Miracle-dz/UniFAR-FTUs huggingface dataset:
Antigenic and Cryo-Electron Microscopy Structure Analysis of a Chimeric Sapovirus Capsid

ABSTRACT The capsid protein (VP1) of all caliciviruses forms an icosahedral particle with two principal domains, shell (S) and protruding (P) domains, which are connected via a flexible hinge region. The S domain forms a scaffold surrounding the nucleic acid, while the P domains form a homodimer that interacts with receptors. The P domain is further subdivided into two subdomains, termed P1 and P2. The P2 subdomain is likely an insertion in the P1 subdomain; consequently, the P domain is divided into the P1-1, P2, and P1-2 subdomains. In order to investigate capsid antigenicity, N-terminal (N-term)/S/P1-1 and P2/P1-2 were switched between two sapovirus genotypes GI.1 and GI.5. The chimeric VP1 constructs were expressed in insect cells and were shown to self-assemble into virus-like particles (VLPs) morphologically similar to the parental VLPs. Interestingly, the chimeric VLPs had higher levels of cross-reactivities to heterogeneous antisera than the parental VLPs. In order to better understand the antigenicity from a structural perspective, we determined an intermediate-resolution (8.5-Å) cryo-electron microscopy (cryo-EM) structure of a chimeric VLP and developed a VP1 homology model. The cryo-EM structure revealed that the P domain dimers were raised slightly (∼5 Å) above the S domain. The VP1 homology model allowed us predict the S domain (67–229) and P1-1 (229–280), P2 (281–447), and P1-2 (448–567) subdomains. Our results suggested that the raised P dimers might expose immunoreactive S/P1-1 subdomain epitopes. Consequently, the higher levels of cross-reactivities with the chimeric VLPs resulted from a combination of GI.1 and GI.5 epitopes. IMPORTANCE We developed sapovirus chimeric VP1 constructs and produced the chimeric VLPs in insect cells. We found that both chimeric VLPs had a higher level of cross-reactivity against heterogeneous VLP antisera than the parental VLPs. The cryo-EM structure of one chimeric VLP (Yokote/Mc114) was solved to 8.5-Å resolution. A homology model of the VP1 indicated for the first time the putative S and P (P1-1, P2, and P1-2) domains. The overall structure of Yokote/Mc114 contained features common among other caliciviruses. We showed that the P2 subdomain was mainly involved in the homodimeric interface, whereas a large gap between the P1 subdomains had fewer interactions.
Extending UML Meta-model for Android Application

UML is a standardized general-purpose software modeling language. Using the UML, a developer can model any systems easily because the UML provides well-defined modeling concepts and notations to describe elements of a system. The UML provides a mechanism to communicate between a developer and others when they are involved in modeling a system. However, it does not provide delicate concepts to express peculiar features of a specific system. Thus, in order to cope with the problem, the UML provides the extension mechanisms. Each feature of a specific system can be described with the UML extension mechanisms. In this article, we propose a meta-model for developing an application operated on the Android platform using the UML extension mechanisms. Since the modeling elements for the Android platform do not be supported by the standard UML we are convinced that the extended meta-model will facilitate efficient modeling when developing an Android application.
Comprehensive review of JAK inhibitors in myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem-cell disorders, characterized phenotypically by the abnormal accumulation of mature-appearing myeloid cells. Polycythemia vera, essential thrombocythemia, primary myelofibrosis (also known as ‘BCR-ABL1-negative’ MPNs), and chronic myeloid leukemia (CML) are the primary types of MPNs. After the discovery of the BCR-ABL1 fusion protein in CML, several oncogenic tyrosine kinases have been identified in ‘BCR-ABL1-negative’ MPNs, most importantly, JAK2V617F mutation. The similarity in the clinical characteristics of the BCR-ABL1-negative MPN patients along with the prevalence of the Janus kinase mutation in this patient population provided a strong rationale for the development of a new class of pharmacologic inhibitors that target this pathway. The first of its class, ruxolitinib, has now been approved by the food and drug administration (FDA) for the management of patients with intermediate- to high-risk myelofibrosis. Ruxolitinib provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease. Although noncurative, ruxolitinib represents a milestone in the treatment of myelofibrosis patients. Other types of JAK2 inhibitors are being tested in various clinical trials at this point and may provide better efficacy data and safety profile than its predecessor. In this article, we comprehensively reviewed and summarized the available preclinical and clinical trials pertaining to JAK inhibitors.
Analysis and Evaluation of DC-Link Capacitors for High-Power-Density Electric Vehicle Drive Systems

