Miracle-dz/UniFAR-FTUs huggingface dataset:
Rotavirus VP6 as an Adjuvant for Bivalent Norovirus Vaccine Produced in Nicotiana benthamiana

Rotaviruses (RVs) and noroviruses (NoVs) are major causes of childhood acute gastroenteritis. During development of a combination vaccine based on NoV virus-like particles (VLP) and RV VP6 produced in baculovirus expression system in insect cells, a dual role of VP6 as a vaccine antigen and an adjuvant for NoV-specific immune responses was discovered. Here the VP6 adjuvant effect on bivalent GI.4 and GII.4-2006a NoV VLPs produced in Nicotiana benthamiana was investigated. BALB/c mice were immunized intradermally with suboptimal (0.3 µg) dose of each NoV VLP alone or combined with 10 µg of VP6, or equal doses of NoV VLPs and VP6 (1 µg/antigen). NoV-specific serum IgG antibodies and their blocking activity were analyzed using vaccine-homologous and heterologous NoV VLPs. Immunization with 0.3 µg NoV VLPs alone was insufficient to induce NoV-specific immune responses, but with co-administration of 10 µg of VP6, antibodies against vaccine-derived and heterologous NoV genotypes were generated. Furthermore, corresponding adjuvant effect of VP6 was observed with 1 µg dose. Efficient uptake and presentation of VP6 by dendritic cells was demonstrated in vitro. These results show that adjuvant effect of VP6 on bivalent NoV VLP vaccine is independent of the cell source used for vaccine production.
The Causes and Consequences of Genetic Interactions (Epistasis).

The same mutation can have different effects in different individuals. One important reason for this is that the outcome of a mutation can depend on the genetic context in which it occurs. This dependency is known as epistasis. In recent years, there has been a concerted effort to quantify the extent of pairwise and higher-order genetic interactions between mutations through deep mutagenesis of proteins and RNAs. This research has revealed two major components of epistasis: nonspecific genetic interactions caused by nonlinearities in genotype-to-phenotype maps, and specific interactions between particular mutations. Here, we provide an overview of our current understanding of the mechanisms causing epistasis at the molecular level, the consequences of genetic interactions for evolution and genetic prediction, and the applications of epistasis for understanding biology and determining macromolecular structures. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 20 is August 30, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Analysis of Dissipative Losses in Modular Reconfigurable Energy Storage Systems Using SystemC TLM and SystemC-AMS

Battery storage systems are becoming more popular in the automotive industry as well as in stationary applications. To fulfill the requirements in terms of power and energy, the literature is increasingly discussing electrically reconfigurable interconnection topologies. However, these topologies use switching elements on the cell and module level that exhibit an electric resistance due to their design and hence generate undesirable dissipative losses. In this article, we propose a new analysis and optimization framework to examine and minimize the losses in such topologies. For this purpose, we develop a SystemC model to investigate static and dynamic load scenarios, e.g., from the automotive domain. The model uses SystemC TLM for the digital subsystem, SystemC-AMS for the mixed-signal subsystem, and host-compiled simulation for the microcontroller executing the embedded software. Here, we analyze the impact of the dissipative losses on the system efficiency that depend on the modularization level, implying the number of serial and parallel switching elements. Our analysis clearly shows that in reconfigurable topologies, the modularization level has a significant influence on the losses, which in our automotive example covers several orders of magnitude. For the topologies we have investigated, the highest efficiency can be reached when a parallel-only modularization is aspired and the number of serial switching elements is minimized. It is also shown that the losses of the state-of-the-art topology with one battery pack protection switch are almost as high as in a smart cell approach in which each energy storage cell has its own switching element. However, due to the high number of switching elements, this results in a reduction of energy density and increases the system costs, showing that this is a multi-criteria optimization problem.
Low dose gemcitabine increases the cytotoxicity of human Vγ9Vδ2 T cells in bladder cancer cells in vitro and in an orthotopic xenograft model

