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(1→3)-β-D-glucan is a major component of the fungal cell wall. It is commonly used to evaluate human exposure to fungi. A personal sampling system was developed to size-selectively evaluate the workplace protection factors (WPFs) of N95 filtering facepiece respirators (FFRs) and surgical masks (SMs) against fungi. This field study was performed with human subjects wearing an N95 FFR or a SM during farming activities. The geometric means of the WPFs of N95 FFRs and SMs were 156.2 and 12.2 for the total culturable fungi, 55.4 and 9.0 for the total fungi, and 10.5 and 11.1 for (1→3)-β-D-glucan. The WPFs for N95 FFRs against fungal contaminants were mostly greater than those for SMs; however, about 4.8%–35.0% of WPFs in the spore size range > 1.8 µm were still below 10 (the assigned protection factor designated for N95 FFRs by the US Occupational Safety and Health Administration). The WPFs of N95 FFRs and SMs against culturable fungi and (1→3)-β-D-glucan increased with the particle size. The total (1→3)-β-D-glucan significantly correlated with the total fungi (r = 0.588, p < 0.001) and total culturable fungi (r = 0.463, p = 0.002), which suggests that (1→3)-β-D-glucan can be used as an indicator to assess respiratory protection against airborne fungi on agricultural farms.

Selective-area growth (SAG) of single-crystal wurtzite GaN nanorods (NRs) directly onto Si(001) substrates with un-etched native SiOx amorphous layer, assisted by a patterning TiNx mask fabricated by nanosphere lithography (NSL), has been realized by reactive magnetron sputter epitaxy (MSE). The GaN NRs were grown vertically to the substrate surface with the growth direction along c-axis in the well-defined nano-opening areas. A 5-step structural and morphological evolution of the SAG NRs observed at different sputtering times depicts a comprehensive growth model, listed in sequence as: formation of a polycrystalline wetting layer, predominating c-axis oriented nucleation, coarsening and coalescence of multi-islands, single NR evolution, and finally quasi-equilibrium crystal shape formation. Room-temperature cathodoluminescence spectroscopy shows a strong GaN bandedge emission with a uniform luminescence across the NRs, indicating that the SAG NRs are grown with high quality and purity. In addition, single-longitudinal-mode lasing, attributed to well-faceted NR geometry forming a Fabry-Perot cavity, was achieved by optical pumping, paving a way for fabricating high-performance laser optoelectronics using MSE. Funding Agencies|Swedish Research Council (VR) [621-2012-4420, 621-2013- 5360]; Swedish Governmental Agency for Innovation Systems (VINNOVA) under the VINNMER international qualification program; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [SFO-Mat-LiU 2009-00971]; Swedish Foundation for Strategic Research (SSF) through the Research Infrastructure Fellow [RIF 14-0074]; Knut and Alice Wallenberg Foundation; Myfab National Access program at MC2 NanoFabrication Laboratory, Chalmers University of Technology; Ministry of Science and Technology (MOST) of Taiwan [MOST 105-2112-M-006-004-MY3]

Tolerance interval is an important statistical tool for determining the threshold of a certain reference. We propose to utilize nonparametric one-sided tolerance limits with three look-back window sizes for return spreads in order to find trading entry and exit signals. We illustrate how the proposed method help uncover arbitrage opportunities via the daily return spreads of 12 stock pairs in the U.S. markets and then report the performance of pair trading for two out-of-sample periods. The empirical results suggest that combining the minimum squared distance method and nonparametric one-sided tolerance limits generates positive excess returns, relative to the underlying stocks.

This study constructs a simultaneous confidence region for two combinations of coefficients of linear models and their ratios based on the concept of generalized pivotal quantities. Many biological studies, such as those on genetics, assessment of drug effectiveness, and health economics, are interested in a comparison of several dose groups with a placebo group and the group ratios. The Bonferroni correction and the plug-in method based on the multivariate-t distribution have been proposed for the simultaneous region estimation. However, the two methods are asymptotic procedures, and their performance in finite sample sizes has not been thoroughly investigated. Based on the concept of generalized pivotal quantity, we propose a Bonferroni correction procedure and a generalized variable (GV) procedure to construct the simultaneous confidence regions. To address a genetic concern of the dominance ratio, we conduct a simulation study to empirically investigate the probability coverage and expected le...

