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What happens to macromolecules in vivo? What drives the structure–activity relationship and in vivostability for antibody-drug conjugates (ADCs)? These interrelated questions are increasingly relevant due to the re-emerging importance of ADCs as an impactful therapeutic modality and the gaps that exist in our understanding of ADC structural determinants that underlie ADC in vivostability. Complex macromolecules, such as ADCs, may undergo changes in vivodue to their intricate structure as biotransformations may occur on the linker, the payload, and/or at the modified conjugation site. Furthermore, the dissection of ADC metabolism presents a substantial analytical challenge due to the difficulty in the identification or quantification of minor changes on a large macromolecule. We employed immunocapture-LCMS methods to evaluate in vivochanges in the drug-antibody ratio (DAR) profile in four different lead ADCs. This comprehensive characterization revealed that a critical structural determinant contributing to the ADC design was the linker, and competition of the thio-succinimide hydrolysis reaction over retro-Michael deconjugation can result in superb conjugation stability in vivo. These data, in conjunction with additional factors, informed the selection of AZD8205, puxitatug samrotecan, a B7-H4-directed cysteine-conjugated ADC bearing a novel topoisomerase I inhibitor payload, with durable DAR, currently being studied in the clinic for the potential treatment of solid malignancies (NCT05123482). These results highlight the relevance of studying macromolecule biotransformation and elucidating the ADC structure–in vivostability relationship. The comprehensive nature of this work increases our confidence in the understanding of these processes. We hope this analytical approach can inform future development of bioconjugate drug candidates.

Antibody-drug conjugate (ADC) is a therapeutic modality that aims to improve payload delivery specificity and reduce systemic toxicity. Considering the complex structure of ADCs, various bioanalytical methods by liquid chromatography coupled with mass spectrometry (LC-MS), ligand binding assay (LBA) and hybrid LBA-LC-MS approaches have been established for ADC characterization and quantification. LCMS-based assays enable drug-antibody ratio (DAR) sensitive quantification of the conjugated payload. Typically, for quantitative, DAR-sensitive, assessment by LC-MS/MS,the conjugated payload is enzymatically liberated and quantified. Despite recent advances in ADC bioanalytical methods, the DAR-sensitive quantification of noncleavable linker ADCs by LC-MS/MS remains challenging. Thus, we developed a novel digestion-free middle-down mass spectrometry (DF-MDMS) using a collision-induced dissociation approach for absolute quantification of conjugated payload from four different ADCs in a biological matrix with minimum sample preparation. These results demonstrate that ADCs with different linker-payload structures can be quantified, including a noncleavable linker ADC, trastuzumab emtansine. It also shows that the assay sensitivity is comparable to the conventional ADC quantification method by linker-payload cleavage using enzyme, while the assay dynamic range depends on factors including payload ionization and dissociation efficiency, DAR and its distribution, and species abundance. By demonstrating absolute quantification of both cleavable and noncleavable linker ADCs, this novel middle-down ADC approach demonstrates its potential application in bioanalysis and analytical characterization, especially for early discovery where high-throughput screening is required as the new approach saves time and resources by not requiring enzymatic digestion for cleavable ADCs or development of anti-payload antibodies for noncleavable linker ADCs.

Petroleum-based plastics have been associated with several environmental issues, including land and water pollution, greenhouse gas emissions, and waste accumulation due to their non-biodegradable properties. Bioplastics derived from renewable natural resources have emerged as an eco-friendly substitute for conventional plastics, leading to a reduced carbon footprint and conservation of non-renewable fossil fuels. Seaweed is an attractive material for bioplastic production due to its abundant polysaccharide content, high biomass, rapid growth rate and suitability for consumption. This work aimed to explore the feasibility of producing seaweed bioplastics, specifically starch and carrageenan from Kappaphycus alvarezii, along with chitin extracted from ramshorn snails (Planorbarius corneus). The surface morphology of the bioplastics was assessed through scanning electron microscopy (SEM), and their biodegradability was also examined through a soil burial biodegradation test. Starch-based bioplastics incorporated with carrageenan and chitin exhibited a more substantial network structure, rougher surface texture and smaller void sizes with improved mechanical strength and water barrier properties. The bioplastics underwent decomposition, resulting in fragmentation into small pieces (with more than 76% weight loss) or complete degradation through the enzymatic activity of Acinetobacterspp. and Burkholderia cepacia. Therefore, seaweed-chitin-based bioplastics demonstrate their potential as a sustainable and environmentally friendly alternative to conventional plastics.

