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Drug-related problems (DRPs) are common in recipients of solid organ transplants. Pharmacist-led medication therapy management (MTM) has cost benefits in kidney and liver transplants; however, whether MTM is also beneficial in heart transplants remains unclear. This study explored the cost benefits of involving pharmacists in the heart transplant clinic. This retrospective study evaluated DRPs for 1 year after implementation of pharmacist-led MTM in a heart transplant clinic. The DRPs were compared between patients receiving transplantation for <1 and >1 year. The risk matrix method was used to assess each DRP in terms of the estimated probability and severity of consequent adverse drug events (ADEs). For cost analysis, both estimated cost savings and avoidance were calculated. During the 1-year MTM, 372 DRPs were identified by the pharmacist, among which 169 (45%) and 203 (55%) were from patients at <1-year and ≥1-year post-transplant periods, respectively. The 2 post-transplant periods (<1 year and ≥1 year) exhibited significant differences in the distribution of the dosage or frequency problems (30% vs 18%, P =.005) and the suggestion of more appropriate medication (4% vs 10%, P =.024). In all, 92 (29%) DRPs had an ADE probability of >10%; and 63 (17%) DRPs were estimated to cause ADEs with moderate severity or higher. The estimated cost savings and cost avoidance were US $4902 and US $4519, which equaled a cost–benefit ratio of 2.39. Integration of pharmacists into heart transplant clinics could help address DRPs and may have cost benefits. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy and its incidence is increasing. It is currently mainly treated by clinical chemotherapy, but chemoresistance remains poorly understood. Prefolded proteins 4 (PFDN4) are molecular chaperone complexes that bind to newly synthesized polypeptides and allow them to fold correctly to stabilize protein formation. This study aimed to investigate the role of PFDN4 in chemotherapy resistance in breast cancer. Our study found that PFDN4 was highly expressed in breast cancer compared to normal tissues and was statistically significantly associated with stage, nodal status, subclasses (luminal, HER2 positive and triple negative), triple-negative subtype and disease-specific survival by TCGA database analysis. CRISPR knockout of PFDN4 inhibited the growth of 89% of breast cancer cell lines, and the triple-negative cell line exhibited a stronger inhibitory effect than the non-triple-negative cell line. High PFDN4 expression was associated with poor overall survival in chemotherapy and resistance to doxorubicin and paclitaxel through the CREBP1/AURKA pathway in the triple-negative MDAMB231 cell line. This study provides insightful evidence for the value of PFDN4 in poor prognosis and chemotherapy resistance in breast cancer patients. [ABSTRACT FROM AUTHOR]

Trigate Si nanowire (NW) MOSFETs have been fabricated and characterized at temperature between 77 and 300 K in the dark and under light pumping. The NW width W and height H, the gate length Lg, and the gate oxide thickness tox, respectively, were 7–25, 16, 34–52, and 7 nm. The interesting aspects of Si NW MOSFETs with W/Lg = \25\ \nm/\52\ \nm, 24 nm/34 nm, 7 nm/47 nm, and 10 nm/37 nm measured at low drain voltage are that the drain current exhibited not only inverse temperature dependence in strong accumulation but also clear current plateaus/oscillations near the threshold regime at temperature up to 300 K. Notably, such current plateaus diminished or were invisible in the device of W/Lg = \24\ \nm/\42\ \nm. The observed current behaviors are inferred from the interplay of quantum interference and intersubband scattering effects. Additional current plateaus due to photogenerated excitons were also observed in the studied devices, evidencing photoexcitation effects on quantum transports through a Si NW. [ABSTRACT FROM PUBLISHER]

