Miracle-dz/UniFAR-FTUs huggingface dataset:
Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases

The study aimed to develop evidence-based recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases. The task force comprised an expert group of specialists in rheumatology, dermatology and gastroenterology, and pharmacologists, patients and a regulator from ten countries. Four key topics regarding biosimilars were identified through a process of discussion and consensus. Using a Delphi process, specific questions were then formulated to guide a systematic literature review. Relevant English-language publications through November 2016 were searched systematically for each topic using Medline; selected papers and pertinent reviews were examined for additional relevant references; and abstracts presented at the 2015 and 2016 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) annual scientific meetings were searched for those about biosimilars. The experts used evidence obtained from these studies to develop a set of overarching principles and consensus recommendations. The level of evidence and grade of recommendation were determined for each. By the search strategy, 490 references were identified. Of these, 29 full-text papers were included in the systematic review. Additionally, 20 abstracts were retrieved from the ACR and EULAR conference abstract databases. Five overarching principles and eight consensus recommendations were generated, encompassing considerations regarding clinical trials, immunogenicity, extrapolation of indications, switching between bio-originators and biosimilars and among biosimilars, and cost. The level of evidence and grade of recommendation for each varied according to available published evidence. Five overarching principles and eight consensus recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases were developed using research-based evidence and expert opinion.
Role of nerve–muscle interactions and reactive oxygen species in regulation of muscle proteostasis with ageing

Skeletal muscle ageing is characterised by atrophy, a deficit in specific force generation, increased susceptibility to injury, and incomplete recovery after severe damage. The hypothesis that increased generation of reactive oxygen species (ROS) in vivo plays a key role in the ageing process has been extensively studied, but remains controversial. Skeletal muscle generates ROS at rest and during exercise. ROS can cause oxidative damage particularly to proteins. Indeed, products of oxidative damage accumulate in skeletal muscle during ageing and the ability of muscle cells to respond to increased ROS becomes defective. The aim of this review is to examine the evidence that ROS manipulation in peripheral nerves and/or muscle modifies mechanisms of proteostasis in skeletal muscle and plays a key role in initiating sarcopenia.
Angiotensin‐converting enzyme 2: a new target for neurogenic hypertension

Overactivity of the renin–angiotensin system (RAS) is involved in the pathogenesis of hypertension, and an overactive brain RAS has been highlighted in several genetic and experimental models. Until now, angiotensin II (Ang II) was thought to be the main effector of this system, and the angiotensin‐converting enzyme (ACE)–Ang II–Ang II type 1 receptor axis was the main target for antihypertensive therapies. A new member of the RAS, ACE2 (angiotensin‐converting enzyme type 2), has been identified in organs and tissues related to cardiovascular function (e.g. heart, kidney and blood vessels) and appears to be part of a counter‐regulatory pathway to buffer the excess of Ang II. We recently identified the ACE2 protein in brain regions involved in the central regulation of blood pressure and showed that it regulates, and is regulated by, other components of the RAS. Here, we present evidence for the involvement of brain ACE2 in the central regulation of blood pressure, autonomic and cardiac function. We show that lack of ACE2 is deleterious for the central regulation of blood pressure and that brain ACE2 gene therapy can restore baroreflex and autonomic functions and prevent the development of hypertension. Additionally, and independently of a reduction in Ang II levels, we will highlight some of the mechanisms responsible for the beneficial effects of central ACE2 in cardiovascular function.
Fatty Acid Infusion Selectively Impairs Insulin Action on Akt1 and Protein Kinase C λ/ζ but Not on Glycogen Synthase Kinase-3*

To determine the mechanism(s) for insulin resistance induced by fatty acids, we measured the ability of insulin to activate phosphoinositide 3-kinase (PI3K) and multiple distal pathways in rats. Following a 5-h infusion of lipid or glycerol (control), rats underwent a euglycemic hyperinsulinemic clamp. Insulin stimulated IRS-1-associated PI3K activity in muscle of glycerol-infused rats 2.4-fold but had no effect in lipid-infused rats. IRS-2- and phosphotyrosine-associated PI3K activity were increased 3.5- and 4.8-fold, respectively, by insulin in glycerol-infused rats but only 1.6- and 2.3-fold in lipid-infused rats. Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats. Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C λ/ζ activity was reduced 47%. Insulin inhibited glycogen synthase kinase 3α (GSK-3α) activity by 30% and GSK-3β activity by ∼65% and increased protein phosphatase-1 activity by 40–47% in both glycerol- and lipid-infused rats. Insulin stimulated glycogen synthase activity 2.0-fold in glycerol-infused rats but only 1.4-fold in lipid-infused rats. Thus, 1) elevation of fatty acids differentially affects insulin action on pathways distal to PI3K, impairing activation of Akt1 and protein kinase C λ/ζ and 2) insulin action on glycogen synthase can be regulated independent of effects on GSK-3 and protein phosphatase-1 activity in vivo.
Liquidity expansion in China and the U.S. economy