Image cartoon-texture decomposition is an important problem in image processing. In recent years, by exploiting low-rank priors of images, low-rank minimization methods have been widely adopted for image cartoon-texture decomposition. Since matrix rank minimization is an NP-hard problem, the convex nuclear norm is often used as a substitute for the matrix's rank to realize the low-rank minimization methods. In this paper, we utilize a generalized non-convex surrogate of the matrix rank function to develop a novel low-rank minimization model for image cartoon-texture decomposition. We design a proximal alternating algorithm to solve the non-convex model and further demonstrate the global convergence of the algorithm. Numerical experiments illustrate that the proposed method can show much better performances than the existing state-of-the-art methods for image cartoon-texture decomposition. [ABSTRACT FROM AUTHOR]

CAR T-cell therapy is a promising approach for cancer treatment, utilizing a patient's own T-cells (autologous cell) or T-cells from a healthy donor (allogeneic cell) to target and destroy cancer cells. Over the last decade, significant advancements have been made in this field, including the development of novel CAR constructs, improved understanding of biology and mechanisms of action, and expanded clinical applications for treating a wider range of cancers. In this review, we provide an overview of the steps involved in the production of CAR T-cells and their mechanism of action. We also introduce different CAR T-cell therapies available, including their implementation, dosage, administration, treatment cost, efficacy, and resistance. Common side effects of CAR T-cell therapy are also discussed. The CAR T-cell products highlighted in this review are FDA-approved products, which include Kymriah®(tisagenlecleucel), Tecartus®(brexucabtagene autoleucel), Abecma®(Idecabtagene vicleucel), Breyanzi®(lisocabtagene maraleucel), and Yescarta®(axicabtagene ciloleucel). In conclusion, CAR T-cell therapy has made tremendous progress over the past decade and has the potential to revolutionize cancer treatment. This review paper provides insights into the progress, challenges, and future directions of CAR T-cell therapy, offering valuable information for researchers, clinicians, and patients.

Multiplicative noise removal is a challenging problem in image denoising. In this paper, we develop a nonlocal matrix rank minimization method for the multiplicative noise removal problem. By utilizing the logarithm transformation, we convert the problem into an additive noise removal problem and propose a maximum a posteriori (MAP) estimation-based matrix rank minimization model for this kind of additive noise removal. A proximal alternating algorithm is designed to solve the matrix rank minimization model. The convergence of the algorithm is demonstrated by the famous Kurdyka-Łojasiewicz property. Taking advantage of the proposed matrix rank minimization model and its proximal alternating algorithm, a multiplicative noise removal method is finally developed. Numerical experiments illustrate that the proposed method can remove multiplicative noise in images much better than the existing state-of-the-art methods in terms of both image recovered measure quantities and visual qualities.

Background: Mutations in the TP53 gene are the most common among genetic alterations in human cancers, resulting in the formation of mutant p53 protein (mutp53). Mutp53 promotes proliferation, migration, invasion, and metastasis in cancer cells. Not only does the initiation of oncogenesis ensue due to mutp53, but resistance towards chemotherapy and radiotherapy in cancer cells also occurs. This review aims to summarise and discuss the oncogenesis of mutant p53 in cancer cells and introduce the various mutant p53 inhibitors currently being evaluated at the pre-clinical and clinical stages. Compounds that induce the wild-type conformation on the targeted p53 missense mutation, restore or enhance the DNA binding of mutant p53, and inhibit cancer cells' growth are highlighted. In addition, the progression and development of the mutant p53 inhibitors in clinical trials are updated.Conclusion: The progress of developing a cancer treatment that may successfully and efficiently target mutant p53 is on the verge of development. Mutant p53 proteins not only initiate oncogenesis but also cause resistance in cancer cells to certain chemo or radiotherapies, further endorse cancer cell survival and promote migration as well as metastasis of cancerous cells. With this regard, many mutant p53 inhibitors have been developed, some of which are currently being evaluated at the pre-clinical level and have been identified and discussed. To date, APR-246 is the most prominent one that has progressed to the Phase III clinical trial.

The expression of receptor activator of Nuclear Factor Kappa Beta (RANK) and its ligand (RANKL), as well as osteoprotegrin (OPG), in the alveolar bone (AB), may improve bone remodeling during orthodontic tooth movement (OTM). It is hypothesized that hypoxia-preconditioned gingival mesenchymal stem cells (GMSC) may be more effective than normoxia-preconditioned GMSC in this regard. This study aims to investigate the expression of RANK, RANKL, and OPG in the compression and tension sides of AB after allogeneic administration of GMSC that were normoxia or hypoxia-preconditioned in rabbits (Oryctolagus cuniculus) undergoing OTM.

