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.     

Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse

A DNA fragment containing the recA gene of Gluconobacter oxydans was isolated and further characterized for its nucleotide sequence and ability to functionally complement various recA mutations. When expressed in an Escherichia coli recA host, the G. oxydans recA protein could efficiently function in homologous recombination and DNA damage repair. The recA gene's nucleotide sequence analysis revealed a protein of 344 amino acids with a molecular mass of 38 kDa. We observed an E. coli-like LexA repressor-binding site in the G. oxydans recA gene promoter region, suggesting that a LexA-like mediated response system may exist in G. oxydans. The expression of G. oxydans recA in E. coli RR1, a recA+ strain, surprisingly caused a remarkable reduction of the host wild-type recA gene function, whereas the expression of both Serratia marcescens recA and Pseudomonas aeruginosa recA gene caused only a slight inhibitory effect on function of the host wild-type recA gene product. Compared with the E. coli RecA protein, the identity of the amino acid sequence of G. oxydans RecA protein is much lower than those RecA proteins of both S. marcescens and Pseudomonas aeruginosa. This result suggests that the expression of another wild-type RecA could interfere with host wild-type recA gene's function, and the extent of such an interference is possibly correlated to the identity of the amino acid sequence between the two classes of RecA protein.     

Rapid, sensitive procedure to determine buspirone levels in rat brains using gas chromatography with nitrogen-phosphorus detection

Reported here is a rapid, sensitive and relatively inexpensive procedure using gas chromatography with nitrogen-phosphorus detection (GC-NPD) to quantify buspirone levels in brains of rats. The analyte was directly extracted from brain homogenate with toluene after basification and then subjected to GC-NPD analysis using a capillary column. The calibration curves were linear over the range of 10 to 320 ng per 2 ml of brain homogenate, with typical r2 values >0.99. The assay was highly reproducible and gave peaks with excellent chromatographic properties.     

Greedy hot-potato routing on the two-dimensional mesh

Summary We propose hot-potato (or, deflection) packet routing algorithms on the two-dimensional mesh. The algorithms are strongly greedy in the sense that they attempt to send packets in good directions whenever possible. Furthermore, the routing operations are simple and independent of the time that has elapsed. The first algorithm gives the best evacuation time known for delivering all the packets to their destinations. A batch ofk packets with maximal source-to-destination distanced _max is delivered in 2(k-1)+d _max. The second algorithm improves this bound tok+d _max when all packets are destined to the same node. This also implies a new bound for the multitarget case, which is the first to take into account the number of in-edges of a node. The third algorithm is designed for routing permutations with source-to-destination distance at most three, in which case the algorithm terminates in at most seven steps. We also show a lower bound of five steps for this problem. Ishai Ben-Aroya received the B.A. and M.Sc. in computer science from the Technion (Israel Institute of Technology). He is currently working with Microsoft Israel R&D group. His main interests include Routing Algorithms, Cryptography and Computer Security. Tamar Eilam received the B.A. degree in Computer Science from the Technion IIL in 1995, and is currently studying towards her M.A. degree. Assaf Schuster received his B.A., M.A. and Ph.D. degrees in Computer Science from the Hebrew University of Jerusalem (the last one in 1991). He is currently a lecturer at the Technion IIL. His main interests include Networks and Routing Algorithms, Parallel and Distributed Computation, Optical Computation and Communication, Dynamically Reconfiguring Networks, and Greedy Hot Potato Routing.This work was supported in part by the French-Israeli grant for cooperation in Computer Science, and by a grant from the Israeli Ministry of Science. An extended abstract appeared in proc. 2nd European Symposium on Algorithms, September 1994     

Aggressive experience affects the sensitivity of neurons towards pharmacological treatment in the hypothalamic attack area

Early investigators of brain stimulation-evoked complex behaviours (attack, escape, feeding, self-grooming, sexual behaviour) reported that experience may affect the behavioural outcome of brain stimulation. This intriguing example of functional neuronal plasticity was later totally neglected. The present experiment investigated the behavioural outcome of in vivo microdialysis perfusion of the glutamate agonist kainate and/or the GABAA antagonist bicuculline into the hypothalamic attack area (HAA) of (1) animals naive to dyadic encounters; (2) animals with a recent aggressive experience (the probe being implanted 6-24 h after the last of a series of dyadic encounters); and (3) animals with an earlier aggressive experience (probe being implanted 2 weeks after the last aggressive experience). On the experimental day, rats received two 5-min infusions during a dyadic encounter lasting 35 min with an unknown opponent. Flow rate was 1.5-2 microliters/min, drug concentrations were 1.8 x 10(-5) and 1.5 x 10(-5) M for kainate and bicuculline, respectively. Behaviour was analysed before, during and after perfusions. Only the combined kainate + bicuculline treatment had significant effects on behaviour at the doses studied. A significant increase in aggressive behaviour was elicited only in animals with a recent aggressive experience, while naive animals and with an earlier experience responded to the treatments by grooming. These results appear to support early observations indicating that one important aspect of brain stimulation effects is previous experience.     

Comparison of ribosomal DNA length and restriction site polymorphisms in Gremmeniella and Ascocalyx isolates

The small subunit (SSU) and the internal transcribed spacer (ITS) of nuclear ribosomal DNA genes from 27 specimens of the fungal genera Gremmeniella and Ascocalyx were amplified by PCR. Length polymorphisms were observed in the SSU and allowed the differentiation of four groups among the isolates tested: (i) Ascocalyx abietis; (ii) Gremmeniella isolates from Picea spp.; (iii) Gremmeniella isolates from Abies balsamea; and (iv) Gremmeniella isolates from Abies sacchalinensis, Larix spp., and Pinus spp. The amplified ITS was the same length for all Gremmeniella specimens and was 60 bp longer in A. abietis. Phylogenetic analysis of length polymorphisms and of 24 restriction sites in the SSU and ITS showed that Gremmeniella isolates were more related to each other than to the Ascocalyx isolate. Furthermore, seven groups were evident within the genus Gremmeniella. Our results confirm that Gremmeniella and Ascocalyx should be kept as different taxa and suggest that the taxonomy of the former could be revised to consider isolates from Abies balsamea and from Picea spp. to be two different varieties while incorporating Gremmeniella laricina into G. abietina, as a new variety.     

Investigation of the titanium–indium system

The phase diagram of the Ti–In system was determined using DTA, XRD and EDX analyses. The existence of the phases Ti₂In₅ [Mn₂Hg₅ type structure, space group P4/mbm, a=0.99995(3), c=0.29960(2) nm] and Ti₃In [Ni₃Sn type structure, space group P6₃/mmc, a=0.5978(1), c=0.4812(1) nm] was confirmed. The phase previously labeled Ti₃In₂ was found to exist in a narrow homogeneity region near Ti₅₆In₄₄. Rietveld refinement of the XRD powder pattern yielded solutions compatible with a Cu₃Au-type or a BiIn-type crystal structure, but not with a CuAu-type crystal structure. Furthermore, at 38.5 at.% In, a new phase was observed having a γ-brass related crystal structure [Ti₈In₅, space group , a=0.99578(6) nm]. The intermetallic phases were formed by a cascade of peritectic reactions ending in a eutectic at >99 at.% indium between Ti₂In₅ and (In) at 0.4 K below the melting temperature of pure indium.