Consideration of conformational transitions and racemization during process development of recombinant glucagon-like peptide-1

This article summarizes the results of a combined analysis from two identical multicenter clinical trials that investigated the efficacy and safety of sertraline versus placebo for treating panic disorder. Patients with panic disorder who were treated with sertraline had a statistically significant reduction in the mean number of panic attacks per week (the primary efficacy measure) as compared with placebo (4.8 vs. 2.5, p < .001). Sertraline-treated patients also showed greater improvement that was statistically significant on several ratings of panic disorder symptomatology and functioning. The design characteristics, clinical rating measures, and outcome measures in these trials included most of the features deemed essential by Shear and Maser (1994) in their summary of the NIMH Consensus Conference for the development of standardized assessments for panic disorder. This suggests that the NIMH Consensus Conference played a key role in developing successful multicenter pharmacological treatment studies, such as this one that ultimately demonstrated that sertraline was an effective treatment for panic disorder.     

Multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms associated with vertical subluxation and atlanto-occipital subluxation in ankylosing spondylitis

Ankylosing spondylitis (AS) results in disease-specific inflammation at the site of ligamentous insertion into the bone. Atlantoaxial joint subluxation and vertical subluxation of the axis may occur as a consequence of instability resulting from the inflammatory process. Spontaneous anterior atlantoaxial subluxation is a well recognized complication in about 2% of patients with AS, and presents with or without signs of spinal cord compression. Vertical subluxation may follow anterior or posterior subluxation. It was noted in 3-8% of patients with rheumatoid arthritis, but is an exceedingly rare complication of AS. Moreover, it has never been reported that multiple cerebellar infarction and bulbar symptoms developed spontaneously due to atlanto-occipital subluxation and vertical subluxation in a patient with a long [corrected] history of AS. We describe a man with AS who developed multiple cerebellar infarction due to vertebral artery obstruction and bulbar symptoms associated with atlanto-occipital subluxation and vertical subluxation.     

Synthesis and electrical properties of poly[2-(2-(4-trifluoromethyl)phenyl)ethenyl-1,4-phenylenevinylene] and PPV copolymers

Summary Poly[2-(2-(4-(trifluoromethyl)phenyl)ethenyl)-5-methoxy-1,4-phenylenevinylene] (PFEMPV) and a series of PPV copolymers containing 1,4-phenylenevinylene (PV) units were synthesized through a water-soluble precursor route, and their electrical and third-order nonlinear optical properties were studied. The PFEMPV films could not be doped with I₂, but FeCl₃-doped films showed an electrical conductivity of 5.0x10^-4 S/cm. The conductivities of FeCl₃-doped copolymer films ranged from 2.0x10^-3 to 2.0 S/cm depending on their copolymer compositions. The third-order nonlinear optical susceptibility, ⁽³⁾(–;,,–), was also investigated by the degenerate four wave mixing technique at 602 nm. The ⁽³⁾ value of PFEMPV was 6.9x10^-11 esu. The photoluminescence spectrum of PFEMPV shows its emission maximum at 550 nm.     

Electrical conductivity of polyblends of poly(1,4-phenylene vinylene) and poly(2,5-dimethoxy-1,4-phenylene vinylene)

Summary A series of polyblends of poly(1,4-phenylene vinylene), PPV, and poly(2,5-dimethoxy-1,4-phenylene vinylene), PDMPV, were prepared in film form from precursor polyblends of the respective sulfonium salt polymers, which were separately prepared from the respectivebis(sulfonium salt) monomers. The blend films were doped with I₂ at room temperature to obtain a wide range of electrical conductivities (10^–2 to 10²Scm^–1) depending on the blend composition. The higher the content of PDMPV in the blends the higher was the conductivity.     

Cure kinetics of high performance epoxy resin systems

Summary Isothermal cure kinetics ofEPON HPT 1071/DDS system have been performed by means of differential scanning calorimetry. The maximum cure rate and the extent of conversion at various DDS concentrations were studied as a function of cure temperature. Maximum cure rate increases with increasing cure temperature and DDS concentration. At various DDS concentrations, the maximum cure rate occured between 19–22% conversion. In order to evaluate the kinetic parameters, numerical calculations by means of a Newton-Raphson technique and experimental results obtained from the peak of reaction rate curve were undertaken.     

Improvement of cyclodextrin glucanotransferase as an antistaling enzyme by error-prone PCR

In an effort to improve the properties of cyclodextrin glucanotransferase (CGTase) as an antistaling enzyme, error-prone PCR was used to introduce random mutations into a CGTase cloned from alkalophilic Bacillus sp. I-5 (CGTase I-5). A mutant CGTase[3-18] with the three mutations M234T, F259I and V591A was selected by agar plate assay. Sequence alignment of various CGTases indicated that M234 and F259 are located in the vicinity of the catalytic sites of the enzyme and V591 in the starch binding domain E. The cyclization activity of CGTase[3-18] was dramatically decreased by 10-fold, while the hydrolyzing activity was increased by up to 15-fold. These mutations near subsite +1 (M234T) and at subsite +2 (F259I) are likely to alter the enzyme activity in a concerted manner, promoting hydrolysis of substrate while retarding cyclization. The addition of CGTase[3-18] reduced the retrogradation rate of bread by as much as did the commercial antistaling enzyme Novamyl during 7-day storage at 4 degrees C. No cyclodextrin (CD) was detected in bread treated with CGTase[3-18], whereas 21 mg of CD per 10 g of bread was produced in bread treated with wild-type CGTase.     

Synthesis of liquid crystalline epoxy and its mechanical and electrical characteristics—curing reaction of LCE with diamines by DSC analysis

An aromatic liquid crystalline epoxy monomer based on biphenyl mesogen was synthesized and cured with three different aromatic diamines. The curing reaction characteristics were analyzed by DSC, and the data were introduced to the Kissinger equation to attain the kinetic parameters. Diglycidyl ether of 4,4′‐biphenyl (DGEBP)/4,4′‐diaminobiphenyl (DABP), and DGEBP/4,4′‐methylenediamine (MDA) systems showed an exotherm curing reaction after comelting of the monomers; the DGEBP/p‐phenylenediamine (PDA) system's curing reaction took place in the solid state without melting of monomers. The activation energy and preexponential factor for the DGEBP/DABP system were 55.6 kJ/mol and 4.0 × 10⁶ min^?1, respectively. Those values for DGEBP/MDA and DGEBP/PDA systems were 55.1 kJ/mol and 1.0 × 10⁶ min^?1 and 148.8 kJ/mol and 7.7 × 10¹⁹ min^?1, respectively. The rate constant at 100°C for DGEBP/PDA is 2 times higher than those for DGEBP/DABP and DGEBP/MDA, which have almost the same values. Strictly speaking, the rate constant of DGEBP/DABP is a little higher than that of DGEBP/MDA, and these results are in good agreement with the DSC curves. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 2419–2425, 2002