A phytochemical study has been carried out on CH2 Cl2 extract of Alphonsea cylindrica leaves, resulting in the isolation of three new morphinan alkaloids. They are kinomenine (1), N -methylkinomenine (2), and hydroxymethylkinomenine (3). The structures of these compounds were elucidated by extensive spectroscopic analysis (1D and 2D NMR, IR, UV, HRESIMS) and comparison with the data reported in literature for similar alkaloids. Kinomenine (1) and N -methylkinomenine (2) showed weak inhibition against S. aureus (MIC values of 1 and 2 = 500 µg/mL; pIC50 values in 95% C. I. of: 1 = 2.9 to 3.0; 2 = 2.9 to 3.1), while kinomenine (1) also showed weak inhibition against E. coli (MIC values of 1 = 500 µg/mL; pIC50 value in 95% C. I. of: 1 = 2.9) by broth microdilution method. The results obtained can be used as future referencefor the discovery of morphinans and the potential of A. cylindrica as an antibacterial source. [ABSTRACT FROM AUTHOR]

Isobaric labeling-based proteomics is widely applied in deep proteome quantification. Among the platforms for isobaric labeled proteomic data analysis, the commercial software Proteome Discoverer (PD) is widely used, incorporating the search engine CHIMERYS, while FragPipe (FP) is relatively new, free for noncommercial purposes, and integrates the engine MSFragger. Here, we compared PD and FP over three public proteomic data sets labeled using 6plex, 10plex, and 16plex tandem mass tags. Our results showed the protein abundances generated by the two software are highly correlated. PD quantified more proteins (10.02%, 15.44%, 8.19%) than FP with comparable NA ratios (0.00% vs. 0.00%, 0.85% vs. 0.38%, and 11.74% vs. 10.52%) in the three data sets. Using the 16plex data set, PD and FP outputs showed high consistency in quantifying technical replicates, batch effects, and functional enrichment in differentially expressed proteins. However, FP saved 93.93%, 96.65%, and 96.41% of processing time compared to PD for analyzing the three data sets, respectively. In conclusion, while PD is a well-maintained commercial software integrating various additional functions and can quantify more proteins, FP is freely available and achieves similar output with a shorter computational time. Our results will guide users in choosing the most suitable quantification software for their needs.

Falsified lamivudine/zidovudine/nevirapine tablets: rapid identification using X-ray fluorescence technique The X-ray fluorescence (XRF) technique was used to determine bromine (Br) concentration in lamivudine/zidovudine/nevirapine (Zidolam-N[R]) tablets from fourteen batches drawn from [...]

Problem Statement: Traditional DEA models deal with measurements of relative efficiency of DMUs regarding multiple-inputs vs. multiple-outputs. One of the drawbacks of these models is the neglect of intermediate products or linking activities. The objectives of this study were: (i) This research was shown how to use DEA by two stages, with outputs from the first stage becoming inputs in the second stage. (ii) Comparative analysis of efficiency of bank manageable in Hong Kong. Approach: The research conducts a comparative analysis of efficiency of bank manageable in Hong Kong using a two-stage model, which evaluates their Operational Efficiency (OE) and Profitability Efficiency (PE). The study period covered 2004-2006 and used two-stage Data Envelopment Analysis (DEA). Results: Large-sized banks are generally more efficient than small-sized ones in the operational efficiency; while small efficient banks are easily to become benchmarks, large efficient banks are deemed as competitive niche players. This means that the large banks have better competitive power than those of smaller ones. Conclusion: Using this model, we can evaluate divisional efficiencies along with the overall efficiency of decision making units (DMUs). Key words: Date envelopment analysis, stock exchange, Over The Counter (OTC), two-stage, operational efficiency, profitability efficiency, INTRODUCTION The Hong Kong had a long tradition of being a laissez-faire economy and has committed to maintaining the free market stance since its sovereignty was returned to China in [...]

This is a significant problem for the property-liability insurance industry. The study first uses Modified Delphi Method to sift influence property-liability insurance effects out norms. Moreover, the evaluation weights are determined using Analytic Network Process (ANP). Finally, the technique for ordering preference by similarity to the ideal solution (TOPSIS) constructs performance evaluation model of property-liability insurance companies in Taiwan. This research use financial statements of property-liability insurance industry calculated efficiency placing and through the positive research. Findings may do for the government the important reference of the insure policy. Analytic Network Process (ANP), performance evaluation, property-liability insurance industry, modified delphi method, TOPSIS, INTRODUCTION According to Sweden Reinsurance sigma 2007 global insurance industry statistical data, North America total premium income shares rate is 35.66%, the Europe premium income is 33.55%. Regarding the ratios [...]

Fast neutron flux measurements with high count rates and high time resolution have important applications in equipment such as tokamaks. In this study, real-time neutron and gamma discrimination was implemented on a self-developed 500-Msps, 12-bit digitizer, and the neutron and gamma spectra were calculated directly on an FPGA. A fast neutron flux measurement system with BC-501A and EJ-309 liquid scintillator detectors was developed and a fast neutron measurement experiment was successfully performed on the HL-2 M tokamak at the Southwestern Institute of Physics, China. The experimental results demonstrated that the system obtained the neutron and gamma spectra with a time accuracy of 1 ms. At count rates of up to 1 Mcps, the figure of merit was greater than 1.05 for energies between 50 keV and 2.8 MeV

