Issue in Implementing Customer Operations Performance Center (COPC)

Customer Operations Performance Center Inc (COPC) is the world’s leading authority on Contact Center Operations Management. The COPC 2000 Standard is a comprehensive operating model for Contact Centre Operations. It is a world-wide benchmark and certification for contact centers. As well as an overall performance management system, COPC is designed to reduce costs, increase revenue, and improve service, quality and customer satisfaction. However, many COPC implementation projects failed. In this study, we first review the process of implementing COPC. Then, we identify major barriers in implementing COPC. Organizations should take proper measures in overcoming these barriers to ensure successful implementation of COPC

Monocyte Metabolic Reprogramming Promotes Pro-Inflammatory Activity and Staphylococcus Aureus Biofilm Clearance

Biofilm-associated prosthetic joint infections (PJIs) cause significant morbidity due to their recalcitrance to immune-mediated clearance and antibiotics, with Staphylococcus aureus (S. aureus) among the most prevalent pathogens. We previously demonstrated that S. aureus biofilm-associated monocytes are polarized to an anti-inflammatory phenotype and the adoptive transfer of pro-inflammatory macrophages attenuated biofilm burden, highlighting the critical role of monocyte/macrophage inflammatory status in dictating biofilm persistence. The inflammatory properties of leukocytes are linked to their metabolic state, and here we demonstrate that biofilm-associated monocytes exhibit a metabolic bias favoring oxidative phosphorylation (OxPhos) and less aerobic glycolysis to facilitate their anti-inflammatory activity and biofilm persistence. To shift monocyte metabolism in vivo and reprogram cells to a pro-inflammatory state, a nanoparticle approach was utilized to deliver the OxPhos inhibitor oligomycin to monocytes. Using a mouse model of S. aureus PJI, oligomycin nanoparticles were preferentially internalized by monocytes, which significantly reduced S. aureus biofilm burden by altering metabolism and promoting the pro-inflammatory properties of infiltrating monocytes as revealed by metabolomics and RT-qPCR, respectively. Injection of oligomycin alone had no effect on monocyte metabolism or biofilm burden, establishing that intracellular delivery of oligomycin is required to reprogram monocyte metabolic activity and that oligomycin lacks antibacterial activity against S. aureus biofilms. Remarkably, monocyte metabolic reprogramming with oligomycin nanoparticles was effective at clearing established biofilms in combination with systemic antibiotics. These findings suggest that metabolic reprogramming of biofilm-associated monocytes may represent a novel therapeutic approach for PJI

