Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmaceutical and Pharmacokinetic Evaluation of a Novel Fast Dissolving Film Formulation of Flupentixol Dihydrochloride

The objective of the present study was to develop fast dissolving oral film of the antipsychotic drug, flupentixol dihydrochloride, to enhance its bioavailability, optimize its therapeutic effect when used to treat depression with anxiety, and increase the convenience and compliance by the mentally ill, developmentally disable, elderly, and pediatric patients. Six formulae were prepared with different concentrations of water-soluble polymers vis. hydroxypropyl methylcellulose (HPMC E5) and carboxymethyl cellulose (CMC) by solvent casting technique. The prepared films were subjected to characterization for folding endurance, weight variations, thickness, disintegration time, drug release pattern, and drug content. Physical compatibility between the drug and excipients was guaranteed in the selected formulation (2% HPMC) by means of differential scanning calorimetry analysis and Fourier-transform infrared spectroscopy. This formulation revealed high stability after testing according to the International Conference on Harmonisation guidelines. In vivo studies based on single phase parallel design were carried out for the optimized formulation in healthy human volunteers. The concentration of flupentixol dihydrochloride in plasma samples was analyzed by a developed validated LC-MS/MS assay method and the pharmacokinetic parameters of the established formulation were compared with the commercially available oral tablets. Faster rate of absorption of flupentixol could be obtained from the oral film formulation and the relative bioavailability was found to be 151.06% compared to the marketed product.
The Effect of Face-to-face Interactions on Chocie: The Role of Expressiveness

This thesis examines the role of face-to-face interactions on individual choice. In particular, I explore the effect of face-to-face requests (compared to other forms of requests) on compliance. I propose that individuals expect facial feedback from their interactive partner in response to their decisions and behaviors in face-to-face interactions. In an effort to avoid anticipated negative feedback, people comply with the request. Drawing from literature on compliance, the face, faceto-face interactions, empathy, and anticipation, I develop and test this proposed theoretical account in five experiments. 1) Experiment 1 demonstrates the effect of face-to-face interactions on compliance with requests relative to other forms of making the requests and rules out some alternative explanations. 2) Experiment 2 replicates the effect in a real world setting, and shows that the effect can be moderated by sensitizing individuals to the face. iii 3) Experiment 3 shows that the effect can be moderated by facial expressiveness and sensitivity to face. Experiment 3 also shows that anticipation of feedback (rather than actual feedback) drives the effect. 4) Experiment 4 shows that the effect can be moderated by the expressiveness, timeliness, and consistency of facial feedback. It provides further evidence for the role of anticipated facial feedback. 5) Experiment 5 shows that individuals strategically choose different modes of interaction (i.e., face-to-face or impersonal) as a function of the feedback they expect to receive. Theoretically, this thesis provides a new understanding of how face-to-face interactions and facial expressiveness impact individual choice. In contrast to previous research, I examine the feedback mechanism that such interactions create, and the role of facial expressiveness. By providing an account in which the anticipation of feedback plays a role, this research provides a way of extending the effect of face-to-face interactions on individual compliance to faceless transactions. Moreover, I identify and test the effect of three dimensions of facial expressiveness on individual choice, thereby adding to marketing literature, compliance literature, and communication literature. The current research has managerial implications in personal selling, customer service, employee training, and online transactions.
Feature-Based Configuration of Vendor-Independent Deployments on IaaS

Infrastructure as a Service (IaaS) is commonly used to deploy distributed systems like Web applications. For every component of a distributed system, IaaS consumers need to select, configure, and deploy a virtual machine (VM), the image to run on the VM, and software to install on the image. These tasks involve multiple decisions, require complex and error-prone manual effort, and may occur unexpectedly. To deal with these challenges, we present a feature-based configuration and vendor-independent deployment approach. An IaaS deployment model allows to describe and automatically perform the distributed system deployment vendor-independently. We use service feature modeling to support the decisions required for configuration. These modeling approaches are combined in a feature-based configuration and deployment process. It can be performed automatically and can be triggered in reaction to unexpected events. We present a proof-of-concept implementation that we use to perform a use case about deploying the Web application of the Barcoo service, showing the approach's applicability.
Clinical Mutations in the L1 Neural Cell Adhesion Molecule Affect Cell-Surface Expression