Abstract: Biofilm formation by pathogenic bacteria plays a key role in their pathogenesis. Previously, the pstA gene was shown to be involved in the virulence of Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne''s disease in cattle and a potential risk factor for Crohn''s disease. Scanning electron microscopy and colonization levels of the M. ap mutant indicated that the pstA gene significantly contributes to the ability of M. ap to form biofilms. Digital measurements taken during electron microscopy identified a unique morphology for the ΔpstA mutant, which consisted of significantly shorter bacilli than the wild type. Analysis of the lipid profiles of the mycobacterial strains identified a novel lipopeptide that was present in the cell wall extracts of wild-type M. ap, but missing from the ΔpstA mutant. Interestingly, the calf infection model suggested that pstA contributes to intestinal invasion of M. ap. Furthermore, immunoblot analysis of peptides encoded by pstA identified a specific and significant level of immunogenicity. Taken together, our analysis revealed a novel cell wall component that could contribute to biofilm formation and to the virulence and immunogenicity of M. ap. Molecular tools to better control M. ap infections could be developed utilizing the presented findings. [Copyright &y& Elsevier]

We address the problem of integrating web taxonomies from different real Internet applications. Integrating web taxonomies is to transfer instances from a source to target taxonomy. Unlike the conventional text categorization problem, in taxonomy integration, the source taxonomy contains extra information that can be used to improve the categorization. The major existing methods can be divided in two types: those that use neighboring categories to smooth the document term vector and those that consider the semantic relationship between corresponding categories of the target and source taxonomies to facilitate categorization. In contrast to the first type of approach, which only uses a flattened hierarchy for smoothing, we apply a hierarchy shrinkage algorithm to smooth child documents by their parents. We also discuss the effect of using different hierarchical levels for smoothing. To extend the second type of approach, we extract fine-grain semantic relationships, which consider the relationships between lower-level categories. In addition, we use the cosine similarity to measure the semantic relationships, which achieves better performance than existing methods. Finally, we integrate the existing approaches and the proposed methods into one machine learning model to find the best feature configuration. The results of experiments on real Internet data demonstrate that our system outperforms standard text classifiers by about 10%. [Copyright &y& Elsevier]

Abstract: Performance-based seismic design (PBSD) has been widely recognized as an ideal method for use in the future practice of seismic design. This paper summarizes the development of the seismic design draft code for buildings in Taiwan using performance-based seismic design methodology and presents the results of comparisons and case studies following the guideline in this paper. First, the current seismic design code provisions are examined according to the theoretical basis of PBSD to identify which methodologies of PBSD need to be incorporated into the current seismic design code. Then, a PBSD flowchart is presented. Finally, a draft of the proposed code is described. Transparent seismic design objectives for buildings of different use groups have been established qualitatively and interpreted quantitatively as performance criteria including drift limits. Site feasibility requirements, conceptual design scopes and basic rules have been proposed. Performance objective-oriented procedures for preliminary design and seismic performance evaluation have been presented. Suggestions on seismic performance criteria and the evaluation of existing buildings have been made. In order to provide clear, easy to follow guidelines, comparisons and case studies have also been conducted. It is believed that PBSD methodology will bring a new era to engineering practices with increased confidence in, and reliability on, seismic performance and safety. [Copyright &y& Elsevier]

Abstract: This paper presents several approaches for practical engineers to accomplish a displacement-based preliminarily seismic design for buildings by employing the conventional analysis methods, design tools and current structural design codes. The performance objectives are pre-quantified by the inter-storey drift limit, allowable ductility ratio and the minimum vertical load carrying capacity. A simple yet effective displacement-based procedure is mainly employed. Although the procedure has been successfully applied to both two-dimensional and three-dimensional steel and RC frames without significant irregularity, the paper only focused on a two-dimensional three-bay five-storey steel moment resisting frame on a rigid foundation for the simplicity of illustrating the design approach step by step. A conventional strength-based design approach, a stiffness-based design approach and/or a graphical approach for structural detailing are investigated. If the inter-storey drift limit controls the design, the stiffness-based approach is more efficient, while for other cases, the strength-based approach is recommended. The feasibility of the proposed procedure is demonstrated through nonlinear pushover analysis. Factors affecting the difference between the final design model in terms of required design base shear and initial stiffness and the nonlinear pushover results are examined. It is found that nonlinear pushover analysis may not be necessary in the preliminary design but could be eventually performed to define the best design parameters that will meet the performance requirements. Its advantage over the traditional force-based design procedure is also highlighted. [Copyright &y& Elsevier]

