Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.     

A tutorial on wavelets from an electrical engineering perspective.I. Discrete wavelet techniques

The objective of this paper is to present the subject of wavelets from a filter-theory perspective, which is quite familiar to electrical engineers. Such a presentation provides both physical and mathematical insights into the problem. It is shown that taking the discrete wavelet transform of a function is equivalent to filtering it by a bank of constant-Q filters, the non-overlapping bandwidths of which differ by an octave. The discrete wavelets are presented, and a recipe is provided for generating such entities. One of the goals of this tutorial is to illustrate how the wavelet decomposition is carried out, starting from the fundamentals, and how the scaling functions and wavelets are generated from the filter-theory perspective. Examples (including image compression) are presented to illustrate the class of problems for which the discrete wavelet techniques are ideally suited. It is interesting to note that it is not necessary to generate the wavelets or the scaling functions in order to implement the discrete wavelet transform. Finally, it is shown how wavelet techniques can be used to solve operator/matrix equations. It is shown that the “orthogonal-transform property” of the discrete wavelet techniques does not hold in numerical computations     

Assessment of cocaine use with quantitative urinalysis and estimation of new uses

Qualitative urinalysis methods of monitoring cocaine use may over-detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non-treatment-seeking subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use.     

Slot-coupled microstrip antenna with a triplate line feed whereparallel-plate mode is suppressed

In a slot-coupled microstrip antenna with a triplate line feed, the parallel-plate mode is excited by the slot, resulting in a decrease of radiation efficiency. The authors present a technique for suppressing the parallel-plate mode in this type of the antenna. Measured results confirm the effective performance of the proposed method     

High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer

The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.     

The cross product of interconnection networks

We study the cross product as a method for generating and analyzing interconnection network topologies for multiprocessor systems. Consider two interconnection graphs G₁ and G₂ each with some established properties such as symmetry, low degree and diameter, scalability, simple optimal routing, recursive structure (partitionability), fault tolerance, existence of node-disjoint paths, low cost embedding, and efficient broadcasting. We investigate and evaluate the corresponding properties for the cross product of G₁ and G₂ based on the properties of G₁ and those of G₂. We also give a mathematical characterization of product families of graphs which are closed under the cross product operation. This investigation is useful in two ways. On one hand, it gives a new tool for further studying some of the known interconnection topologies, such as the hypercube and the mesh, which can be defined using the cross product operation. On the other hand, it can be used in defining and evaluating new interconnection graphs using the cross product operation on known topologies     

Long-term observation of subcutaneous tissue reaction to synthetic auditory ossicle (Apaceram) in rats

The present study evaluates histological characteristics of the soft tissue response to long-term implantation of Apaceram discs composed of dense hydroxyapatite in rats. Discs were implanted into the subcutaneous tissue of 76 rats for six to 20 months. Decalcified histological sections stained with haematoxylin and eosin (H & E) and Mallory's azan were examined. Different cell types surrounding implants were counted. The greatest proportion of macrophages was found at six months (13.5 per cent). This proportion gradually decreased to four per cent at 20 months. Small numbers of lymphocytes and foreign body giant cells were observed in every group, but neither neutrophils nor osteogenesis were observed in any specimens. Results of the present study and previous related studies indicate that despite reappearance of a small number of macrophages six months after implantation, Apaceram is useful for reconstructive surgery.