This paper investigates the influence of liquidity shocks in China on the U.S. economy over 1996-2012. The influence on the U.S. is through China’s influence on demand for imports, particularly that of commodities. In all models estimated a positive innovation in China’s liquidity is associated with: 1) a positive and statistically significant effect on oil and commodity prices that builds up rapidly over three months and then persists for twenty months; 2) a positive and statistically significant effect on U.S. CPI inflation that builds up over about six months or so and then persists; 3) a statistically significant depreciation of the real trade-weighted U.S. currency after about two or three months that achieves maximum absolute value after five to eight months and that then persists.
Determination of minimum guaranteed purchasing price from renewable sources at distribution network buses with consideration investment dynamics

With presence of renewable energy sources (RES) in electric distribution networks, utilities have the options to purchase energy from RES units and/or directly from the wholesale electricity market. The utility's desired purchasing price of RES energy depends on their impacts on network, and as well as wholesale market price. This paper proposes a method to determine the minimum guaranteed purchasing price of RESs energy with consideration their impacts on loss, investment deferral, and air pollution. These prices are as efficient economical signal so that lead the investors to installation of RES at buses with more positive technically impact in distribution network. The investment dynamics is also considered in the proposed method. (4 pages)
Microbiology of the infected knee arthroplasty: Report from the Swedish Knee Arthroplasty Register on 426 surgically revised cases

Surgically revised deep infected primary knee arthroplasties reported to the Swedish knee arthroplasty register during the years 1986–2000 were studied with respect to microbiology, antimicrobial susceptibility pattern and changes over time. In early, delayed and late infections, coagulase-negative staphylococci (CoNS) were most prevalent (105/299, 35.1%), and twice as common as Staphylococcus aureus (55/299, 18.4%). In haematogenous infections, S. aureus was the dominating pathogen (67/99, 67.7%), followed by streptococci and Gram-negative bacteria. Methicillin resistance was found in 1/84 tested isolates of S. aureus and 62/100 tested isolates of CoNS. During the study period, methicillin resistance among CoNS increased (p=0.002). Gentamicin resistance was found in 1/28 tested isolates of S. aureus and 19/29 tested CoNS isolates. A relative decrease in infections caused by S. aureus was observed, while enterococci increased. In empiric treatment of infected knee arthroplasty the type of infection should direct the choice of antibiotics. Awareness of the fact that most early infections are caused by CoNS can increase the chances of successful treatment with retained implant. Due to the high rate of gentamicin resistance among CoNS in infected knee arthroplasty, other antibiotics should be used in bone cement at revision.
A novel tracking algorithm of hypersonic target

Aimed at the near space hypersonic target of high speed and strong maneuvering, a strong tracking square-root Cubature Kalman filter algorithm based on normalized residuals is proposed. The algorithm is based on the square-root Cubature Kalman filter, introducing the idea of strong tracking filter. In view of the shortcoming of residuals asymmetry caused by the different order of magnitude of the residuals, the normalized processing of residuals is used to make the information equilibrium of the residuals and maximize extraction of the information, which improves accuracy, instantaneity, and robustness. The algorithm is applied to the near space hypersonic target as a new method, the simulation results show effectiveness the algorithm.
The Anatomy of Restaurant Reviews

Abstract A content analysis of newspaper restaurant reviews from five U.S. cities was conducted. Descriptors critics used to describe their experiences were cataloged. The descriptors were then classified into eight categories based on theoretical constructs used in the restaurant customer evaluation literature. The constructs catalogued in this study were: (1) Quality of food and beverage (2) Quantity of food (3) Quality of service (4)Ambience and atmosphere (5) Menu variety (6) Price and value (7) Other customers (8) Professionalism. Critics' primarily focused their comments on Quality of food and Ambience and atmosphere. This is consistent with the importance customers report in criteria for dining out. Service and pricing were reflected in symbolized scales accompanying many reviews. When an exception occurred during the dining experience, the critic would discuss price, service, and other exceptions to their expectations. Both positive and negative exceptions were covered in reviews. Restaurants newly opened or recently changed may expect a reviewer's visit. To prepare, the restaurateur must insure the food and the ambience are consistent with the experience they want to create for their guests. Quality of service and Price and value are hygiene factors. They are problematic to reviewers when they do notmeet the standard but receive little attention if they exceed the standard.
Cutaneous reactivity of the hands in nickel‐sensitive patients with hand eczema