ABSTRACT Human γδT cell immunotherapy is well tolerated and has shown promising results in clinical trials; however, its antitumor efficacy is limited, including results in solid tumors. Ex-vivo expanded γδT cell stimulated by zoledronic acid (ZOL) activates the γδT cell subpopulation of so called Vγ9Vδ2 T cells. To improve the clinical outcomes of Vγ9Vδ2 T cell (abbreviated as γδT cell here) immunotherapy, we aimed to increase the cytotoxicity of γδT cells by focusing on two issues: recognition of tumor cells by γδT cells and the effector (γδT cell)-to-target (tumor cell) (E/T) ratio. Ex vivo-expanded γδT cells showed potent cytotoxicity against urinary bladder cancer (UBC) cells in in vitro assays. Combination treatment with standard anticancer agents showed that low dose gemcitabine pretreatment significantly enhanced the cytotoxicity of γδT cells by upregulating the expression of MICA and MICB (MICA/B), which are tumor-associated antigens recognized by γδT cells. These effects were abrogated by small interfering RNA-mediated knockdown of MICA/B in UBC cells, suggesting that pre-exposing cancer cells to anticancer agents could be a promising strategy. A bladder instillation approach was used to increase the E/T ratio. The efficacy of ex vivo-expanded γδT cell immunotherapy was examined in an orthotopic xenograft model. In Vivo Imaging System analysis revealed the potent cytotoxicity of weekly intravesical administration of γδT cells, and weekly gemcitabine pretreatment enhanced the cytotoxicity of γδT cells in vivo. In conclusion, intravesical γδT cell immunotherapy and combination therapy with low dose gemcitabine may be a promising strategy in UBC.
Cold Tolerance of the Tribolium castaneum (Coleoptera: Tenebrionidae), Under Different Thermal Regimes: Impact of Cold Acclimation

Abstract The red flour beetle, Tribolium castaneum (Herbst), is a serious pest of stored product worldwide. Cold tolerance or cold hardiness is an important ecophysiological trait related directly to survival, fitness, and distribution of insects. In this study, the effects of four thermal regimes, i.e., control (C), cold acclimation (CA), rapid cold hardening (RCH), and fluctuating-acclimation (FA), were examined for their effects on cold tolerance, supercooling point (SCP), lower lethal temperature (LLT), and chill-coma recovery time (CCRT) of the red flour beetle. In addition, changes in cryoprotectant (trehalose, sorbitol, and myo-inositol) levels were investigated under each thermal treatment. The results documented a substantial enhancement in the SCP, cold hardiness, and cryoprotectant levels of the adults of T. castaneum under CA regimes. The lowest SCP, highest trehalose and myo-inositol contents, and, subsequently, the greatest survival rate were observed in cold-acclimated beetles. In addition, coordination between cryoprotectant level, SCP, and cold tolerance of the pest was observed. The highest and lowest CCRT were observed at control and CA, respectively. In RCH regime with the highest impact, LLT reached the lowest level of –22°C. As most of the mortality of T. castaneum occurred at a temperature above the SCP, so this pest could be considered as a chill-susceptible insect.
Asset pricing with heterogeneous beliefs and illiquidity

This paper studies the equilibrium price of an asset that is traded in continuous time between N agents who have heterogeneous beliefs about the state process underlying the asset's payoff. We propose a tractable model where agents maximize expected returns under quadratic costs on inventories and trading rates. The unique equilibrium price is characterized by a weakly coupled system of linear parabolic equations which shows that holding and liquidity costs play dual roles. We derive the leading‐order asymptotics for small transaction and holding costs which give further insight into the equilibrium and the consequences of illiquidity.
Involvement of BIG5 and BIG3 in BRI1 Trafficking Reveals Diverse Functions of BIG-subfamily ARF-GEFs in Plant Growth and Gravitropism

ADP-ribosylation factor-guanine nucleotide exchange factors (ARF-GEFs) act as key regulators of vesicle trafficking in all eukaryotes. In Arabidopsis, there are eight ARF-GEFs, including three members of the GBF1 subfamily and five members of the BIG subfamily. These ARF-GEFs have different subcellular localizations and regulate different trafficking pathways. Until now, the roles of these BIG-subfamily ARF-GEFs have not been fully revealed. Here, analysis of the BIGs expression patterns showed that BIG3 and BIG5 have similar expression patterns. big5-1 displayed a dwarf growth and big3-1 big5-1 double mutant showed more severe defects, indicating functional redundancy between BIG3 and BIG5. Moreover, both big5-1 and big3-1 big5-1 exhibited a reduced sensitivity to Brassinosteroid (BR) treatment. Brefeldin A (BFA)-induced BR receptor Brassinosteroid insensitive 1 (BRI1) aggregation was reduced in big5-1 mutant, indicating that the action of BIG5 is required for BRI1 recycling. Furthermore, BR-induced dephosphorylation of transcription factor BZR1 was decreased in big3-1 big5-1 double mutants. The introduction of the gain-of-function of BZR1 mutant BZR1-1D in big3-1 big5-1 mutants can partially rescue the big3-1 big5-1 growth defects. Our findings revealed that BIG5 functions redundantly with BIG3 in plant growth and gravitropism, and BIG5 participates in BR signal transduction pathway through regulating BRI1 trafficking.
Multi-Phase Flow Metering in Offshore Oil and Gas Transportation Pipelines: Trends and Perspectives

