A Novel Docetaxel-Biotin Chemical Conjugate for Prostate Cancer Treatment

A novel conjugate of docetaxel and biotin (designated as IDD-1010) was designed and chemically synthesized via an ester linkage at position 2’ carbon in docetaxel. The synthesized pure IDD-1010 exhibits a potent anti-cancer activity in in vitro and in vivo studies. At 10 nM, IDD-1010 has induced increased apoptosis and mitotic arrest of PC3-Luc prostate cancer cells, causing aneuploidy and cell death at higher concentrations. Toxicology studies indicate that the maximal tolerated dose (MTD) of IDD-1010 is 150 mg/kg in mice; equivalent to about 12.2 mg/kg of body weight, or to about an 850 mg dose for a patient weighing 70 kg. The MTD-treated mice exhibited weight gain similar to that of the control group, with no gross pathological signs at 14 days post-dosing. At a lower dose, IDD-1010 treatment did not lead to any significant weight loss in mice, although decreased the tumor volume stemming from injecting cancer cells into the dorsal loop of mouse prostate, and it was found to be more potent than Paclitaxel (reference drug). Similarly, IDD-1010 treatment significantly reduced tumor weight and thereby increased the percentage of mice survival as compared to reference drug-treated and control groups. To summarize, the described experiments using IDD-1010, as compared to the reference drug, strongly suggest a potential treatment utility with a wider therapeutic window for prostate cancer. Henceforth, clinical research on such a novel drug candidate would be greatly worthwhile.     

A one-dimensional local tuning algorithm for solving GO problems with partially defined constraints

Lipschitz one-dimensional constrained global optimization (GO) problems where both the objective function and constraints can be multiextremal and non-differentiable are considered in this paper. Problems, where the constraints are verified in a priori given order fixed by the nature of the problem are studied. Moreover, if a constraint is not satisfied at a point, then the remaining constraints and the objective function can be undefined at this point. The constrained problem is reduced to a discontinuous unconstrained problem by the index scheme without introducing additional parameters or variables. A new geometric method using adaptive estimates of local Lipschitz constants is introduced. The estimates are calculated by using the local tuning technique proposed recently. Numerical experiments show quite a satisfactory performance of the new method in comparison with the penalty approach and a method using a priori given Lipschitz constants.This research was supported by the following grants: FIRB RBNE01WBBB, FIRB RBAU01JYPN, PRIN 2005017083-002, and RFBR 04-01-00455-a. The authors would like to thank anonymous referees for their subtle suggestions.     

Crystal structure and cation transport properties of the layered monodiphosphates Rb6Bi4(PO4)2(P2O7)3

Single crystals of the new Bi(III) phosphates, Rb₆Bi₄(PO₄)₂(P₂O₇)₃, have been isolated and their structure has been determined by X-ray diffraction techniques. This compound crystallizes in the monoclinic space group P2₁/c with a=9.077(1)Å, b=9.268(2)Å, c=36.418(6)Å, β=95.75(1)° and Z=8. The crystal structure is made up of BiO₅ and BiO₆ polyhedra sharing the corners with PO₄ tetrahedra and P₂O₇ diphosphate groups. The structure can be described as infinite anionic layers with composition [Bi₄(PO₄)₂(P₂O₇)₃]_∞⁶⁻ parallel to the [301] plane, connected via P-O-Bi bridges to form a three-dimensional open framework. This framework delimits tunnels running along [100] and [010] directions, where the rubidium ions reside. This compound exhibits a rubidium ion conduction but with rather low conductivity value at 640 K.     

A Facile One‐Pot Synthesis and Anticancer Evaluation of Novel Substituted 1,2‐Dihydropyridine and 1,2,3,4‐Tetrahydropyrimidine Analogues

Current paper involves the one‐pot synthesis of various 1,2‐dihydropyridine and 1,2,3,4‐tetrahydropyrimidine analogues. The antitumor activity of the synthesized compounds has been carried out against various human cancer cell lines, and some of the analogues are found to be potent.     