This study aims to enhance the bioactive property of cottage cheese by incorporating mulberry leaf extract (MLE) and applying probiotic fermentation. The MLE was produced via ultrasound-assisted water extraction (UW), pectinase-pretreated ultrasound-assisted water extraction (PUW) and cellulase-pretreated ultrasound-assisted water extraction. The MLE with the highest DPPH, FRAP, α-amylase inhibition (AI) and albumin denaturation inhibition (ADI) activities was selected to incorporate into the cheese. Lastly, the cheese was fermented with Lactobacillus plantarumTAR4. Results obtained reveal that UW and PUW produced MLE with the best bioactivities. Total phenolics, flavonoids, DPPH, FRAP, AI and ADI activities of the cottage cheeses were significantly enhanced with the fortification of MLE. Fermentation with L. plantarumTAR4 further enhanced the DPPH, FRAP, AI and ADI activities of the cheeses. Results of in-vitro digestion proved that the bioactivities exhibited by the cheeses did not diminished after digestion. Among the cheeses, fermented cheese fortified with MLE produced via UW (UW-LAB) showed the best bioactivity. After digestion, UW-LAB cheese exhibited 2.09 ± 0.12 mg g1of FRAP, 74.77 ± 1.90% of DPPH, 64.91 ± 1.16% of AI and 38.83 ± 2.50% of ADI activities. This study recommends that combined MLE fortification with L. plantarumTAR4 fermentation was the best approach to improve nutrition value of cottage cheese.

Quantitation of therapeutic monoclonal antibodies (mAbs) in human serum could ensure that patients have adequate levels of mAbs for effective treatment. This research describes the use of affinity, glass-fiber membranes in a 96-well-plate format for rapid (<5 min) quantitation of the therapeutic mAb trastuzumab and a mAb against the SARS-CoV-2 spike protein. Adsorption of a poly(acrylic acid)-containing film in membrane pores and activation of the −COOH groups in the film enable covalent-linking of affinity peptides or proteins to the membrane. Passage of mAb-containing serum through the affinity membrane results in mAb capture within 1 min. Subsequent rinsing, binding of a secondary antibody conjugated to a fluorophore, and a second rinse yield mAb-concentration-dependent fluorescence intensities in the wells. Calibration curves established from analyses on different days have low variability and allow determination of mAb levels in separately prepared samples with an average error <10%, although errors in single-replicate measurements may reach 40%. The assays can occur in diluted serum with physiologically relevant mAb concentrations, as well as in undiluted serum. Thus, the combination of 96-well plates containing affinity membranes, a microplate reader, and a simple vacuum manifold affords convenient mAb quantitation in <5 min.

Mulberry (Morusspp.) fruits and leaves have been proven to possess nutraceutical properties. Due to its fast and easy growing characteristics, mulberry fruits (MF) and leaves (ML) potentially emerge as a great source of functional foods. This study aims to enhance bioactivities (antioxidant, anti-inflammation, and hypoglycemic activity) of MF and ML via submerged fermentation using bacteria (Lactobacillus plantarumTAR 4), yeast (Baker’s yeast and red yeast) and fungi (Tempehand Tapaistarter).

Regularization methods have been substantially applied in image restoration due to the ill-posedness of the image restoration problem. Different assumptions or priors on images are applied in the construction of image regularization methods. In recent years, matrix low-rank approximation has been successfully introduced in the image denoising problem and significant denoising effects have been achieved. Low-rank matrix minimization is an NP-hard problem and it is often replaced with the matrix’s weighted nuclear norm minimization (WNNM). The assumption that an image contains an extensive amount of self-similarity is the basis for the construction of the matrix low-rank approximation-based image denoising method. In this paper, we develop a model for image restoration using the sum of block matching matrices’ weighted nuclear norm to be the regularization term in the cost function. An alternating iterative algorithm is designed to solve the proposed model and the convergence analyses of the algorithm are also presented. Numerical experiments show that the proposed method can recover the images much better than the existing regularization methods in terms of both recovered quantities and visual qualities.

To develop English learners' (ELs) fluency, instruction needs to focus on improving their vocabulary knowledge; grammar, reading, and writing skills; and conversational competencies. Many teachers take the communicative language teaching [...]

Effective monoclonal antibody (mAb) therapies require a threshold mAb concentration in patient serum. Moreover, the serum concentration of the mAb Bevacizumab should reside in a specific range to avoid side effects. Methods for conveniently determining the levels of mAbs in patient sera could allow for personalized dosage schedules that lead to more successful treatments. This work utilizes microporous nylon membranes functionalized with antibody-binding peptides to capture Bevacizumab, Rituximab, or Panitumumab from diluted (25%) serum. Modification of the capture-peptide terminus is often crucial to creating the affinity necessary for effective binding. The high purity of eluted mAbs allows for their quantitation using native fluorescence, and membranes are effective in spin devices that can be used in any laboratory. The technique is effective over the therapeutic range of Bevacizumab concentrations. Future work aims at further modifications to develop rapid point-of-care devices and decrease detection limits.

