Miracle-dz/UniFAR-FTUs huggingface dataset:
Internal Ribosome Entry Site-Based Attenuation of a Flavivirus Candidate Vaccine and Evaluation of the Effect of Beta Interferon Coexpression on Vaccine Properties

ABSTRACT Infectious clone technologies allow the rational design of live attenuated viral vaccines with the possibility of vaccine-driven coexpression of immunomodulatory molecules for additional vaccine safety and efficacy. The latter could lead to novel strategies for vaccine protection against infectious diseases where traditional approaches have failed. Here we show for the flavivirus Murray Valley encephalitis virus (MVEV) that incorporation of the internal ribosome entry site (IRES) of Encephalomyocarditis virus between the capsid and prM genes strongly attenuated virulence and that the resulting bicistronic virus was both genetically stable and potently immunogenic. Furthermore, the novel bicistronic genome organization facilitated the generation of a recombinant virus carrying an beta interferon (IFN-β) gene. Given the importance of IFNs in limiting virus dissemination and in efficient induction of memory B and T cell antiviral immunity, we hypothesized that coexpression of the cytokine with the live vaccine might further increase virulence attenuation without loss of immunogenicity. We found that bicistronic mouse IFN-β coexpressing MVEV yielded high virus and IFN titers in cultured cells that do not respond to the coexpressed IFN. However, in IFN response-sufficient cell cultures and mice, the virus produced a self-limiting infection. Nevertheless, the attenuated virus triggered robust innate and adaptive immune responses evidenced by the induced expression of Mx proteins (used as a sensitive biomarker for measuring the type I IFN response) and the generation of neutralizing antibodies, respectively. IMPORTANCE The family Flaviviridae includes a number of important human pathogens, such as Dengue virus, Yellow fever virus, Japanese encephalitis virus, West Nile virus, and Hepatitis C virus. Flaviviruses infect large numbers of individuals on all continents. For example, as many as 100 million people are infected annually with Dengue virus, and 150 million people suffer a chronic infection with Hepatitis C virus. However, protective vaccines against dengue and hepatitis C are still missing, and improved vaccines against other flaviviral diseases are needed. The present study investigated the effects of a redesigned flaviviral genome and the coexpression of an antiviral protein (interferon) on virus replication, pathogenicity, and immunogenicity. Our findings may aid in the rational design of a new class of well-tolerated and safe vaccines.
Pairing broadband noise with cortical stimulation induces extensive suppression of ascending sensory activity

Objective. The corticofugal system can alter coding along the ascending sensory pathway. Within the auditory system, electrical stimulation of the auditory cortex (AC) paired with a pure tone can cause egocentric shifts in the tuning of auditory neurons, making them more sensitive to the pure tone frequency. Since tinnitus has been linked with hyperactivity across auditory neurons, we sought to develop a new neuromodulation approach that could suppress a wide range of neurons rather than enhance specific frequency-tuned neurons. Approach. We performed experiments in the guinea pig to assess the effects of cortical stimulation paired with broadband noise (PN-Stim) on ascending auditory activity within the central nucleus of the inferior colliculus (CNIC), a widely studied region for AC stimulation paradigms. Main results. All eight stimulated AC subregions induced extensive suppression of activity across the CNIC that was not possible with noise stimulation alone. This suppression built up over time and remained after the PN-Stim paradigm. Significance. We propose that the corticofugal system is designed to decrease the brain’s input gain to irrelevant stimuli and PN-Stim is able to artificially amplify this effect to suppress neural firing across the auditory system. The PN-Stim concept may have potential for treating tinnitus and other neurological disorders.
Scerra 1 EFFECT OF SENSORY MODALITY ON PERFORMANCE , WORKLOAD , AND FRONTAL LOBE OXYGENATION IN A STANDARD VIGILANCE TASK

The purpose of this research was to compare vigilance performance over time for visual, auditory, and vibrotactile tasks, while simultaneously recording oxygenation in the frontal lobe to assess physiological resource utilization. Subjective workload was assessed in each condition using the NASA Task Load Index (NASA-TLX). The data indicate a significant effect of time-on-task in all experimental conditions, with the vigilance decrement asserting in each modality condition within the first twenty minutes of the task. Significant differences in overall hit rates and nonparametric sensitivity (A′) were found between the loosely coupled visual modality and the closely coupled tactile and auditory modalities. Conversely, frontal lobe oxygenation increased with time-on-task, possibly reflecting increased processing demands as cognitive resources wane. The results suggest that although the vigilance decrement exists for all modality conditions, tactile vigilance tasks may be performed as efficiently as auditory vigils, with no significant differences in workload or physiological resource utilization.
Monitoring: Functional or Fashionable?

