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A new carbon paste electrode (Ag-CPE) modified with a nitrogen heterocyclic silver(I) complex, [Ag2(BBP)2](pic)2·CH3OH (BBP = 1,3-bis(1H-benzimidazol-2-yl)propane, pic = picrate), was developed as a highly sensitive and simple electrochemical sensor for the determination of hydrogen peroxide. The Ag(I) complex was prepared by an interface reaction and characterized by elemental analysis, IR and UV/Vis spectra and single crystal X-ray diffraction. The Ag(I) complex shows a dinuclear cluster structure, which is formed by two BBP ligands bridging two Ag (I) centers and an Ag–Ag interaction (d Ag–Ag = 3.0875 Å). Cyclic voltammetry and chronoamperometry studies showed that the electrochemical sensing performance of Ag-CPE for H2O2 was improved in 0.2 m phosphate buffer solution (PBS, pH = 6). The electrochemical H2O2 sensor Ag-CPE exhibits a wide linear detection range from 0.5 to 4.0 mm and a lower detection limit of 0.39 μm with a relatively high sensitivity of 6.77 μA mm −1. Moreover, the sensor also shows good anti-interference properties and stability. The results prove that the Ag(I) complex based on the bis(benzimidazole) ligand may be an efficient component of electrode materials.

Oral fluids (OFs) have been broadly used as non-invasive samples for evaluating protective IgG antibodies from natural infection or vaccination, especially in pediatric populations.Paired OF and serum were collected from both individuals who received a booster dose of the inactive coronavirus disease 2019 (COVID-19) vaccine as well as those who did not have a history of COVID-19 vaccination and infection (as the control group). The total human IgG antibody (HIgG) content was evaluated as a marker of OF sampling quality. An in-house adapted magnetic particle-based chemiluminescence immunoassay was used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody detection in the OF. The SARS-CoV-2 IgG antibody in the serum samples was detected using a commercial immunoassay.In total, 579 paired OF and serum samples were collected. An additional 172 OF samples were collected from preschool children. The results indicated that the HIgG concentration in qualified OF samples should be higher than 0.3 µg/mL. Compared to the serum assay, the in-house OF immunoassay for detecting IgG antibodies against SARS-CoV-2 had 95.06% accuracy, 95.03% sensitivity, and 100% specificity.Overall, the in-house immunoassay for detecting SARS-CoV-2 IgG antibodies in OF showed high potential for application towards serological surveillance and immunization effect assessment after large-scale, inactive COVID-19 vaccination in China.

The exploration of carbonation routine utilizing BOFs, CRW and CO2 has a significant effect on terminated treatment of metallurgical wastes resourceful disposal at a low cost. This paper investigated the collaborative effect of CRW composition on slag carbonation degree and CRW decalcification rate in CO2 sequestration system, furthermore, the effect of reaction time etc. on both were also discussed under optimal composition. Moreover, the carbonation process was simulated by Aspen software for comparing with the experimental results. The results showed that slag carbonation degree and CRW decalcification rate increased as CRW hardness increased, and kept stable. The optimal calcium conversion was 50.4 %, corresponding to 15.9g CO2/100g slag, and the decalcification rate was 87.1 %, respectively, at 80 °C and 10 L/kg for 60 min. The Aspen simulation results showed the correlation degrees were 0.94 for calcium conversion and 0.98 for decalcification rate.

BACKGROUND: Triple negative breast cancer (TNBC) is characterized by invasiveness and short survival. Identifying novel TNBC-targeted therapies, to potentiate standard of care (SOC) therapy, is an unmet need. Progranulin (PGRN/GP88) is a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC). PGRN/GP88 tissue expression is an independent prognostic factor of recurrence while elevated serum PGRN/GP88 level is associated with poor outcomes. Since PGRN/GP88 expression is elevated in 30% TNBC, we investigated the involvement of progranulin on TNBC. METHODS: The effect of inhibiting PGRN/GP88 expression in TNBC cells by siRNA was investigated. The effects of a neutralizing anti-human PGRN/GP88 monoclonal antibody AG01 on the proliferation and migration of two TNBC cell lines expressing PGRN/GP88 were then examined in vitro and in vivo. RESULTS: Inhibition of GP88 expression by siRNA and AG01 treatment to block PGRN/GP88 action reduced proliferation and migration in a dose-dependent fashion in MDA-MB-231 and HS578-T cells. Western blot analysis showed decreased expression of phosphorylated protein kinases p-Src, p-AKT, and p-ERK upon AG01 treatment, as well as inhibition of tumor growth and Ki67 expression in vivo. CONCLUSION: PGRN/GP88 represents a therapeutic target with companion diagnostics. Blocking PGRN/GP88 with antibody treatment may provide novel-targeted solutions in TNBC treatment which could eventually address the issue of toxicity and unresponsiveness associated with SOC.

QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is well known for improving the myocardial remodelling, but the dose‐effect relationship of its intervention in the reparative myocardial fibrosis is still unclear. We investigated the effect of QSYQ on the reparative myocardial fibrosis in cardiac myosin‐induced rats and explored its mechanism of action by regulating autophagy. The results indicated that QSYQ increased LVEF and LVFS, and decreased the LVEDD, LVESD, HMI, LVMI, myocardial inflammation histology score, and collagen volume fraction in a dose‐dependent manner. In addition, QSYQ declined the number of autophagosomes, down‐regulated the expression of myocardial Beclin‐1 and LC3B, up‐regulated the expression of myocardial p62 and increased the ratios of myocardial p‐PI3K/PI3K, p‐Akt/Akt and p‐mTOR/mTOR. We provided evidence for that QSYQ could inhibit excessive myocardial autophagy by regulating the PI3K/Akt‐mTOR pathway and can be a potential therapeutic approach in treating the cardiovascular diseases such as myocarditis and dilated cardiomyopathy.