A growing number of software tools have been developed for metabolomics data processing and analysis. Many new tools are contributed by metabolomics practitioners who have limited prior experience with software development, and the tools are subsequently implemented by users with expertise that ranges from basic point-and-click data analysis to advanced coding. This Perspective is intended to introduce metabolomics software users and developers to important considerations that determine the overall impact of a publicly available tool within the scientific community. The recommendations reflect the collective experience of an NIH-sponsored Metabolomics Consortium working group that was formed with the goal of researching guidelines and best practices for metabolomics tool development. The recommendations are aimed at metabolomics researchers with little formal background in programming and are organized into three stages: (i) preparation, (ii) tool development, and (iii) distribution and maintenance.

Direct oral anticoagulants (DOACs) are increasingly becoming the treatment of choice for venous thromboembolism (VTE). To ensure safe prescription and prevent delay of supply for dischargeable patients with deep venous thrombosis (DVT) presenting to the Emergency Department (ED) outside pharmacy hours, we implemented a “Rivaroxaban after‐hours pack” system, that requires prescribers to assess suitability via criteria detailed in a decision support system GuidanceMS, prior to pack provision. Pharmacist and clinic follow up is also provided. To assess the safety and effectiveness of the program, a retrospective case series review was undertaken of DVT patients discharged from the ED with an after‐hours pack from April 2015 to December 2017. Patients were assessed for compliance with recommendations for treatment from their baseline demographics, biochemistry, medication history, bleeding and thrombotic risk. Any bleeding episodes or clot extension were recorded. The number of admissions for hospital DVT treatment for the study period was compared to the preceding 30 months. Of the 120 patients reviewed, all patients had adequate renal function, 96.3% had liver function tests <3× the upper limit normal. Three patients (2.5%) had active malignancy and no patients had a mechanical valve or antiphospholipid syndrome. All patients received a pharmacist telephone follow‐up education conversation and referral to Thrombosis Outpatients. Twelve patients reported clinically relevant non‐major bleeding, while two patients had clot extension despite compliance. There was marked reduction in hospital and/or hospital‐in‐the‐home admissions compared to the previous 30 months (P< 0.001). In conclusion, all DVT patients were safely prescribed Rivaroxaban using this system, with a reduction in hospital and/or hospital‐in‐the‐home admissions. This system is efficient in ensuring safe provision of Rivaroxaban outside of pharmacy hours, with potential for extension to the primary care setting.

Shotgun proteomics using liquid chromatography coupled to mass spectrometry (LC-MS) is commonly used to identify peptides containing post-translational modifications. With the emergence of fast database search tools such as MSFragger, the approach of enlarging precursor mass tolerances during the search (termed “open search”) has been increasingly used for comprehensive characterization of post-translational and chemical modifications of protein samples. However, not all mass shifts detected using the open search strategy represent true modifications, as artifacts exist from sources such as unaccounted missed cleavages or peptide co-fragmentation (chimeric MS/MS spectra). Here, we present Crystal-C, a computational tool that detects and removes such artifacts from open search results. Our analysis using Crystal-C shows that, in a typical shotgun proteomics data set, the number of such observations is relatively small. Nevertheless, removing these artifacts helps to simplify the interpretation of the mass shift histograms, which in turn should improve the ability of open search-based tools to detect potentially interesting mass shifts for follow-up investigation.

Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.g., Ara-C, DNR, 6-MP) induced the expression of niche-protecting cytokines (GDF15, CCL3 and CCL4) in both ALL cell lines and primary cells in vitro. The ATM and NF-κB pathways were activated after chemotherapy treatment, and the pharmacological or genetic inhibition of these pathways significantly reversed the cytokine upregulation. Besides, chemotherapy-induced NF-κB activation was dependent on ATM-TRAF6 signaling, and NF-κB transcription factor p65 directly regulated the cytokines expression. Furthermore, we found that both pharmacological and genetic perturbation of ATM and p65 significantly decreased the residual ALL cells after Ara-C treatment in ALL xenograft mouse models. Together, these results demonstrated that ATM-dependent NF-κB activation mediated the cytokines induction by chemotherapy and ALL resistance to chemotherapeutics. Inhibition of ATM-dependent NF-κB pathway can sensitize ALL to chemotherapeutics, providing a new strategy to eradicate residual chemo-resistant ALL cells.

Rapid, convenient methods for monoclonal antibody (mAb) isolation are critical for determining the concentrations of therapeutic mAbs in human serum. This work uses porous nylon membranes modified with a HER2 peptide mimotope, KGSGSGSQLGPYELWELSH (KH19), for rapid affinity capture of Herceptin, a mAb used to treat breast cancer. Covalent linking of KH19 to poly(acrylic acid)-containing films in porous nylon leads to a Herceptin-binding capacity of 10 mg per mL of membrane and allows selective Herceptin capture from diluted (1:3) human serum in 5 min. Liquid chromatography-mass spectrometry demonstrates the high purity of eluted Herceptin. Moreover, the fluorescence intensity of the protein eluted from membranes increases linearly with the amount of Herceptin spiked in loading solutions containing diluted (1:3) human serum. These results demonstrate the promise of mimotope-modified membranes for Herceptin analysis that does not require secondary antibodies or derivatization with fluorescent labels. Thus, mimotope-containing membranes may form part of a simple benchtop analysis system for assessing the concentrations of therapeutic mAbs.