This study compares the cutaneous reactivity between the hand and the back for 7 female patients with active hand eczema, who were found to be nickel‐sensitive on routine patch testing with the European standard series. Patients were patch tested to a dilution series of nickel sulfate on the back in order to determine the threshold concentration for elicitation of allergic contact dermatitis, and based upon this result a lower concentration of nickel was then used for patch tests on the hand. We found that in the majority of patients (6/7) the cutaneous responsiveness of the hand was not increased compared with that of the back. However, the hand of 1 patient was more sensitive to nickel and patch testing was accompanied with a flare of her eczema, which suggests that cutaneous hyperreactivity may be important in individual patients with hand eczema.
Effect of 910-MHz Electromagnetic Field on Rat Bone Marrow

Aiming to investigate the possibility of electromagnetic fields (EMF) developed by nonionizing radiation to be a noxious agent capable of inducing genotoxicity to humans, in the current study we have investigated the effect of 910-MHz EMF in rat bone marrow. Rats were exposed daily for 2 h over a period of 30 consecutive days. Studying bone marrow smears from EMF-exposed and sham-exposed animals, we observed an almost threefold increase of micronuclei (MN) in polychromatic erythrocytes (PCEs) after EMF exposure. An induction of MN was also observed in polymorphonuclear cells. The induction of MN in female rats was less than that in male rats. The results indicate that 910-MHz EMF could be considered as a noxious agent capable of producing genotoxic effects.
Development of the antibody response in acute HIV-1 infection

Background: Cytotoxic T lymphocytes have been shown to reduce viraemia during acute HIV-1 infection; however the role of neutralizing antibodies in this process is unclear. One confounding factor may be artefacts introduced by viral culture. Objective: To assess the development of autologous neutralizing and non-neutralizing antibodies following acute HIV-1 infection using recombinant viruses with envelopes amplified directly from patient peripheral blood mononuclear cells, thereby avoiding in vitro selection. Methods: Disease progression in four homosexual men was monitored from acute infection for up to 2.5 years, in the absence of antiretroviral therapy. Antibodies to viral envelope protein were quantified by enzyme-linked immunosorbent assay. Development of neutralizing antibodies was monitored using a quantitative infectivity reduction assay, sequential serum, recombinant viruses and target cells with defined receptor expression. Results: The time to development of neutralizing antibodies after onset of symptoms was 3, 5, 7 and 16 months in the four patients. There was no correlation between development of neutralizing antibodies and the resolution of viraemia in any of the patients. However, antibodies to the envelope were detectable as early as 2 weeks after onset of symptoms. Conclusions: Neutralizing antibodies do not contribute to the control of viraemia in acute HIV-1 infection. However, antibodies to the envelope could be detected at the time of reduction in plasma viraemia and so other effector functions of antibodies may play a role in viral clearance.
E-government and the transformation of public administrations in EU countries: Beyond NPM or just a second wave of reforms?

The adoption of web-based technologies to deliver government services has become a global trend in public administration. E-government inherits the administrative reform policies inspired by New Public Management (NPM) reforms implemented throughout the EU over the past twenty years. However, e-government aims at going beyond NPM reforms, since its goal is to transform the relationships between the public sector and society and to explore new channels of service delivery. The construction and management of websites is becoming an essential element of modern public administration, but little is known about how these initiatives are being implemented. Given the substantial investment in time and other resources in governmental online initiatives, it is essential to begin to evaluate governmental Web site initiatives in terms of quality and effectiveness. The objective of this paper is to study the development of e-government initiatives at regional and local level in the EU through the opinion of those agents directly involved in the projects.
Is caveolin-1 a viable therapeutic target to reduce cancer metastasis?

Caveolin-1 is the major structural protein in caveolae; small Ω-shaped invaginations within the plasma membrane. Caveolae are involved in signal transduction, wherein caveolin-1 acts as a scaffold to organise multiple molecular complexes regulating a variety of cellular events. Caveolin-1 has both tumour suppressor and oncogenic activities. However, recent evidence suggests a role for caveolin-1 in promoting cancer cell migration and metastasis with both loss and overexpression of caveolin-1 being described as a marker for progression in a variety of tumour types. Further studies are beginning to determine the molecular mechanisms by which caveolin-1 acts in promoting a metastatic phenotype. Targeting caveolin-1 expression may present a novel means of preventing metastasis. The purpose of this review is twofold: firstly, to survey the current knowledge of the contribution of caveolin-1 in promoting a metastasis, and secondly, to explore the viability of targeting caveolin-1 with novel therapeutics.
Worker insecurity and aggregate wage growth

