Teaching Elementary Mathematics with Educational Robotics

Current education reforms call for engaging students in learning science, technology, engineering, and mathematics (STEM) in an integrative way. This critical case study of one fourth grade teacher investigated the use of educational robots (ER) not only for teaching coding, but as an instructional support in teaching mathematical concepts. To support teachers in teaching coding in an integrative and logical manner, our team developed the Collective Argumentation Learning and Coding (CALC) approach. The CALC approach consists of three elements: choice of task, coding content, and teacher support for argumentation. After a cohort of elementary teachers completed a professional development course, we followed them into their classrooms to support and document implementation of the CALC approach. Data for this case consisted of video recordings of two lessons, a Pre-interview, and Post-interview after each lesson. Research questions included: How does an elementary teacher use the CALC approach (integrative STEM approach) to teach mathematics concepts with ER? What are the teacher’s perspectives towards teaching mathematics with ER using an integrative STEM approach? Results from this critical case provide evidence that teachers can successfully integrate ER into the mathematics curriculum without losing coherence of mathematics topics and while remaining sensitive to students’ needs

Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain

Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB. Notably, upregulation of ICAM-1, a common process in inflammation, promotes Mϕ exosomes uptake in the BBB cells. We further demonstrate in vivo that naïve Mϕ exosomes, after intravenous (IV) administration, cross the BBB and deliver a cargo protein, the brain derived neurotrophic factor (BDNF), to the brain. This delivery is enhanced in the presence of brain inflammation, a condition often present in CNS diseases. Taken together, the findings are of interest to basic science and possible use of Mϕ-derived exosomes as nanocarriers for brain delivery of therapeutic proteins to treat CNS diseases

Vision, challenges and opportunities for a Plant Cell Atlas

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.</jats:p

Highly Stable Silver-Loaded Membrane Prepared by Interfacial Polymerization for Olefin Separation

The separation of light olefins from paraffins by a silver-loaded facilitated transport membrane has received wide attention in recent years. However, the undesirable instability of carriers Ag+ has consistently restricted its further application. In this work, a silver-loaded facilitated transport membrane is developed by interfacial polymerization on PDMS/PSF support. A part of Ag+ in the prepared membrane is presented as silver(I)-polyetheramine (Ag(I)-PEA) complexes that can effectively enhance the stability of Ag+. To eliminate nonselective voids and bring more carriers (Ag+), secondary aqueous phase treatment was conducted. And the effect of PEA and TMC concentrations, ratio of PEA to AgNO3, as well as secondary aqueous phase treatment on the gas transport is systematically investigated. The results show that the facilitated transport of Ag+ to C3H6 can offset the increase in diffusion resistance induced by the incremental membrane thickness and cross-linking degree as well as the additional AgCl particles on the membrane. Finally, the optimum C3H6/C3H8 selectivity of the silver-loaded membrane is trebled over the membrane without silver. Remarkably, the TMC0.6%-PEA(10%)(AgNO3)(10:9)-2/PDMS/PSF membranes show great long-term stability of about 29 days. In this work, both monomer synthesis and preparation methods are facile and versatile, presenting a promising strategy for the preparation of silver-loaded membranes with a long-term separation property

Highly Stable Silver-Loaded Membrane Prepared by Interfacial Polymerization for Olefin Separation

The separation of light olefins from paraffins by a silver-loaded facilitated transport membrane has received wide attention in recent years. However, the undesirable instability of carriers Ag+ has consistently restricted its further application. In this work, a silver-loaded facilitated transport membrane is developed by interfacial polymerization on PDMS/PSF support. A part of Ag+ in the prepared membrane is presented as silver(I)-polyetheramine (Ag(I)-PEA) complexes that can effectively enhance the stability of Ag+. To eliminate nonselective voids and bring more carriers (Ag+), secondary aqueous phase treatment was conducted. And the effect of PEA and TMC concentrations, ratio of PEA to AgNO3, as well as secondary aqueous phase treatment on the gas transport is systematically investigated. The results show that the facilitated transport of Ag+ to C3H6 can offset the increase in diffusion resistance induced by the incremental membrane thickness and cross-linking degree as well as the additional AgCl particles on the membrane. Finally, the optimum C3H6/C3H8 selectivity of the silver-loaded membrane is trebled over the membrane without silver. Remarkably, the TMC0.6%-PEA(10%)(AgNO3)(10:9)-2/PDMS/PSF membranes show great long-term stability of about 29 days. In this work, both monomer synthesis and preparation methods are facile and versatile, presenting a promising strategy for the preparation of silver-loaded membranes with a long-term separation property

