Miracle-dz/UniFAR-FTUs huggingface dataset:
AASLD practice guidelines on chronic hepatitis B and HBV infection in Italy

We thank Fazili et al. for their interest in our article. The development of antibodies to hepatitis B e antigen (anti-HBe) and hepatitis B surface antigen (anti-HBs) were lower in the lamivudine-treated group relative to placebo, although these did not reach statistical significance. We concur with Fazili et al. that it is an important observation, and it seems plausible that interruption of the protective host immune response may be a consequence of pharmacologic therapy. Because virus-specific antibody-producing B cells are enriched early after acute viral infection,1 the host immune system needs to be exposed to viral antigen during the early phase in order to induce production of neutralizing antibodies. Therefore, giving lamivudine early may inhibit the production of neutralizing antibodies to some extent.2 A previous study also reported that after the use of lamivudine in treating acute viral hepatitis B, 18.18% of patients lost serum HBsAg but did not develop anti-HBs during treatment and follow-up.3 Nevertheless, it has also been reported that anti-HBs did not develop in 10% of untreated patients with acute hepatitis B.4 As rightly mentioned, only a long-term follow-up of such patients would help us know the risk of reactivation of hepatitis B virus (HBV) in patients treated with antiviral therapy. We do believe however that treatment of patients with severe acute hepatitis B with lamivudine is not harmful. Lamivudine or other more potent antivirals may be useful in a small subset of patients with acute hepatitis B who have more severe disease at presentation and high HBV DNA. Although there are no studies defining the patients with more severe disease, we suggest that such patients might include individuals with fulminant acute hepatitis B,5 or individuals who fulfill any 2 of the following criteria:3,6 (1) hepatic encephalopathy; (2) serum bilirubin 10.0 mg/dL; and (3) international normalized ratio (INR) 1.6, especially if it is increasing. Because patients belonging to the above categories would often need liver transplantation, it would be best to achieve, through use of potent antiviral drugs, HBV DNA levels which are undetectable or as low as possible at the time of liver transplantation, as measured with current real-time polymerase chain reaction methods. Whether such a therapeutic approach may translate into spontaneous recovery in a proportion of patients awaiting transplantation can only be predicted by the use of antiviral drugs in proper RCTs including such a group of patients.
Molecular Events Initiating Exit of a Copper-transporting ATPase ATP7B from the Trans-Golgi Network*

Background: ATP7B trafficking from Golgi to vesicles is essential for copper homeostasis. Results: Mutating Ser-340/341 alters the inter-domain contacts, diminishes protein phosphorylation, and shifts ATP7B localization to vesicles. Conclusion: Spatial arrangement of functional domains determines ATP7B readiness to traffic, whereas phosphorylation may maintain the trafficking-compatible state. Significance: The proposed mechanism explains how unrelated signals trigger similar trafficking responses from ATP7B. The copper-transporting ATPase ATP7B has a dual intracellular localization: the trans-Golgi network (TGN) and cytosolic vesicles. Changes in copper levels, kinase-mediated phosphorylation, and mutations associated with Wilson disease alter the steady-state distribution of ATP7B between these compartments. To identify a primary molecular event that triggers ATP7B exit from the TGN, we characterized the folding, activity, and trafficking of the ATP7B variants with mutations within the regulatory N-terminal domain (N-ATP7B). We found that structural changes disrupting the inter-domain contacts facilitate ATP7B exit from the TGN. Mutating Ser-340/341 in the N-ATP7B individually or together to Ala, Gly, Thr, or Asp produced active protein and shifted the steady-state localization of ATP7B to vesicles, independently of copper levels. The Ser340/341G mutant had a lower kinase-mediated phosphorylation under basal conditions and no copper-dependent phosphorylation. Thus, negative charges introduced by copper-dependent phosphorylation are not obligatory for ATP7B trafficking from the TGN. The Ser340/341A mutation did not alter the overall fold of N-ATP7B, but significantly decreased interactions with the nucleotide-binding domain, mimicking consequences of copper binding to N-ATP7B. We propose that structural changes that specifically alter the inter-domain contacts initiate exit of ATP7B from the TGN, whereas increased phosphorylation may be needed to maintain an open interface between the domains.
[Cortical response to age-related macular degeneration (Part II). Functional MRI study].