The epidemic of 2019 novel coronavirus, later named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still gradually spreading worldwide. The nucleic acid test or genetic sequencing serves as the gold standard method for confirmation of infection, yet several recent studies have reported false-negative results of real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Here, we report two representative false-negative cases and discuss the supplementary role of clinical data with rRT-PCR, including laboratory examination results and computed tomography features. Coinfection with SARS-COV-2 and other viruses has been discussed as well.

Chromium leaching from stainless steel slag should be dealt with when utilized them as construction materials, an original idea of increasing calcite coating compactness in slag matrix is proposed for solving this problem. The paper originally proposes a carbonation strategy balancing carbon dioxide sequestration efficiency and chromium leaching inhibition kinetics through forming calcite coating. 48–75 μm stainless steel slag is carbonated at 300 °C and 0.4 MPa for 120 min, carbonated slag and fresh slag are applied for chromium leaching tests, aiming to discuss the inhibition kinetics of calcite coating combining with XRD, SEM–EDS, FT-IR and EMPA analysis. The results show that 7.9% valorization degree can be achieved for stainless steel slag under the conditions, and a thin layer of calcite coating is formed in slag matrix. Diffusion rates of chromium are in the range from 1.32 × 10−11 to 2.12 × 10–11 min−1 and from 0.617 × 10−11 to 1.47 × 10−11 min−1 for fresh and carbonated slag, respectively. Inhibition efficiency of calcite coating on diffusion rate is about 30% to 53%, and diffusion active energies for fresh slag and carbonated slag are 6.84 kJ/mol and 12.51 kJ/mol, respectively, which represents that carbonation strategy is indeed valid for inhibiting chromium leaching, when stainless steel slag is utilized as construction materials or road-based aggregates.

Population stratification is always a concern in association analysis. There is a debate on the extent of the problem in less extreme situations (Thomas and Witte [1], Wacholder et al. [2]). Wacholder et al. [3] and Ardlie et al. [4] showed that hidden population structure is not a serious threat to case-control designs. We propose a method of assessing the seriousness of the population stratification before designing association studies. If population stratification is not a serious problem, one may consider using case-control study instead of family-based design to get more power. In a case-control design, we compare chi-square statistics from a structured population (a union of two subpopulations) and a homogeneous population with the same prevalence and allele frequencies. We provide an explicit formula to calculate the chi-square statistics from 17 parameters, such as proportions of subpopulation, allele frequencies in subpopulations, etc. We choose these factors because they have potential to cause false associations. Each parameter takes a random value in a chosen range. We then calculate the likelihood of getting opposite conclusions in the structured and the homogeneous populations. This is the likelihood of having false positives caused by population stratification. The advantage of this method is to provide a cost effective way to choose between using case-control data and using family data before actually collecting those data. We conclude that sample sizes have a significant effect on the likelihood of false positive caused by population stratification. The larger the sample size is, the more likely to have false positive if the population structure is ignored. If the sample size will be smaller than 200 by budget constraints, then case-control study may be a better choice because of its power.

© 2020 World Scientific Publishing Company. Optimization Spiking Neural P System (OSNPS) is the first membrane computing model to directly derive an approximate solution of combinatorial problems with a specific reference to the 0/1 knapsack problem. OSNPS is composed of a family of parallel Spiking Neural P Systems (SNPS) that generate candidate solutions of the binary combinatorial problem and a Guider algorithm that adjusts the spiking probabilities of the neurons of the P systems. Although OSNPS is a pioneering structure in membrane computing optimization, its performance is competitive with that of modern and sophisticated metaheuristics for the knapsack problem only in low dimensional cases. In order to overcome the limitations of OSNPS, this paper proposes a novel Dynamic Guider algorithm which employs an adaptive learning and a diversity-based adaptation to control its moving operators. The resulting novel membrane computing model for optimization is here named Adaptive Optimization Spiking Neural P System (AOSNPS). Numerical result shows that the proposed approach is effective to solve the 0/1 knapsack problems and outperforms multiple various algorithms proposed in the literature to solve the same class of problems even for a large number of items (high dimensionality). Furthermore, case studies show that a AOSNPS is effective in fault sections estimation of power systems in different types of fault cases: including a single fault, multiple faults and multiple faults with incomplete and uncertain information in the IEEE 39 bus system and IEEE 118 bus system.

Antibody-drug conjugates (ADC) are effective antibody-based therapeutics for hematopoietic and lymphoid tumors. However, there is need to identify new targets for ADCs, particularly for solid tumors and cancers with unmet needs. From a hybridoma library developed against cancer cells, we selected the mouse monoclonal antibody 33B7, which was able to bind to, and internalize, cancer cell lines. This antibody was used for identification of the target by immunoprecipitation and mass spectrometric analysis, followed by target validation. After target validation, 33B7 binding and target positivity were tested by flow cytometry and western blot analysis in several cancer cell lines. The ability of 33B7 conjugated to saporin to inhibit in vitro proliferation of PTFRN positive cell lines was investigated, as well as the 33B7 ADC in vivo effect on tumor growth in athymic mice. All flow cytometry and in vitro internalization assays were analyzed for statistical significance using a Welsh’s T-test. Animal studies were analyzed using Two-Way Analysis of Variance (ANOVA) utilizing post-hoc Bonferroni analysis, and/or Mixed Effects analysis. The 33B7 cell surface target was identified as Prostaglandin F2 Receptor Negative Regulator (PTGFRN), a transmembrane protein in the Tetraspanin family. This target was confirmed by showing that PTGFRN-expressing cells bound and internalized 33B7, compared to PTGFRN negative cells. Cells able to bind 33B7 were PTGFRN-positive by Western blot analysis. In vitro treatment PTGFRN-positive cancer cell lines with the 33B7-saporin ADC inhibited their proliferation in a dose-dependent fashion. 33B7 conjugated to saporin was also able to block tumor growth in vivo in mouse xenografts when compared to a control ADC. These findings show that screening antibody libraries for internalizing antibodies in cancer cell lines is a good approach to identify new cancer targets for ADC development. These results suggest PTGFRN is a possible therapeutic target via antibody-based approach for certain cancers.

