Fabrication and photoresponse of n-$$\hbox {WS}_{2}/$$p-V$$_{0.25}$$0.25W$$_{0.75}$$0.75Se$$_{2}$$2 van der Waals heterojunction

Excitation functions for \(\alpha \)-induced reactions on natural vanadium were measured in the energy range up to 20 MeV. The stacked-foil activation technique was used. The experimental results were compared with the theoretical calculations using EMPIRE-3.1, EMPIRE-3.2.2 and TENDL 2015, and with earlier experimental results. Thick target yields were calculated for the production of \(^{54}\hbox {Mn}\) and for the associated impurity \(^{52}\hbox {Mn}\).     

Structural Insights in Mammalian Sialyltransferases and Fucosyltransferases: We Have Come a Long Way,but It Is Still a Long Way Down

Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. In the past, several advances in glycostructural biology have been made with the determination of crystal structures of several important STs and FUTs in mammals. Additionally, how the independent evolution of STs and FUTs occurred with a limited set of global folds and the diverse modular ability of catalytic domains toward substrates has been elucidated. This review highlights advances in the understanding of the structural architecture, substrate binding interactions, and catalysis of STs and FUTs in mammals. While this general understanding is emerging, use of this information to design inhibitors of STs and FUTs will be helpful in providing further insights into their role in the manifestation of cancer and developing targeted therapeutics in cancer.     

Symmetric sums of squares over k-subset hypercubes

Mathematical Programming - We consider the problem of finding sum of squares (sos) expressions to establish the non-negativity of a symmetric polynomial over a discrete hypercube whose coordinates...     

Accelerating Branch-and-Bound through a Modeling Language Construct for Relaxation-Specific Constraints

In the tradition of modeling languages for optimization, a single model is passed to a solver for solution. In this paper, we extend BARON’s modeling language in order to facilitate the communication of problem-specific relaxation information from the modeler to the branch-and-bound solver. This effectively results into two models being passed from the modeling language to the solver. Three important application areas are identified and computational experiments are presented. In all cases, nonlinear constraints are provided only to the relaxation constructor in order to strengthen the lower bounding step of the algorithm without complicating the local search process. In the first application area, nonlinear constraints from the reformulation–linearization technique (RLT) are added to strengthen a problem formulation. This approach is illustrated for the pooling problem and computational results show that it results in a scheme that makes global optimization nearly as fast as local optimization for pooling problems from the literature. In the second application area, we communicate with the relaxation constructor the first-order optimality conditions for unconstrained global optimization problems. Computational experiments with polynomial programs demonstrate that this approach leads to a significant reduction of the size of the branch-and-bound search tree. In the third application, problem-specific nonlinear optimality conditions for the satisfiability problem are used to strengthen the lower bounding step and are found to significantly expedite the branch-and-bound algorithm when applied to a nonlinear formulation of this problem.     

Separation and Characterization of New Forced Degradation Products of Macitentan: A Dual Endothelin Receptor Antagonist

Macitentan (MCT) is an endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension. In the present study, MCT was subjected to forced degradation as per ICH guidelines. The drug degraded extensively in acidic, basic as well as neutral hydrolytic conditions and seven degradation products (DPs) were formed. All these DPs were selectively separated using high-performance liquid chromatography (HPLC) with a stationary phase of Inertsil C₁₈ column (150 × 4.6 mm, 5 μm) and a mobile phase consisting of gradient mixture of 0.02% trifluoroacetic acid (TFA) and acetonitrile (ACN). The developed HPLC method was transferred to LC–ESI–QTOF–MS/MS for identification of DPs. The final mass spectrometric conditions were optimized for better ionization of drug and DPs with optimum mass signal sensitivity. All the formed DPs were new and well separated with sufficient resolution. The developed HPLC method was validated as per ICH-guidelines and can be used in drug testing labs for determination of quality of MCT in bulk and finished formulations.     

Nickel boride mediated chemoselective deprotection of 1,1-diacetates to aldehydes and deprotection with concomitant reduction to alcohols at ambient temperature

A variety of 1,1-diacetates have been chemoselectively and efficiently deprotected to the corresponding aldehydes as well as deprotected and concomitantly reduced to the corresponding alcohols in high yields at ambient temperature with nickel boride generated in situ using different molar ratios of sodium borohydride and nickel (II) chloride in methanol at room temperature. Deprotection and reduction of a variety of aromatic, aliphatic and heterocyclic acylals have been achieved efficiently. Mild reaction conditions, easy work-up, high yields and chemoselectivity demonstrate the efficiency of this new method.     

l-Proline catalyzed domino Michael addition of N-substituted anilines

Here we report l-proline catalyzed 3-component reaction of indoles, aldehydes and N-substituted anilines in water as solvent at room temperature for the synthesis of 3-(α,α-diarylmethyl)indoles. The reaction is in fact a Michael addition of N-substituted anilines to alkylideneindolenines. The reaction is very clean, high yielding and having broad substrate scope. A tentative mechanism is proposed.     

Semidefinite Relaxations of Fractional Programs via Novel Convexification Techniques

In a recent work, we introduced the concept of convex extensions for lower semi-continuous functions and studied their properties. In this work, we present new techniques for constructing convex and concave envelopes of nonlinear functions using the theory of convex extensions. In particular, we develop the convex envelope and concave envelope of z=x/y over a hypercube. We show that the convex envelope is strictly tighter than previously known convex underestimators of x/y. We then propose a new relaxation technique for fractional programs which includes the derived envelopes. The resulting relaxation is shown to be a semidefinite program. Finally, we derive the convex envelope for a class of functions of the type f(x,y) over a hypercube under the assumption that f is concave in x and convex in y.     

Water-Promoted Synthesis of 3,3′-Di(indolyl)oxindoles

The reaction of isatin and indoles in refluxing water/ethanol (7:3) affords 3,3′-di(indolyl)oxindoles in excellent yields.