Background ZNF322A is an oncogenic transcription factor that belongs to the Cys2His2-type zinc-finger protein family. Accumulating evidence suggests that ZNF322A may contribute to the tumorigenesis of lung cancer, however, the ZNF322A-mediated downstream signaling pathways remain unknown. Methods To uncover ZNF322A-mediated functional network, we applied phosphopeptide enrichment and isobaric labeling strategies with mass spectrometry-based proteomics using A549 lung cancer cells, and analyzed the differentially expressed proteins of phosphoproteomic and proteomic profiles to determine ZNF322A-modulated pathways. Results ZNF322A highlighted a previously unidentified insulin signaling, heat stress, and signal attenuation at the post-translational level. Consistently, protein-phosphoprotein-kinase interaction network analysis revealed phosphorylation of IRS1 and HSP27 were altered upon ZNF322A-silenced lung cancer cells. Thus, we further investigated the molecular regulation of ZNF322A, and found the inhibitory transcriptional regulation of ZNF322A on PIM3, which was able to phosphorylate IRS1 at serine1101 in order to manipulate glucose uptake via the PI3K/AKT/mTOR signaling pathway. Moreover, ZNF322A also affects the unfolded protein response by phosphorylation of HSP27S82 and eIF2aS51, and triggers autophagosome formation in lung cancer cells. Conclusions These findings not only give new information about the molecular regulation of the cellular proteins through ZNF322A at the post-translational level, but also provides a resource for the study of lung cancer therapy.

Additional file 1: Figure S1. mRNA and protein expressions of ZNF322A in ZNF322A silenced A549 lung cancer cells. Figure S2. Distribution of phosphorylated site ratios. Figure S3. Snapshot of the ChIP-seq binding profile of ZNF322A at IRS1 gene in lung cancer cell. Figure S4. Analysis of protein-phosphoprotein-kinase interactions in ZNF322A silenced A549 lung cancer cells. Figure S5. IRS1S1101 and HSP27S82 phosphorylation in ZNF322A silenced H1299 lung cancer.

Additional file 2: Table S1. Sequence of primers and annealing conditions for real-time quantitative PCR. Table S2. The list of significantly regulated phosphosites of siZNF322A in A549 lung cancer cells. Table S3. Gene list of Gene Ontology analysis of siZNF322A in A549 lung cancer cells. Table S4. Signaling pathway enrichment analysis of siZNF322A phosphoproteomics in A549 lung cancer cells by REACTOME.

Air pollution is one of the most important global environmental issues. Taiwan Environmental Protection Agency (EPA) is currently using an Air Quality Index (AQI) to measure and monitor its national air quality. The main objective of this study is to assess the air quality per hour every month in Taichung City of Taiwan from 2014 to 2016 based on the nonconformance probability of the AQI index. The nonconformance probability is defined as the probability that a characteristic of interest falls outside of an acceptance region. A lower confidence bound for the nonconformance probability is applied to test whether the AQI index value exceeds a warning threshold, and then the government could issue warnings according to the decision made by such statistical inference. An unbalanced two-way random effects model is presented for fitting the AQI index values. We evaluate three different lower confidence bound construction methods, including a t-based, an adjusted t-based and a generalized pivotal quantity (GPQ) based methods, through a detailed simulation study. Finally, a hybrid method of the t-based and the adjusted t-based estimators is recommended for practical use.

Iloprost, a stable prostaglandin I

Tuning the electronic band structure of black titania to improve photocatalytic performance through conventional band engineering methods has been challenging because of the defect-induced charge carrier and trapping sites. In this study, KSCN-modified hydrogenated nickel nanocluster-modified black TiO