Reaction of bis(3-methoxysalicylidene)-3-oxapentane-1,5-diamine (H2L) with Ce(NO3)3 afforded a new Ce(III) complex with composition [Ce(H2L)(NO3)3] (1). Complex 1 reacts with zinc acetate and terephthalic acid to prepare complex 2, [Zn4Ce2(L)4(terephthalate)2][Ce(DMF)(NO3)5]. They have been characterized by elemental analysis, UV/Vis and IR spectroscopy, and single-crystal X-ray diffraction. The structure analysis revealed that 1 is mononuclear, whereas 2 is d-f heteronuclear. The fluorescence properties of the ligand and complexes 1 and 2 were studied in the solid state. The significantly blue-shifted emissions and enhancement of fluorescence in 1 and 2 relative to the ligand were attributed to coordination of ligand with metal ions. The results show that the structure and fluorescence of the Ce(III) complexes can be modified by introducing Zn(II) ion and auxiliary ligand terephthalate.

QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is used to treat cardiovascular diseases. However, the dose-effect relationship of its intervention in the reactive myocardial fibrosis is elusive. In this work, rat models of reactive myocardial fibrosis induced by partial abdominal aortic coarctation were constructed and randomly classified into the model group, 3-methyladenine group, rapamycin group, QSYQ low-dose group, QSYQ medium-dose group, QSYQ high-dose group, and sham-operated rats (control group). We revealed that QSYQ lowered the heart mass index (HMI), left ventricular mass index (LVMI), and myocardial collagen volume fraction (CVF) levels in a dose-dependent mechanism. Additionally, QSYQ increased the number of autophagosomes, and the expression of myocardial Beclin-1 and LC3B. In contrast, it reduced the expression of myocardial p62 and decreased the ratios of myocardial p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. In conclusion, our results have revealed that QSYQ impacts anti-reactive myocardial fibrosis in a dose-dependent mechanism which is mediated by the activation of myocardial autophagy via the PI3K/AKT/mTOR pathway.

Better adaptive kinetics model for CO

Memetic Algorithms are traditionally composed of an evolutionary framework and one or more local search elements. However, modern generation Memetic Algorithms do not necessarily follow a pre-established scheme and are hybrid structures of various types. By following these modern trends, the present paper proposes an original and unconventional adaptive memetic structure generated by the hybridisation of a set of theoretical computational models, namely P Systems, and an evolutionary algorithm employing adaptation rules and moving operators inspired by Evolution Strategies. The resulting memetic algorithm, namely Adaptive Optimisation Spiking Neural P System (AOSNPS), is a tailored algorithm to solve optimisation problems with binary encoding.More specifically AOSNPS is composed of a family of parallel spiking neural P systems, each of them generating a binary vector representing a candidate solution on the basis of internal probability parameters and an adaptive Evolutionary Guider Algorithm that evolves the probabilities encoded in each P system. Numerical result shows that the proposed approach is effective to solve the 0/1 knapsack problem and outperforms various algorithms proposed in the literature to solve the same class of problems.

The wastes network system exploration in metallurgical process imposes of great significance for advancing green circular economy in steel plant. This paper originally proposes a closed-circulating CO

Integration consideration of end-point reproductions like molten slag waste heat high-efficiently recovery and resourceful disposal has a significant influence on establishing more economical and environmental wastes circular network system, due to 0.75billiontonne metallurgical slag with nearly 1500 °C is produced annually, corresponding to 40milliontonne coal theoretically calculated by 100% heat recovery. In this review, the technologies’ limitations and their priorities of prevailing heat recovery processes including physical or chemical methods through evaluating the key parameters such as heat recovery rate and granulation performance were discussed. Physical methods like centrifugal granulation have a recovery rate of less than 65% except for better slag particle diameter, and the heat only in the high-temperature range can be recovered efficiently. By contrast, chemical methods have a better heat recovery rate through combustible gas preparation based on slag catalysis, but slag granulation performance cannot be guaranteed. Thus, the collaboration of physical and chemical methods like slag granulation-coal gasification system was proposed, which had an ingenious integration of energy cascade recovery at a wider temperature range, combustible gas preparation like hydrogen and slag granulation. However, this process will consume a great quantity of fossil fuel and emerge some other dangers to the environment, therefore, a cleaner routine of molten slag-waste plastics system was proposed for triple targets above on the premise of carbon dioxide storage and sequestration, which will provide a smart strategy for terminal energy conservation and establishing more economical and environmental wastes circular network system in steelmaking plant.

