The development and application of a novel E-commerce recommendation system used in electric power B2B sector

The advent of the digital era has transformed E-commerce platforms into critical tools for industry, yet traditional recommendation systems often fall short in the specialized context of the electric power industry. These systems typically struggle with the industry's unique challenges, such as infrequent and high-stakes transactions, prolonged decision-making processes, and sparse data. This research has developed a novel recommendation engine tailored to these specific conditions, such as to handle the low frequency and long cycle nature of Business-to-Business (B2B) transactions. This approach includes algorithmic enhancements to better process and interpret the limited data available, and data pre-processing techniques designed to enrich the sparse datasets characteristic of this industry. This research also introduces a methodological innovation that integrates multi-dimensional data, combining user E-commerce activities, product specifics, and essential non-tendering information. The proposed engine employs advanced machine learning techniques to provide more accurate and relevant recommendations. The results demonstrate a marked improvement over traditional models, offering a more robust and effective tool for facilitating B2B transactions in the electric power industry. This research not only addresses the sector's unique challenges but also provides a blueprint for adapting recommendation systems to other industries with similar B2B characteristics

14-3-3σ Contributes to Radioresistance by Regulating DNA Repair and Cell Cycle via PARP1 and CHK2

14-3-3σ has been implicated in the development of chemo and radiation resistance and in poor prognosis of multiple human cancers. While it has been postulated that 14-3-3σ contributes to these resistances via inhibiting apoptosis and arresting cells in G2–M phase of the cell cycle, the molecular basis of this regulation is currently unknown. In this study, we tested the hypothesis that 14-3-3σ causes resistance to DNA-damaging treatments by enhancing DNA repair in cells arrested in G2–M phase following DNA-damaging treatments. We showed that 14-3-3σ contributed to ionizing radiation (IR) resistance by arresting cancer cells in G2–M phase following IR and by increasing non-homologous end joining (NHEJ) repair of the IR-induced DNA double strand breaks (DSB). The increased NHEJ repair activity was due to 14-3-3σ–mediated upregulation of PARP1 expression that promoted the recruitment of DNA-PKcs to the DNA damage sites for repair of DSBs. On the other hand, the increased G2–M arrest following IR was due to 14-3-3σ–induced Chk2 expression. Implications: These findings reveal an important molecular basis of 14-3-3σ function in cancer cell resistance to chemo/radiation therapy and in poor prognosis of human cancers

A Novel Two Mode-Acting Inhibitor of ABCG2-Mediated Multidrug Transport and Resistance in Cancer Chemotherapy

Multidrug resistance (MDR) is a major problem in successful treatment of cancers. Human ABCG2, a member of the ATP-binding cassette transporter superfamily, plays a key role in MDR and an important role in protecting cancer stem cells. Knockout of ABCG2 had no apparent adverse effect on the mice. Thus, ABCG2 is an ideal target for development of chemo-sensitizing agents for better treatment of drug resistant cancers and helping eradicate cancer stem cells.Using rational screening of representatives from a chemical compound library, we found a novel inhibitor of ABCG2, PZ-39 (N-(4-chlorophenyl)-2-[(6-{[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]amino}-1,3-benzothiazol-2-yl)sulfanyl]acetamide), that has two modes of actions by inhibiting ABCG2 activity and by accelerating its lysosome-dependent degradation. PZ-39 has no effect on ABCB1 and ABCC1-mediated drug efflux, resistance, and their expression, indicating that it may be specific to ABCG2. Analyses of its analogue compounds showed that the pharmacophore of PZ-39 is benzothiazole linked to a triazine ring backbone.Unlike any previously known ABCG2 transporter inhibitors, PZ-39 has a novel two-mode action by inhibiting ABCG2 activity, an acute effect, and by accelerating lysosome-dependent degradation, a chronic effect. PZ-39 is potentially a valuable probe for structure-function studies of ABCG2 and a lead compound for developing therapeutics targeting ABCG2-mediated MDR in combinational cancer chemotherapy

Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which are now curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, the level of 14-3-3σ mRNA was found to be increased in pancreatic cancers and this increased expression may contribute to the failure in treatment of pancreatic cancers. In the present study, we tested this hypothesis.</p> <p>Methods</p> <p>Western blot analysis was used to determine 14-3-3σ protein level in fresh frozen tissues and was correlated to clinical outcome. A stable cell line expressing 14-3-3σ was established and the effect of 14-3-3σ over-expression on cellular response to radiation and anticancer drugs were tested using SRB assay and clonogenic assays. Cell cycle distribution and apoptosis analyses were performed using propidium iodide staining and PARP cleavage assays.</p> <p>Results</p> <p>We found that 14-3-3σ protein level was increased significantly in about 71% (17 of 24) of human pancreatic cancer tissues and that the 14-3-3σ protein level in cancers correlated with lymph node metastasis and poor prognosis. Furthermore, we demonstrated that over-expression of 14-3-3σ in a pancreatic cancer cell line caused resistance to γ-irradiation as well as anticancer drugs by causing resistance to treatment-induced apoptosis and G2/M arrest.</p> <p>Conclusion</p> <p>The increased level of 14-3-3σ protein likely contributes to the poor clinical outcome of human pancreatic cancers by causing resistance to radiation and anticancer drugs. Thus, 14-3-3σ may serve as a prognosis marker predicting survival of pancreatic cancer patients and guide the clinical treatment of these patients.</p

Nf1 haploinsufficiency alters myeloid lineage commitment and function, leading to deranged skeletal homeostasis

