Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in HPV18 E1^E4 Impact Virus Capsid Assembly, Infectivity Competence, and Maturation

The most highly expressed protein during the productive phase of the human papillomavirus (HPV) life cycle is E1^E4. Its full role during infection remains to be established. HPV E1^E4 is expressed during both the early and late stages of the virus life cycle and contributes to viral genome amplification. In an attempt to further outline the functions of E1^E4, and determine whether it plays a role in viral capsid assembly and viral infectivity, we examined wild-type E1^E4 as well as four E1^E4 truncation mutants. Our study revealed that HPV18 genomes containing the shortest truncated form of E1^E4, the 17/18 mutant, produced viral titers that were similar to wild-type virus and significantly higher compared to virions containing the three longer E1^E4 mutants. Additionally, the infectivity of virus containing the shortest E1^E4 mutation was equivalent to wild-type and significantly higher than the other three mutants. In contrast, infectivity was completely abrogated for virus containing the longer E1^E4 mutants, regardless of virion maturity. Taken together, our results indicate for the first time that HPV18 E1^E4 impacts capsid assembly and viral infectivity as well as virus maturation.
Heavy metal ATPase 3 (HMA3) confers cadmium hypertolerance on the cadmium/zinc hyperaccumulator Sedum plumbizincicola.

Cadmium (Cd) is highly toxic to most organisms, but some rare plant species can hyperaccumulate Cd in aboveground tissues without suffering from toxicity. The mechanism underlying Cd detoxification by hyperaccumulators is interesting but unclear. Here, the heavy metal ATPase 3 (SpHMA3) gene responsible for Cd detoxification was isolated from the Cd/zinc (Zn) hyperaccumulator Sedum plumbizincicola. RNA interference (RNAi)-mediated silencing and overexpression of SpHMA3 were induced to investigate its physiological functions in S. plumbizincicola and a nonhyperaccumulating ecotype of Sedum alfredii. Heterologous expression of SpHMA3 in Saccharomyces cerevisiae showed Cd-specific transport activity. SpHMA3 was highly expressed in the shoots and the protein was localized to the tonoplast. The SpHMA3-RNAi lines were hypersensitive to Cd but not to Zn, with the growth of shoots and young leaves being severely inhibited by Cd. Overexpressing SpHMA3 in the nonhyperaccumulating ecotype of S. alfredii greatly increased its tolerance to and accumulation of Cd, but not Zn. These results indicate that elevated expression of the tonoplast-localized SpHMA3 in the shoots plays an essential role in Cd detoxification, which contributes to the maintenance of the normal growth of young leaves of S. plumbizincicola in Cd-contaminated soils.
A Dynamic Oligopoly Game of the US Airline Industry: Estimation and Policy Experiments

This paper studies the contribution of demand, costs, and strategic factors to the adoption of hub-and-spoke networks in the US airline industry. Our results are based on the estimation of a dynamic game of network competition using data from the Airline Origin and Destination Survey with information on quantities, prices, and entry and exit decisions for every airline company in the routes between the 55 largest US cities. As methodological contributions of the paper, we propose and apply a method to reduce the dimension of the state space in dynamic games, and a procedure to deal with the problem of multiple equilibria when implementing counterfactual experiments. Our empirical results show that the most important factor to explain the adoption of hub-and-spoke networks is that the sunk cost of entry in a route declines importantly with the number of cities that the airline connects from the origin and destination airports of the route. For some carriers, the entry deterrence motive is the second most important factor to explain hub-and-spoke networks.
Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen

ABSTRACT Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to DENV4) that affect millions of people worldwide, causing a significant number of deaths. There are vaccines based on chimeric viruses, but they still are not in clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are promising alternatives to those based on whole virus or structural proteins. The DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based immune responses in humans. In this study, we purified a soluble recombinant form of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after optimization of expression conditions and purification steps. The purified DENV2 NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected patients in an epitope-conformation-dependent manner. In addition, immunization of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and expansion of gamma interferon- and tumor necrosis factor alpha-producing T cells. Moreover, mice immunized with purified NS5 were partially protected from lethal challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These results indicate that the recombinant NS5 protein preserves immunological determinants of the native protein and is a promising vaccine antigen capable of inducing protective immune responses.
Cyclosporine 0.05% Ophthalmic Emulsion for Dry Eye in Korea: A Prospective, Multicenter, Open-Label, Surveillance Study

