to direct the hyperpolarization to the protein of interest, maintaining comparable signal enhancement with about 400-fold less radicals than conventionally used. We could selectively filter out our target protein directly from crude cell lysate obtained from only 8 mL of fully isotope-enriched cell culture. Our approach offers effective means to study proteins with atomic resolution in increasingly native concentrations and environments.
Tens Femtogram Resoluble Piezoresistive Cantilever Sensors with Optimized High-Mode Resonance Excitation

Ultra-sensitive mass sensor is demanded for bio/chemical molecular detection. A piezoresistive resonant cantilever sensor with optimized is developed with an optimized electromagnetic excitation for high-mode flexure resonance. In our experiment, it has been proved that the quality factor of the resonant sensor can be improved by this optimized high-mode resonance exciting technique. Experimental results have shown that the optimized excitation for the resonant cantilever sensor can effectively improve the mass-sensing resolution to 29fg, thereby, improving the bio/chemical sensor performance.
Intellectual capital in Malaysian hotel industry: a case study of Malacca

Intellectual capital is recognised as a crucial strategic asset that provides organisations with a competitive edge and sustainable growth in a cutthroat business environment. There is an increasing comprehension that intellectual capital is critical to organisational performance, this is still an emerging area of inquiry in tourism industry in Malaysia. Therefore, this study was undertaken with the aim to demonstrate the impact of intellectual capital on the organisational performance of hotel industry operating in Malacca, Malaysia. Six components of intellectual capital were used in the study. A total of 193 individuals were involved in this study to test the proposed research hypotheses. The results of multiple regression analysis demonstrated that four out of seven research hypotheses were supported. This study will extend the understanding of the concept and applications of intellectual capital in hotel industry in Malaysia. Moreover, this study will be a milestone for the potential researchers to conduct their further studies in hotel industry.
Edited magnetic resonance spectroscopy detects an age-related decline in monkey brain GABA levels

v LIST OF TABLES . ix LIST OF FIGURES . x INTRODUCTION . 1 Purpose of this study . 1 Background . 1 Magnetic resonance spectroscopy Basics . 2 GABA detection using MEGA-PRESS . 4 METHODS . 6 The workflow chart . 6 Subjects . 7 MRI and MRS acquisition. 7 MRS setting . 7 The VOI localization . 8
Fiber Laser Hydrophone Based on Double Diaphragms: Theory and Experiment

A fiber laser hydrophone with enhanced sensitivity is demonstrated. Two diaphragms with a hard core fixed at each center are used as the sensing element. Theoretical analysis shows that the Young's modulus of the diaphragm and the radius of the hard core have significant effect on the acoustic sensitivity. Experiments are carried out to test this effect and the performance of the hydrophone. The experimental result agrees well with the theoretical result, and a sensitivity of 7 nm/MPa has been achieved.