The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to establish pharmacophore groups and analyze the ACE2 binding site of the spike protein with the ZINC drug database and DrugBank database by molecular docking and molecular dynamics simulations. Screening results showed that Venetoclax, a treatment drug for chronic lymphocytic leukemia, has a potential ability to bind to the spike protein of SARS-CoV-2. In addition, our in vitro study found that Venetoclax degraded the expression of the spike protein of SARS-CoV-2 through amino acids Q493 and S494 and blocked the interaction with the ACE2 receptor. Our results suggest that Venetoclax is a candidate for clinical prevention and treatment and deserves further research. [ABSTRACT FROM AUTHOR]

Endometriosis is a common disease in women and may be one of the factors that induces malignant epithelial ovarian tumors. Previous studies suggested that endometriosis is related to ARID1A mutation mediating the expression of HDAC6, but the detailed pathogenic mechanism is still unclear. First, we collected endometriosis-associated ovarian carcinoma (EAOC) clinical samples and examined the expression of HDAC6. Our results found that the high HDAC6 expression group was positively correlated with EAOC histology (P = 0.015), stage (P < 0.000), and tumor size (P < 0.000) and inversely correlated with survival (P < 0.000). We also found that ARID1A6488delG/HDAC6 induced M2 polarization of macrophages through IL-10. In addition, the HDAC inhibitor (HDACi) vorinostat inhibited cell growth and blocked the effect of HDAC6. Tomographic microscopy was used to monitor the live cell morphology of these treated cells, and we found that vorinostat treatment resulted in substantial cell apoptosis by 3 h 42 min. Next, we established a transgenic mouse model of EAOC and found that vorinostat significantly reduced the size of ovarian tumors by inhibiting M2 macrophage polarization in mice. Together, these data demonstrate that the signaling pathway of E4F1/ARID1A6488delG/HDAC6/GATA3 mediates macrophage polarization and provides a novel immune cell-associated therapeutic strategy targeting IL-10 in EAOC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide that is characterized by abnormal lesions or malignant hyperplasia of soft and hard tissues in the oral cavity. Previous research has found that HDAC6 may be a potential therapeutic target for cancer patients and has the ability to regulate immune cells. However, the mechanism of HDAC6 in OSCC pathogenesis is unclear. We collected clinical samples and analyzed the level of HDAC6 in OSCC patients. The results showed that in the high HDAC6 expression group, HDAC6 expression was positively correlated with the grade of OSCC (R = 0.182, P = 0.036) and that this group had a 3.248-fold increase in the mortality risk compared with the low HDAC6 expression group (P = 0.003). Survival analysis also identified a correlation between the expression of HDAC6 and overall survival in OSCC patients, and it was found that the expression of HDAC6 was inversely correlated with survival (P ≤ 0.001). In addition, we found that HDAC6 induced IL-13 expression through AP-1, resulting in M2 polarization of macrophages. Together, these results demonstrate that the level of HDAC6 may be a useful prognostic biomarker and offer a novel immune cell-related therapeutic strategy of targeting IL-13 in OSCC. [ABSTRACT FROM AUTHOR]

Abstract: The TiO2/UV photocatalytic degradation of Acridine Orange (AO) was investigated in aqueous heterogeneous suspension. The results indicated that photocatalytic reactions were enhanced in alkaline medium. While the rate of photocatalytic degradation of the dye increased with increasing concentration of TiO2, at high doses of TiO2, the rate of reaction was reduced as a result of light attenuation. To obtain a better understanding of the mechanistic details of this TiO2 assisted dye photodegradation, the intermediates of the processes were separated, identified, and characterized using HPLC–ESI-MS. It was found that N-de-methylation degradation of the dye took place in a stepwise manner to yield mono-, di-, tri-, and tetra-N-de-methylated species. The probable photodegradation pathways are proposed and discussed. [Copyright &y& Elsevier]

Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) is a protein expressed constitutively during EBV latency. It is required to support the replication of the EBV genome once per cell cycle via the latent origin of replication, oriP. EBNA-1 also can activate transcription through binding to the family repeats of oriP. We wished to identify candidate cellular protein(s) that may interact with EBNA-1 and mediate these functions. A 32-kd protein was co-immunoprecipitated with EBNA-1 from 293 cells using a monoclonal antibody EBNA.OT1x. The regions of EBNA-1 which interact with this protein were studied using two deletion clones and mapped to EBNA-1 residues 1–102 and 325–357. Deletion of this region was shown previously in a mutant of EBNA-1 which had dominant-negative effects on both DNA replication and transactivation assays. The 32-kd protein was found to react with a polyclonal antiserum against P32/TAP (HIV Tat associated protein), which is known to interact with other RNA binding proteins and the RNA splicing factor SF2. The function of P32 was therefore proposed to involve RNA processing. In addition, this molecule was recently identified as hyaluronectin, which binds hyaluronic acid. Because several reports documented that intracellular hyaluronic acid can potentially affect cell proliferation, the association between EBNA-1 and P32/TAP/hyaluronectin may help the maintenance of episomal viral DNA within proliferating cells. [ABSTRACT FROM AUTHOR]

Abstract: Increasing environmental concern has led to the restrictive use of chromate conversion coatings to protect Al-alloys from corrosion. Our research is under way to find environmentally compliant substitute coating such as Si/Zr/Ce hybrid coating. The corrosion protection effect of green pretreatment reagent consisted of Si-containing base solution, Ce- and Zr-containing sealing solutions on the corrosion protection of Al-alloys was studied with a 3.5% NaCl aqueous testing solution. The correlation between the corrosion resistance measured by electrochemical impedance spectroscopy (EIS) and surface chemical composition of the hybrid coating measured by time-of-flight secondary ion mass spectroscopy (ToF-SIMS) was studied. The proposed green pretreatment reagent was found improve the corrosion protection of Al-alloys, presumably due to the formation of protective oxide film acting as an oxygen barrier. [Copyright &y& Elsevier]

This study utilized a microfluidic mixer for the sample pretreatment of cell extracts for target protein quantification by mass spectrometers, including protein immunoprecipitation and protein enzymatic digestion. The time of sample pretreatment was reduced and thus the throughput of quantitative mutant proteins was increased by using the proposed method. Whole cell lysates of the cancer cell line HT-29 with gene mutations were used as the sample. The target protein BRAF was immunoprecipitated using magnetic beads in a pneumatic micromixer. Purified protein was then eluted and digested by trypsin in another two micromixers to yield peptide fragments in the solution. Using stable isotope-labeled standard as the internal control, wild-type and mutant BRAF proteins were quantified using mass spectrometry, which could be used for cancer screening. Compared with conventional methods in which protein immunoprecipitation lasts overnight, the micromixer procedure takes only 1 h, likely improving the throughput of mutant BRAF protein quantification by mass spectrometry.Three micromixers were used to reduce the sample pretreatment time of cell extracts for target protein quantification by mass spectrometers, including protein immunoprecipitation, protein elution, and protein enzymatic digestion. [ABSTRACT FROM AUTHOR]

Objective Germinal center kinase-like kinase (GLK; also called MAPKKKK-3) activates protein kinase Cθ (PKCθ) during T cell activation and controls autoimmunity in lupus patients. Intracellular kinases are involved in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine the role of GLK in RA. Methods The severity of collagen-induced arthritis (CIA) was studied in GLK-deficient mice. Expression levels of GLK from RA patients were determined by Western blotting, flow cytometry, real-time polymerase chain reaction, and immunohistochemical staining. Localization of GLK in T cells was identified by confocal microscopy. RA disease activity was assessed using the Disease Activity Score in 28 joints. Results GLK-deficient mice displayed impaired CIA development and decreased inflammatory cytokine levels. Local T cell infiltration and collagen restimulation responses were impaired by GLK deficiency. RA patients showed significantly higher GLK protein and messenger RNA levels in peripheral blood T cells than did healthy controls. GLK-overexpressing T cells in synovial fluid and synovial tissue samples from RA patients were increased compared with those from osteoarthritis patients. Confocal microscopy and flow cytometry showed that GLK colocalized and coexisted with phosphorylated PKCθ in T cells from RA patients. Frequencies of GLK-expressing T cells were significantly correlated with RA disease activity. Conclusion GLK overexpression in T cells contributes to the pathogenesis of RA, indicating that GLK is a novel biomarker for autoimmune disease severity and a potential therapeutic target for RA. [ABSTRACT FROM AUTHOR]