Introduction: Antibody-drug conjugates (ADC) are effective antibody-based therapeutics for a growing number of cancers, particularly hematopoietic and lymphoid tumors. There is need to identify new targets for ADCs, particularly for cancers with unmet needs. Methods: Our strategy has been to develop hybridoma libraries developed against cancer cells surface proteins and select antibody able to bind and internalize in cancer cell lines. Selected antibody can then be used for identification of the cancer cell surface target by immunoprecipitation (IP) and mass spectrometric analysis (Mass-spec), followed by target validation. After target validation, binding and target positivity can be tested by flow cytometry and western blot analysis on several cancer cell lines. The in vitro and in vivo efficacy of the antibody conjugated to a cytotoxic payload as ADC can then be evaluated with the target positive cancer cell lines.Results: Using the strategy described above, we have selected a monoclonal antibody named 33B7 able to bind and internalize in several cancer cell lines. The cell surface target binding 33B7 was identified by IP/Mass-spec as Prostaglandin F2 Receptor Negative Regulator (PTGFRN), a transmembrane protein in the Tetraspanin family. This target was then validated by showing that cells transfected with PTGFRN cDNA bound and internalized the antibody. Screening by Flow bidning and by western blot identified several human cancer cells lines expressing PTGFRN. In vitro treatment of these cell lines with the 33B7-saporin ADC inhibited their proliferation in a dose-dependent fashion. 33B7 conjugated to saporin was also able to block tumor growth in vivo in mouse xenografts when compared to a control ADC. Conclusion: These findings show that screening antibody libraries for internalizing antibodies in cancer cell lines is a good approach to identify new cancer targets for ADC development. These results suggest PTGFRN is a possible therapeutic target via antibody-based approach for certain cancers. The elucidation of PTGFRN role in cancer cells, particularly in possibly mediating metastasis is presently being carried out. Citation Format: Jorge Marquez, Jianping Dong, Chun Dong, Ginette Serrero. Prostaglandin F2 Receptor Negative Regulator (PTGFRN) is a novel target to inhibit tumor growth via antibody drug conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB116.

Two new one-dimensional (1D) double-chain Ag(I) coordination polymers, namely: {[Ag(Hcn)(bpy)]·2CH3OH}n (1), [Ag2(Hidc)(H2O)2]n (2) (Hcn = 2-hydroxycinnamate, bpy = 4,4′-bipyridine, Hidc = 4,5-imidazoledicarboxylate), were synthesized by volatilization method and characterized by single-crystal X-ray diffraction, elemental analysis, IR and UV–vis spectra. Single-crystal analyses show that although two Ag(I) CPs are both 1D double-chain structure constructed by Ag-Ag bonds, CP 1 is linear, while CP 2 is zigzagged. This difference in the structure may be due to the symmetry of the repeat unit of the Ag(I) CPs and the linkage pattern of the Ag-Ag bonds, in which the repeat unit of CP 1 is symmetric, whereas that of CP 2 is asymmetric. The fluorescence properties of the ligands and CPs 1-2 in the solid-state were studied. The fluorescence peaks of the two Ag(I) CPs were weakened compared to the ligands, which is attributed to ligand-centered fluorescence. The partial quenching of the aggregates may be due to the Ag-Ag interactions. In addition, cyclic voltammograms of CPs 1-2 indicated an irreversible Ag+/Ag couple with the order of reversibility being 1 > 2.

Three heteronuclear Cd–Ln clusters based on open-chain ether Schiff (bis(5-bromine-3-methoxysalicylidene)-3-oxapentane-1,5-diamine (H2L) and niacin (NA), with composition [Cd6Ln4L5 (OAc)5(NA)5(CH3OH)5](NO3)4·x(CH3OH)·y(CH2Cl2) (1 Ln = Sm, x = 1, y = 1; 2 Ln = Eu, x = 0, y = 1; 3 Ln = Tb, x = 2, y = 1), have been synthesized and structural characterizated. The structure analysis reveals that 1–3 contain the similar sandwich-type polycationic unit [Cd6Ln4L5(OAc)5(NA)5(CH3OH)5]4+. Solid-state luminescence studies show that the emission peaks of the H2L ligand located in the range of 340 ~ 373 nm in 1–3. The characteristic emission peaks of Sm3+ ion appear in cluster 1, but there is no Eu3+ or Tb3+ ion emission peak in clusters 2 and 3. The fluorescence spectra of 1–3 in N,N-dimethylformamide (DMF) solution only appear emission peaks of π*→π transition of [CdL] coordination units, but characteristic emission peaks of Ln3+ ions didn’t emerge. It is possible that the DMF molecules impeded the energy transfer from [CdL] coordination units to the lanthanum(III) ions. Moreover, antioxidation properties indicate that H2L and 1–3 have outstanding biological activity in scavenging oxygen free radicals.

In this paper, we deal with parameter estimation of the log-logistic distribution. It is widely known that the maximum likelihood estimators (MLEs) are usually biased in the case of the finite sample size. This motivates a study of obtaining unbiased or nearly unbiased estimators for this distribution. Specifically, we consider a certain ‘corrective’ approach and Efron’s bootstrap resampling method, which both can reduce the biases of the MLEs to the second order of magnitude. As a comparison, the commonly used generalized moments method is also considered for estimating parameters. Monte Carlo simulation studies are conducted to compare the performances of the various estimators under consideration. Finally, two real-data examples are analyzed to illustrate the potential usefulness of the proposed estimators, especially when the sample size is small or moderate.