UHPLC-MS/MS Assay for Quantification of Legubicin, a Novel Doxorubicin-Based Legumain-Activated Prodrug, and Its Application to Pharmacokinetic and Tissue Distribution Studies

Legubicin, a novel prodrug based on doxorubicin, has both albumin-binding and legumain-activating properties. The aim of this study was to develop and validate a UHPLC-MS/MS method for investigating the in vivo pharmacokinetics and tissue distribution profiles of legubicin in rats and tumor-bearing mice following intravenous administration, and to compare this prodrug with the positive control drug doxorubicin. The study employed a UHLC-MS/MS method to determine the levels of albumin-bound of legubicin and two metabolites (free Leu-DOX and DOX) in plasma, tumor, and tissue samples. This method was validated for good selectivity, high sensitivity, excellent extraction recovery, and short run time. The results showed that legubicin was present in the circulation in vivo mainly in a protein-bound form with larger AUC values and lower clearance and distribution, and essentially released small amounts of doxorubicin. Compared to administration of equimolar doses of doxorubicin, legubicin showed increased exposure of the active drug in the tumor and decreased the level of the active drug in the heart and kidney. This study provides valuable information on the pharmacokinetics and tissue distribution of legubicin, implicating its potential as a novel and effective drug candidate for anti-cancer therapies

Dysregulation of PAK1 Is Associated with DNA Damage and Is of Prognostic Importance in Primary Esophageal Small Cell Carcinoma

Primary esophageal small cell carcinoma (PESCC) is a rare, but fatal subtype of esophageal carcinoma. No effective therapeutic regimen for it. P21-activated kinase 1 (PAK1) is known to function as an integrator and an indispensable node of major growth factor signaling and the molecular therapy targeting PAK1 has been clinical in pipeline. We thus set to examine the expression and clinical impact of PAK1 in PESCC. The expression of PAK1 was detected in a semi-quantitative manner by performing immunohistochemistry. PAK1 was overexpressed in 22 of 34 PESCC tumors, but in only 2 of 18 adjacent non-cancerous tissues. Overexpression of PAK1 was significantly associated with tumor location (p = 0.011), lymph node metastasis (p = 0.026) and patient survival (p = 0.032). We also investigated the association of PAK1 with DNA damage, a driven cause for malignancy progression. γH2AX, a DNA damage marker, was detectable in 18 of 24 (75.0%) cases, and PAK1 expression was associated with γH2AX (p = 0.027). Together, PAK1 is important in metastasis and progression of PESCC. The contribution of PAK1 to clinical outcomes may be involved in its regulating DNA damage pathway. Further studies are worth determining the potentials of PAK1 as prognostic indicator and therapeutic target for PESCC

Clinical Impact of Tumor-Infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma

Primary small cell esophageal carcinoma is a rare and aggressive type of gastrointestinal cancer with poor prognosis. In the present study, the impact of tumour infiltrating inflammatory cells on clinico-pathological characteristics and the patients’ prognosis were analysed. A total of 36 small cell esophageal carcinomas, 19 adjacent normal tissues and 16 esophageal squamous cell carcinoma samples were collected. Qualified pathologists examined eosinophils, neutrophils, lymphocytes and macrophages on histochemical slides. The infiltration of eosinophils and macrophages in small cell esophageal carcinoma was significantly increased as compared with tumor adjacent normal tissues, and was significantly less in esophageal squamous cell carcinoma. Macrophage count was significantly associated with (p = 0.015) lymph node—stage in small cell esophageal carcinoma. When we grouped patients into two groups by counts of infiltrated inflammatory cells, Kaplan-Meier analysis revealed that high macrophage infiltration group (p = 0.004) and high eosinophil infiltration group (p = 0.027) had significantly enhanced survival. In addition, multivariate analysis unveiled that eosinophil count (p = 0.002) and chemotherapy (Yes vs. No, p = 0.001) were independent prognostic indicators. Taken together, infiltration of macrophages and eosinophils into the solid tumor appear to be important in the progression of small cell esophageal carcinoma and patients’ prognosis