Abstract: Most of commercial dyes and pigments have rather complicated polyaromatic chemical structures with prolonged lifetime surviving in the Mother Nature. However, TiO2 has been reported as one of the best photocatalytic candidates for degrading dye pollutants. In this report, TiO2 film/Ti foil was prepared by hydrothermal reaction in alkali solution, the porous TiO2 film with microcrystalline structure has been obtained. The porous structure of TiO2 film was analyzed and characterized by XRD, FE-SEM and XPS. This is the first report that demonstrates that TiO2 film/Ti foil has an excellent commercial application potential for photocatalytic degradation of Ethyl Violet (EV). Especially, because of refluxing at 100°C, the porous TiO2 film structure remained undisturbed, and EV decomposed in the period of 20h. In addition, porous TiO2-mediated EV photo degradation mechanism has been proposed, as intermediates are isolated and clearly identified by GC-MS and HPLC-PDA-ESI-MS. [Copyright &y& Elsevier]

Abstract: This study explored the reaction characteristics and the burning properties of Zirconium/Boron type and Titanium/Boron type alloy delay compositions. Firstly, the initial reaction temperature and reaction heat of these two type delay compositions were measured by means of differential scanning calorimeter (DSC), which can aid to understand the reaction characteristics in advance. Afterward these delay compositions of different formulas were processed to be cylindrical pellets and were characterized by measuring their burning properties including igniting ability, burning rate and output flame temperature. In the experiments, the cylindrical pellets were packed into a heat-resisting quartz tube and were ignited by an electrical-heating wire. A high-speed video camera and a digital-image processing device were used simultaneously for recording of their combustion phenomena such as ignition and flame propagation. In addition, the output flame temperature was detected by placing a thermocouple at the end of the quartz tube. The influence of each ingredient of the formula on the reaction characteristics and the burning properties were analyzed from the experimental results. The consequences of these analyses will contribute to the evaluation of applied feasibility and limiting factors of these two type alloy delay compositions in the self-destruction mechanism module of fuse. [Copyright &y& Elsevier]

TiO2-mediated photocatalytic process has been successfully applied to degrade dye pollutants. In order to obtain a better understanding on the mechanistic details of the TiO2-assisted photodegradation of crystal violet (CV, N,N,N′,N′,N″,N″-hexamethylpararosaniline) dye with UV irradiation, 17 intermediates of the process were separated, identified and characterized by HPLC–ESI-MS techniques in this study. The results indicated that the N-de-methylation degradation of CV dye took place in a stepwise manner to yield mono-, di-, tri-, tetra-, penta-, and hexa-N-de-methylated CV species with N-hydroxymethylated intermediates, which were found for the first time, generated during the processes. Several probable photodegradation pathways were proposed and discussed. The reaction mechanisms of TiO2/UV proposed in this study would be useful for future application of this technology for decoloration of dyes. [Copyright &y& Elsevier]

Mutant RAS genes play an important role in regulating tumors through lysine residue 104 to impair GEF-induced nucleotide exchange, but the regulatory role of KRAS K104 modification on the KRASG12D mutant remains unclear. Therefore, we simulated the acetylation site on the KRASG12D three-dimensional protein structure, including KRASG12D, KRASG12D/K104A and KRASG12D/K104Q, and determined their trajectories and binding free energy with GEF. KRASG12D/K104Q induced structural changes in the α2- and α3-helices, promoted KRAS instability and hampered GEF binding (ΔΔG = 6.14 kJ/mol). We found decreased binding to the Raf1 RBD by KRASG12D/K104Q and reduced cell growth, invasion and migration. Based on whole-genome cDNA microarray analysis, KRASG12D/K104Q decreased expression of NPIPA2, DUSP1 and IL6 in lung and ovarian cancer cells. This study reports computational and experimental analyses of Lys104 of KRASG12D and GEF, and the findings provide a target for exploration for future treatment. [ABSTRACT FROM AUTHOR]