Synthesis and Biological Evaluation of Imidazo[2,1‐b][1,3,4]thiadiazole‐Linked Oxindoles as Potent Tubulin Polymerization Inhibitors

A series of imidazo[2,1‐b][1,3,4]thiadiazole‐linked oxindoles composed of an A, B, C and D ring system were synthesized and investigated for anti‐proliferative activity in various human cancer cell lines; test compounds were variously substituted at rings C and D. Among them, compounds 7 ((E)‐5‐fluoro‐3‐((6‐p‐tolyl‐2‐(3,4,5‐trimethoxyphenyl)‐imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one), 11 ((E)‐3‐((6‐p‐tolyl‐2‐(3,4,5‐trimethoxyphenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one), and 15 ((E)‐6‐chloro‐3‐((6‐phenyl‐2‐(3,4,5‐trimethoxyphenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one) exhibited potent anti‐proliferative activity. Treatment with these three compounds resulted in accumulation of cells in G₂/M phase, inhibition of tubulin assembly, and increased cyclin‐B1 protein levels. Compound 7 displayed potent cytotoxicity, with an IC₅₀ range of 1.1–1.6 μM , and inhibited tubulin polymerization with an IC₅₀ value (0.15 μM ) lower than that of combretastatin A‐4 (1.16 μM ). Docking studies reveal that compounds 7 and 11 bind with αAsn101, βThr179, and βCys241 in the colchicine binding site of tubulin.     

Letter to the Editor: A List of New Group Divisible Designs

Group divisible designs are the most important class of partially balanced incomplete block (PBIB) designs. A list of new group divisible designs with r, k ⩽ 10 is provided.     

MRI of the brain in patients with miliary pulmonary tuberculosis without symptoms or signs of central nervous system involvement

MRI was performed on patients with miliary pulmonary tuberculosis to look for brain involvement and to study the features sequentially, during treatment. We studied seven patients with typical radiographic tuberculosis, and no symptoms or signs of central nervous system involvement. Conventional spin-echo (SE) imaging, including contrast enhanced images, was performed in all cases. All patients showed brain involvement: four patients showed lesions mainly less than 3 mm in diameter, better seen on contrast-enhanced images. These patients showed oedema around the lesions after 2 months of treatment, with subsequent regression on follow-up. The remaining three patients had multiple lesions, 3 mm or more in diameter, which showed a gradual decrease on follow-up. We conclude that the brain may commonly be involved in miliary pulmonary tuberculosis. The response to treatment depends on the stage of the granuloma and shows a definite pattern of healing on follow-up.     

On the steady flow produced in fluid-particle suspension by an infinite rotating disk with surface suction

The steady flow of a fluid-particle suspension over an infinite rotating disk with uniform suction is considered. The equations of motion are reduced to ordinary differential equations by similarity transformations and solved numerically by using a least-squares finite-element method. Some typical results for both fluid and particle phases and density distributions of the particles are presented graphically for the suction parameter A = 3.0 in order to illustrate some interesting features of the solutions. It is observed that the radial velocity of the particle attains its maximum on the surface of the disk and the particles slip in the tangential direction on the disk. The magnitudes of the radial velocity components of both the fluid and particle phases are found to decrease rapidly as suction increases.     

A Differential CMOS Current-Mode Variable Gain Amplifier with Digital dB-Linear Gain Control

A novel CMOS variable gain amplifier operating on current signals with a dB-linear gain control is presented. The gain control is achieved by multiplying a digitally synthesized exponentially varying control current signal by a differential input signal in the current domain. A current amplifier at the output sets the gain to the desired level. Current-mode operation allows for a reduced supply voltage by minimizing the voltage swing at the low impedance nodes of the circuit. Multiple circuit realizations for various blocks are presented allowing for designs meeting different constraints. Experimental realization of the variable gain amplifier shows the validity of the presented approach.     

Analysis of the stress-strain curves of a modified 9Cr-1Mo steel by the voce equation

The representation of stress-strain curves by empirical relations can give first-hand information on the deformation behavior of a material. Although the constants in these equations are simple numerals for smooth fitting of the curves, a theoretical basis using dislocation interaction has been out forth bv Berastrom.[1]     

A CMOS RF front-end for a multistandard WLAN receiver

This letter describes the design and performance of a dual band tri-mode receiver front-end compliant with the IEEE 802.11a, b, and g standards. The receiver front-end was built in a 0.18-/spl mu/m CMOS process and achieves a noise figure of 4.7 dB/5.1 dB for the 2.4-GHz/5-GHz bands, respectively. The receiver front-end provides a dual gain mode of 5 dB/30 dB with an IIP3 of -1dBm for the low gain mode. The front-end draws 25 mA/27 mA from a 1.8-V supply for the 2.4-GHz/5-GHz bands, respectively.     

Some aspects of dislocation-precipitate interaction in under-aged aluminium-germanium alloy

The glide dislocation-precipitate interaction in under-aged alloy is investigated by microscopy and low-temperature deformation techniques. Slip-line features of room temperature deformed samples were observed by optical microscopy. From tensile tests at various temperatures the variation of flow stress withT ^2/3 was established. Comparing the present results with those obtained on the peak-hardened condition of the same alloy it is concluded that moving dislocation shear through the small rod-shaped germanium precipitates.