The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are ‘activated’ by various environmental cues. While the mechanisms of PSC activation are increasingly being described in literature, the influence of matrix stiffness on PSC activation is largely unexplored. To test the hypothesis that matrix stiffness affects myofibroblastic activation of PSCs, we have prepared cell-laden hydrogels capable of being dynamically stiffened through an enzymatic reaction. The stiffening of the microenvironment was created by using a peptide linker with additional tyrosine residues, which were susceptible to tyrosinase-mediated crosslinking. Tyrosinase catalyzes the oxidation of tyrosine into dihydroxyphenylalanine (DOPA), DOPA quinone, and finally into DOPA dimer. The formation of DOPA dimer led to additional crosslinks and thus stiffening the cell-laden hydrogel. In addition to systematically studying the various parameters relevant to the enzymatic reaction and hydrogel stiffening, we also designed experiments to probe the influence of dynamic matrix stiffening on cell fate. Protease-sensitive peptides were used to crosslink hydrogels, whereas integrin-binding ligands (e.g., RGD motif) were immobilized in the network to afford cell-matrix interaction. PSC-laden hydrogels were placed in media containing tyrosinase for 6 h to achieve in situ gel stiffening. We found that PSCs encapsulated and cultured in a stiffened matrix expressed higher levels of αSMA and hypoxia-inducible factor 1α (HIF-1α), suggestive of a myofibroblastic phenotype. This hydrogel platform offers a facile means of in situ stiffening of cell-laden matrices and should be valuable for probing cell fate process dictated by dynamic matrix stiffness. Statement of Significance Hydrogels with spatial-temporal controls over crosslinking kinetics (i.e., dynamic hydrogel) are increasingly being developed for studying mechanobiology in 3D. The general principle of designing dynamic hydrogel is to perform cell encapsulation within a hydrogel network that allows for postgelation modification in gel crosslinking density. The enzyme-mediated in situ gel stiffening is innovative because of the specificity and efficiency of enzymatic reaction. Although tyrosinase has been used for hydrogel crosslinking and in situ cell encapsulation, to the best of our knowledge tyrosinase-mediated DOPA formation has not been explored for in situ stiffening of cell-laden hydrogels. Furthermore, the current work provides a gradual matrix stiffening strategy that may more closely mimic the process of tumor development.

Pair trading is a widely used market neutral strategy and also a statistical arbitrage method that allows investors to take a position in two assets with similar trends in their historical data in order to gain low-risk profits. Combining both “diversification” and “pair trading”, this study proposes a statistical learning method to explore the most promising pair among multiple pair assets for each trading time. We incorporate estimated volatility into tolerance limits as a predictive function for finding buying and selling signals in order to capitalize on market inefficiencies. One-step-ahead volatility prediction follows either the exponentially weighted moving average (EWMA) method or the GARCH model. The study selects five artificial intelligence (AI) stocks in the U.S. equities market to target profitability through the proposed strategy with a rolling window training approach over two annual testing periods from April 2017 to March 2019. We recommend that conservative investors use p -content at 95%, which is less adventurous and can generate positive excess profits. The idea behind this strategy is to help investments be more diversified and also more profitable.

Iloprost, a stable prostaglandin I2 (PGI2) analog, can inhibit allergic inflammation in an OVA-induced asthma model via inhibition of airway dendritic cell (DC) function. However, the underlying mechanism of PGI2 signaling-mediated immunosuppression remains unclear. This study explored whether iloprost-treated DCs can suppress inflammation by promoting antigen-specific regulatory T cell (Treg) differentiation. We established an allergic lung inflammation model using a hydrogel biomaterial delivery system and observed that iloprost significantly suppressed OVA-induced Th2 lung inflammation and increased the frequency of OVA-specific Tregs in vivo. We further observed that iloprost-treated DCs displayed tolerogenic characteristics, including low inflammatory cytokine (IL-12p70, TNF-α, IL-6, IL-23) expression levels, high anti-inflammatory cytokine (IL-10) production, and a semimature phenotype. In addition, iloprost-treated DCs increased OVA-specific CD4+Foxp3+ T cell differentiation from naïve T cells in vitro and in vivo. Blocking experiments showed that iloprost-treated DCs promoted Treg differentiation, at least in part, through PD-L1. Furthermore, iloprost treatment suppressed DC-mediated airway inflammation and increased the frequency of OVA-specific Tregs through PD-L1 in vivo. Taken together, these results show that PGI2 signaling in DCs may lead to immune tolerance, suggesting that the PGI2 analog has the potential to be applied therapeutically for tolerogenic DC immunotherapy in autoimmune diseases or allergic asthma.