Purpose To assess the effectiveness and tolerability of cyclosporine ophthalmic emulsion (CsA) 0.05% in patients with moderate to severe dry eye disease in Korea. Methods This was a prospective, multicenter, open-label, surveillance study of 392 Korean patients with moderate to severe dry eye disease who were treated with CsA 0.05% for three months. An assessment of effectiveness was performed at baseline, and after 1, 2, and 3 months. The primary effectiveness outcomes were changes in ocular symptoms and Schirmer score. The secondary effectiveness outcomes were a change in conjunctival staining, use of artificial tears, global evaluation of treatment, and patient satisfaction. The primary safety outcome was the incidence and nature of adverse events. Results A total of 362 patients completed the study. After three months, all ocular symptom scores were significantly reduced compared to the baseline values, while the Schirmer scores were significantly increased relative to baseline (p < 0.0001). After three months, there were significant reductions from baseline in conjunctival staining (p < 0.01) and use of artificial tears (p < 0.0001). According to clinicians' global evaluations, most patients (>50%) experienced at least a 25% to 50% improvement in symptoms from baseline at each follow-up visit. The majority of patients (72.0%) were satisfied with the treatment results, and 57.2% reported having no or mild symptoms after treatment. The most common adverse events were ocular pain (11.0%). Conclusions Our findings indicate that CsA 0.05% is an effective and tolerable treatment for dry eye disease in Korean clinical practice.
Development of an Online and Offline Integration Hypothesis for Healthy Internet Use: Theory and Preliminary Evidence

The Internet has become an integral part of our daily life, and how to make the best use of the Internet is important to both individuals and the society. Based on previous studies, an Online and Offline Integration Hypothesis is proposed to suggest a framework for considering harmonious and balanced Internet use. The Integration Hypothesis proposes that healthier patterns of Internet usage may be achieved through harmonious integration of people’s online and offline worlds. An online/offline integration is proposed to unite self-identity, interpersonal relationships, and social functioning with both cognitive and behavioral aspects by following the principles of communication, transfer, consistency, and “offline-first” priorities. To begin to test the hypothesis regarding the relationship between integration level and psychological outcomes, data for the present study were collected from 626 undergraduate students (41.5% males). Participants completed scales for online and offline integration, Internet addiction, pros and cons of Internet use, loneliness, extraversion, and life satisfaction. The findings revealed that subjects with higher level of online/offline integration have higher life satisfaction, greater extraversion, and more positive perceptions of the Internet and less loneliness, lower Internet addiction, and fewer negative perceptions of the Internet. Integration mediates the link between extraversion and psychological outcomes, and it may be the mechanism underlying the difference between the “rich get richer” and social compensation hypotheses. The implications of the online and offline integration hypothesis are discussed.
Epitaxial BiFeO3 Multiferroic Thin Film Heterostructures

Enhancement of polarization and related properties in heteroepitaxially constrained thin films of the ferroelectromagnet, BiFeO3, is reported. Structure analysis indicates that the crystal structure of film is monoclinic in contrast to bulk, which is rhombohedral. The films display a room-temperature spontaneous polarization (50 to 60 microcoulombs per square centimeter) almost an order of magnitude higher than that of the bulk (6.1 microcoulombs per square centimeter). The observed enhancement is corroborated by first-principles calculations and found to originate from a high sensitivity of the polarization to small changes in lattice parameters. The films also exhibit enhanced thickness-dependent magnetism compared with the bulk. These enhanced and combined functional responses in thin film form present an opportunity to create and implement thin film devices that actively couple the magnetic and ferroelectric order parameters.
Modulators of Redox Metabolism in Head and Neck Cancer.

SIGNIFICANCE Head and neck squamous cell cancer (HNSCC) is a complex disease characterized by high genetic and metabolic heterogeneity. Radiation therapy (RT) alone or combined with systemic chemotherapy is widely used for treatment of HNSCC as definitive treatment or as adjuvant treatment after surgery. Antibodies against epidermal growth factor receptor are used in definitive or palliative treatment. Recent Advances: Emerging targeted therapies against other proteins of interest as well as programmed cell death protein 1 and programmed death-ligand 1 immunotherapies are being explored in clinical trials. CRITICAL ISSUES The disease heterogeneity, invasiveness, and resistance to standard of care RT or chemoradiation therapy continue to constitute significant roadblocks for treatment and patients' quality of life (QOL) despite improvements in treatment modality and the emergence of new therapies over the past two decades. FUTURE DIRECTIONS As reviewed here, alterations in redox metabolism occur at all stages of HNSCC management, providing opportunities for improved prevention, early detection, response to therapies, and QOL. Bioinformatics and computational systems biology approaches are key to integrate redox effects with multiomics data from cells and clinical specimens and to identify redox modifiers or modifiable target proteins to achieve improved clinical outcomes. Antioxid. Redox Signal.
Adhesion and contact in soft and hard materials: From organic electronics to medical devices

