Predicting sequence-dependent melting stability of short duplex DNA oligomers

Many important applications of DNA sequence-dependent hybridization reactions have recently emerged. This has sparked a renewed interest in analytical calculations of sequence-dependent melting stability of duplex DNA. In particular, for many applications it is often desirable to accurately predict the transition temperature, or tm of short duplex DNA oligomers (approximately 20 base pairs or less) from their sequence and concentration. The thermodynamic analytical method underlying these predictive calculations is based on the nearest-neighbor model. At least 11 sets of nearest-neighbor sequence-dependent thermodynamic parameters for DNA have been published. These sets are compared. Use of the nearest-neighbor sets in predicting tm from the DNA sequence is demonstrated, and the ability of the nearest-neighbor parameters to provide accurate predictions of experimental tm's of short duplex DNA oligomers is assessed.     

The trkA receptor mediates growth cone turning toward a localized source of nerve growth factor

We have developed an in vitro system for studying the interaction of chick dorsal root ganglion neuronal growth cones with a localized source of nerve growth factor (NGF) covalently conjugated to polystyrene beads. Growth cones rapidly turned and migrated under NGF-coated beads in a process that involved the initial formation of persistent contact with a bead, followed by directed flow of cytoplasm toward the point of contact. A role for the local activation of the high-affinity NGF receptor trkA was suggested by a strong inhibition of the turning response by (1) the addition of an antibody against the extracellular portion of trkA, (2) the elevation of the background concentration of NGF to saturate trkA, or (3) the presence of a concentration of the drug K252a that inhibits trkA activation. NGF binding to the pan-neurotrophin receptor p75 is also involved but is not required for turning. These data show a new role for both the trkA and the p75 receptors: the mediation of local events in the guidance of nerve growth cones.     

BEM-based SISO detection of orthogonal space-time block codes over frequency flat-fading channels

The expectation-maximization algorithm for maximum a posteriori (MAP) estimation of a random vector is applied to the problem of detection of orthogonal space-time block codes over time-selective Rayleigh fading channels. This results in a soft-in soft-out detection algorithm suitable for iterative detection/decoding schemes. Simulation results show that the error performance of the proposed detection algorithm is very close to that of a MAP detector endowed with an ideal knowledge of the channel state if the fading rate is not too fast.     

Patient satisfaction with a reusable undergarment for urinary incontinence

PURPOSE: We investigated patient satisfaction with a reusable undergarment for urinary incontinence. SUBJECTS AND SETTING: One hundred seventy-five participants with reported urinary incontinence from two urology-based clinics at large teaching hospitals and one prostate cancer support group participated in the study. METHODOLOGY: Each participant was given a minimum of one reusable undergarment for urinary incontinence. Participants used the undergarment for an average of 10 days (range 1 to 60 days). During the trial period, subjects alternated the reusable undergarment with their previous urine-containment devices, usually disposable pads, while the undergarment was being washed. Patient satisfaction was evaluated with a questionnaire. PRIMARY OUTCOME MEASURES: Patient satisfaction with the reusable undergarment was measured for six categories: (1) physical comfort, (2) ability to keep skin dry, (3) ability to prevent wet spots, (4) discretion, (5) odor control, and (6) confidence when wearing the garment versus previously used containment devices. RESULTS: Of the 175 subjects, 126 (33% female and 67% male) completed and returned the 7-page questionnaire. All respondents reported at least one urinary incontinent episode while wearing the reusable undergarment. Occurrence and degree of leakage by self-report varied from light leakage (33%) to moderate leakage (48%) and heavy leakage (17%). Patient satisfaction was measured as follows: (1) 83% rated the overall comfort of the undergarment as very good or excellent; (2) 52% said they felt very dry or dry when wearing the product after an incontinent episodes; (3) 75% rated the ability to prevent wet spots on outer clothing as adequate or excellent; (4) 75% rated the discretion of this product as excellent; (5) 80% rated the ability to control odor as adequate or excellent; and (6) 67% felt more confidence with this reusable undergarment than with other products with which they were familiar. CONCLUSION: The reusable garment provided effective containment from urine loss among this group of incontinent women and men.     