Although nullizygous loss of NF1 leads to myeloid malignancies, haploinsufficient loss of NF1 (Nf1) has been shown to contribute to osteopenia and osteoporosis which occurs in approximately 50% of neurofibromatosis type 1 (NF1) patients. Bone marrow mononuclear cells of haploinsufficient NF1 patients and Nf1(+/-) mice exhibit increased osteoclastogenesis and accelerated bone turnover; however, the culprit hematopoietic lineages responsible for perpetuating these osteolytic manifestations have yet to be elucidated. Here we demonstrate that conditional inactivation of a single Nf1 allele within the myeloid progenitor cell population (Nf1-LysM) is necessary and sufficient to promote multiple osteoclast gains-in-function, resulting in enhanced osteoclastogenesis and accelerated osteoclast bone lytic activity in response to proresorptive challenge in vivo. Surprisingly, mice conditionally Nf1 heterozygous in mature, terminally differentiated osteoclasts (Nf1-Ctsk) do not exhibit any of these skeletal phenotypes, indicating a critical requirement for Nf1 haploinsufficiency at a more primitive/progenitor stage of myeloid development in perpetuating osteolytic activity. We further identified p21Ras-dependent hyperphosphorylation of Pu.1 within the nucleus of Nf1 haploinsufficient myelomonocytic osteoclast precursors, providing a novel therapeutic target for the potential treatment of NF1 associated osteolytic manifestations

Measurement of soil lead bioavailability and influence of soil types and properties:a review

Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one’s ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices

Measurement of soil lead bioavailability and influence of soil types and properties:a review

Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one’s ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices

Using publicly available data, a physiologically-based pharmacokinetic model and Bayesian simulation to improve arsenic non-cancer dose-response

Publicly available data can potentially examine the relationship between environmental exposure and public health, however, it has not yet been widely applied. Arsenic is of environmental concern, and previous studies mathematically parameterized exposure duration to create a link between duration of exposure and increase in risk. However, since the dose metric emerging from exposure duration is not a linear or explicit variable, it is difficult to address the effects of exposure duration simply by using mathematical functions. To relate cumulative dose metric to public health requires a lifetime physiologically-based pharmacokinetic (PBPK) model, yet this model is not available at a population level. In this study, the data from the U.S. total diet study (TDS, 2006–2011) was employed to assess exposure: daily dietary intakes for total arsenic (tAs) and inorganic arsenic (iAs) were estimated to be 0.15 and 0.028 μg/kg/day, respectively. Meanwhile, using National Health and Nutrition Examination Survey (NHANES, 2011–2012) data, the fraction of urinary As(III) levels (geometric mean: 0.31 μg/L) in tAs (geometric mean: 7.75 μg/L) was firstly reported to be approximately 4%. Together with Bayesian technique, the assessed exposure and urinary As(III) concentration were input to successfully optimize a lifetime population PBPK model. Finally, this optimized PBPK model was used to derive an oral reference dose (Rfd) of 0.8 μg/kg/day for iAs exposure. Our study also suggests the previous approach (by using mathematical functions to account for exposure duration) may result in a conservative Rfd estimation

Charge Measurement of Cosmic Ray Nuclei with the Plastic Scintillator Detector of DAMPE

One of the main purposes of the DArk Matter Particle Explorer (DAMPE) is to measure the cosmic ray nuclei up to several tens of TeV or beyond, whose origin and propagation remains a hot topic in astrophysics. The Plastic Scintillator Detector (PSD) on top of DAMPE is designed to measure the charges of cosmic ray nuclei from H to Fe and serves as a veto detector for discriminating gamma-rays from charged particles. We propose in this paper a charge reconstruction procedure to optimize the PSD performance in charge measurement. Essentials of our approach, including track finding, alignment of PSD, light attenuation correction, quenching and equalization correction are described detailedly in this paper after a brief description of the structure and operational principle of the PSD. Our results show that the PSD works very well and almost all the elements in cosmic rays from H to Fe are clearly identified in the charge spectrum.Comment: 20 pages, 4 figure

Comparison of oral bioavailability of benzo[a]pyrene in soils using rat and swine and the implications for human health risk assessment

Background: There are many uncertainties concerning variations in benzo[a]pyrene (B[a]P) soil guidelines protecting human health based on carcinogenic data obtained in animal studies. Although swine is recognised as being much more representative of the human child in terms of body size, gut physiology and genetic profile the rat/mice model is commonly used in practice. Objectives: We compare B[a]P bioavailability using a rat model to that estimated in a swine model, to investigate the correlation between these two animal models. This may help reduce uncertainty in applying bioavailability to human health risk assessment. Methods: Twelve spiked soil samples and a spiked silica sand (reference material) were dosed to rats in parallel with a swine study. B[a]P bioavailability was estimated by the area under the plasma B[a]P concentration-time curve (AUC) and faecal excretion as well in the rats. Direct comparison between the two animal models was made for: firstly, relative bioavailability (RB) using AUC assay; and secondly, the two assays in the rat model. Results: Both AUC and faecal excretion assays showed linear dose-response for the reference material. However, absolute bioavailability was significantly higher when using faecal excretion assay (p < 0.001). In aged soils faecal excretion estimated based on solvent extraction was not accurate due to the form of non-extractable fraction through ageing. A significant correlation existed between the two models using RB for soil samples (RBrat = 0.26RBswine + 17.3, R2 = 0.70, p < 0.001), despite the regression slope coefficient revealing that the rat model would underestimate RB by about one quarter compared to using swine. Conclusions: In the comparison employed in this study, an interspecies difference of four in RB using AUC assay was identified between the rat and swine models regarding pharmacokinetic differences, which supported the body weight scaling method recommended by US EPA. Future research should focus on the carcinogenic competency (pharmacodynamics) used in experiment animals and humans