Mutations in the L1 neural cell adhesion molecule, a transmembrane glycoprotein, cause a spectrum of congenital neurological syndromes, ranging from hydrocephalus to mental retardation. Many of these mutations are single amino acid changes that are distributed throughout the various domains of the protein. Defective herpes simplex virus vectors were used to express L1 protein with the clinical missense mutations R184Q and D598N in the Ig2 and Ig6 extracellular domains, respectively, and S1194L in the cytoplasmic domain. All three mutant proteins were expressed at similar levels in infected cells. Neurite outgrowth of cerebellar granule cells was stimulated on astrocytes expressing wild-type or S1194L L1, whereas those expressing R184Q and D598N L1 failed to increase neurite length. Live cell immunofluorescent staining of L1 demonstrated that most defective vector-infected cells did not express R184Q or D598N L1 on their cell surface. This greatly diminished cell-surface expression occurred in astrocytes, neurons, and non-neural cells. In contrast to wild-type or S1194L L1, the R184Q and D598N L1 proteins had altered apparent molecular weights and remained completely endoglycosidase H (endoH)-sensitive, suggesting incomplete post-translational processing. We propose that some missense mutations in human L1 impede correct protein trafficking, with functional consequences independent of protein activity. This provides a rationale for how expressed, full-length proteins with single amino acid changes could cause clinical phenotypes similar in severity to knock-out mutants.
Effects of Rifampin on the Disposition of Gepirone ER and Its Metabolites

Objective: To investigate the effects of rifampin on the steady-state pharmacokinetics of gepirone and metabo- lites after multiple dosing of both drugs. Methods: 24 subjects completed a randomized crossover study with 2 study phases separated by a washout period of at least 4 weeks. The subjects received multiple dosing of gepirone extended-release (gepirone ER) (20 mg daily for 2 days titrated to 40 mg daily for 5 days) with and without concurrent use of rifampin 600 mg daily. Plasma concentrations of gepirone and two principal metabolites were determined for up to 48 hours after dosing on day 7. Urinary 6￻ - hydroxycortisol:cortisol ratio was also used to assess the extent of enzyme induction during both study periods. Results: Rifampin significantly decreased the area under the plasma concentration-time curves (AUC) of gepirone and 3´-OH-gepirone by 95% and 65%, respectively. The peak concentration (Cmax) values also were reduced by 92% and 58%, respectively. On the other hand, there were minimal changes in AUC and Cmax of 1-PP during concurrent use of rifampin. Gepirone dosing did not change the urinary 6￻ -hydroxycortisol:cortisol ratio, in contrast to a 4.1-fold increase in the ratio with concurrent use of rifampin. Conclusions: Rifampin significantly decreased the systemic exposure of gepirone and 3´-OH-gepirone. The likely mecha- nism is induction of CYP3A4-mediated first-pass metabolism in the intestine and the liver. Concurrent use of potent CYP3A4 enzyme inducers might lead to significant reduction in pharmacologic effect of gepirone. On the other hand, gepirone does not appear to have CYP3A4 induction or inhibition effects.
Bicuculline-Sensitive Primary Afferent Depolarization Remains after Greatly Restricting Synaptic Transmission in the Mammalian Spinal Cord

Primary afferent neurotransmission is the fundamental first step in the central processing of sensory stimuli. A major mechanism producing afferent presynaptic inhibition is via a channel-mediated depolarization of their intraspinal terminals which can be recorded extracellularly as a dorsal root potential (DRP). Based on measures of DRP latency it has been inferred that this primary afferent depolarization (PAD) of low-threshold afferents is mediated by minimally trisynaptic pathways with GABAergic interneurons forming last-order axoaxonic synapses onto afferent terminals. We used an in vitro rat spinal cord preparation under conditions that restrict synaptic transmission to test whether more direct low-threshold pathways can produce PAD. Mephenesin or high divalent cation solutions were used to limit oligosynaptic transmission. Recordings of synaptic currents in dorsal horn neurons and population synaptic potentials in ventral roots provided evidence that conventional transmission was chiefly restricted to monosynaptic actions. Under these conditions, DRP amplitude was largely unchanged but with faster time to peak and reduced duration. Similar results were obtained following stimulation of peripheral nerves. Even following near complete block of transmission with high Mg2+/low Ca2+-containing solution, the evoked DRP was reduced but not blocked. In comparison, in nominally Ca2+-free or EGTA-containing solution, the DRP was completely blocked confirming that Ca2+ entry mediated synaptic transmission is required for DRP genesis. Overall these results demonstrate that PAD of low-threshold primary afferents can occur by more direct synaptic mechanisms, including the possibility of direct negative-feedback or nonspiking dendroaxonic pathways.
Studying situational effects of setting characteristics : Research examples from the study of peers, activities, and neighborhoods