WTO’s stagnation in the Doha Round negotiation has proven its declining role as a forum for new rule creation. The systemic implication might be that the WTO could only operate on outmoded laws, which will not be able to address the needs of business caused by new trade problems. However, in contrast, within Free Trade Agreements (FTAs), various new trade rules have been created and expanded, which go far beyond the scope of the WTO. For instance, in the CPTPP and CETA, rules on investment, environment, labor, competition, e-commerce and state enterprises are established. As FTAs proliferate around the world, the shifting of paradigm has also changed the profile of international trade. The WTO currently faces its systemic risks from the U.S.-China trade tension and Appellate Body nominations. Obviously, what will be the future role for the WTO to play in the decentralization of governance would not only relate to the existence of the WTO, but also mark a turning point for future world trade order. In the view of the writer, the ICSID-BITs model in international investment law provides an insightful approach for international trade. As practiced, the investment law regime is generally evolved through bifurcation, without a central authority. On the one hand, foreign investments are protected through substantive rules in various BITs. On the other hand, most investor-state disputes under BITs are resolved in light of the ICSID arbitral proceedings. Through opt-in model contained in BITs and foreign investors’ wider use, the ICSID has successfully sustained and facilitated the development of BITs. Modelled on investment law, the writer suggests that the future development of trade law run on the shared responsibilities by important FTAs and the WTO. That is, FTAs could serve as the main platform for creating new substantive trade rules in response to new economic realities. The WTO, through its effective dispute settlement mechanism, could function as ICSID-like forum, giving its robust back-up to the FTAs and FTA parties who are also WTO members. In this sense, it is suggested that WTO should transform itself to be more inclusive, flexible and accessible to all FTA-related disputes.

This study evaluates the sustained analgesic effect of ketorolac-eluting thermosensitive biodegradable hydrogel in the plantar incisional pain model of the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol-gel phase transition and in vitro drug release profile. The effect of keto-hydrogel on postoperative pain (POP) was assessed using the established plantar incisional pain model in hind-paw of rats and compared to that of ketorolac solution. Pain and sensory threshold, as well as pain scoring, were evaluated with behavioral tests by means of anesthesiometer and incapacitance apparatus, respectively. Pro-inflammatory cytokine levels (TNF-α, IL-6, VEGF, and IL-1β) around incisional wounds were measured by ELISA. Tissue histology was assessed using hematoxylin and eosin and Masson’s trichrome staining. Ten mg/mL (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4°C with a 10-day sustained drug release profile in vitro. Compared to ketorolac solution group, the concentration of ketorolac in tissue fluid was higher in the keto-hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain and sensory threshold, increased weight-bearing capacity, and significantly reduced the levels of TNF-α, IL-6, and IL-1β while enhanced VEGF in tissue fluid. Histologic analysis reveals greater epithelialization and collagen deposition around wound treated with keto-hydrogel. In conclusion, our study suggests that keto-hydrogel is an ideal compound to treat POP with a secondary gain of improved incisional wound healing.

The human cluster of differentiation 19 (CD19) is highly expressed in most leukemia, rendering is a promising therapeutic target. In this study, we generated anti-CD19 single-chain variable fragments (scFv) from immunized chickens by phage display technology. After constructing a scFv antibody library with 2.5 × 10

To understand the mechanism for inhibition of hepatitis B virus (HBV) infection is important. In this study, single-chain variable fragment (scFv) antibodies were generated and directed to the pre-S2 epitope of HBV surface antigen (HBsAg). These human scFvs were isolated from a person with history of HBV infection by phage display technology. An evaluation of panning efficiency revealed that the eluted phage titer was increased, indicating that specific clones were enriched after panning. Selected scFvs were characterized with the recombinant HBsAg through Western blotting and enzyme-linked immunosorbent assay to confirm the binding ability. Flow cytometry analysis and immunocytochemical staining revealed that one scFv, S17, could recognize endogenous HBsAg expressed on the HepG2215 cell membrane. Moreover, the binding affinity of scFv S17 to the pre-S2 epitope was determined to be 4.2 × 10-8 M. Two ion interactions were observed as the major driving forces for scFv S17 interacting with pre-S2 by performing a rational molecular docking analysis. This study provides insights into the structural basis to understand the interactions between an antibody and the pre-S2 epitope. The functional scFv format can potentially be used in future immunotherapeutic applications.

The boundary and shape of evolving investment regimes are heavily influenced by investors’ claims. Bringing a host state’s obligations under other trade agreements as a part of the Fair and Equitable Treatment (FET) standard in investment treaties represents a new challenge. As argued here, a host state’s violation of the World Trade Organization (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) establishing a violation of the FET standard not only serves as a unique single issue to be decided in an investment dispute, but would also have important legal implications. That is, investor-state arbitration might function as a competing forum with the WTO for setting future trade matters, and the risk of fragmenting WTO law in various arbitral awards would be increased. Ultimately, the security and predictability of the WTO law system would be undermined and eroded in the context of investment treaties. It is suggested that WTO Members should develop more efficient rules to safeguard the integrity of WTO law from undue interferences by investors in their investment treaties.