In this paper, we develop Bayes factor based testing procedures for the presence of a correlation or a partial correlation. The proposed Bayesian tests are obtained by restricting the class of the alternative hypotheses to maximize the probability of rejecting the null hypothesis when the Bayes factor is larger than a specified threshold. It turns out that they depend simply on the frequentist t-statistics with the associated critical values and can thus be easily calculated by using a spreadsheet in Excel and in fact by just adding one more step after one has performed the frequentist correlation tests. In addition, they are able to yield an identical decision with the frequentist paradigm, provided that the evidence threshold of the Bayesian tests is determined by the significance level of the frequentist paradigm. We illustrate the performance of the proposed procedures through simulated and real-data examples.

As an important variant of membrane computing models, fuzzy reasoning spiking neural P systems (FRSN P systems) were introduced to build a link between P systems and fault diagnosis applications. An FRSN P system offers an intuitive illustration based on a strictly mathematical expression, a good fault-tolerant capacity, a good description for the relationships between protective devices and faults, and an understandable diagnosis model-building process. However, the implementation of FRSN P systems is still at a manual process, which is a time-consuming and hard labor work, especially impossible to perform on large-scale complex power systems. This manual process seriously limits the use of FRSN P systems to diagnose faults in large-scale complex power systems and has always been a challenging and ongoing task for many years. In this work we develop an automatic implementation method for automatically fulfilling the hard task, named membrane computing fault diagnosis (MCFD) method. This is a very significant attempt in the development of FRSN P systems and even of the membrane computing applications. MCFD is realized by automating input and output, and diagnosis processes consists of network topology analysis, suspicious fault component analysis, construction of FRSN P systems for suspicious fault components, and fuzzy inference. Also, the feasibility of the FRSN P system is verified on the IEEE14, IEEE 39, and IEEE 118 node systems.

The space-fractional Schrodinger equation for a local potential is difficult to solve because the fractional Riesz operator in it is nonlocal. In fractional quantum mechanics, the infinite wall is a basic problem and has not been solved yet. In this paper, we consider a free particle in an infinite wall region. Making use of the Levy path integral method, we derive the Levy path integral amplitude of the particle and take advantage of it to get the solution of the fractional Schrodinger equation for an infinite wall. Then, the infinite wall potential with a delta-function perturbation is also studied. According to Fox’s H-function, we get an equation of bound state energies of a free particle moving in an infinite wall region perturbed by the δ-function for two situations, E 0. We give a transcendental equation that determines energy levels when E 0. The asymptotic behaviors of the center of the delta function approaching to the origin and the infinite are also shown. The results of this paper include special cases in standard quantum mechanics.

Better adaptive kinetics model for CO2 sequestration utilizing wastes in steelmaking plant has a big significance for establishing green out-circulating network system. This work investigated the effect of temperature, L/S ratio and cold-rolling wastewater concentration on carbonation degree in basic oxygen furnace slag and CRW carbonation process, then their kinetics was discussed by surface coverage model and shrinking core model, respectively, in order to evaluate their adaptability and accuracy. Furthermore, CO2 sequestration intensifying factor was originally proposed for considering the carbonation depth, through comparing diffusion coefficient of CO2 between water carbonation and wastewater carbonation. The results showed that carbonation conversion increased as temperature and CRW concentration increased except for L/S ratio, and the maximum carbonation could reach 41.499 ± 1.240%. Because higher prediction error existed in surface coverage model, the shrinking core model had a better adaptability and accuracy for analyzing carbonation process in autoclave. Meanwhile, the CO2 sequestration intensifying factor was 1.6 times as big as carbonation process in distilled water as a result of DCO2 value. CO2 sequestration reaction in our work was controlled by calcium diffused because of DCO2 (0.700–0.976 × 10−4 cm2 s−1) and DCa (0.935–1.149 × 10−5 cm2 s−1). The results above will be helpful for us to better comprehend the reaction kinetics at micro-scale, when the idea of triple wastes self-circulation system network will be established to industrial application.

Backgrounds: Although many disease-associated common variants have been discovered through genome-wide association studies, much of the genetic effects of complex diseases have not been explained. Population-based association studies are vulnerable to population stratification. A possible solution is to use family-based tests. However, if tests only estimate the genetic effect from the within-family variation to avoid population stratification, they may ignore the useful genetic information from between-family variation and lose power. Methods: We have developed an adaptive weighted sum test for family-based association studies. The new test uses data driven weights to combine two test statistics, and the weights measure the strength of population stratification. When population stratification is strong, the proposed test will automatically put more weight on one statistic derived from within-family variation to maintain robustness against spurious positives. On the other hand, when the effect of population stratification is relatively weak, the proposed test will automatically put more weight on the other statistic derived from both within-family and between-family variation to make use of both sources of genetic variation; and at the same time, the degrees of freedom of the test will be reduced and power of the test will be increased. Results: In our study, the proposed method achieves a higher power in most scenarios of linkage disequilibrium structure as well as Hap Map data from different genes under different population structures while still keeping its robustness against population stratification.

The wastes network system exploration in metallurgical process imposes of great significance for advancing green circular economy in steel plant. This paper originally proposes a closed-circulating CO2 sequestering process for wastes appreciation and harmless disposal, and the effect of two circulation strategy, i.e. Slag circulation strategy and cold-rolling waste water(CRW) circulation strategy, on the CO2 uptake efficiency, carbonation degree and desalination rate were systemically discussed. Then, their kinetics are analyzed by model and molecular simulation in detail, respectively. In addition, the energy consumption and the cost are simulated for comprehensively evaluating its superiority. The experimental and molecular simulation results all show that the peak values for both strategies could be achieved when circulation times is in the range of three to five. CRW circulation strategy has a better CO2 uptake efficiency than slag circulation strategy, the CO2 uptake efficiency is about 487kgCO2/tslag and corresponding desalination rate is 48.9%, when CRW is circulated for five times at 60 °C and 20 L/g for 90 min. Adopting CRW circulation strategy, the CO2 sequestration efficiency is averagely doubled comparing to previous results. 129%–183% energy consumption and 35.6% cost would be reduced, which represents that the proposed routine is economical to step forward to industrial application.