UNLABELLED PURPOSE AND MATERIALS: To evaluate the cortical response to visual stimulation in patients with age-related macular degeneration (ARMD), we conducted a functional MRI study in ten patients presenting unilateral or bilateral ARMD and five age-matched controls, using white flashes during activation phases (see Part I). RESULTS After anatomical conformation, eight patients and four controls showed significant cortical hemodynamic response to monocular stimulations. Individual analysis was preferred to group evaluation, because of the differences in visual loss in a small number of patients. In controls, we observed cortical response in the primary visual cortex, especially at occipital poles corresponding to the macula. Patients showed a qualitative and quantitative restriction in cortical response and exclusion of occipital poles after stimulation of the affected eye, whereas activation was found in the peripheral striate and peristriate cortex. Cortical response showed hemispheric asymmetry in some patients. DISCUSSION Our study demonstrated an activation defect in the macular projected striate cortex, corresponding to visual impairment in ARMD patients. Nevertheless, at a given visual acuity, cortical response may vary among subjects. Patients' subjective apprehension may account for such variations, as well as objective visual capacity stemming from residual functional retinal areas within the affected macula. The hemispheric asymmetry in cortical activation may result from gaze deviation onto the new fixation area in the perimacular retina, thus altering the global visual field. Enhancement in the peripheral striate and peristriate areas suggests changes in cortical interactions, possibly by a lowering of the feedback from macular projected V1. Finally, cortical evaluations must take into account degenerative phenomena delaying the hemodynamic response in the elderly. CONCLUSION Aiming at a specific population of weakened patients with a serious visual impairment, we obtained significant results concerning cortical plasticity for visual perception in central vision deletion. Our preliminary findings must be confirmed in a larger population and correlated with other techniques exploring vision, in particular with multifocal electroretinography for retinal evaluation.
Key performance indicators for measuring construction success

The construction industry is dynamic in nature. The concept of project success has remained ambiguously defined in the construction industry. Project success is almost the ultimate goal for every project. However, it means different things to different people. While some writers consider time, cost and quality as predominant criteria, others suggest that success is something more complex. The aim of this paper is to develop a framework for measuring success of construction projects. In this paper, a set of key performance indicators (KPIs), measured both objectively and subjectively are developed through a comprehensive literature review. The validity of the proposed KPIs is also tested by three case studies. Then, the limitations of the suggested KPIs are discussed. With the development of KPIs, a benchmark for measuring the performance of a construction project can be set. It also provides significant insights into developing a general and comprehensive base for further research.
Development and Testing of a Model of Consideration Set Composition

The authors develop a model of consideration set composition. The approach taken is to compare the marginal expected benefits of including an additional brand in the consideration set with its associated costs of consideration. From an expression of the utility that a brand needs to gain membership in an existing consideration set, the authors derive an expression for set composition and optimal set size. They develop a measurement method to test the model at the individual level and apply it to the ready-to-eat cereal market. The model is tested in two ways. First, the utility function is calibrated at the individual level and the model is used to predict consideration of existing brands. The calibrated model also is used to forecast individual consideration of three new product concepts. Second, the predictive ability of a two-stage model of consideration and choice is tested against a traditional one-stage choice model. The authors conclude with a discussion of management implications of the model in terms of auditing currently available brands and new product management.
Chaotic map-based time-aware multi-keyword search scheme with designated server

The cloud storage service has been widely used in daily life because of its convenience. However, the service frequently suffers confidentiality problems. To address this problem, some efforts have been made on keyword search over encrypted data schemes. For instance, the chaotic-based keyword search scheme over encrypted data has been proposed recently. However, the scheme just only support single- keyword search each time, which severely limits its utilization in cloud storage. This article proposes a novel chaotic-based time-aware multi-keyword search scheme with designated server. Inner product similarity is adopted in our scheme to realize multiple keyword search and remove the constraint of single-keyword search each time. Timed-release encryption is integrated into the proposed scheme at the same time, which enables the data sender to specify the time when the cloud servers can search the encrypted data. Analysis indicates that our scheme not only can counter off-line guessing attacks to the ciphertext and trapdoor, but also supports ranked search with a reasonable computational cost. Copyright © 2015 John Wiley & Sons, Ltd.
Comparison of analgesic techniques for antler removal in halothane-anaesthetized red deer (Cervus elaphus): electroencephalographic responses.