Investigation of effect of thiophene-2-acetic acid as an electron anchoring group for a photovoltaic device

Different anchoring groups such as thiophene-2-acetic and malonic acid were investigated for synthesis of new photosensitizers. The new dyes (photosensitizers) were made pure and determined by various analytical techniques. The chemical structure of synthesized materials was certified by analytical studies. UV-Visible and fluorescence spectra revealed intense fluorescence and absorption for organic photosensitizers. The cyclic voltammetry results showed that the two photosensitizers were suitable for dye sensitized solar cell preparation. The work electrode was gathered using tin (IV) oxide nanoparticles in dye-sensitized solar cells structure. The new photosensitizers and tin (IV) oxide were used for photovoltaic devices preparation. The power conversion efficiency was obtained as about 4.12 and 4.29% for Dye 1 and Dye 2, respectively.     

Experimental Study of the Influence of Different Load Changes in Inlet Gas and Solvent Flow Rate on CO2 Absorption in a Sieve Tray Column

An experimental study was conducted in a sieve tray column. This study used a simulated flue gas consisting of 30% CO₂ and 70%. A 10% mass fraction of methyl diethanolamine (MDEA) aqueous solution was used as a solvent. Three ramp-up tests were performed to investigate the effect of different load changes in inlet gas and solvent flow rate on CO₂ absorption. The rate of change in gas flow rate was 0.1 Nm³/h/s, and the rate of change in MDEA aqueous solution was about 0.7 NL/h/s. It was found that different load changes in inlet gas and solvent flow rate significantly affect the CO₂ volume fraction at the outlet during the transient state. The CO₂ volume fraction reaches a peak value during the transient state. The effect of different load changes in inlet gas and solvent flow rate on the hydrodynamic properties of the sieve tray were also investigated. The authors studied the correlation between the performance of the absorber column for CO₂ capture during the transient state and the hydrodynamic properties of the sieve tray. In addition, this paper presents an experimental investigation of the bubble-liquid interaction as a contributor to entropy generation on a sieve tray in the absorption column used for CO₂ absorption during the transient state of different load changes.     

Possibility designing half-wave and full-wave molecular rectifiers by using single benzene molecule

This work focused on possibility designing half-wave and full-wave molecular rectifiers by using single and two benzene rings, respectively. The benzene rings were threaded by a magnetic flux that changes over time. The quantum interference effect was considered as the basic idea in the rectification action, the para and meta configurations were investigated. All the calculations are performed by using steady-state theoretical model, which is based on the time-dependent Hamiltonian model. The electrical conductance and the electric current are considered as DC output signals of half-wave and full-wave molecular rectifiers. The finding in this work opens up the exciting potential to use these molecular rectifiers in molecular electronics.     

Study on bioequivalence of beraprost in healthy volunteers by liquid chromatography with tandem mass spectrometry

Beraprost sodium is an oral prostacyclin analog that was first approved in 1992 (Japan) for the treatment of peripheral vascular disorders. It is administered orally as a tablet available in strength 20 μg. In this paper, we described a liquid chromatography tandem mass spectrometry method that was developed for the quantification of beraprost in human plasma with high sensitivity at picogram per milliliter concentration. The method had been validated in terms of selectivity, sensitivity, accuracy and precision, matrix effect, linearity, recovery and carry‐over according to the Guideline on Bioanalytical Validation from the European Medicines Agency. The standard calibration curve for beraprost was 9.5–1419 pg/mL. This method has been applied successfully to a bioequivalence study with 60 μg of beraprost (three tablets) in 29 healthy volunteers. The results showed that the two formulations of beraprost are bioequivalent.     

Ascents of size less than <Emphasis Type="Italic">d</Emphasis> in compositions

A composition of a positive integer n is a finite sequence π₁π₂...π _m of positive integers such that π₁+...+π _m = n. Let d be a fixed number. We say that we have an ascent of size d or more (respectively, less than d) if π _i+1 ≥ π _i +d (respectively, π _i < π _i+1 < π _i + d). Recently, Brennan and Knopfmacher determined the mean, variance and limiting distribution of the number of ascents of size d or more in the set of compositions of n. In this paper, we find an explicit formula for the multi-variable generating function for the number of compositions of n according to the number of parts, ascents of size d or more, ascents of size less than d, descents and levels. Also, we extend the results of Brennan and Knopfmacher to the case of ascents of size less than d. More precisely, we determine the mean, variance and limiting distribution of the number of ascents of size less than d in the set of compositions of n.