The 88 kDa glycoprotein GP88 (Progranulin, PCDGF, acrogranin) is the largest member of the granulin/epithelin family of growth modulators identified as a driver of tumorigenesis. GP88 (PGRN) was also shown to be overexpressed in invasive ductal carcinoma (IDC)whereas it was negative in benign tumors and normal mammry epithelial tissue, thereby establishing GP88 as a therapeutic and diagnostic target in breast cancer (BC). Our laboratory has developed validated tools to measure GP88 in tumor biopsies and biological fluids as well as blocking its action. WE showed that GP88 was secreted and detected in the serum of BC patients at an increased level when compared to healthy subjects. Pathological studies with 530 cases of ER+ IDC with clinical outcomes showed that GP88 tumor expression was an independent prognostic indicator of recurrence in early stage BC patients. Training study followed by an independent validation study demonstrated that high GP88 tissue expression (GP88 3+) was associated with a 4-fold increase in risk of recurrence at 5 years. A neutralizing anti-GP88 antibody AG1 was expressed in a high yield CHO cell line was developed. The present study examined the effect of AG1 in letrozole resistant cell line AGLetR developed by long term selection in letrozole supplemented medium. This cell line showed decreased letrozole responsiveness in vivo and therefore constituted an excellent model for investigating letrozole resistance in vitro as well as in vivo. Here we report the results of studies investigating the effect of various doses of AG1 on LetR tumor development in combination with letrozole for AGLetR. We show that treatment with AG1 (10 mg/kg i.p.) in combination with letrozole was efficient to maintain long term responsiveness and inhibit tumor growth. Letrozole alone (5mg/kg) was unable to inhibit tumor growth and showed a doubling of tumor volume. Interestingly, long term combination treatment lead to tumor regression and inhibited tumor growth. These data suggest that inhibiting GP88 could provide a novel and alternative therapeutic strategy for patients with resistance to anti-estrogen therapy, being tamoxifen or letrozole. This works is supported by 2R44CA124179, HHSN 261201200060C, and HHSN2612014400C from NCI. Citation Format: Serrero G, Dong J, Yue B, Hicks D, Hayashi J. Combination of anti-progranulin (GP88/PGRN) antibody and letrozole inhibits tumor formation of letrozole resistant breast cancer cell lines. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-05-12.

Mesothelioma is an aggressive but rare form of cancer with a poor prognosis. 1-year survival is ~40% and 5-year survival remains in single digits. Treatment involves a combination of surgery, chemotherapy, and radiation therapy. Mesothelioma is a disease with unmet medical needs and deserving development of novel targeted therapies. Our laboratory is focused on developing novel antibodies useful in treating rare cancers such as mesothelioma. We have raised a mouse antibody library against human cancer cell surface proteins (CSPs). Antibodies were screened against several cancer cells including mesothelioma to identify antibodies specific for cancer CSP as druggable candidates. Screening identified antibodies that bound to and internalized into cancer cells. Such candidates were further characterized. One such antibody (AG02) was identified as having superior binding and internalization characteristics to the other antibodies. The therapeutic potential of AG02 was established as follows; 1) the cell surface protein named CSP-1 against which AG02 bound on the cell surface of selected cancer cells was identified by immunoprecipitation followed by mass spectrometry. Identified CSP-1 was demonstrated as being associated with metastatic potential thus emphasizing its potential as an important target for development of an anti-cancer agent; 2) We demonstrated that upon binding to CSP-1, AG02 antibody internalized the CSP-1 target; 3) We confirmed that AG02 antibody was first-in-class as no other internalizing antibody to this CSP-1 had been developed; 4) Since AG02 is an internalizing antibody, we developed ADC by conjugating AG02 to a generic cytotoxic drug saporin, routinely used as a cost-effective payload in ADCs for proof-of-concept (POC) study. Our POC AG02ADC was tested against a panel of cancer cells and found to bind strongly to CSPs in several cancers with orphan status and unmet needs including mesothelioma. In vitro and in vivo studies established that: (1) AG02 conjugated to saporin at 10nM was able to kill cells expressing CSP while it did not kill non-CSP-1 expressing cells, natural or transfected. (2) AG02-ADC acted in a dose dependent fashion, (3) when tested against different know cancer cell types, AG02-ADC killed >50% of cancer cells while a non-specific mouse IgG-ADC or Drug alone had no effect. (4) Using AG02-ADC treatment in nude mice, we demonstrated tumor growth inhibition >50% in several xenografts. While saporin was used in these studies as payload and shows efficacy, we expect more potent drugs such as MMAE or DM1 to have considerably more efficacy. In summary, we have demonstrated that: AG02 is specific for a CSP-1 overexpressed in certain cancers and involved in metastasis; AG02 is internalized in CSP-1 expressing natural cancer cells; AG02-ADC kills CSP-1 expressing cancer cells. Targeting mesothelioma may enable AG02-ADC to benefit of the FDA’s Orphan Drug Program as it nears drug and clinical development. Citation Format: Jorge Marquez, Chun Dong, Jianping Dong, Binbin Yue, Ginette Serrero. Novel antibody drug conjugate to inhibit mesothelioma tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 210.