An increasing stream of monitoring activities has entered the public sector. In the Netherlands there are hundreds of monitors on a wide range, so it can be stated that monitoring is fashionable in the Netherlands. But monitoring seems to be functional, too. Without monitoring, organisations would not even survive. Research about the use of research information and evaluations makes clear that information is not always used in a direct and transparent way. This statement raises three, interrelated research questions, which we try to answer in our paper: (1) What is the amount and the character of (intragovernmental) monitors in the public sector in the Netherlands? (2) What forms of utilisation can be distilled and how are intragovernmental monitors used in practice? (3) How do these functions of monitors relate to recent insights in the complexity of governmental performance and the role information can play in complex systems? The paper concludes with the observation that the current mode of monitoring is dominated by rationalistic assumptions. Important functions from a complexity perspective, as learning and communicating, seem to be underestimated. Monitoring is fashionable, but it seems to be less functional.
Simultaneous editing of multiple nucleic acid and protein sequences with ESEE

We have developed a full-function multiple sequence editor (ESEE) for use with IBM-PC compatible microcomputers. ESEE permits the simultaneous editing, manipulation and display of several macromolecular sequences with the same degree of ease and generality afforded by commercial word processors, but with correct line wrapping. In addition to multiple sequence alignment, ESEE can serve as a universal front-end for analysis programs and as a utility for producing publication-quality figures
Beta Cell Mass Regulation in the Rat Pancreas Through Glucocorticoids and Thyroid Hormones

Objectives: To compare the effects of glucocorticoids and thyroid hormones on the regulation of the beta cell mass in the pancreas, the rats were treated and analyzed for cell cycle changes in islet and duct cells as a source for beta cell neogenesis. Methods: Different rat pancreases were morphometrically analyzed after immunohistochemical staining for markers of proliferation and apoptosis. Results: Hydrocortisone increased the beta cell mass of rat pancreases through an increase of proliferation. This effect was counteracted by an increase of apoptosis. In contrast, thyroxine decreased the beta cell mass through an increase of apoptosis. This effect was counteracted by an increased rate of proliferation. Combined treatment with both hormones nullified the antagonistic effects on proliferation, apoptosis, and beta cell mass, thereby contributing to the maintenance of a stable total beta cell volume of the pancreas. Conclusions: Hydrocortisone and thyroxine induced analogous changes in pancreatic duct cells, which represent a crucial pool for new beta cells through neogenesis. This may explain the positive effects of glucocorticoids in the immunosuppressive therapy regimen after whole pancreas transplantation upon long-term insulin independence, which is not achievable with isolated islets because of the loss of duct cells during the islet process before transplantation.
Do video reviews of therapy sessions help people with mild intellectual disabilities describe their perceptions of cognitive behaviour therapy?

BACKGROUND This study examined the potential of a retrospective video reviewing process [Burford Reviewing Process (BRP)] for enabling people with intellectual disabilities to describe their experiences of cognitive behaviour therapy (CBT). It is the first time that the BRP, described in this paper, has been used with people with intellectual disabilities and the aim was to assess the feasibility of the procedure and gain a picture of the information it might yield. METHODS Using the BRP, 12 clients reviewed tapes of their fourth and ninth CBT sessions and six reviewed the fourth session only. All reviews were audio recorded for later verbatim transcriptions of clients' comments. Reviews and transcriptions were conducted by non-clinical researchers. Thematic analysis was applied to the transcripts by a researcher who was not CBT-trained. RESULTS All clients were able to follow the instructions for the BRP. Three broadly based themes encapsulated their responses - how they felt about themselves, how they felt the therapist was helping and how CBT was helping. A fourth theme referred to comments on issues that were currently troubling clients, which were prompted by watching the video but did not refer to actual events on screen. CONCLUSIONS The BRP seems a feasible approach with this client group and gave insights into their feelings and opinions on CBT. Clinical implications of the results and the potential for further developments are discussed.
A Novel Allosteric Activator of Free Fatty Acid 2 Receptor Displays Unique Gi-functional Bias*

