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Predicting and mapping high water table elevation in coastal landscapes is critical for both science application projects like inundation risk analysis and engineering projects like pond design and maintenance. Previous studies of water table mapping focused on the application of geostatistical methods, which cannot predict values beyond an observation spatial domain or generate an ideal pattern for regions with sparse measurements. In this study, we evaluated the multiple linear regression (MLR) and support vector machine (SVM) techniques for high water table prediction and mapping using fine spatial resolution lidar-derived Digital Elevation Model (DEM) data, and designed an application protocol of these two techniques for high water table mapping in a coastal landscape where groundwater, tide, and surface water are related. Testing results showed that SVM largely improved the high water table prediction with a mean absolute error (MAE) of 1.22 feet and root mean square error (RMSE) of 2.22 feet compared to the application of the ordinary Kriging method which could not generate a reasonable water table. MLR was also promising with a MAE of around 2 feet and RMSE of around 3 feet. The study suggests that both MLR and SVM are valuable alternatives to estimate high water table elevation in Florida. Fine resolution lidar DEMs are beneficial for high water table prediction and mapping.

Immunotoxins are Ab‐cytotoxin chimeric molecules with mighty cytotoxicity. Programmed cell death 1‐ligand 1 (PD‐L1), is a transmembrane protein expressed mainly in inflammatory tumor tissues and plays a pivotal role in immune escape and tumor progression. Although PD‐L1 immune checkpoint therapy has been successful in some cases, many patients have not benefited enough due to primary/secondary resistance. In order to optimize the therapeutic efficacy of anti‐PD‐L1 mAb, we used durvalumab as the payload and CUS245C, a type I ribosome‐inactivating protein isolated from Cucurbita moschata, as the toxin moiety, to construct PD‐L1‐specific immunotoxin (named D‐CUS245C) through the engineered cysteine residue. In vitro, D‐CUS245C selectively killed PD‐L1+ tumor cells. In vivo studies also showed that D‐CUS245C had obvious antitumor effect on PD‐L1+ human xenograft tumors in nude mice. In conclusion, in the combination of the toxin with mAb, this study developed a new immunotoxin targeting PD‐L1, emphasizing a novel and promising treatment strategy and providing a valuable way to optimize cancer immunotherapy., Programmed cell death 1‐ligand 1 is a potential target for immunotoxins. Synthesis and purification of a chemically conjugated immunotoxin D‐CUS245C kills the cells mediated by the apoptosis pathway and shows potent antitumor activity both in vitro and in vivo.

BACKGROUND To define a new quantitative grading criterion for retinal haemorrhages in term newborns based on the segmentation results of a deep convolutional neural network. METHODS We constructed a dataset of 1543 retina images acquired from 847 term newborns, and developed a deep convolutional neural network to segment retinal haemorrhages, blood vessels and optic discs and locate the macular region. Based on the ratio of areas of retinal haemorrhage to optic disc, and the location of retinal haemorrhages relative to the macular region, we defined a new criterion to grade the degree of retinal haemorrhages in term newborns. RESULTS The F1 scores of the proposed network for segmenting retinal haemorrhages, blood vessels and optic discs were 0.84, 0.73 and 0.94, respectively. Compared with two commonly used retinal haemorrhage grading criteria, this new method is more accurate, objective and quantitative, with the relative location of the retinal haemorrhages to the macula as an important factor. CONCLUSIONS Based on a deep convolutional neural network, we can segment retinal haemorrhages, blood vessels and optic disc with high accuracy. The proposed grading criterion considers not only the area of the haemorrhages but also the locations relative to the macular region. It provides a more objective and comprehensive evaluation criterion. The developed deep convolutional neural network offers an end-to-end solution that can assist doctors to grade retinal haemorrhages in term newborns.

A borrowing-hydrogen reaction between amines and alcohols is an atom-economic way to prepare alkylamines, ideally with water as the sole byproduct. Herein, nickel catalysts are used for direct N-alkylation of hydrazides and arylamines using racemic alcohols. Moreover, a nickel catalyst of (S)-binapine was used for an asymmetric N-alkylation of benzohydrazide with racemic benzylic alcohols.

Photodynamic therapy (PDT) has emerged as an important minimally invasive tumor treatment technology. The search for an effective photosensitizer to realize selective cancer treatment has become one of the major focus in recent developments of PDT technology. Controllable singlet-oxygen release based on specific cancer-associated events, as another major layer of selectivity mode, has attracted great attention in recent years. Here, for the first time, we demonstrated that a novel mixed-metal functionalized metal-organic framework nanoparticle (MOF NP) photosensitizer can be activated by a hydrogen sulfide (H2S) signaling molecule in a specific tumor microenvironment for PDT against cancer with controllable singlet-oxygen release in living cells. The effective removal of tumors in vivo further confirmed the satisfactory treatment effect of the MOF NP photosensitizer.