Multi-phase flow meters are of huge importance to the offshore oil and gas industry. Unreliable measurements can lead to many disadvantages and even wrong decision-making. It is especially important for mature reservoirs as the gas volume fraction and water cut is increasing during the lifetime of a well. Hence, it is essential to accurately monitor the multi-phase flow of oil, water and gas inside the transportation pipelines. The objective of this review paper is to present the current trends and technologies within multi-phase flow measurements and to introduce the most promising methods based on parameters such as accuracy, footprint, safety, maintenance and calibration. Typical meters, such as tomography, gamma densitometry and virtual flow meters are described and compared based on their performance with respect to multi-phase flow measurements. Both experimental prototypes and commercial solutions are presented and evaluated. For a non-intrusive, non-invasive and inexpensive meter solution, this review paper predicts a progress for virtual flow meters in the near future. The application of multi-phase flows meters are expected to further expand in the future as fields are maturing, thus, efficient utilization of existing fields are in focus, to decide if a field is still financially profitable.
The Validity of a Mixed Reality-Based Automated Functional Mobility Assessment

Functional mobility assessments (i.e., Timed Up and Go) are commonly used clinical tools for mobility and fall risk screening in older adults. In this work, we proposed a new Mixed Reality (MR)-based assessment that utilized a Microsoft HoloLensTM headset to automatically lead and track the performance of functional mobility tests, and subsequently evaluated its validity in comparison with reference inertial sensors. Twenty-two healthy adults (10 older and 12 young adults) participated in this study. An automated functional mobility assessment app was developed, based on the HoloLens platform. The mobility performance was recorded with the headset built-in sensor and reference inertial sensor (Opal, APDM) taped on the headset and lower back. The results indicate that the vertical kinematic measurements by HoloLens were in good agreement with the reference sensor (Normalized RMSE ~ 10%, except for cases where the inertial sensor drift correction was not viable). Additionally, the HoloLens-based test completion time was in perfect agreement with the clinical standard stopwatch measure. Overall, our preliminary investigation indicates that it is possible to use an MR headset to automatically guide users (without severe mobility deficit) to complete common mobility tests, and this approach has the potential to provide an objective and efficient sensor-based mobility assessment that does not require any direct research/clinical oversight.
Multiplicities of dihedral discriminants

Given the discriminant dk of a quadratic field k, the number of cyclic relative extensions N\k of fixed odd prime degree p with dihedral absolute Galois group of order 2p , which share a common conductor /, is called the multiplicity of the dihedral discriminant d^ = f2^p~^d^ . In this paper, general formulas for multiplicities of dihedral discriminants are derived by analyzing the p-rank of the ring class group mod / of k . For the special case p = 3 , c4 = -3 , an elementary proof is given additionally. The theory is illustrated by a discussion of all known discriminants of multiplicity > 5 of totally real and complex cubic fields. Introduction Let p be an odd prime and AT|Q a cyclic extension of degree p. Then it is well known [9, 15, 7] that the conductor of K must have the form / = Pe 'Qi • ■ ■ It> where e = 0 or e = 2, /> 0, and the qi are pairwise distinct rational primes satisfying qi = X (mod p) for i = X, . , t. The discriminant of K is just a power of the conductor, di( = fp~x . If, for any positive integer /, the number of cyclic extensions K\Q of degree p which share the same conductor / is denoted by m(f), then /-i/ p where p = dimF,(Qx(/)/Q* -qx(f)p) = dimr,(SyL, U(Z/fZ) ®Zp ¥p) = t + w with ®x(f) = {r£®x \(r,f) = X}, Q; = {reQx \r= X (mod*/)}, and w = \e. Moebius inversion yields an explicit formula for m(f): m(pe-qx---qt) = (p-l),+w-1 . It is the aim of the present paper to establish similar formulas for multiplicities of discriminants in the case of non-Galois extensions L|Q of degree p with dihedral normal closure yV of degree 2p. For the sake of illustration, the formulas are applied to discriminants with multiplicities up to 16 of non-Galois Received December 10, 1990; revised April 5, 1991. 1991 Mathematics Subject Classification. Primary 11R20, 11R11, 11R16.
Comparison of Endoscopic and Histological Findings between Typical and Atypical Celiac Disease in Children