This chapter addresses methods to study situational influences of setting characteristics on adolescent offending. In particular, it describes data collection methods (space-time budget interviews, census data, community surveys, and systematic social observations) that enable precise measurement of what respondents do, with whom they undertake these activities, and in what kind of places (both the geographical area and the function of the location) they find themselves. Such data capture presence in and exposure to different kinds of settings during particular periods in time. This chapter illustrates the usefulness of these method for criminological research by summarizing the results of three sub-studies from the Study of Peers, Activities, and Neighborhoods (SPAN) conducted in the Netherlands. It first discusses the design of the SPAN data collection and the instruments that were used in it. It then reviews each study in turn by summarizing its theoretical motivation, data structure, and analytical strategy, and by describing the main findings it has generated.
Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia

Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD) together, represent the second most common cause of dementia, after Alzheimer’s disease (AD). The synaptic dysfunctions underlying the cognitive decline and psychiatric symptoms observed throughout the development of PDD and DLB are still under investigation. In this study we examined the expression level of Dynamin1 and phospho-CaMKII, key proteins of endocytosis and synaptic plasticity respectively, as potential markers of molecular processes specifically deregulated with DLB and/or PDD. In order to measure the levels of these proteins, we isolated grey matter from post-mortem prefrontal cortex area (BA9), anterior cingulated gyrus (BA24) and parietal cortex (BA40) from DLB and PDD patients in comparison to age-matched controls and a group of AD cases. Clinical and pathological data available included the MMSE score, neuropsychiatric history, and semi-quantitative scores for AD pathology (plaques - tangles) and for α-synuclein (Lewy bodies). Changes in the expression of the synaptic markers, and correlates with neuropathological features and cognitive decline were predominantly found in the prefrontal cortex. On one hand, levels of Dynamin1 were significantly reduced, and correlated with a higher rate of cognitive decline observed in cases from three dementia groups. On the other hand, the fraction of phospho-CaMKII was decreased, and correlated with a high score of plaques and tangles in BA9. Interestingly, the correlation between the rate of cognitive decline and the level of Dynamin1 remained when the analysis was restricted to the PDD and DLB cases, highlighting an association of Dynamin1 with cognitive decline in people with Lewy Body dementia.
State-Dependent Dendritic Computation in Hippocampal CA1 Pyramidal Neurons

Depending on the behavioral state, hippocampal CA1 pyramidal neurons receive very distinct patterns of synaptic input and likewise produce very different output patterns. We have used simultaneous dendritic and somatic recordings and multisite glutamate uncaging to investigate the relationship between synaptic input pattern, the form of dendritic integration, and action potential output in CA1 neurons. We found that when synaptic input arrives asynchronously or highly distributed in space, the dendritic arbor performs a linear integration that allows the action potential rate and timing to vary as a function of the quantity of the input. In contrast, when synaptic input arrives synchronously and spatially clustered, the dendritic compartment receiving the clustered input produces a highly nonlinear integration that leads to an action potential output that is extraordinarily precise and invariant. We also present evidence that both of these forms of information processing may be independently engaged during the two distinct behavioral states of the hippocampus such that individual CA1 pyramidal neurons could perform two different state-dependent computations: input strength encoding during theta states and feature detection during sharp waves.
Amyotrophic Lateral Sclerosis & Frontotemporal Impairment: A Qualitative Study of the Caregiving Experience

Living with amyotrophic lateral sclerosis (ALS) is a complex and difficult experience that necessitates numerous lifestyle changes for the patient and caregiver. Although ALS was previously regarded as a disease that primarily affects the motor system and spares non-motor functions, it is now recognized that a sizable proportion of the ALS population demonstrates frontotemporal impairment (ALS+FTI), with a subset of the population meeting criteria for frontotemporal dementia. Clinically, ALS and FTI differ in many respects; however, both diseases are progressive and necessitate dependence on caregivers for assistance with activities of daily living and beyond. Although the relationship between ALS and FTI has received empirical attention, the experience of the caregiver remains largely unexplored. The aim of this qualitative study was to explore and describe caregivers’ thoughts, feelings, behaviors, practical daily challenges, and rewards in caring for persons with ALS+FTI. Four female spousal caregivers participated in semi-structured interviews; they also completed self-report measures to assess quality of life, level of care, and FTI symptoms exhibited by the care recipients. Findings indicated that although each caregiver faced her own set of unique challenges, there were commonalities across narratives. Three major themes were identified: witnessing the effects of ALS+FTI, the impact of the caregiving experience, and coping with life as a caregiver. Findings were interpreted within the context of the existing caregiving literature and suggestions for improving FTI assessment within the ALS population were provided.
SOFTWARE TOOLS FOR HEART RATE VARIABILITY ANALYSIS