We have developed a Cu(II) -, Ag(I) -, and NaOTf-mediated intramolecular quaternization by arylation reactions to synthesize a variety of N-heterocyclic carbene (NHC) precursors with a benzene-fused backbone. The methodology also provides a convenient alternative route for the synthesis of 6-H-phenanthridine derivatives. A novel silver-NHC complex was prepared by treatment of Ag2 O with the free carbene, which was in situ prepared from the deprotonation of a representative quinazolinonium salt.

3 D capacitance: Hierarchical porous carbon-based electrode materials with a composite structure are prepared from a biomass waste by a facile carbonization and activation process without using any additional templates. Benefiting from the composite structure, the ions experience a variety of environments, which contribute significantly to the excellent electrochemical properties of supercapacitors.

Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p

Several anion-π complexes of isocyanuric acid, thioderivatives and their halogen substituted derivatives with chloride anion have been studied. The geometric and energetic features, charges transfer from chloride anion to the aromatic rings and “atoms-in-molecules” analysis are performed and discussed for these complexes. The results show that the strength of the anion-π interaction between cyanuric derivatives and chloride anion can be tuned by halogen-substituting. The localized molecular orbital energy decomposition analyses shows that, in the total interaction, exchange and electrostatic energies are the dominant stabilizing forces, and the polarization energies also make a favorable contribution. Finally, solvent effect significantly weakens the anion-π interaction between the isocyanuric derivatives and chloride anion, especially in polar solvents. © 2015 Wiley Periodicals, Inc.

Although doxorubicin (Dox) is widely used in clinical treatment for solid tumors, it causes many side-effects such as heart and kidney damage, bone marrow suppression, and drug resistance. Legumain is a lysosomal protease that is elevated and associated with an invasive and metastatic phenotype in a number of solid tumors. In this study, we designed and synthesized a Dox prodrug, N-benzyloxycarbonyl-Ala-Ala-Asn-Doxorubicin (CBZ-AAN-Dox), with 94% purity. Single substrate kinetic assays demonstrated hLegumain-specific enzymatic cleavage and activation of the prodrug in vitro, and this enzymatic cleavage of the prodrug substrate was more sensitive in acidic conditions, releasing more than 70% of Dox after 24 h. Treatment of tumor cells with our prodrug demonstrated a much higher IC50 value, significantly enhanced uptake of the prodrug, and considerably less cellular toxicity compared to Dox treatment alone. Our study presents a novel prodrug, CBZ-AAN-Dox, to potentially increase both the safety and efficacy of clinical treatment of tumors by exploiting the tumor's innate expression of legumain.

Three TRAPP (transport protein particle) complexes have been identified in Saccharomyces cerevisiae. GTPases Ypt1 and Ypt31/32 suppress autophagic defects in the mutants of TRAPPIII-specific subunit (Trs85) and TRAPPII-specific subunits (Trs130 and Trs120), respectively. However, the roles of the common TRAPP subunits (which also form the TRAPPI complex) in autophagy and their relationship to Rab GTPases in autophagy remain unclear. As Bet3 (a common TRAPP subunit) cannot be mutated together with either Trs85 or Trs130, we examined starvation-induced autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway in bet3ts cells. The results demonstrated that GFP-Atg8 was dispersed in the cytoplasm and Ape1 accumulated as a unique dot on the vacuolar membrane in bet3ts cells. Further analysis revealed that Ape1 maturation and GFP-Atg8 processing are defective in these cells. However, prApe1 (precursor form of Ape1) and GFP-Atg8 are protease-accessible in bet3ts cells under starvation, which indicates that Bet3 functions before autophagosome closure. Furthermore, active Ypt1, but not Ypt31, partly rescued the autophagic defects of bet3ts cells. We conclude that Bet3 is involved in autophagy and propose that it participates in autophagy through TRAPP complexes mostly via Ypt1 in yeast.

Functional polymorphisms of tumor necrosis factor-alpha (TNF-α) may play a critical role in the regulation of immune and inflammatory responses and could affect transcriptional levels of the TNF-α gene and thus contribute to carcinogenesis and outcomes of cancer patients. In a cohort study, we explored the associations between TNF-α polymorphisms and risk of recurrence of squamous cell carcinoma of the nonoropharynx (SCCNOP). We used log-rank test and multivariable Cox models to evaluate the associations between TNF-α polymorphisms and risk of recurrence. In overall comparisons, patients with the TNF-α -857 CC, TNF-α -863 CC and TNF-α -1031 TT genotypes had significantly worse disease-free survival (log-rank, p = 0.014, log-rank, p = .020, and log-rank, p = .002, respectively) and higher risk of disease recurrence than patients with the corresponding variant genotypes, respectively (hazard ratio [HR], 1.4, 95% CI, 1.1-1.9, HR, 1.4, 95% CI, 1.0-1.8 and HR, 1.6, 95% CI, 1.2-2.2, respectively). However, no significant association was detected for the TNF-α -308 polymorphism. Moreover, in further stratified analyses based on smoking status and treatment, we found that the associations of the TNF-α -857, TNF-α -863 and TNF-α -1031 polymorphisms with risk of recurrence were more pronounced in smokers and patients treated with chemoradiation. Our findings support a significant role of the TNF-α -857, TNF-α -863 and TNF-α -1031 polymorphisms in recurrence of SCCNOP, especially in smokers and patients treated with chemoradiation. Future prospective studies with larger sample size are needed to confirm these findings.