Contact and adhesion between different components in many structures are crucial for the performance and life-time of these structures. This study presents the results of a combined experimental and computational study of adhesion and contact between soft and hard materials in small structures that are relevant to biomedical applications and organic electronics. These structures include: drug-eluting stents that are used for the treatment of cardiovascular disease, bio-inspired functionally graded nanocomposite dental multilayers, and large-area organic light emitting diodes. In each of these areas, this work combined nano-scale experimental measurements of adhesion with analytical and computational models that enabled the prediction of adhesion at the microand macro-scales. Also, a range of materials/mechanical characterization techniques were used to obtain useful inputs into mechanics models of contact and adhesion. The study of drug-eluting stents explored new ways of characterizing and modeling the adhesion of polymeric drug-containing coatings to metallic substrates. Atomic force microscope (AFM) was used to measure the pull-off force between bi-materials pairs. The adhesion energies were then obtained from the measured pull-off forces and adhesion theories. Subsequently, the adhesion energies were incorporated into an interfacial fracture mechanics zone model that was used to determine the mode mixity dependence of the interfacial fracture toughness. The mode mixity dependent fracture toughness conditions were then integrated into finite element method (FEM) models that were used to compute the critical push-out forces of the suspended polymeric iii -
Effect of high-dose preoperative methylprednisolone on recovery after total hip arthroplasty: a randomized, double-blind, placebo-controlled trial.

BACKGROUND High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip arthroplasty (THA). METHODS Forty-eight patients undergoing unilateral THA under spinal anaesthesia were consecutively included in this randomized, double-blind, placebo-controlled trial receiving preoperative i.v. MP or saline. All patients received a standardized, multimodal analgesic regime with paracetamol, celecoxib, and gabapentin. The primary outcome was time to meet well-defined functional discharge criteria. Secondary outcomes were handgrip strength and endurance, pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic-, and hypnotic medicine requirements. The inflammatory response measured by C-reactive protein (CRP) and actual length of stay were also registered. Discharge criteria were assessed twice daily (at 09:00 and 14:00 h) until discharge. Other outcomes were assessed at 2, 4, 6, 8, and 24 h after operation, and also in a questionnaire from postoperative day (POD) 1-4. RESULTS Time to meet discharge criteria was [median (IQR) (95% CI), MP vs placebo]: 23.5 (23.3-23.7) (17.8-43.8) vs 23.5 (23.0-23.8) (20.0-46.8) h, the mean difference (95% CI) being -1.3 (-4.7 to 2.2) h, P=0.65. Overall pain for the first 24 h after surgery was significantly reduced in the MP vs the placebo group (P<0.01), as was CRP at 24 h (P<0.0001). No other between-group differences were observed. No drug-related complications were observed at follow-up on POD30. CONCLUSIONS MP 125 mg i.v. before surgery added to a multimodal oral analgesic regime did not reduce time to meet functional discharge criteria after THA, but improved analgesia for the first 24 h.
Standard Genotyping Overestimates Transmission of Mycobacterium tuberculosis among Immigrants in a Low-Incidence Country

ABSTRACT Immigrants from regions with a high incidence of tuberculosis (TB) are a risk group for TB in low-incidence countries such as Switzerland. In a previous analysis of a nationwide collection of 520 Mycobacterium tuberculosis isolates from 2000 to 2008, we identified 35 clusters comprising 90 patients based on standard genotyping (24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat [MIRU-VNTR] typing and spoligotyping). Here, we used whole-genome sequencing (WGS) to revisit these transmission clusters. Genome-based transmission clusters were defined as isolate pairs separated by ≤12 single nucleotide polymorphisms (SNPs). WGS confirmed 17/35 (49%) MIRU-VNTR typing clusters; the other 18 clusters contained pairs separated by >12 SNPs. Most transmission clusters (3/4) of Swiss-born patients were confirmed by WGS, as opposed to 25% (4/16) of the clusters involving only foreign-born patients. The overall clustering proportion was 17% (90 patients; 95% confidence interval [CI], 14 to 21%) by standard genotyping but only 8% (43 patients; 95% CI, 6 to 11%) by WGS. The clustering proportion was 17% (67/401; 95% CI, 13 to 21%) by standard genotyping and 7% (26/401; 95% CI, 4 to 9%) by WGS among foreign-born patients and 19% (23/119; 95% CI, 13 to 28%) and 14% (17/119; 95% CI, 9 to 22%), respectively, among Swiss-born patients. Using weighted logistic regression, we found weak evidence of an association between birth origin and transmission (adjusted odds ratio of 2.2 and 95% CI of 0.9 to 5.5 comparing Swiss-born patients to others). In conclusion, standard genotyping overestimated recent TB transmission in Switzerland compared to WGS, particularly among immigrants from regions with a high TB incidence, where genetically closely related strains often predominate. We recommend the use of WGS to identify transmission clusters in settings with a low incidence of TB.
Preoperative biliary drainage using a fully covered self-expandable metallic stent for pancreatic head cancer: A prospective feasibility study