Ligand-Installed Polymeric Nanocarriers for Combination Chemotherapy

Combination chemotherapy remains the mainstay of cancer treatment because such strategy targets different cell signaling pathways to decrease the likelihood of developing protective mechanisms by cancer cells, thereby delaying the onset of recurrence and prolonging the survival. The co-delivery of binary drug combination via a single nanocarrier provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo, spatial-temporal synchronization of drug exposure, and synergistic therapeutic effects. Rational design of such regimen is crucial for maximizing the therapeutic effects since only certain drug ratios exposed to the target might be synergistic while other ratios exert additive or even antagonistic effects. Cisplatin-based chemotherapy has shown great responses in several cancer types and has been used as the standard systemic anticancer treatment, such as triple negative breast cancer (TNBC) and ovarian cancer. However, tumor cells are becoming less responsive to cisplatin, which arises from altered signaling patterns of cancer cells, such as activation of pro-survival signal transduction (e.g., epidermal growth factor receptor (EGFR), AKT, PI3-kinase) and DNA-damage repair, etc. EGFR is a member of the HER family of oncogenic receptor tyrosine kinases (RTK), which actively participates in sustaining the growth and the survival of carcinoma cells as well as the pathogenesis and progression of different carcinoma types. It is frequently overexpressed in various cancer types, such as TNBC and ovarian cancer, making it a major therapeutic target for the development of targeted drug delivery. A combination of EGFR inhibitors with cisplatin have shown strong synergistic effects in EGFR overexpressing cancers both in preclinical and clinical studies. Moreover, the combined regimen significantly outperformed the single treatment as reported. It has been shown preclinically that EGFR inhibitors significantly potentiate the cytotoxic effects of cisplatin in tumors with overexpressed EGFR through blocking oncogenic signal transduction and unfavored pro-survival signals induced by platinum-based therapy. However, inhibiting EGFR could trigger underappreciated resistance and activate the parallel oncogenic signaling pathways through other members of HER family. Using a pan-HER inhibitor is a common strategy to avoid this limitation. To this end, neratinib (NRT) (an FDA-approved pan-HER inhibitor) and cisplatin (CDDP) were selected as the combination regimen to treat EGFR+ cancers: TNBC and ovarian cancer. To incorporate these two molecules with varied physicochemical properties in the same carrier, we designed a biocompatible crosslinked polypeptide-based nanogel (NG) with multifunctional compartments. Such biodegradable platform provides flexibility in adjusting size, loading capacity, surface properties, deformability, softness, and responsive behaviors by tuning the chemical compositions as well as crosslinking levels. For the purpose of the current study, NGs prepared from copolymers poly (ethylene glycol)-block-poly (L-glutamic acid) modified with phenylalanine functionalities ((PEG-P(Glu-Glu/Phex)150) were developed for simultaneous loading and delivery of binary CDDP and NRT combination. Such NGs have 1) a hydrophilic PEG shell for less RES uptake and extended circulation, 2) an anionic crosslinked core, which incorporates CDDP through coordination with the carboxylic groups of PGlu, 3) hydrophobic regions formed by Phe moieties, which serves as a reservoir for NRT solubilization. By tuning ratio of constituent hydrophilic and hydrophobic moieties, NGs displayed varied dimensions, drug loading capacities, deformability, performance in killing tumor cells, as well as penetrations in multicellular 3D tumor models. Consistent with properties of chemical composition, NGs with high hydrophobic fraction displayed less swelling ability and more efficient hydrophobic drug loading. Resulting binary drug combination-loaded NGs functionalized with 50 units of hydrophobic Phe were able to encapsulate both CDDP and NRT at a molar ratio of 2:1 and displayed the strongest synergistic effect towards EGFR+ TNBC cells compared with other screened regimens. Such superior synergy was found to be selective and only displayed in the EGFR+ TNBC cell line. Notably, NRT was found to reverse pro-survival signal transduction by CDDP mediated EGFR/Akt/Erk activation as well as increased Cyclin D1 expression, which was believed to be the molecular basis for the synergistic effect of the combination of CDDP and NRT. Drug-loaded carrier system exerted the highest synergy was selected in the following studies targeting EGFR overexpressing ovarian cancer. However, this carrier system solely depends on the EPR effect for drug accumulation in tumor sites, which is limited by heterogeneity among tumor masses as well as vascular density nearby influencing the permeability of nanocarriers. Installing targeting ligands on the surface of carriers to specifically target biomarkers overexpressed on the surface of tumor cells is a well-suited strategy to overcome mentioned limitations and increase retention of payloads in tumors. In the next part of our study, two targeting ligands aiming to bind with EGFR was chosen in our study: L-AE peptide and EGFR-A protein with reported high binding specificity and affinity to EGFR with acceptable stability. Two types of ligand-installed NGs both demonstrated success in significantly increased cellular uptake in EGFR+ ovarian cancer cells as compared to nontargeted NGs. Further optimization was conducted by extending the thickness of PEG stealth layer from 114 monomer units to 228 units for sufficient protection from opsonization. Optimized PEG-based polymeric NGs displayed more favored PK properties, such as remarkably less spleen uptake, higher drug retention in tumor sites, slower clearance from circulation, and more drug exposure. NGs with EGFR targeting ligands further improved the PK profile by directing remarkably more drugs to the target sites. When tested in vivo, EGFR targeted peptide and protein decorated NGs carrying CDDP and NRT drug combination significantly suppressed the growth of intraperitoneal high-grade serous ovarian tumor xenografts outperforming their nontargeted counterparts without extending their cytotoxicity to the normal tissues. We also confirmed the importance of simultaneous administration of the (CDDP+NRT) via a single NG system which provides more therapeutic benefits than a cocktail of individual drug-loaded NGs administered at equivalent doses. Lastly, our data demonstrated the benefits of local treatment by showing that intraperitoneal (IP) administration of targeted binary drug combination-loaded NGs can be more effective in terms of tumor growth suppression. These data have shown the power of our carrier system in the delivery of a drug combination to treat EGFR overexpressing cancers

Allelic Variation and Transcriptional Isoforms of Wheat TaMYC1 Gene Regulating Anthocyanin Synthesis in Pericarp