The promoter variants of TNF-α, a major regulator of immune and inflammation responses, have been implicated in cancer development and prognosis. Thus, we investigated associations between four TNF-α promoter variants and risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated associations of four TNF-α polymorphisms with risk of recurrence in a cohort of 846 patients with SCCOP. Log-rank test and multivariable Cox models were used to evaluate associations. Compared with patients with variant genotypes of the TNF-α -308 and TNF-α -863 polymorphisms, patients with common homozygous genotypes had worse disease-free survival (log-rank p = 0.0002 and p < 0.0001, respectively) and increased risk of SCCOP recurrence (HR, 1.9, 95% CI, 1.3–2.8 and HR, 1.9, 95% CI, 1.3–2.7, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of the TNF-α -308 and -863 polymorphisms had worse disease-free survival (log-rank p = 0.005 and p = 0.007, respectively) and higher recurrence risk than patients with variant genotypes of these polymorphisms (HR, 5.1, 95% CI, 1.4–18.4 and HR, 3.7, 95% CI, 1.5–9.1, respectively), while no such significant associations were found for TNF-α -857 or -1031 polymorphisms. Our findings suggest that TNF-α -308 and -863 polymorphisms may modulate the risk of SCCOP recurrence in patients with HPV16-positive tumors. However, larger studies are needed to validate these results.

The sensing mechanism of the N-Phenyl-N′-(3-quinolinyl)urea (PQU) chemosensor for fluoride anion has been investigated by density functional theory/time-dependent density function theory. The double intermolecular hydrogen bonds are formed between the three anions (X−F−, AcO−, Cl−) and the urea fragment of PQU. In the S0 states, the HbX− hydrogen bonds are slightly stronger than the HaX− hydrogen bonds and the fluoride-induced deprotonation occurs at the NHb position rather than at the NHa position. Consequently, the absorption peaks, including an intramolecular charge transfer transition and a ππ* transition, are significantly red-shifted. Thermodynamic calculations confirm that the deprotonation in the ground state is favorable in energy only when excess fluoride anion exists. Along with the S0 S1 transition, the HaX− hydrogen bonds strengthen and the HbX− hydrogen bonds weaken. However, the emission spectra of [PQU-Hb]−, instead of [PQU-Ha]−, are observed upon addition of fluoride anion. © 2013 Wiley Periodicals, Inc.

We have developed I2 - or N-iodosuccinimide (NIS)-mediated amidiniumation of N-alkenyl formamidines for the syntheses of cyclic formamidinium salts, some of which could be directly used as N-heterocyclic carbene (NHC) precursors. Treatment of iodine-containing formamidinium salts with Al2 O3 led to the formation of cyclic formamidinium salts with an unsaturated backbone. A rhodium(I) complex ligated by a representative NHC was prepared by the reaction of [Rh(cod)Cl]2 (cod=1,5-cyclooctadiene) with the free carbene obtained in situ from deprotonation of the corresponding formamidinium salts. The NHCs prepared in situ can also react with S8 to afford the corresponding thiones.

Two 4-coordinated titanocene complexes, [(η5-C5H5)2Ti(O,O′)(5-NO2-OCC6H3)] (I) and [(η5-C5H5)2Ti(2-OH-5-NO2-O2CC6H3)2] (II), have been synthesized by reaction of Cp2TiCl2 and 5-nitrosalicylic acid in aqueous media. Single-crystal X-ray analyses of I and II display the mononuclear forms of TiIV, and geometries at titanium atoms are distorted tetrahedrons, while the coordination environment at TiIV in complex I is different from that in complex II. Crystallographic characterization revealed that each of the complexes exhibits a three-dimensional framework constructed through weak interactions, which are H-bonding, π–π stacking and C–H·π interactions, but they differ greatly when forming the three-dimensional network structure in both complexes. The results show that the dramatic change of conditions has great effect on the molecular structure of 5-nitrosalicylate titanocene, thereby significantly influencing the weak interactions and the specific framework structure. Copyright © 2005 John Wiley & Sons, Ltd.