In electric vehicle (EV) inverter systems, direct-current-link capacitors, which are bulky, heavy, and susceptible to degradation from self heating, can become a critical obstacle to high power density. This paper presents a comprehensive method for the analysis and comparative evaluation of dc-link capacitor applications to minimize the volume, mass, and capacitance. Models of equivalent series resistance that are valid over a range of frequency and operating temperature are derived and experimentally validated. The root-mean-square values and frequency spectra of the capacitor current are analyzed with respect to three modulation strategies and various operating conditions over practical ranges of load power factor and modulation index in EV drive systems. The modeling and analysis also consider the self-heating process and resulting core temperature of the dc-link capacitors, which impacts their lifetimes. Based on an 80-kW permanent-magnet (PM) motor drive system, the application of electrolytic capacitors and film capacitors has been evaluated by both simulation and experimental tests. The inverter power density is improved from 2.99 kW/L to 13.3 kW/L, without sacrificing the system performance in terms of power loss, core temperature, and lifetime.
Active Suspension System Based on Linear Switched Reluctance Actuator and Control Schemes

In this paper, an active suspension system utilizing a low-cost high-performance linear switched reluctance actuator with proportional-derivative (PD) control is presented. With the tracking differentiator (TD) calculating the displacement and its derivatives directly under the presence of noise, velocity and acceleration can be evaluated, and accurate position control can be achieved. Comparison is made between linear and nonlinear PD control methods in terms of various system parameters and road profiles. A nonlinear PD controller with better dynamic responses is evaluated and developed for real-time suspension application. The proposed PD control schemes are simulated, tested, and analyzed to prove its robustness and reliability. Finally, a quarter-car active suspension system prototype is built to demonstrate the effectiveness of the proposed control schemes with experiment results.
A Mobile Device-Based Mobile AP Detection Scheme Using NAT Behavior

This paper proposes the scheme to detect the Mobile AP from mobile devices independently without the help of additional nodes. The proposed scheme is for detecting the Mobile AP that does not have any security configuration which is highly likely to occur as the Rogue AP in real wireless network environment. The device inspects the NAT Behavior and Open Port at the time of specific AP connection to detect the presence of Mobile AP, and reduces the security threat for the Rogue AP. The Rogue AP detection scheme s presented previously are generally based on the detection of Rogue AP in the form of Evil Twin, and the Rogue AP of various forms cannot be detected easily with such techniques. In addition, such techniques require regular monitoring or additional network infrastructure, thus making it difficult to apply to mobile devices, and are not suitable in real public wireless network environment. The proposed technique enables detection of mobile AP, which does not have any security configuration, from mobile devices in public wireless network environment independently without the help of additional nodes, and therefore, represents the detection scheme that is easily applicable and proved its performance in the experiment under real wireless network environment.
Management of patients with Alzheimer’s disease: pharmacological treatment and quality of life

A methodological approach to quality of life (QoL) assessment in Alzheimer’s disease (AD) is challenging and few clinical trials have included it among outcomes, with conflicting results. In this review an indirect appraisal of evidence has been performed, searching the literature for the effect of drug treatments on determinants of QoL in AD. Among clinical factors associated with QoL, possible targets of drugs include cognition, which seems to be associated with QoL in early disease and can be positively affected by cholinesterase inhibitors (CIs) in this stage; functional decline, the risk of which can be decreased by CIs and memantine (MEM); behavioral and psychological symptoms, which can be reduced by MEM and atypical antipsychotics. Long-term observational studies have associated CIs and MEM treatment with a reduced institutionalization risk. According to the evidence, drug treatment of depression associated with AD should not be first choice from a QoL perspective, while treatment of pain can have beneficial effects on wellbeing indicators also in the late stages of the disease. Possible drug-related adverse events can affect QoL and should always be weighed against expected benefits from the patient’s perspective. For this reason antipsychotic treatment is often problematic in AD and should be limited to severe psychosis and aggression, using the lowest effective doses for the shortest possible period. Conversely titration of CIs is necessary to reach the most effective dosages, although dose-related risk of adverse events has to be taken into account. Finally, CIs and MEM have been shown to reduce caregiver burden in randomized trials, possibly affecting caregivers’ QoL.
A taxonomy of perceived information security and privacy threats among IT security students

The purpose of this study is to explore students' perceived information security and privacy (IS&P) threats and to classify them in a way that helps in analyzing the problem, creating awareness measures and further improving students' IS&P education. Using a qualitative research approach, a group of forty two Master's degree IT students identified seventy five IS&P threats related to them. The identified threats were classified into fourteen categories. Further, using the affinity diagraming technique, the categories were grouped into four domains - Personnel, Devices, Intranet and Internet. In this way, we defined a taxonomy of students' perceived IS&P threats as well as a model that highlights the domains where students consider themselves prone to IS&P threats. The proposed taxonomy and the domain model can be used as a benchmark for designing information security awareness assessment instruments as well as preparing information security awareness programs. The taxonomy can also be used for highlighting areas where students lack information security related knowledge.
Gastrointestinal bacterial overgrowth: pathogenesis and clinical significance