The short chain fatty acid receptor FFA2 is able to stimulate signaling via both Gi- and Gq/G11-promoted pathways. These pathways are believed to control distinct physiological end points but FFA2 receptor ligands appropriate to test this hypothesis have been lacking. Herein, we characterize AZ1729, a novel FFA2 regulator that acts as a direct allosteric agonist and as a positive allosteric modulator, increasing the activity of the endogenously produced short chain fatty acid propionate in Gi-mediated pathways, but not at those transduced by Gq/G11. Using AZ1729 in combination with direct inhibitors of Gi and Gq/G11 family G proteins demonstrated that although both arms contribute to propionate-mediated regulation of phospho-ERK1/2 MAP kinase signaling in FFA2-expressing 293 cells, the Gq/G11-mediated pathway is predominant. We extend these studies by employing AZ1729 to dissect physiological FFA2 signaling pathways. The capacity of AZ1729 to act at FFA2 receptors to inhibit β-adrenoreceptor agonist-promoted lipolysis in primary mouse adipocytes and to promote chemotaxis of isolated human neutrophils confirmed these as FFA2 processes mediated by Gi signaling, whereas, in concert with blockade by the Gq/G11 inhibitor FR900359, the inability of AZ1729 to mimic or regulate propionate-mediated release of GLP-1 from mouse colonic preparations defined this physiological response as an end point transduced via activation of Gq/G11.
Cheap and disposable? The impact of the global economic crisis on the migration of Ethiopian women domestic workers to the Gulf

This paper investigates the impact of the global economic crisis on the migration of Ethiopian women domestic workers to the Gulf. It argues that migration as a strategy to cope with existing crises in Ethiopia will be severely constrained by post-downturn policy shifts, which have already produced a significant decline in numbers of recorded migrants and remittances. Evidence suggests the consequence will be an increase in the flows of unrecorded migrants. The conclusion discusses policy responses to mitigate some of the negative consequences of the global economic crisis on the migration of Ethiopian domestic workers.
Ethical behavior in accounting: Some evidence from Turkey

In today’s business environment, the role of accountants is significant. Managers and other decisionmakers base their decision mainly on information that accountants provide. Since accuracy of decisions depends on the reliability of accounting information, the ethical dimension of the profession has gained considerable attention recently. Furthermore, major corporate failures such as Enron, Arthur Anderson and WorldCom have made ethical issues a paramount concern to those working in business and accounting. With this understanding, this study examined whether ethics is teachable or not based on a survey conducted among business students in two Turkish universities. Overall, research findings suggest a strong support for the inclusion of ethics in business and accounting curriculum.
Transcriptionally active immediate-early protein of pseudorabies virus binds to specific sites on class II gene promoters

In the presence of partially purified pseudorabies virus immediate-early protein, multiple sites of DNase I protection were observed on the adenovirus major late and human hsp 70 promoters. Southwestern (DNA-protein blot) analysis demonstrated that the immediate-early protein bound directly to the sequences contained in these sites. These sequences share only limited homology, differ in their affinities for the immediate-early protein, and are located at different positions on these two promoters. In addition, the site-specific binding of a temperature-sensitive immediate-early protein was eliminated by the same heat treatment which eliminates its transcriptional activating function, whereas the binding of the wild-type protein was unaffected by heat treatment. Thus, site-specific binding requires a functionally active immediate-early protein. Furthermore, immediate-early-protein-dependent in vitro transcription from the major late promoter was preferentially inhibited by oligonucleotides which are homologous to the high-affinity binding sites on the major late or hsp 70 promoters. These observations suggest that transcriptional stimulation by the immediate-early protein involves binding to cis-acting elements.
Building Goal Alignment in Federal Agencies’ Performance Appraisal Programs

Public managers wrestle with how to influence organizational performance. Results-based management approaches point to the goal alignment’s importance in performance management programs for meeting organizational goals. This research examines the extent to which federal agency organizational factors allow for performance appraisal goal alignment. Goal alignment is operationalized in two ways: embedding of strategic plan goals into employee performance plans and employee knowledge of how their work relates to the agency’s goals and priorities. Using data from U.S. Office of Personnel Management’s evaluation of federal agency appraisal programs, results indicate leadership support of the program is a determining factor of plan alignment. Communication of the organization’s goals, the climate fit for achieving results, and whether the strategic plan was written for the agency program level tend to predict employee alignment. Strategic plan level is particularly important for strategic management literature, which has limited empirical evidence for the effectiveness of program-level strategic plans.
Stochastic Optimization Applied to Self-Financing Portfolio: Does Bequest Matter?