To adequately evaluate claims that increased worker insecurity had reduced wage growth in the 1990s, research must answer two questions: (1) Has worker insecurity increase? , and (2) Does worker insecurity reduce wage growth? Examining data on displacement rates from the Displaced Workers Surveys and data on workers' perceptions of job security from the General Social Survey, we conclude that worker insecurity has been high in the 1990s relative to what would have been expected on the basis of the falling unemployment rate. Moreover, examining the relationship between measures of displacement and aggregate wage growth using panel data covering the 50 states over the years 1979 to 1997, we conclude that worker insecurity does reduce wage growth for classes of workers. However, we only find evidence of an effect of insecurity on wage workers without college degrees and the increase in insecurity during the 1990s is limited mainly workers with college degrees. Thus we concluded that increased worker insecurity many not have had a large effect on aggregate wage growth.
Argumentation through a distributed self-stabilizing approach

Argumentation is receiving an increasing attention as a technique for practical and uncertain reasoning underlying the realization of intelligent autonomous agents. Since a decentralized organization has been proposed by several authors as an appropriate paradigm for the design of agent architectures, we propose in this article, a distributed approach to argumentation, in which several independent asynchronous processes carry out argumentation activity, by exploiting local information only. The final result of this process is the computation of the defeat status of the arguments: we devise a general distributed algorithm, which does not rely on any specific notion of defeat between arguments. The issue of coordination has been explicitly tackled by ensuring the property of self-stabilization for the algorithm. A proof of its correctness, as well as an analysis of its complexity, is provided.
A Centralized Network Selection Algorithm Based on Access Router Discovery in Heterogeneous Wireless Networks

Seamless mobility across heterogeneous wireless networks requires a certain level of Quality of Service (QoS) to be assured as it determines the packet loss and delay during handoff procedure. Selecting the target network in an appropriate time plays a crucial role towards achieving ubiquitous networks. This paper proposes a network discovery and selection method called Improved Access Router Discovery (IARD) in a heterogeneous environment comprising of WLAN and UMTS networks. In this method, the nomination of potential networks is performed in core network using a special Weighted Mean (MW) algorithm with each network ranked based on several criteria and the highest rank network is proposed as the target network. This method was tested by means of simulation under various conditions with different traffic types and was shown to result in more appropriate network selections as compared to other methods.
The Two Price Systems in the Copper Industry

During three periods from the end of World War II through 1970, some or all of the major copper producers held their price below the level that would have cleared the market and rationed their "available supplies. " The central question posed by the two price systems is that of why any of the major producers would ever choose to ration. Bound up with this issue is the question of why several of the major producers rationed at times when the others did not. Two circumstances in which rationing may be profitable are identified. First, it is shown that rationing may be a profitable response to a large, unanticipated increase in demand if there is long-run substitution in demand; capacity cannot be quickly expanded; marginal cost is increasing; and price discrimination is infeasible. Second, it is shown that a partially integrated copper producer may find rationing profitable as a means of partially achieving the effects of price discrimination given that price discrimination itself is infeasible. Taken together, these motives for rationing provide an internally consistent set of hypotheses that account for the broad features of the two price systems. It is suggested on the basis of structural characteristics of the industry that these hypotheses are valid. However, the argument is not conclusive, so it can be claimed only that the results obtained provide a plausible explanation of the two price systems.
A dynamic programming approach for constrained multi-stage problems via multi-parametric programming

This paper presents a new algorithm for multi-stage decision problems with hard constraints. The algorithm is based upon the concepts of dynamic programming and multi-parametric programming. The multi-stage problem is considered within a framework of dynamic programming where each echelon of problem is formulated and solved as a multi-parametric program. The state-space of a given stage constitutes the parametric space whereas the state-space of the next stage represents the space of control or optimisation variables. The solution of the resulting multi-parametric program is given by the control or the optimization variables as a set of explicit functions of the parameters. The dynamic recursive nature of the multi-stage problem is preserved and a set of sequential and simpler multi-parametric programs which are constrained by a reduced number of inequalities is obtained. This results in a reduction in the complexity of the overall problem. The underlying theory is described in detail and numerical examples are presented to illustrate the potential of this new approach.
Dynamic behavior improvement in a microgrid with multiple DG units using a power sharing approach

This paper investigates dynamic behavior of a distribution subsystem (microgrid) with three distributed generation (DG) units to planned and accidental switching event. Three DG units are one gas-turbine synchronous generator and a variable-speed wind turbine with doubly fed induction generator (DFIG) and a converter based DG. A power control approach is proposed for DG units to provide both voltage and frequency regulation capability and hence an improvement on transients and dynamic behavior of a microgrid system. Two distinct operation modes, i.e. grid-connected and islanding mode are used in the proposed approach for proper transfer from normal to islanding operation. Case studies are simulated based on both planned and unplanned islanding scenarios to evaluate the performance of the control approach. The study results show that the proposed power sharing approach for DGs in the microgrid may contribute to mitigate microgrid system transients, improving dynamic performance, and reducing frequency changes following disturbances that subsequent to islanding.