d‑α-Tocopherol Polyethylene Glycol Succinate-Based Redox-Sensitive Paclitaxel Prodrug for Overcoming Multidrug Resistance in Cancer Cells

To overcome the multidrug resistance (MDR) of P-glycoprotein (P-gp) substrate anticancer drugs, such as paclitaxel (PTX), a novel dual-functional prodrug, D-α-tocopherol polyethylene glycol succinate (TPGS) based PTX prodrug (TPGS-S-S-PTX), was synthesized here to fulfill the synergistic effect of P-gp inhibiting and intracellular redox-sensitive release. The prodrug could self-assemble into stable micelles in physiological environment with a diameter of ∼140 nm, while it disassociated in reductive condition and released PTX and TPGS active derivatives rapidly. High cell cytotoxicity in PTX-resistant human ovarian cell line A2780/T was observed with enhanced PTX accumulation due to the P-gp inhibition by the TPGS moiety. The IC₅₀ of TPGS-S-S-PTX was 55% and 91% more effective than that of Taxol (clinical formulation of PTX) and uncleavable TPGS-C-C-PTX prodrug, respectively. This was found to be related with the increased apoptosis/necrosis and cell arrest in G2/M phase. <i>In vivo</i> evaluation of the TPGS-S-S-PTX prodrug exhibited an extended half-life, increased AUC (area under the concentration–time curve), enhanced tumor distribution and significant tumor growth inhibition with reduced side effects as compared to Taxol and TPGS-C-C-PTX. This prodrug has great potential in improving efficiency in the treatment of MDR tumors

Negative Air Ion (NAI) Dynamics over Zhejiang Province, China, Based on Multivariate Remote Sensing Products

Negative air ions (NAIs), which are known as the &ldquo;air vitamin&rdquo;, have been widely used as a measure of air cleanness. Field observation provides an alternative way to record site-level NAIs. However, these observations fail to capture the regional distribution of NAIs due to the limited number of sites. In this study, satellite-based bio-geophysical parameters from the climate, topography, air quality, vegetation, and anthropogenic intensity were used to estimate the daily NAIs with the Random Forest model (RF). In situ NAI observations over Zhejiang Province, China were incorporated into the model. Daily NAIs were averaged to capture the spatio-temporal distribution. The results showed that (1) the RF algorithm performed better than traditional regression analysis and the common BP neural network to generate regional NAIs at a spatial scale of 500 m over the larger scale, with an RMSE of 258.62, R2 of 0.878 for model training, and R2 of 0.732 for model testing; (2) in the variable importance measures (VIM) analysis, 87.96% of the NAI variance was caused by the elevation, aspect, slope, surface temperature, solar-induced chlorophyll fluorescence (SIF), relative humidity (RH), and the concentration of carbon monoxide (CO), while path analysis indicated that SIF was one of the most important factors affecting NAI concentration across the whole region; (3) NAI concentrations in 87.16% of the region were classified above grade III (&gt;500 ions cm&minus;3), which was able to meet the needs of human health maintenance; (4) the highest NAI concentration was distributed over the southwest of the Zhejiang Province, where forest land dominates. The lowest NAI concentration was mostly found in the northeast regions, where urban areas are well-developed; and (5) among different land types, the NAI concentrations were ranked as forest land &gt; water bodies &gt; barren &gt; grassland &gt; croplands &gt; urban and built-up. Among different seasons, summer and winter have the highest and lowest NAIs, respectively. Our study provided a substantial reference for ecosystem services assessment in Zhejiang Province