Rank minimization problem has a wide range of applications in different areas. However, since this problem is NP-hard and non-convex, the frequently used method is to replace the matrix rank minimization with nuclear norm minimization. Nuclear norm is the convex envelope of the matrix rank and it is more computationally tractable. Matrix completion is a special case of rank minimization problem. In this paper, we consider directly using matrix rank as the regularization term instead of nuclear norm in the cost function for matrix completion problem. The solution is analyzed and obtained by a hard-thresholding operation on the singular values of the observed matrix. Then by exploiting patch-based nonlocal self-similarity scheme, we apply the proposed rank minimization algorithm to remove white Gaussian additive noise in images. Gamma multiplicative noise is also removed in logarithm domain. The experimental results illustrate that the proposed algorithm can remove noises in images more efficiently than nuclear norm can do. And the results are also competitive with those obtained by using the existing state-of-the-art noise removal methods in the literature. [ABSTRACT FROM AUTHOR]

Abstract:Cladophorahas a global distribution and provides a habitat and food for numerous organisms. However, the taxonomy of Cladophorais confusing and poorly defined. In this study, 69 freshwater and brackish-water Cladophorasamples from inland China were collected, and both morphological and phylogenetic analyses of these samples were performed. The concatenated molecular phylogenies based on ribosomal DNA sequences showed that these inland samples belonged to two groups: freshwater Cladophoraand non-freshwater Cladophora. The phylogenetic results showed that there were eight clades in the freshwater group. The results of morphological observation showed characteristic similarities among the clades, and the samples in each clade exhibited different degrees of phenotypic plasticity. The prediction model for internal transcribed spacer 2 secondary structure showed that freshwater Cladophoracontain one ring structure with three main helices (helices I–III), in which the helix III-2 region was most variable. The high phenotypic plasticity and lack of diagnostic characteristics of the freshwater Cladophoragroup made delineating species difficult and challenging. Further sampling from a broader range in combination with more efficient molecular markers are necessary to clarify the taxonomy of Cladophorain the future.

In this work, a new hybrid MPGD consisting of two GEM foils and a metallic mesh was proposed. Based on the simulation studies, this design can significantly reduce the rise time of signal and has a better performance in respect of particle identification compared with the triple GEM design. The gain with various voltages setting was computed in order to provide us references for future experiment. The simulation results also show that the time and space resolution compared to the triple GEM detector are also improved. The time and space resolution of hybrid detector with $$\hbox {Ar/CO}_2$$ Ar/CO2 (70/30) and Ar/isobutane(95/5) were investigated for various drift electric field intensities. This new hybrid detector shows excellent potential for both fundamental research and imaging applications.

With advancing technology, “literacy” evolves to include new forms of literacy made possible by digital technologies. “New literacy” refers to using technology to research, locate, evaluate, synthesize and communication information. The purpose of the study is to develop a framework to guide science teachers' new literacy practices, and examine the impact of new literacy approach on students' science learning and new literacy skills. The authors worked with 25 middle school science teachers through a two-year professional development (PD), and followed their implementation to investigate the PD impact on their classroom practices and students' learning outcomes. The authors adopted mixed-methods to examine change in teachers' new literacy practices, students' science learning outcomes, and students' confidence in new literacy skills. The study results showed increases in teachers' frequency and types of new literacy practices, positive impact on students' science learning and confidence in new literacy skills. Factors affecting teachers' new literacy practice are also reported.

A polymer inclusion membrane (PIM) based sampling probe was developed for electrokinetic extraction of drugs from biological fluids. The probe was fabricated by dip-coating a nonconductive glass capillary tube in a homogeneous PIM solution for three cycles. The PIM solution comprised cellulose triacetate (CTA), 2-nitrophenyl octyl ether (NPOE), and 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [EMIM][NTf2] in a ratio of 5:4:2. The developed probe electrokinetically extracted doxorubicin from human plasma, human serum, and dried blood spot (DBS). The practicability and reliability of the electrokinetic extraction were evaluated by LC-MS/MS to quantify the desorption of extracted doxorubicin. Under the optimized conditions, a quantification limit of 0.2–2 ng/mL was achieved for the three biological samples. The probe was further integrated into a portable battery-powered device for safe low-voltage (36 V) electrokinetic extraction. The developed technique is envisioned to provide a more efficient analytical workflow in the laboratory.