Background/Aims: The role of endoscopic preoperative biliary drainage (PBD) for pancreatic head cancer is controversial because of the high incidence of stent occlusion before surgery. This study was performed to evaluate the feasibility and safety of PBD using a fully covered self-expandable metallic stent (FCSEMS). Patients and Methods: This multicenter prospective study involved 26 patients treated for pancreatic head cancer with distal bile duct obstruction from April 2011 to March 2013. An FCSEMS was endoscopically placed in 24 patients. Among these, 7 patients were diagnosed with unresectable cancer, and 17 underwent surgery at a median of 18 days after FCSEMS placement. The main outcome measure was preoperative and postoperative adverse events. Results: Two adverse events (cholecystitis and insufficient resolution of jaundice) occurred between FCSEMS placement and surgery (12%). Postoperative adverse events occurred in eight patients (47%). The cumulative incidence of stent-related adverse events 4 and 8 weeks after FCSEMS placement among the 24 patients who underwent this procedure were 19%. Conclusions: PBD using an FCSEMS is feasible in patients with resectable pancreatic head cancer. Placement of an FCSEMS can be an alternative PBD technique when surgery without delay is impossible. A larger randomized controlled trial is warranted.
Regional Similarities and Consistent Patterns of Local Variation in Beach Sand Bacterial Communities throughout the Northern Hemisphere

ABSTRACT Recent characterization of the bacterial community structure in beach sands has revealed patterns of biogeography similar to those observed in aquatic environments. Studies to date, however, have mainly focused on subtidal sediments from marine beaches. Here, we investigate the bacterial diversity, using Illumina-based sequencing of the V5-V6 region of the 16S rRNA gene, at 11 beaches representing those next to the Great Lakes, Florida, and the Pacific Ocean. The alpha diversity differed significantly among regions (P < 0.0001), while the within-region diversity was more similar. The beta diversity also differed by region (P < 0.001), where freshwater sands had significantly higher abundances of taxa within the Actinobacteria, Betaproteobacteria, and Verrucomicrobia than marine environments. In contrast, marine sands harbored greater abundances of Gammaproteobacteria and Planctomycetes, and those from Florida had more Deltaproteobacteria and Firmicutes. Marine beaches had significantly different phylogenetic community structures (P ≤ 0.018), but freshwater and Florida beaches showed fewer within-region phylogenetic differences. Furthermore, regionally distinct patterns in taxonomic variation were observed in backshore sands, which had communities distinct from those in nearshore sands (P < 0.001). Sample depth minimally influenced the community composition. The results of this study reveal distinct bacterial community structures in sand on a broad geographic scale but moderate regional similarity and suggest that local variation is primarily related to the distance from the shoreline. This study offers a novel comparison of the bacterial communities in freshwater and marine beach sands and provides an important basis for future comparisons and analyses to elucidate factors affecting microbial ecology in this underexplored environment. IMPORTANCE This study presents a large-scale geographic characterization of the bacterial communities present in beach sands. While previous studies have evaluated how environmental factors influence bacterial community composition, few have evaluated bacterial communities in freshwater sands. Furthermore, the use of a consistent methodology to characterize bacterial communities here allowed a novel comparison of communities across geographic regions. We reveal that while the community composition in sands at individual beaches is distinct, beach sands within the same region harbor similar assemblages of bacteria and these assemblages differ greatly between regions. In addition, moisture, associated with distance from the shoreline, strongly influences the bacteria present in sands and more strongly influences the bacteria present than sample depth does. Thus, the data presented here offer an important basis for a broader characterization of the ecology of bacteria in sands, which may also be relevant to public health and resource management initiatives.
Root neighborhoods of a polynomial

The root neighborhoods of p (z), a polynomial over the complex field, are the sets of complex numbers that are the roots of polynomials which are near to p(z). The term 'near' means that the coefficients of the polynomials are within some fixed magnitude of the coefficients of p(z). A necessary and sufficient condition for a complex number to be in the root neighborhoods is given and it is proved that each root neighborhood contains at least one root of p ( Z) and the same number of roots of each near polynomial. Finally, a necessary and sufficient condition is given for a root neighborhood to contain more than one root of p(z), and consequently more than one root of any of the near polynomials.
Death Anxiety and Pain Catastrophizing Among Male Inmates With Nonsuicidal Self-Injury Behavior: A Comparative Study

Most of the studies concerning nonsuicidal self-injury behaviors of persons deprived of liberty were on female participants. This cross-sectional comparative study compared the levels of death anxiety, pain catastrophizing, dissociative experiences, and state-trait anger among male inmates with nonsuicidal self-injury behaviors and noninjuring controls. The results indicated high levels of death anxiety, dissociation, and pain catastrophizing in both groups of participants and the absence of significant differences between the groups. The implications of the results suggest the need of taking into consideration these variables in the behavior management plans used with inmates who engage in self-injurious behavior.