OBJECTIVE To provide evidence for an analgesic effect of antler pedicle compression or lidocaine 'ring block' by comparing changes in median and spectral edge frequencies and total electroencephalographic (EEG) power during the application of each technique followed by antler removal. ANIMALS Twenty-nine 2-year-old red deer (Cervus elaphus) stags weighing 106-131 kg each were used in this study. Stags were carrying immature growing antler suitable for commercial harvest. MATERIALS AND METHODS Anaesthesia was induced using propofol (8.25 +/- 1.28 mg kg(-1)) and ketamine (2.18 +/- 0.15 mg kg(-1)) and maintained with halothane in oxygen. End-tidal halothane (Fe'HAL), expired CO(2) tension (Pe'CO(2)), SpO(2), EEG, ECG, and direct arterial blood pressures were recorded continuously. Respiratory rate and somatic responses were recorded at specific time points. After stabilization of anaesthesia (Fe'HAL was approximately 0.8%) baseline data were recorded. Stags were randomly allocated to one of three treatment groups; control, local anaesthesia, or compression band. One antler was removed 4 minutes after the application of treatment. Electroencephalographic responses to application of treatment and antler removal were analysed using area under the curve (AUC) analysis. Mean AUC was compared between groups using anova, and when significant differences were found, groups were compared post hoc with two-tailed t-tests. Significance levels were set at p </= 0.05. RESULTS Median frequency (F(50)) was increased during antler removal in the control group and during both application and antler removal in the compression group. In the lidocaine group, F(50) was decreased during both application and antler removal. Spectral edge frequency (F(95)) was increased during the antler removal period in the control group and during both application and antler removal in the compression group. In the lidocaine group, F(95) was decreased in the application time period. Total EEG power (P(tot)) was decreased in the removal period in the control group. In the compression group, P(tot) was decreased in the removal period. In the lidocaine group, P(tot) was decreased in the application period. There were no significant differences in EEG variables between antler removal in the control group and application of compression (p = 0.19-0.96). CONCLUSIONS These data suggest that lidocaine 'ring block' of the antler pedicle provides adequate analgesia for velvet antler removal. The use of antler pedicle compression bands represents a noxious stimulus in its own right and is not as protective as lidocaine 'ring block' against the noxious stimulus of surgical antler removal. CLINICAL RELEVANCE Compression of the antler pedicle has been recommended as an alternative to lidocaine 'ring block' for velvet antler removal. The results of this study suggest that antler pedicle compression is noxious. In addition, antler pedicle compression offers less effective analgesia than lidocaine 'ring block'.
Qualified Retirement Plans: Analysis of Distribution and Rollover Activity

One potential downside when employees have the freedom to manage their own retirement accumulations is “leakage” prior to the end of their working careers, which is proxied here using age 60. Leakage occurs when employees take withdrawals prior to retirement, when they cash out distributions at job separation, or when they fail to pay back loans taken out against their accounts. Although leakage has the potential to undermine a participant-driven retirement system, trend analysis shows that aggregate pre-retirement leakage is modest and trending down relative to assets, and stable as a share of gross contributions. The probability of receiving a distribution and the fraction of gross distributions cashed out are roughly equal across income groups, but the portion cashed out represents a higher percentage of income for the lower-income groups. Corresponding author, Department of Economics, University of Maryland, College Park, Maryland 20742. Phone: (301) 367-3149. Email: sabelhaus@econ.umd. edu. The Investment Company Institute, 1401 H Street NW, Washington, DC 20005. Statistics of Income Division, Internal Revenue Service, Washington, DC. Views here do not represent those of the Investment Company Institute or the Internal Revenue Service. This paper was presented at the 2010 National Tax Association meetings in Chicago, Il. We are grateful to Steve Utkus for comments on an earlier version of the paper.
Strategic orientation and characteristics of upper management

Every organization reflects the background of its most powerful top managers; what the organization does and the way it carries out its functions could be explained, in part at least, by the profile of its upper echelon. The relationship between the strategic orientation of three tobacco companies, the proportion of executives recruited from outside the company and the proportion of executives from different functional backgrounds in the upper echelon of the companies is the focus of this paper.
CRISPR genome editing: A general view

How to cite this article: Kumar RMR. CRISPR genome editing: A general view. J Genet Med Gene Ther. 2017; 1: 001-002. https://doi.org/10.29328/journal.jgmgt. 1001001 CRISPR technology has presented a path forward for genomic engineering and gene modi ication. The framework for the use of CRISPR technology to manipulate the human genome is of great interest and the form of its development and application has excited the researchers and biotech communities as the number of publications citing CRISPR gene targeting system has rose predominantly as indexed in PubMed. From a technical standpoint of view, most of us think that this would be relatively straightforward process, but technical feasibility is never the only consideration in doing experiments. Much of the discussion about CRISPR engineering has revolved mostly around its ability for treating disease or editing the genes of human embryos. In the real sense, what the biologists desire about CRISPR is its speci icity: the ability to target and determine particular DNA sequences in the genome circuit.
Fiinancial Stability and Reform of the Financial System