Localized sources of neurotrophins initiate axon collateral sprouting

The sprouting of axon collateral branches is important in the establishment and refinement of neuronal connections during both development and regeneration. Collateral branches are initiated by the appearance of localized filopodial activity along quiescent axonal shafts. We report here that sensory neuron axonal shafts rapidly sprout filopodia at sites of contact with nerve growth factor-coated polystyrene beads. Some sprouts can extend up to at least 60 micro(m) through multiple bead contacts. Axonal filopodial sprouts often contained microtubules and exhibited a debundling of axonal microtubules at the site of bead-axon contact. Cytochalasin treatment abolished the filopodial sprouting, but not the accumulation of actin filaments at sites of bead-axon contact. The axonal sprouting response is mediated by the trkA receptor and likely acts through a phosphoinositide-3 kinase-dependent pathway, in a manner independent of intracellular Ca2+ fluctuations. These findings implicate neurotrophins as local cues that directly stimulate the formation of collateral axon branches.     

Automatic activation of phonological information in reading: evidence from the semantic relatedness decision task

A semantic relatedness decision task was used to investigate whether phonological recording occurs automatically and whether it mediates lexical access in visual word recognition and reading. In this task, subjects read a pair of words and decided whether they were related or unrelated in meaning. In Experiment 1, unrelated word-homophone pairs (e.g., LION-BARE) and their visual controls (e.g., LION-BEAN) as well as related word pairs (e.g., FISH-NET) were presented. Homophone pairs were more likely to be judged as related or more slowly rejected as unrelated than their control pairs, suggesting phonological access of word meanings. In Experiment 2, word-pseudohomophone pairs (e.g., TABLE-CHARE) and their visual controls (e.g., TABLE-CHARK) as well as related and unrelated word pairs were presented. Pseudohomophone pairs were more likely to be judged as related or more slowly rejected as unrelated than their control pairs, again suggesting automatic phonological recording in reading.     

Opioid-immune interactions in autism: behavioural and immunological assessment during a double-blind treatment with naltrexone

The chemical derivatization of biologically active microbial metabolites continues to be a promising approach to the identification of new drugs. We recently synthesized the novel antiproliferative compound SDZ 281-977, 5-[2-(2,5-dimethoxy-phenyl)ethyl]-2-hydroxy-benzoic acid methylester, a derivative of the EGF receptor tyrosine kinase inhibitor lavendustin A. Here we report on our studies of the anticancer efficacy and the mode of action of SDZ 281-977. The growth of both the human pancreatic tumor cells MIA PaCa-2 and the human vulvar carcinoma cells A431 was inhibited in the low micromolar range. Tumors from these cells were induced in nude mice and were shown to respond to orally or intravenously administered SDZ 281-977. In contrast, no antitumor effect was detected in rats bearing dimethylbenzanthracene-induced mammary tumors. Studies in mice indicated that SDZ 281-977 was neither immunosuppressive nor hematosuppressive at doses effectively inhibiting tumor growth. Surprisingly, the mode of action of SDZ 281-977 apparently does not involve inhibition of EGF receptor tryosine kinase, because, in contrast to lavendustin A, SDZ 281-977 failed to inhibit this enzyme in a cell-free assay. The mechanism of the antiproliferative effect can be explained on a cellular level by the ability of the compound to arrest cells in mitosis. SDZ 281-977 is thus the first example of an antimitotic agent derived from the potent tyrosine kinase inhibitor lavendustin A. The therapeutic potential of SDZ 281-977 is enhanced by the fact that it is not subject to multidrug resistance, because tumor cells expressing the multidrug resistance phenotype were as sensitive to SDZ 281-977 as their nonresistant counterparts. In conclusion, SDZ 281-977 represents a novel lavendustin A derivative with potent antiproliferative properties in vitro and in vivo that may be explained on the basis of its antimitotic effects. SDZ 281-977 may be a candidate drug for the treatment of selected cancers, including those expressing the multidrug resistance phenotype.     

Seroepidemiology of emerging tickborne infectious diseases in a Northern California community

A seroprevalence and risk factor study of emerging tickborne infectious diseases (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of a semirural community in Sonoma County, California. Over 50% of residents reported finding a tick on themselves in the preceding 12 months. Samples from 51(23%) residents were seroreactive to antigens from one or more tickborne disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%) of these seroreactive residents reported one or more symptoms compatible with these diseases. Seroreactivity was significantly associated with younger age (<16 years), longer residence in the community (11-20 years), and having had a physician's diagnosis of Lyme disease. In northern California, the risk of infection with these emerging tickborne diseases, particularly in children, may be greater than previously recognized.