Long noncoding RNA (lncRNA) GASL1 was identified as a novel lncRNA, which plays an important role in the proliferation and apoptosis of cells. This study aimed to compare the expression of GASL1 mRNA in kidney cancer cells and normal cells and detect the biological role of GASL1 in kidney cancer cell line A498. Polymerase chain reaction (PCR) was performed to examine the expression of GASL1 mRNA in kidney cancer tissues, normal tissues, and the cell lines. GASL1 overexpression was achieved in kidney cancer cell lines A498 through transfection. MTT was used to detect the effects of GASL1 overexpression in A498 cells. GASL1 mRNA was significantly overexpressed in adjacent normal tissues compared with renal cell carcinoma. The expression of GASL1 is lower in kidney cancer cell lines than in normal kidney epithelium cell line HREpiC. Overexpression of GASL1 inhibits the proliferation of renal carcinoma cell lines. GASL1 mRNA was down-regulated in kidney cancer tissues and may play a role in kidney cancer cell proliferation.

By finite element method (FEM), dielectric nanocup coating effect on the resonant optical properties of individual Au nanosphere was investigated. It is demonstrated not deleterious to the sensing signals of the nanosphere. The proposed nanocomposite provides an interesting localized surface plasmon resonance (LSPR) sensor with quadratic response, which refractive index (RI) sensitivity is revealed to increase with the RI both of its surrounding and local environment. The differences between the LSPR peak positions of the nanocomposite measured from far-field and near-field spectra are discussed, too. It is believed to shed light on the future applications in surface enhanced Raman spectroscopy, biochemical sensing, and detections.

The many-body space fractional quantum system is studied using the density matrix method. We give the new results of the Thomas–Fermi model, obtain the quantum pressure of the free electron gas. We also show the validity of the Hohenberg–Kohn theorems in the space fractional quantum mechanics and generalize the density functional theory to the fractional quantum mechanics.

For haplotype analysis of the X chromosome, haplotype-sharing (HS) statistics with sliding windows are defined for males and females separately, which are then combined to a single HS test for the X chromosome. When independent replication samples are not available, the training-testing sets approach is used to validate this procedure and a permutation method is used to obtain its P-value. We applied this method to the X chromosome (with 1804 SNPs) for age-related macular degeneration (AMD). We found a window of five SNPs over a 272 kb region associated with AMD after Bonferroni correction. An examination of the odds ratio and the population attributable risks revealed a disease-preventive haplotype, ATGAC, on these five SNPs. For elderly females without this haplotype, the likelihood of AMD is increased by a factor of 4.75 with a 95% confidence interval (1.43, 15.82). The frequency of ATGAC in HapMap CEU is 0.276. These five SNPs are covered by the gene DIAPH2, which is known to cause premature ovarian failure (POF) in females. Our results indicated that DIAPH2 may be a polygenic pleiotropy for POF and AMD.

Fractional quantum mechanics in the non-relativistic case is described by the space-fractional Schrodinger equation containing the fractional Riesz operator, which is a non-local operator. The non-locality makes it difficult to solve the fractional Schrodinger equation in the local potentials. In this paper, we study the solution of the fractional Schrodinger equation of a free particle moving on a circle by use of the Levy path integrals approach. We present the Levy path integrals propagator of a particle on circle and then use it to get the wave functions and energy eigenvalues of the free particle case. In addition, the Laplace transform, energy-time transform, and momentum representation of the free particle kernel are also obtained. The results of this paper contain the ones in standard quantum mechanics as special cases. The problem of a particle on circle is a fundamental problem of path integrals with topological constraints in quantum systems, and the method of Levy path integrals can be generalized to study more complex local potentials.

Breast cancer (BC) is the second leading cause of death in women worldwide. 15-20% of BC is triple negative breast cancer (TNBC).This subtype is very important clinically because of its high, invasiveness and short metastasis-free survival. Because of the lack of ER, PR and Her2 receptors, TNBC patients cannot be treated with anti-estrogen or Her2 targeted therapies. Standard of care (SOC) includes chemotherapies like anthracyclines, cyclophosphamide, taxanes and radiation therapy. There is an unmet need for novel targeted therapies for TNBC that can be used as single agent or in combination to potentiate SOC therapy to avoid or reduce toxicity, non-specific effects and unresponsiveness. Therefore it is very important to identify biomarkers overexpressed in TNBC that play a critical role in TNBC invasiveness and can be used as therapeutic targets. Progranulin (PGRN, GP88) is a secreted glycoprotein autocrine growth/survival factor functions as a biological driver of tumor cell proliferation, tumorigenesis, survival, invasiveness and drug resistance in several cancers, including breast cancer (BC). In ER+ BC, GP88 stimulates proliferation and survival and its overexpression confers estrogen independence and anti-estrogen resistance. GP88 is overexpressed in ER+ BC and in TNBC. GP88 expression in ER+ tumor biopsies is an independent prognostic factor of recurrence. High GP88 is also found in 30% of TNBC. GP88 is secreted in the serum of BC patients at an increased level compared to healthy subjects. GP88 represents an important therapeutic and diagnostic target in breast cancer. We have developed a recombinant neutralizing anti-human progranulin monoclonal antibody AG01 that inhibits its biological effect in vitro and in vivo and has fulfilled IND-enabling activities including toxicology study in non-human primates. Since GP88 is associated with poor outcome in BC patients, we investigated AG01 effect on the proliferation, survival, migration and invasion of TNBC MDA-MB-231 cells that overexpress PGRN/GP88.. AG01 reduced cell proliferation, migration and invasion significantly in a dose and time-dependent fashion. Western blot analysis showed evidence of regulatory changes upon AG01 treatment such as decreased expression of Ki67, p-Src, p-AKT, p-FAK and p-MAPK in these cells. In addition, AG01 treatment significantly reduced MDA-MB-231 cell migration and cell invasion in transwell assays. These data will be presented here along with in vivo tumor inhibition study. PGRN/GP88 represents a potential therapeutic with companion diagnostic target to provide novel solutions in TNBC and address the issue of toxicity, non-specific therapy and unresponsiveness often associated with SOC. We plan to further our in vivo studies based on on-going anti-PGRN pharmacokinetic study in athymic nude mice to help in the selection of in vivo efficacious AG01 dose in upcoming human phase 1 clinical study. Citation Format: Rupa Guha, Jianping Dong, Binbin Yue, Ginette Serrero. Anti-Progranulin (GP88) antibody AG01 therapeutic effect in triple negative breast cancer invasiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1934.