Purpose Celiac disease is a common non-communicable disease with varied presentations. Purpose of this study was to find the duodeno-endoscopic features in celiac disease and to compare duodeno-endoscopic and histological findings between typical and atypical celiac disease in children. Methods Hospital based observational study was conducted at Sir Padampat Mother and Child Health Institute, Jaipur from June 2015 to May 2016. Patients were selected and divided in two groups- typical and atypical celiac disease based upon the presenting symptoms. Upper gastrointestinal endoscopy and duodenal biopsy was performed for serology positive patients. Results were analysed using appropriate statistical test of significance. Results Out of 101 enrolled patients, 47.5% were male. Age ranged from 1 to 18 years. Study showed that 54.5% were typical and 45.5% were atypical. Patients presenting with atypical symptoms were predominantly of older age group. On endoscopy, scalloping, mosaic pattern, reduced fold height and absent fold height; and in histology, advanced Marsh stage were significantly higher in the typical group. Conclusion Awareness of atypical presentations as well as duodeno-endoscopic features may have considerable practical importance for the diagnosis of celiac disease in children. Scalloping, mosaic pattern, reduced fold height and nodularity are main endoscopic markers of celiac disease in children. Endoscopic markers of duodenal mucosa may be important in early diagnosis of celiac disease, in children subjected to endoscopy for atypical presentations or indication other than suspected celiac disease.
Fluoro-Modulated Molecular Geometry in Diketopyrrolopyrrole-Based Low-Bandgap Copolymers for Tuning the Photovoltaic Performance

Fluorination of conjugated polymers is an effective strategy to tune the energy levels for obtaining high power conversion efficiency (PCE) in organic solar cells. In this work, we have developed fluoro-modulated molecular geometries in diketopyrrolopyrrole based low-bandgap copolymers. In these polymers, planar conformation can be locked by intramolecular non-covalent interaction (intramolecular supramolecular interaction) between the sulfur atoms and the introduced F atoms (F···S interaction). By varying the fluorinated moieties, such a planarity can be disturbed and the molecular geometry is tuned. As a result, the polymer' properties can be modulated, including the ultraviolet-visible absorption spectrum to become broaden, charge mobility to be enhanced, open-circuit voltage (Voc) and short-circuited current (Jsc) to be elevated, and thus photovoltaic performance to be improved. The photovoltaic device based on PCFB, one of the fluorinated terpolymers, exhibited a high PCE near 8.5% with simultaneously enhanced Voc and Jsc relative to the non-fluorinated one (PCB).
Gluten Intake and Risk of Celiac Disease: Long-Term Follow-up of an At-Risk Birth Cohort.

OBJECTIVES To determine the association between the amount of gluten intake in childhood and later celiac disease (CD), for which data are currently scarce. METHODS The prospective Diabetes Autoimmunity Study in the Young cohort includes 1875 at-risk children with annual estimates of gluten intake (grams/d) from age 1 year. From 1993 through January 2017, 161 children, using repeated tissue transglutaminase (tTGA) screening, were identified with CD autoimmunity (CDA) and persistent tTGA positivity; of these children, 85 fulfilled CD criteria of biopsy-verified histopathology or persistently high tTGA levels. Cox regression, modeling gluten intake between ages 1 and 2 years (i.e., in 1-year-olds), and joint modeling of cumulative gluten intake throughout childhood were used to estimate hazard ratios adjusted for confounders (aHR). RESULTS Children in the highest third of gluten intake between the ages of 1 and 2 years had a 2-fold greater hazard of CDA (aHR 2.17; 95% confidence interval [CI], 1.22-3.88; P value = 0.01) and CD (aHR 1.96; 95% CI, 0.90-4.24; P value = 0.09) than those in the lowest third. The risk of developing CDA increased by 5% per daily gram increase in gluten intake (aHR 1.05; 95% CI, 1.00-1.09; P value = 0.04) in 1-year-olds. The association between gluten intake in 1-year-olds and later CDA or CD did not differ by the child's human leukocyte antigen genotype. The incidence of CD increased with increased cumulative gluten intake throughout childhood (e.g., aHR 1.15 per SD increase in cumulative gluten intake at age 6; 95% CI, 1.00-1.32; P value = 0.04). DISCUSSION Gluten intake in 1-year-olds is associated with the future onset of CDA and CD in children at risk for the disease.
Reduced rate of dehiscence after implementation of a novel technique for creating colonic anastomosis in pediatric patients undergoing intestinal anastomosis in a single institute