Mining provides a wealth of mineral raw materials to human beings, while also causes serious damage to environment and ecology. For decades, landscape renovation in mining wastelands has become a multi-disciplinary research focus. However, compared with the developed countries, China has disadvantages of the relevant theoretical researches developing slowly with lacking supporting technology. According to the design principle of “reservation and utilization”, we reviewed and summarized the methods of landscape transformation in mining wastelands, furthermore, using the way of researching successful cases at home and abroad. In lined with the specific circumstances in China, the target of landscape transformation and basic theories as methods of strategy was developed. Finally, the overall thinking and suggestions were put forward for the development of landscape transformation in mining wastelands.

Stanford mobile inquiry-based learning environment (SMILE) is a technology developed to support student learning through student-generated questioning. Literature has shown that student-generated questions can positively affect students' learning motivations and reading comprehension depending on teachers' designs of learning activities. In order to explore ways that teachers may use SMILE to support student-generated questioning practices, we piloted the technology with 26 preservice teachers. They used SMILE to enact student-generated questioning practices that elicit and use higher-order thinking in the learning process. We evaluated questions generated by teachers and reported their implementation experience with K-12 students. Our paper discusses the sense of achievement felt by both teachers and students regarding the student-generated questioning practices. It also addresses perceived satisfaction and the challenges of using SMILE to enhance student-generated questioning practices in the classroom.

Image restoration is a fundamental problem of image processing. In recent years, low-rank minimization (LRM) methods have been extensively applied to this problem to improve the image restoration effects. Due to the theoretical difficulties, the matrix's rank is often replaced by its convex surrogates such as the nuclear norm and the solution can be obtained by solving the Euler-Lagrange equation. In this paper, we propose a model for image restoration by utilizing the matrix rank directly. We design a proximal alternating rank minimization algorithm for solving the model. In each subproblem of the proposed algorithm, the closed-form solution can be easily obtained. The global convergence of the algorithm is also demonstrated by applying the Kudyka-Łojasiewicz property. Numerical experiments show that the proposed method can recover images better than some current state-of-the-art methods in terms of both the recovered measure quantities and visual qualities. [ABSTRACT FROM AUTHOR]

Protein experiment evidence at protein level from mass spectrometry and antibody experiments are essential to characterize the human proteome. neXtProt (2014-09 release) reported 20 055 human proteins, including 16 491 proteins identified at protein level and 3564 proteins unidentified. Excluding 616 proteins at uncertain level, 2948 proteins were regarded as missing proteins. Missing proteins were unidentified partially due to MS limitations and intrinsic properties of proteins, for example, only appearing in specific diseases or tissues. Despite such reasons, it is desirable to explore issues affecting validation of missing proteins from an “ideal” shotgun analysis of human proteome. We thus performed in silico digestions on the human proteins to generate all in silico fully digested peptides. With these presumed peptides, we investigated the identification of proteins without any unique peptide, the effect of sequence variants on protein identification, difficulties in identifying olfactory receptors, and highly similar proteins. Among all proteins with evidence at transcript level, G protein-coupled receptors and olfactory receptors, based on InterPro classification, were the largest families of proteins and exhibited more frequent variants. To identify missing proteins, the above analyses suggested including sequence variants in protein FASTA for database searching. Furthermore, evidence of unique peptides identified from MS experiments would be crucial for experimentally validating missing proteins.

LEAFYis a floral meristem identity gene in Arabidopsis thaliana, which plays a key role during flowering. BrcLEAFY(BrcLFY), a FLO/LFYhomologue, was cloned from Pak Choi by reverse transcription-polymerase chain reaction (RT-PCR), and its expression patterns in different organs and the apex at different developmental stages, as well as during vernalization, were analysed by quantitative real-time PCR (qPCR). The full cDNA of BrcLFYwas 1353 bp in length with an open reading frame of 1260 bp encoding 419 amino acids. qPCR results showed that BrcLFYexpression gradually increased during the vegetative growth stage and increased sharply at flower differentiation stage 1, with the highest expression level at flower differentiation stage 5. When comparing BrcLFYexpression in different organs, we concluded that the level in young and mature leaves was significantly higher than in the apex and other tissues at flower differentiation stage 3 and visible flower bud stage and fully-bloom stage. The BrcLFYexpression in germinated seeds and seedlings with five leaves was analysed during cold treatment for 0 d, 10 d and 20 d at 4 ºC and the results showed that BrcLFYgene expression rose gradually with prolonged low temperature.

n this study, a novel polyhydroxy triazine charring agent (PT-CA) was synthesized through the solid-state reaction of triglycidyl isocyanurate (TGIC) and pentaerythritol. Meanwhile, the molecular structure of the chemical compound was determined by FTIR, elemental analysis and thermalgravimetric analysis (TG).Then it is combined with microencapsulated ammonium polyphosphate (MAPP) and melamine phosphate (MP) to impart flame retardance and dripping resistance for polypropylene (PP).The fire performance of treated PP was investigated by limiting oxygen index (LOI) and vertical burning test (UL-94).It has been found that the treated PP with the optimal flame retardant formulation of MAPP:MA:PTCA=18:6:6 (weight ratio, formulation 10) gives an LOI of 31.5 and UL-94 V-0 rating.