Small intestinal bacterial overgrowth (SIBO) is defined as the presence of an abnormally high number of coliform bacteria in the small bowel. It is associated with a broad range of predisposing small intestinal motility disorders and with surgical procedures that result in bowel stasis. The most common symptoms associated with SIBO include diarrhea, flatulence, abdominal pain and bloating. Quantitative culture of small bowel contents and a variety of indirect tests have been used over the years in an attempt to facilitate the diagnosis of SIBO. The indirect tests include breath tests and biochemical tests based on bacterial metabolism of a variety of substrates. Unfortunately, there is no single valid test for SIBO, and the accuracy of all current tests remains limited due to the failure of culture to be a gold standard and the lack of standardization of the normal bowel flora in the small intestine. Currently, the ideal approach to treat SIBO is to treat the underlying disease, eradicate overgrowth, and address nutritional deficiencies that may be associated with the development of SIBO.
Paroxysmal positional vertigo and labyrintholithiasis: certainties and doubts

Paroxysmal positional vertigo (PPV) is a vestibular disorder with a high prevalence in the general population, so common that it may be considered as one of the most – or even the most frequent type of true dizziness. It was described many years ago (Adler, 1897) and its clinical aspects have been more and more refined to describe a nosological entity universally recognised. The focus on PPV has grown with the introduction of the so-called repositioning and liberatory manoeuvres. These manoeuvres have provided effective therapeutical instruments for this common pathology which is severely disturbing and non-responsive to pharmacological therapy even when symptomatic. Their unquestionable efficacy has solved the frustration of the clinician not to be able to treat PPV and has created great scientific and clinical enthusiasm regarding this topic. This enthusiasm has favoured new research, thanks to which many aspects of PPV are now considered undebatable. Other aspects require more study and reflection. The certainties concern most of all the clinical aspects, diagnosis and therapy. The pathogenesis, the aetiology, the causes and therapy of recurrences, are the more uncertain topics. More than 10,000 cases of PPV that I personally treated in the last 20 years have stimulated my own reflections. In my opinion many aspects are still controversial, but I think that the doubts and reflections here presented can stimulate other discussions and improve knowledge of PPV, helping to find a more effective therapy for the most atypical or unresponsive cases.
The Effects of Hexanol on G&agr;i Subunits of Heterotrimeric G Proteins

Alcohols and other anesthetics interfere with the function of a variety of systems regulated by guanosine triphosphate (GTP)-binding proteins (G proteins). We examined the effect of hexanol on the activity of the &agr; subunit (G&agr;i1) of heterotrimeric G proteins. The GTP hydrolysis activity of recombinant G&agr;i1 was 0.029 mole Pi · mole G&agr;i1−1 · min−1 and was inhibited by hexanol at concentrations larger than 10 mM, with a 50% inhibitory concentration of 22 mM. Circular dichroism spectroscopy revealed that hexanol decreased the denaturation temperature of G&agr;i1 from 47.2°C to 42.5°C without altering its secondary structure at 10°C. Hexanol (30 mM) reduced the amount of monomeric G&agr;i1 in solution measured by size-exclusion chromatography, indicating that hexanol caused protein aggregation. However, the rate of GTP&ggr;S binding to G&agr;i immunoprecipitated from airway smooth muscle membranes was not affected by 30 mM hexanol. Excluding the apparent inhibition of recombinant G&agr;i1 resulting from aggregation-induced artifact, we found no evidence that the hexanol-induced inhibition of receptor-activated G&agr;i-coupled pathways in intact airway smooth muscle resulted from direct inhibition of the intrinsic rate of [35S]GTP&ggr;S binding to G&agr;i.
Subsumption and survivability in bidding for bandwidth

Cooperative agents provide layers of competence to control a telecom network. Higher planning layers coordinate lower layers by seeking to globally optimise the survivability of the network. It is shown that the process of finding the best flow in the network can be viewed as a distributed auction where the prices are obtained from the derivatives of the survivability function. In the application, a simple measure of survivability maps into familiar routing heuristics.
Nonconvex Compressed Sampling of Natural Images and Applications to Compressed MR Imaging

There have been proposed several compressed imaging reconstruction algorithms for natural and MR images. In essence, however, most of them aim at the good reconstruction of edges in the images. In this paper, a nonconvex compressed sampling approach is proposed for structure-preserving image reconstruction, through imposing sparseness regularization on strong edges and also oscillating textures in images. The proposed approach can yield high-quality reconstruction as images are sampled at sampling ratios far below the Nyquist rate, due to the exploitation of a kind of approximate l0 seminorms. Numerous experiments are performed on the natural images and MR images. Compared with several existing algorithms, the proposed approach is more efficient and robust, not only yielding higher signal to noise ratios but also reconstructing images of better visual effects.
Ezetimibe: an update on its clinical usefulness in specific patient groups