Abstract The paper describes the main features of financial stability and the preparation of the reform of the global financial system. The mortgage crisis in the USA brought about the global financial crisis. This crisis was the result of the failure of financial regulation, including supervision, and the failure of the management of the banking industry. Therefore, the international community, including Group 20, urged the appropriate institutions to introduce a comprehensive reform of the financial sector. To avoid a potential financial crisis, the creation of the framework for financial stability would be needed. In line with this, the paper examines the interaction between both monetary and fiscal policies, including micro-and macroprudential policies and their instruments. Although still is going on discussion on definition of macroprudential policy, there is a generally accepted opinion that macroprudential policy should limit systemic risk. In addition, this policy should focus on interaction between the financial system and the real economy. Furthermore, micro- andmacroprudential policy should use appropriate instruments in dealing with the systemic risk. In this regard, the article undescores that put in a place the frameworkfor financial stability will create favorable conditions for decision-makers how they should to respond to financial imbalances. The paper also pointed out some potential economic costs related to the implementation of the overall international reform of the financial sector. Based on comprehensive literature study, the author came to the conclusion that despite the fact that there will be some economic costs related to implementing the overall regulatory reform of the financial sector, the main benefit from the long-term perspective will be avoiding the potential financial crisis in the future. To fulfill all the requirements for global financial reform, international cooperation will be needed.
An evolutionarily conserved U5 snRNP‐specific protein is a GTP‐binding factor closely related to the ribosomal translocase EF‐2

The driving forces behind the many RNA conformational changes occurring in the spliceosome are not well understood. Here we characterize an evolutionarily conserved human U5 small nuclear ribonucleoprotein (snRNP) protein (U5‐116kD) that is strikingly homologous to the ribosomal elongation factor EF‐2 (ribosomal translocase). A 114 kDa protein (Snu114p) homologous to U5‐116kD was identified in Saccharomyces cerevisiae and was shown to be essential for yeast cell viability. Genetic depletion of Snu114p results in accumulation of unspliced pre‐mRNA, indicating that Snu114p is essential for splicing in vivo. Antibodies specific for U5‐116kD inhibit pre‐mRNA splicing in a HeLa nuclear extract in vitro. In HeLa cells, U5‐116kD is located in the nucleus and co‐localizes with snRNP‐containing subnuclear structures referred to as speckles. The G domain of U5‐116kD/Snu114p contains the consensus sequence elements G1–G5 important for binding and hydrolyzing GTP. Consistent with this, U5‐116kD can be cross‐linked specifically to GTP by UV irradiation of U5 snRNPs. Moreover, a single amino acid substitution in the G1 sequence motif of Snu114p, expected to abolish GTP‐binding activity, is lethal, suggesting that GTP binding and probably GTP hydrolysis is important for the function of U5‐116kD/Snu114p. This is to date the first evidence that a G domain‐containing protein plays an essential role in the pre‐mRNA splicing process.
What accountability pressures do MPs in Africa face and how do they respond? Evidence from Ghana*

ABSTRACT How African politicians, especially legislators, behave on a daily basis is still largely unknown. This article gives a unique empirical account of the daily accountability pressures and the strategies that Members of Parliament (MPs) in Ghana employ in responding to the demands that they face. While literature on political clientelism focuses on explanatory factors like lack of political credibility, political machines capable of effective monitoring, autonomy of brokers, high levels of poverty, and political competiveness, the role of institutions has been overlooked. While the existing literature suggests that political clientelism is an optimal strategy in the context of weak institutions, the present analysis finds that the institution of the office of Member of Parliament in Ghana is strong, but shaped by informal norms in ways that favour the provision of private goods in clientelistic networks. The analysis also points to theoretical lessons on how political clientelism can endogenously undermine the conditions for its own existence.
Tax Incentives to Entice Foreign Direct Investment: Should There Be a Distinction between Developed Countries and Developing Countries?

Countries often provide investment incentives with the hope of attracting and retaining foreign investors. Generally, governments employ investment incentives to induce investors to establish a presence, to expand an existing business or not to relocate elsewhere. Countries usually raise various reasons to justify the granting of investment incentives, such as the need to correct market failures. Regardless of the justifications, governments believe that all other things being equal, incentives can influence the decisions of multinational enterprises (MNEs) regarding where and how much to invest. I argue that it cannot be presumed that the net economic impact of FDI will in all circumstances be positive. I demonstrate that there are various cost issues that are associated with the granting of tax incentives, and that the benefits of FDI for host countries might be insufficient to justify FDI promotion policies. Consequently, countries are advised to refrain from providing tax incentives to FDI. I emphasize, however, that the primary objection is to targeted tax incentives as opposed to general tax incentives. In this respect, there should be no distinction between developed countries and developing countries.
Enhancement of stage performances with projected CG and Noh motions

Our goal is to provide a support system for creating rich and flexible presentations in live performances using motion data. We created a live stage performance and a projection system which is for enhancing the performance with videos and CG animations. We choreographed and captured Noh motions, and created animation of CG characters to project. The CG characters were deployed in a responsive manner during a dance performance and integrated with live actors. In this paper, we describe the CG creation using Noh motion data, and our experience using the projection system and the CG in the live stage performance.