Correction: Sun, Y.; et al. Bi-Objective Modelling for Hazardous Materials Road-Rail Multimodal Routing Problem with Railway Schedule-Based Space-Time Constraints. Int. J. Environ. Res. Public Health 2016, 13, 762.

Bi-Objective Modelling for Hazardous Materials Road-Rail Multimodal Routing Problem with Railway Schedule-Based Space-Time Constraints.[...].

Bi-Objective Modelling for Hazardous Materials Road-Rail Multimodal Routing Problem with Railway Schedule-Based Space-Time Constraints.

The transportation of hazardous materials is always accompanied by considerable risk that will impact public and environment security. As an efficient and reliable transportation organization, a multimodal service should participate in the transportation of hazardous materials. In this study, we focus on transporting hazardous materials through the multimodal service network and explore the hazardous materials multimodal routing problem from the operational level of network planning. To formulate this problem more practicably, minimizing the total generalized costs of transporting the hazardous materials and the social risk along the planned routes are set as the optimization objectives. Meanwhile, the following formulation characteristics will be comprehensively modelled: (1) specific customer demands; (2) multiple hazardous material flows; (3) capacitated schedule-based rail service and uncapacitated time-flexible road service; and (4) environmental risk constraint. A bi-objective mixed integer nonlinear programming model is first built to formulate the routing problem that combines the formulation characteristics above. Then linear reformations are developed to linearize and improve the initial model so that it can be effectively solved by exact solution algorithms on standard mathematical programming software. By utilizing the normalized weighted sum method, we can generate the Pareto solutions to the bi-objective optimization problem for a specific case. Finally, a large-scale empirical case study from the Beijing-Tianjin-Hebei Region in China is presented to demonstrate the feasibility of the proposed methods in dealing with the practical problem. Various scenarios are also discussed in the case study.

Click with a boronic acid handle: a neighboring group-assisted click reaction that allows ready secondary functionalization.

The feasibility of a neighboring boronic acid-facilitated facile condensation of an aldehyde is described. This reaction is bio-orthogonal, complete at room temperature within minutes, and suitable for bioconjugation chemistry. The boronic acid group serves the dual purpose of catalyzing the condensation reaction and being a handle for secondary functionalization.

Post-synthesis DNA modifications using a trans-cyclooctene click handle.

Post-synthesis DNA modification is a very useful method for DNA functionalization. This is achieved by using a modified NTP, which has a handle for further modifications, replacing the corresponding natural NTP in polymerase-catalyzed DNA synthesis. Subsequently, the handle can be used for further functionalization after PCR, preferably through a very fast reaction. Herein we describe polymerase-mediated incorporation of trans-cyclooctene modified thymidine triphosphate (TCO-TTP). Subsequently, the trans-cyclooctene group was reacted with a tetrazine tethered to other functional groups through a very fast click reaction. The utility of this DNA functionalization method was demonstrated with the incorporation of a boronic acid group and a fluorophore. The same approach was also successfully used in modifying a known aptamer for fluorescent labelling applications.

A click-and-release approach to CO prodrugs.

Carbon monoxide belongs to the family of signaling molecules and has been shown to possess therapeutic effects. Similar to NO, safe delivery of CO is a key issue in developing CO-based therapeutics. Herein we report a "click and release" CO-prodrug approach, which allows the release of CO under physiological conditions without the need for light irradiation. The system releases CO in a triggered and controllable manner and possesses the potential of tunable release rates.

3,6-Substituted-1,2,4,5-tetrazines: tuning reaction rates for staged labeling applications.

Cycloaddition reactions involving tetrazines have proven to be powerful bioorthogonal tools for various applications. Conceivably, sequential and selective labeling using tetrazine-based reactions can be achieved by tuning the reaction rate. By varying the substituents on tetrazines, cycloaddition rate variations of over 200 fold have been achieved with the same dienophile. Upon coupling with different dienophiles, such as norbornene, the reaction rate difference can be over 14,000 fold. These substituted tetrazines can be very useful for selective labeling under different conditions.

A fast and simple approach to the quantitative evaluation of fibrinogen coagulation.

Fibrinogen is essential in the intrinsic and extrinsic blood coagulation process. Inhibition of fibrinogen aggregation could lead to anticoagulation effects. The availability of methods for easy quantitative evaluation of the coagulation process is critical to studying coagulation and its inhibition. A commonly used method is UV-Vis absorbance (405 nm) detection by a micro-plate reader. However, because of the heterogeneous nature of the resulting mixture in a coagulation process, transmission-based optical measurements give large variations. Herein, a very simple and easy method is developed for the quantitative measurements of the coagulation process. The method was validated using three known thrombin inhibitors: 4-(2-aminoethyl) benzenesulfonyl fluoride (IC50: 0.01 mM), p-amidinophenyl methanesulfonyl fluoride (IC50: 0.18 mM) and PMSF (IC50: 0.23 mM).

Fluorescent conjugate of sLe(x)-selective bisboronic acid for imaging application.

Carbohydrate-based biomarkers such as sialyl Lewis X are known to correlate with cancer formation and progression. By targeting sialyl Lewis X, we have developed a boronolectin-fluorophore conjugate, which was able to selectively label and image xenograft (sc) tumor. This represents the very first example that a small molecule capable of recognizing a carbohydrate biomarker was used for optical imaging application.

Hypoxia inducible factor pathway inhibitors as anticancer therapeutics.

Hypoxia is a significant feature of solid tumor cancers. Hypoxia leads to a more malignant phenotype that is resistant to chemotherapy and radiation, is more invasive and has greater metastatic potential. Hypoxia activates the hypoxia inducible factor (HIF) pathway, which mediates the biological effects of hypoxia in tissues. The HIF complex acts as a transcription factor for many genes that increase tumor survival and proliferation. To date, many HIF pathway inhibitors indirectly affect HIF but there have been no clinically approved direct HIF inhibitors. This can be attributed to the complexity of the HIF pathway, as well as to the challenges of inhibiting protein-protein interactions.

Binding Model for the Interaction of Anticancer Arylsulfonamides with the p300 Transcription Cofactor.

Hypoxia inducible factors (HIFs) are transcription factors that activate expression of multiple gene products and promote tumor adaptation to a hypoxic environment. To become transcriptionally active, HIFs associate with cofactors p300 or CBP. Previously, we found that arylsulfonamides can antagonize HIF transcription in a bioassay, block the p300/HIF-1α interaction, and exert potent anticancer activity in several animal models. In the present work, KCN1-bead affinity pull down, (14)C-labeled KCN1 binding, and KCN1-surface plasmon resonance measurements provide initial support for a mechanism in which KCN1 can bind to the CH1 domain of p300 and likely prevent the p300/HIF-1α assembly. Using a previously reported NMR structure of the p300/HIF-1α complex, we have identified potential binding sites in the p300-CH1 domain. A two-site binding model coupled with IC50 values has allowed establishment of a modest ROC-based enrichment and creation of a guide for future analogue synthesis.

Clicking 1,2,4,5-tetrazine and cyclooctynes with tunable reaction rates.

Substituted tetrazines have been found to undergo facile inverse electron demand Diels-Alder reactions with "tunable" reaction rates.

A novel iodine-mediated tandem cyclization-cycloaddition reaction leading to polyoxacyclic ring systems.

A novel iodine-catalyzed tandem cyclization-cycloaddition reaction of ortho-alkynyl-substituted benzaldehydes leading to polyoxacyclic ring systems has been developed, which represents a useful approach towards the synthesis of the oxabicyclo-[3.2.1]octane ring skeleton found in a variety of natural products.