In this article, we introduce a wavelet threshold estimator to estimate multinomial probabilities. The advantages of the estimator are its adaptability to the roughness and sparseness of the data. The asymptotic behavior of the estimator is investigated through an often-used criteria: the mean sum of squared error (MSSE). We show that the MSSE of the estimator achieves the optimal rate of convergence. Its performance on finite samples is examined through simulation studies which show favorable results for the new estimator over the commonly used kernel estimator.

Survival of spores of Bacillus thuringiensis was determined under various processing conditions for spray drying. The results indicated that the viable spores number of B. thuringiensis decreased with increased inlet air temperature, outlet air temperature and atomising air pressure. When the inlet air temperature ranged from 170 °C to 250 °C, the outlet air temperature (75 °C) and atomising air pressure (0.15 MPa) were fixed, the pseudo- z value (one logarithmic cycle reduction) was 238.1 °C; when the outlet air temperature ranged from 65 °C to 95 °C, the inlet air temperature (200 °C) and atomising air pressure (0.15 MPa) were fixed, the pseudo- z value was 85.5 °C, the activation energy calculated according to the outlet air temperature was 59.96 kJ mol −1 ; when the atomising air pressure ranged from 0.10 MPa to 0.25 MPa, the inlet air temperature (200 °C) and outlet air temperature (75 °C) were fixed, the pseudo- z value was 3.49 MPa, the variance analysis showed that the atomising air pressure has no significant influence to the spores. The diluting solutions between Tween-80 solution and phosphate buffer have significant influence on the plate count of spores. The B. thuringiensis powder prepared by spray drying with inlet air temperature 250 °C, outlet air temperature 97 °C, the spores count of powder decreased obviously. But when the inlet air temperature of 155–165 °C, outlet air temperature of 66–70 °C were employed, the spores count of powder approaches to that of freeze drying powder. The spores count of oven drying powder was lower than that of the freeze drying powder, but close to the spray drying powder which inlet air temperature was 200 °C, outlet air temperature was 75 °C.

The present study introduces new Haplotype Sharing Transmission/Disequilibrium Tests (HS-TDTs) that allow for random genotyping errors. We evaluate the type I error rate and power of the new proposed tests under a variety of scenarios and perform a power comparison among the proposed tests, the HS-TDT and the single-marker TDT. The results indicate that the HS-TDT shows a significant increase in type I error when applied to data in which either Mendelian inconsistent trios are removed or Mendelian inconsistent markers are treated as missing genotypes, and the magnitude of the type I error increases both with an increase in sample size and with an increase in genotyping error rate. The results also show that a simple strategy, that is, merging each rare haplotype to a most similar common haplotype, can control the type I error inflation for a wide range of genotyping error rates, and after merging rare haplotypes, the power of the test is very similar to that without merging the rare haplotypes. Therefore, we conclude that a simple strategy may make the HS-TDT robust to genotyping errors. Our simulation results also show that this strategy may also be applicable to other haplotype-based TDTs.

Simpson's paradox occurs when the direction of a measure of association between two variables is reversed after pooling over a covariate. For example, a treatment can be effective for both males and females, but ineffective when the data for males and females are combined. Since Simpson's original example in his 1951 paper, numerous real-life examples of Simpson's paradox have been reported in many areas and the paradox has been generalized to many forms of association reversals. Necessary and sufficient conditions for Simpson's paradox as well as generalized forms of association reversals are given so we know, for example, when a high-dimensional contingency table can be safely collapsed, avoiding the paradox. It is also of interest to know what the appropriate conclusion is when Simpson's paradox does occur. Keywords: odds ratio; association measure; contingency table; marginal table; pooling; collapsibility; association reversal; amalgamation paradox

A genome-wide association study had showed G-protein–coupled receptor kinase 5 (GRK5) rs10886471 was related to the risk of type 2 diabetes mellitus (T2DM) through upregulated GRK5 mRNA expression. Rs10886471 is located in the intron region of GRK5. However, the mechanism by which intronic SNP affects gene expression remains unclear, whether the effect on gene expression depends on the intronic short tandem repeat (STR) (CA)n splicing regulator or not. Here we investigated the STR (CA)n polymorphism in rs10886471 and further discussed its role in the T2DM risk of Chinese Hainan Island individuals. A total of 1164 subjects were recruited and classified into a normal fasting glucose (NFG) group, an impaired fasting glucose (IFG) group, an impaired glucose tolerance (IGT) group, and a T2DM group. STR (CA)n polymorphisms were detected through polymerase chain reaction and sequencing. Five intronic (CA)n alleles, (CA)15 to (CA)19, were identified in GRK5 rs10886471. Only the (CA)16 allele was significantly associated with increased prediabetes and T2DM risk [odds ratio (OR)>1, P