Recently the TaMYC1 gene encoding bHLH transcription factor has been isolated from the bread wheat (Triticum aestivum L.) genome and shown to co-locate with the Pp3 gene conferring purple pericarp color. As a functional evidence of TaMYC1 and Pp3 being the same, higher transcriptional activity of the TaMYC1 gene in colored pericarp compared to uncolored one has been demonstrated. In the current study, we present additional strong evidences of TaMYC1 to be a synonym of Pp3. Furthermore, we have found differences between dominant and recessive Pp3(TaMyc1) alleles. Light enhancement of TaMYC1 transcription was paralleled with increased AP accumulation only in purple-grain wheat. Coexpression of TaMYC1 and the maize MYB TF gene ZmC1 induced AP accumulation in the coleoptile of white-grain wheat. Suppression of TaMYC1 significantly reduced AP content in purple grains. Two distinct TaMYC1 alleles (TaMYC1p and TaMYC1w) were isolated from purple- and white-grained wheat, respectively. A unique, compound cis-acting regulatory element had six copies in the promoter of TaMYC1p, but was present only once in TaMYC1w. Analysis of recombinant inbred lines showed that TaMYC1p was necessary but not sufficient for AP accumulation in the pericarp tissues. Examination of larger sets of germplasm lines indicated that the evolution of purple pericarp in tetraploid wheat was accompanied by the presence of TaMYC1p. Our findings may promote more systematic basic and applied studies of anthocyanins in common wheat and related Triticeae crops

High-Confidence Sample Generation Technology and Application for Global Land-Cover Classification

Deep learning technology has become one of the most important technologies in remote sensing land classification applications. Its powerful sample-learning and information-mining abilities promote the continuous improvement of classification accuracy. A large volume of high-quality and representative sample data is the premise for the successful application of deep learning technology. Conventional methods of obtaining samples through manual delineation or surface surveys require a great deal of manpower and material resources. Therefore, the inability to obtain sufficient and widely representative high-quality samples is one of the key factors limiting the application of deep learning technology. In this study, the method of generating sample data obtains high-confidence classification results from a variety of existing high-quality classification products as deep learning samples, which are then used to support the application of deep learning technology for land-cover classification. When the three global land-cover classification products, FROM-GLC-2015, GLC_FCS30-2015, and GlobeLand30, have the same type of discrimination, the sample is considered a high-confidence sample. Based on this, a large volume of sample data widely distributed around the world was obtained. Using the extracted samples, a random forest classifier was trained using multiple types of information from the Landsat data, and land-cover classification was achieved. Application experiments were conducted in several typical regions, and the classification results were verified. The results showed that the classification accuracy of random forests under the support of samples generated using the sample extraction method proposed in this article was considerably higher than that of the three land-cover classification products

pH-Responsive Rheological Properties and Microstructure Transition in Mixture of Anionic Gemini/Cationic Monomeric Surfactants

Surfactant aggregates have long been considered as a tool to improve drug delivery and have been widely used in medical products. The pH-responsive aggregation behavior in anionic gemini surfactant 1,3-bis(N-dodecyl-N-propanesulfonate sodium)-propane (C12C3C12(SO3)2) and its mixture with a cationic monomeric surfactant cetyltrimethylammonium bromide (CTAB) have been investigated. The spherical-to-wormlike micelle transition was successfully realized in C12C3C12(SO3)2 through decreasing the pH, while the rheological properties were perfectly enhanced for the formation of wormlike micelles. Especially at 140 mM and pH 6.7, the mixture showed high viscoelasticity, and the maximum of the zero-shear viscosity reached 1530 Pa·s. Acting as a sulfobetaine zwitterionic gemini surfactant, the electrostatic attraction, the hydrogen bond and the short spacer of C12C3C12(SO3)2 molecules were all responsible for the significant micellar growth. Upon adding CTAB, the similar transition could also be realized at a low pH, and the further transformation to branched micelles occurred by adjusting the total concentration. Although the mixtures did not approach the viscosity maximum appearing in the C12C3C12(SO3)2 solution, CTAB addition is more favorable for viscosity enhancement in the wormlike-micelle region. The weakened charges of the headgroups in a catanionic mixed system minimizes the micellar spontaneous curvature and enhances the intermolecular hydrogen-bonding interaction between C12C3C12(SO3)2, facilitating the formation of a viscous solution, which would greatly induce entanglement and even the fusion of wormlike micelles, thus resulting in branched microstructures and a decline of viscosity

Peptide-Mediated Synthesis of Zeolitic Imidazolate Framework-8: Effect of Molecular Hydrophobicity, Charge Number and Charge Location

Three amphiphilic peptides with varied molecular hydrophobicity, charge number and charge location have been designed as regulators to modulate the crystal growth of zeolitic imidazolate framework-8 (ZIF-8). All three peptides can interact with ZIF-8 to inhibit {100} facet growth and produce truncated cubic crystals. The peptide’s molecular hydrophobicity plays a dominant role in defining the final morphology and size of the ZIF-8 crystals. The peptides with less charge and higher hydrophobicity can promote nuclei formation and crystal growth to give smaller ZIF-8 crystals. However, the charge located in the center of the molecular hydrophobic region has little effect on the crystal nucleation and growth due to the shielding of its charge by molecular aggregation. The study provides insights into the effect of molecular charge and hydrophobicity on ZIF-8 crystal growth and is helpful for guiding the molecular design for regulating the synthesis of metal-organic framework materials