The article studies stochastic optimization of an intertemporal consumption model to allocate financial assets between risky and risk-free assets. We use a stochastic optimization technique, in which utility is maximized subject to a self-financing portfolio constraint. The papers in literature have estimated the errors of Euler equations using data from financial markets. It has been shown that it is sufficient to test the first order Euler equation implied by the model. However, they all assume a constant consumption-wealth ratio that constrains the boundary conditions, hence influencing the coefficient of the risk premium. The main contribution of our article is that we drop the assumption of a constant consumption-wealth ratio. We have an analytical solution using a utility maximization model with a stochastic self-financing portfolio. We introduce a terminal condition of wealth with and without bequests. We also simulate the stochastic optimization with a self-financing portfolio, distinguishing risk neutral investors (γ-low) from high risk averse investors (γ-high). We show that the model with bequest has a higher level of wealth and a smoother decline of consumption over time than the model with no bequest at the end of the period. The model with no bequest has the same level of consumption and a sharp fall at the end of the period. Risk averse agents with high return assets have a higher amount of wealth than risk-neutral agents with lower return assets.
From Territory to Smartphone: Smart Fruition of Cultural Heritage for Dynamic Tourism Development

Augmented reality is a new technology that merges the virtual and the real worlds and offers important support in all planning processes. Using mobile devices, planning information can be implemented with smart and participative solutions for a dynamic fruition of cultural heritage [Brondi, R. , Carrozzino, M. , Tecchia, F. , & Bergamasco, M. (2012) Mobile augmented reality for cultural dissemination, in: P. Nesi & R. Santucci (Eds), ECLAP 2012 Conference on Information Technologies for Performing Arts, Media and Entertainment, pp. 113–118 (Firenze: Firenze University Press); Hatzelhoffer, L. , et al. (2012) Smart City in Practice: Innovation Lab Between Vision and Reality (Jovis). Technologies are important tools because they make a city smart by making concrete contributions to trigger dynamic processes of place-based development. Three important factors improve urban planning fruition: participation in the early stages of listening and co-design; enlightened governance and new technology. This paper (1) presents the actual possibilities and challenges of augmented reality in the field of cultural heritage, (2) describes a simulation of one case study in a neighbourhood in Cagliari (Italy), by proposing customized paths with the aim of promoting cultural tourism and (3) explains the benefits of using augmented reality in touristic and place-based processes based on the case study.
Innovation in a creative production system: the case of design

This article addresses the relatively neglected issue of variations in the degree of innovation and creativity within cultural production systems, paying particular attention to the design consultancy industry. It argues that design is a business-facing type of creative industry that differs in important ways from other types of cultural industries. It examines some of the implications of this argument for how we should understand innovation and its geography in the industry. It is argued that previous studies have paid too much attention to place-based creative inspiration, thereby downplaying the business ecosystems and firm architectures that drive innovation. It is argued that design innovation requires the combination of a wide range of different types of knowledge. Design emerges from interactions between different sites that synthesize and recombine knowledge so as to produce emergent effects and new designs. The article examines two of the key sites: the market or agency-client link and the design firm itself. It argues that relations with clients, and firm routines and competences, are much more important to design innovation than inter-firm co-operation or the local cultural environment. In conclusion it argues that economic geographers should be wary about using approaches to innovation derived from either cultural or manufacturing industries to explain the local ecology of design, but should devote more research to examining the distinctive logics of innovation in creative, knowledge intensive business service industries.
Effects of Antimicrobial Agents Used for Therapy of CNS Infections on Dissociated Brain Cell Cultures

ABSTRACT: The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity (p < 0.001 or < 0.01) and to a lesser extent (p < 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections.
Recombinant Antibodies and Non-Antibody Scaffolds for Immunoassays

The measurement of trace amounts of physiologically active small molecules (for example, lipids, drugs, other synthetic chemicals and metals) is critical for both clinical and environmental analyses. Most small molecules can be analyzed using highly sophisticated analytical techniques, including high pressure liquid chromatography (HPLC), gas chromatography (GC), and inductively coupled plasma atomic emission spectroscopy (ICPAES). However, these methods require extensive purification, experienced technicians, and expensive instruments and reagents. Immunoassays offer an alternative to these instrument-intensive methods. Immunoassays rely on an antibody (Ab), or mixture of antibodies, for recognition of the molecule being analyzed (the analyte). Immunoassays are frequently applied to the analysis of both low molecular ligands and macromolecular drugs, and are also applied in such important areas as the quantitation of biomarkers that indicate disease progression and immunogenicity of therapeutic drug candidates. The performance of immunoassays is critically dependent on the binding properties of the antibody used in the analysis, and identification of suitable antibodies is often a major hurdle in assay development. Recombinant antibodies will play a major role in future immunoassay development.