Abstract We aimed to investigate the new continuous horizontal mattress anastomosis for pediatric patients who underwent emergency or electively laparotomy. From June 2012 to June 2017, 858 patients undergoing intestinal anastomosis were reviewed retrospectively, including 369 patients with the new continuous horizontal mattress anastomosis and 489 patients with traditional 2 layer interrupted anastomosis, served as control. Propensity score matching was performed to adjust for selected baseline variables. The primary outcome, anastomosis complications and clinical outcomes, including postoperative gastrointestinal function recovery, overall expenditure, and postoperative hospital stay were compared between the 2 groups. Patients with the new manual anastomosis had advantageous postoperative outcomes than those with the traditional 2 layer interrupted anastomosis. A mean of 11.4 minutes was required to construct the new manual single-layer anastomosis versus 18.5 minutes for the traditional anastomosis (P < .001). A reduction trend for postoperative anastomotic complications was indicated in patients receiving horizontal mattress anastomosis (odds ratio [OD] (95% confidence interval [CI]), 0.56 (0.37–0.84); P = . 004), including peritonitis or abscess (OD [95% CI], 0.56 (0.32–0.98); P = . 026), anastomotic leakage (OD [95% CI], 0.39 [0.12–1.27]; P = .088), and anastomotic strictures (P = .26). Mean length of stay was 10.9 ± 2.9 days for the new manual anastomosis group and 11.3 ± 3.5 days for traditional 2-layer anastomosis patients (P = .12). Beneficial effects of the new manual anastomosis were demonstrated in terms of anastomotic complications, and length of hospital stay in the pediatric patients. Furthermore, it is a novel, feasible and safe method that may simplify the surgical procedure in anastomoses.
Finding the best effective way of treatment for rapid I-131 turnover Graves’ disease patients

Background: Rapid I-131 turnover Graves’ disease patients have low cure rate. We aimed to compare cure percentage at 12 months among 3 treatment doses of I-131 with or without lithium carbonate (LiCO3) in rapid turnover Graves’ disease patients. Methods: Sixty Graves’ disease patients referred for radioactive iodine treatment were randomised into three arms of treatment: Group A, 3.7 MBq I-131/g thyroid plus 600 mg/day LiCO3, Group B, 5.55 MBq I-131/g plus 600 mg/day LiCO3, and Group C, 7.4 MBq I-131/g without LiCO3. Data were collected at baseline, 3, 6, 9, and 12 months. The primary endpoint were cure rates (percentage of euthyroid or hypothyroid) at 12 months. Pairwise comparisons were made across 3 groups using an equality of proportions test. The secondary endpoint, the odds of cure over the total follow-up for group B and C versus group A, was analyzed using generalized estimating equation (GEE). Side effects of I-131 and LiCO3 treatment were evaluated at 1 to 2 weeks after treatment. Results: The cure rate at 12 months was 45% (9/20) for group A, 60% (12/20) for group B and 80% (16/20) for group C. The mean difference in proportion cured at 12 months between group C and group A was 35 (7.0 to 66.8)%; P-value = . 02. There was a statistically significant difference between cure rates over all follow-up of group C and A after adjustment for sex (adjusted OR = 3.09; 95%CI = 1.32–7.20; P-value = .009), but no significant difference was found between group B and A or C and B in the primary and/or secondary efficacy endpoints. Side effects from the treatment were found in 12% (7/60); 2 in group A, 4 in group B, and 1 in group C. Four of these were likely due to LiCO3 side effects. Conclusions: Treatment of rapid turnover Graves’ disease patients with high dose I-131 (7.4 MBq/g) provides significantly higher cure rates at 12 months, and 3 times odds of cure than 3.7 MBq/g I-131 plus LiCO3 with lesser side effects. We thus recommend 7.4 MBq I-131/g for treatment in these patients.