Article History: Received 5, March, 2015 Received in revised form 12, March, 2015 Accepted 6, April, 2015 Published online 28, April, 2015 Heart rate variability (HRV) refers to beat to beat variation in heart rate (R-R intervals) of electrocardiogram (ECG) that quantifies the interplay between sympathetic and parasympathetic activity of autonomic nervous system (ANS). HRV parameters can be categorized in time domain, frequency domain, time-frequency and non-linear methods. Commercially available ECG acquisition equipment does not usually include HRV functionalities due to the lack of standard diagnostic protocols. As an alternative to commercial softwares, many simple, online free, device-independent and portable software tools are developed for HRV analysis and cardiovascular research. This paper briefly reviews the state of the art in the field of HRV analysis softwares. Features of various freely available HRV analysis tools are described in depth.
Constrained switching stabilization of a dc-dc boost converter using piecewise-linear Lyapunov functions

This paper describes a new methodology for designing robust and efficient control laws for power converters. In addition to guaranteed closed-loop robust stability, the proposed design is capable of addressing a number of further key issues, i.e. low complexity of the implementation, accurate nonlinear dynamics incorporation, nonconservative handling of hard state and control constraints, and robustness to supply voltage variations and setpoint changes. The control design is of a set-theoretic nature. The iterative algorithms used for controller generation are based on the ray-gridding approach, that generates piecewise-linear Lyapunov functions and corresponding controlled invariant polytopes, induced by systematic conic decompositions of the state-space and state-dependent switching control actions. The proposed technique is evaluated on a boost converter case study. Simulation results in the MATLAB/SIMULINK™ environment are reported. The bifurcation behaviour of the system is further studied by numerical and analytical nonlinear stability analysis.
Estimation of distribution algorithms on non-separable problems

The evolutionary algorithms discussed in this paper do not use crossover, nor mutation. Instead, they estimate and evolve a marginal probability distribution, the only distribution responsible for generating new populations of chromosomes. So far, the analysis of this class of algorithms was confined to proportional selection and additive decomposable functions. Dropping both assumptions, we consider here truncation selection and non-separable problems with polynomial number of distinct fitness values. The emergent modelling is half theoretical – with respect to selection, completely characterized by stochastic calculus – and half empirical – concerning the generation of new individuals. For the latter operator, we sample the chromosomes arbitrarily, one for each selected level of fitness. That is the break-symmetry point, making the difference between the finite and infinite population cases, and ensuring the convergence of the model.
Bridging academic and everyday language Multilingual students' meaning-making in a lesson about Buddhism

This article presents findings from a Grade 7 religion lesson with 12–13 year-old multilingual Finnish-Swedish students in Finland. Here, focus is on the development of academic language and disciplinary literacy in multilingual environments, as they are crucial to students’ success and an area in need of both attention and support. A total of 117 minutes of six video-recorded group discussions, collected in a classroom study in a Swedish-medium school in Finland, were analyzed. The aim was to explore how students used everyday language and academic language to co-construct meaning of academic text and to investigate resources that were used by multilingual students and teachers to facilitate access to content for students instructed through Swedish. Our findings focus mainly on discussions in one group of four students as they were answering text questions. This group bridged academic and everyday language by creating linguistic chains that linked the two and used multiple resources, such as previous knowledge, the textbook, asking the teacher, and using Finnish in order to ensure each participant’s full understanding of the subject.
Social Contagion – An Empirical Comparison of Seeding Strategies for Viral Marketing

Seeding strategies have a major influence on the success of viral marketing campaigns, but previous studies using computer simulations and analytical models produced conflicting recommendations about the optimal seeding strategy. We therefore compare four different seeding strategies in two complementary small-scale field experiments as well as in one real-life viral marketing campaign that involved more than 200,000 customers of a mobile phone service provider. Our empirical results show that the best seeding strategies can be up to eight times more successful than other seeding strategies. Seeding to well-connected individuals is most successful. They are attractive seeding points for viral marketing campaigns because they are more likely participate, which contradicts a commonly made assumption in other studies. Well-connected individuals also actively make use of their higher reach but they do not do not have more influence on their peers than less-connected individuals.