The aim of pharmacological lipid modification is to reduce low-density lipoprotein cholesterol (LDL-C) as a means of either secondary or primary prevention of cardiovascular disease. Statins are the first-line therapy for pharmacological lipid modification. Ezetimibe is a drug which reduces LDL-C by selectively inhibiting intestinal cholesterol absorption. This provides an alternative pharmacological approach to that of statin therapy to reduce LDL-C. Ezetimibe has been shown to significantly reduce levels of LDL-C and recently, as demonstrated in the IMPROVE-IT trial, to reduce the rate of cardiovascular events in high-risk patients. Ezetimibe therefore has an important role in pharmacological lipid modification. In this paper, we examine the body of research behind ezetimibe and assess its current clinical applications in different patient subgroups.
Lymph Node but Not Intradermal Injection Site Macrophages Are Critical for Germinal Center Formation and Antibody Responses to Rabies Vaccination

ABSTRACT Replication-deficient rabies virus (RABV)-based vaccines induce rapid and potent antibody responses via T cell-independent and T cell-dependent mechanisms. To further investigate early events in vaccine-induced antibody responses against RABV infections, we studied the role of macrophages as mediators of RABV-based vaccine immunogenicity. In this report, we show that a recombinant matrix gene-deleted RABV-based vaccine (rRABV-ΔM) infects and activates primary murine macrophages in vitro. Immunization of mice with live RABV-based vaccines results in accumulation of macrophages at the site of immunization, which suggests that macrophages in tissues support the development of effective anti-RABV B cell responses. However, we show that draining lymph node macrophages, but not macrophages at the site of immunization, are essential for the generation of germinal center B cells, follicular T helper cells, and RABV-specific antibodies. Our findings have implications for the design of new RABV-based vaccines for which early immunological events are important for the protection against RABV in postexposure settings. IMPORTANCE More than two-thirds of the world's population live in regions where rabies is endemic. Postexposure prophylaxis is the primary means of treating humans. Identifying immunological principles that guide the development of rapid and potent antibody responses against rabies infections will greatly increase our ability to produce more-effective rabies vaccines. Here we report that macrophages in the draining lymph node, but not in the tissue at the site of immunization are important for vaccine-induced antibody responses to rabies. Information gleaned from this study may help guide the development of a single-dose vaccine against rabies infections.
Effect of genetic polymorphisms on the development of secondary failure to sulfonylurea in Egyptian patients with type 2 diabetes

Objective: This study investigated the possibility that genetic factors, such as polymorphism of K inward rectifier subunit (Kir6.2), E23K, and Arg972 polymorphism of insulin receptor substrate-1 (IRS-1), may predispose patients to sulfonylurea failure. Methods: A total of 100 unrelated Egyptian patients with type 2 diabetes were recruited. They were divided into two equal groups: group I consisted of patients with secondary failure to sulfonylurea (hemoglobin A1c ≥ 8% despite sulfonylurea therapy) while group II consisted of patients whose condition was controlled with oral therapy. Results: Of all the patients, 45% and 14% were carriers of the K allele and Arg972 variants respectively. The frequency of the K allele was 34% among patients with diabetes that was controlled with oral therapy and 56% among patients with secondary failure to sulfonylurea. The frequency of the Arg972 IRS-1 variant was 6% among patients with diabetes controlled with oral therapy and 22% among patients with secondary failure. Conclusion: The E23K variant of the Kir6.2 gene and Arg972 IRS-1 variants are associated with increased risk for secondary failure to sulfonylurea.
Reply to “Group C Orthobunyavirus Genomic Sequences Require Validation”

Our response to the letter by Forshey et al. (1) is as follows. The group C viruses sequenced in our study (2) were all obtained from the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) at the University of Texas Medical Branch. The group C viruses used by de Brito Magalhães et al. (3) were obtained from the American Type Culture Collection (ATCC) (Table 1). The viruses sequenced by Forshey et al. were obtained from various sources (ATCC, WRCEVA, and NAMRU6); however, the exact strains used and their sources were not clearly identified in the copy of the letter that was sent to us for comment (1). Many of the virus names and identifications of the bunyaviruses currently posted on the ATCC website are incorrect, so it is unclear what virus strains the other two groups (named above) actually received and sequenced. For these reasons, we feel that the results reported by Forshey et al. (1) and by Brito Magalhaes (3) do not necessarily invalidate our own (2), because different viruses and virus strains may have been inadvertently sequenced. We acknowledge that there were errors in the sequence information deposited by us in GenBank in 2005, but these are now being rechecked by full-genome sequencing of the respective viruses, and the errors will be corrected accordingly.