The South–to–North Water Diversion project provides water mainly for Henan and Hebei province , Beijing and Tianjin city . So the ecological environment protection in the water source areas is very important. But the ecological environment of water source areas of the middle route project is damaged becsuse a large amount of fertilizer and pesticide are used in the field, the pollution is heavy, and some lakes are turned into fields at some area. The systematic ecological circulation circles have not been established. This paper puts forward the countermeasures and methods of establishing the ecological circulation circle in the water rource areas of the middle route project after it illustrates the importance of establishing the ecological circulation circle in the water source areas , and analyzes the problems of the ecological circulation circle in the water source areas.

ABSTRACTAlthough the presence of mecAis the genotypic determinant of methicillin-resistant Staphylococcus aureus(MRSA), certain MRSA strains, especially community-associated MRSA (C-MRSA), can display an oxacillin MIC in the Clinical and Laboratory Standards Institute susceptible breakpoint range (=2 µg/ml). Among 91 and 180 isolates thought to be methicillin-susceptible S. aureus(MSSA) with oxacillin MICs of 2 and 1 µg/ml as determined by the Sensititre broth microdilution test initially, 52 (57.1%) and 6 (3.3%), respectively, were mecApositive. These mecA-positive low-oxacillin-MIC isolates belong to the dominant Taiwan C-MRSA clone (clonal complex [CC] 59), 56 of which carried SCCmectype V and were pvlpositive, and 43 of which belonged to spaCC t437. All 271 isolates were retested by Sensititre, as well as by Vitek II and disk diffusion (DD). Based on the oxacillin results, the sensitivities of the Sensititre, Vitek II, and DD methods were 48.3% (28/58), 46.6% (27/58), and 89.6% (52/58), respectively. Although cefoxitin was better at detecting these isolates, 12.1, 10.4, and 5.2% of these isolates were still misidentified as MSSA by Sensititre, Vitek II, and DD, respectively. These results highlight the difficulty in the accurate identification of MRSA with borderline oxacillin MICs in the CC59:SCCmecV clone, which likely has contributed to its spread in the health care and community settings. Since this clone has now been detected in other countries, and since other C-MRSA lineages have also been found to have low-level ß-lactam resistance, the findings of the present study may be relevant to other regions. Further studies are warranted to determine the extent and clinical impact of such misidentification.

Stenotrophomonas maltophiliahas emerged as an important opportunistic pathogen in debilitated hosts. Clinical management of S. maltophiliais challenging due to its intrinsic resistance to a variety of antibiotics. This study investigated the trend and prevalence of antimicrobial resistance in S. maltophiliafrom a nationwide surveillance study in Taiwan.

In this study, a novel phosphorus-nitrogen containing intumescent flame retardant (P-N IFR) poly(melamine 2-carboxyethyl(phenyl) phosphate)(PMCEP) was prepared via the reaction of 2-carboxyethyl (phenyl) phosphinic acid (CEPPA) and melamine (MEL) in two-steps. Meanwhile, the molecular structure of the chemical compound was determined by FTIR,1H-NMR and elemental analysis; and the thermal properties was investigated by means of TGA. Combustion studies revealed high limiting oxygen index (LOI) indicative of better flame-retardancy properties for PBT resin.

Phytoextraction has been recognized as an alternative technique for the remediation of wetland contaminated by heavy metals. The objective of this paper is to investigate the characteristics of heavy metal phytoextaction by phragmites australis and the distribution in soils and phragmites australis of 13 sampling points distributed in fields of Zhaoquanhe, Yangjuanzi and Dongguo in Liaohe estuary.The results showed that the content of heavy metal of Cu and Zn is close in the three phragmites australis fields. The content of heavy metal of Pb in Dongguo field is higher than the others. The content of heavy metal of Cd is lowest for all the heavy metals in the three fields. For the content of heavy metal in different layer soils in the three phragmites australis fields, the content of heavy metal of Cu, Pb, Zn in soils of 0-10 cm, 10-20 cm is higher than in other layer soils. for Cd in soils of 0-30 cm is higher than in other layer soils. And the content of heavy metal in siols of 30-40 cm is lowest for all the heavy metals. The transfer and interaction of Cu, Zn, Cd and Pb in the soil- phragmites australis systems in the three fields is studied, the content of heavy metal of Cu, Zn, Cd is that soils>phragmites australis of aerial part>phragmites australis of underground part, and for the content of heavy metal of Pb, soils>phragmites australis of aerial part˜phragmites australis of underground part. The biological concentration factor of heavy metal of Cu, Zn, Cd is low and transfer coefficient is high relatively .

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