Synthesis, characterization, and water oxidation by a molecular chromophore-catalyst assembly prepared by atomic layer deposition. The "mummy" strategy.

A new strategy for preparing spatially-controlled, multi-component films consisting of molecular light absorbing chromophores and water oxidation catalysts on high surface area, mesoporous metal oxide surfaces is described. Atomic layer deposition (ALD) is used to embed a surface-bound chromophore in a thin layer of inert Al2O3, followed by catalyst binding to the new oxide surface. In a final step, catalyst surface-binding is stabilized by a subsequent ALD overlayer of Al2O3. The ALD assembly procedure bypasses synthetic difficulties arising from the preparation of phosphonic acid derivatized, covalently-linked assemblies. An ALD mummy-based assembly has been used to demonstrate photoelectrochemical dehydrogenation of hydroquinone. Electrocatalytic water oxidation at pH 8.8 is observed over a 2 hour electrolysis period and light-assisted water oxidation over a 6 hour photolysis period with O2 detected with a generator-collector electrode configuration.

EMAAS: an extensible grid-based rich internet application for microarray data analysis and management.

BACKGROUND: Microarray experimentation requires the application of complex analysis methods as well as the use of non-trivial computer technologies to manage the resultant large data sets. This, together with the proliferation of tools and techniques for microarray data analysis, makes it very challenging for a laboratory scientist to keep up-to-date with the latest developments in this field. Our aim was to develop a distributed e-support system for microarray data analysis and management. RESULTS: EMAAS (Extensible MicroArray Analysis System) is a multi-user rich internet application (RIA) providing simple, robust access to up-to-date resources for microarray data storage and analysis, combined with integrated tools to optimise real time user support and training. The system leverages the power of distributed computing to perform microarray analyses, and provides seamless access to resources located at various remote facilities. The EMAAS framework allows users to import microarray data from several sources to an underlying database, to pre-process, quality assess and analyse the data, to perform functional analyses, and to track data analysis steps, all through a single easy to use web portal. This interface offers distance support to users both in the form of video tutorials and via live screen feeds using the web conferencing tool EVO. A number of analysis packages, including R-Bioconductor and Affymetrix Power Tools have been integrated on the server side and are available programmatically through the Postgres-PLR library or on grid compute clusters. Integrated distributed resources include the functional annotation tool DAVID, GeneCards and the microarray data repositories GEO, CELSIUS and MiMiR. EMAAS currently supports analysis of Affymetrix 3' and Exon expression arrays, and the system is extensible to cater for other microarray and transcriptomic platforms. CONCLUSION: EMAAS enables users to track and perform microarray data management and analysis tasks through a single easy-to-use web application. The system architecture is flexible and scalable to allow new array types, analysis algorithms and tools to be added with relative ease and to cope with large increases in data volume.

Dispelling the illusion of invulnerability: the motivations and mechanisms of resistance to persuasion.

Three studies examined the impact of a treatment designed to instill resistance to deceptive persuasive messages. Study 1 demonstrated that after the resistance treatment, ads using illegitimate authority-based appeals became less persuasive, and ads using legitimate appeals became more persuasive. In Study 2, this resistance generalized to novel exemplars, persevered over time, and appeared outside of the laboratory context. In Study 3, a procedure that dispelled participants' illusions of invulnerability to deceptive persuasion maximized resistance to such persuasion. Overall, the present studies demonstrate that attempts to confer resistance to appeals will likely be successful to the extent that they install 2 conceptual features: perceived undue manipulative intent of the source of the appeal and perceived personal vulnerability to such manipulation.

A multicenter, open-label, prospective, randomized, dose-ranging pharmacokinetic study of the anti-TNF-alpha antibody afelimomab in patients with sepsis syndrome.

OBJECTIVE: To investigate the pharmacokinetics and safety of afelimomab, a murine antibody fragment against human tumor necrosis factor (TNF)-alpha in patients with sepsis. DESIGN: Multicenter, randomized, open-label, placebo-controlled phase I/II clinical trial. SETTING: Intensive care units of six academic medical centers in the United States. PATIENTS: Forty-eight patients with a clinical diagnosis of sepsis who received standard supportive care and antimicrobial therapy. INTERVENTIONS: Patients received 0.3, 1.0, or 3.0 mg/kg afelimomab or placebo intravenously over 20 min. Three patients in each dose group received single doses; the remaining nine patients in each group received multiple (nine) doses at 8-h intervals over 72 h. MEASUREMENTS AND MAIN RESULTS: Afelimomab appeared safe and well tolerated. Single- and multiple-dose kinetics were predictable and dose related. The elimination half-life was 44.7 h. Afelimomab treatment resulted in increased serum concentrations of TNF (includes TNF-antibody complexes) and decreased serum interleukin-6 concentrations, whereas no discernible trends were observed in placebo-treated patients. There was no significant treatment effect on 28-day mortality as was expected given the small number of patients. However, overall mortality was significantly (p = 0.001) associated with baseline interleukin-6 concentration. All patients experienced adverse events, but the vast majority were considered unrelated to the study drug and demonstrated no apparent relationship to afelimomab dose. Although 41% of patients developed human anti-murine antibodies, there were no clinical sequelae. CONCLUSIONS: Multidose therapy with afelimomab was safe, well tolerated, and had predictable linear kinetics. A large randomized trial comparing afelimomab to placebo in patients with well defined sepsis has recently been completed.

Effects of catecholamines on calvarial bone resorption in vitro.

Many important diseases in otolaryngology manifest through abnormal bone remodeling or destruction. The mechanisms for such pathological remodeling remain poorly understood. Bone is known to be innervated by norepinephrine-containing sympathetic nerves, and sympathectomy is known to induce bone resorption. The role, however, of norepinephrine as a potential bone-modulatory substance is unknown. Using the calvarial calcium release assay, we conducted the following experiment to evaluate the bone-modulatory activity of norepinephrine, the alpha-agonist octopamine, and the beta-agonist isoproterenol. Each agent was tested at 2 concentrations with and without parathyroid hormone. Norepinephrine was found to have no effect on calcium release. In contrast, octopamine at 10(-8) mol/L exerted a significant stimulatory effect on calcium release, and isoproterenol at 10(-6) mol/L exerted a significant inhibitory effect on parathyroid hormone-induced calcium release. The investigation suggests that a bimodal, concentration-dependent, receptor-specific model for catecholamine-mediated modulation of bone resorption may operate in calvarial bone.

Climate variability and change in the United States: potential impacts on water- and foodborne diseases caused by microbiologic agents.

Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.

A unique case of the rapid onset of a large cystic hygroma in the adult.

Cystic hygroma is an uncommon lymphatic tumor seen rarely in adults, with less than 100 cases reported in the literature. The etiology and pathophysiology of this lesion is still in question. The majority of cystic hygromas occur in the head and neck, particularly in the posterior triangle. Although cystic hygromas tend to enlarge progressively over a span of weeks or months, relatively rapid enlargement over a span of days has been described. We present the unique case of an adult woman who experienced sudden onset of a large cystic hygroma in the neck without history of antecedent swelling, infection, or trauma. Successful surgical removal of the hygroma was performed. A brief review of the literature is presented.

Effect of chemical sympathectomy with 6-hydroxydopamine on osteoclast activity in the gerbilline middle ear bulla.

HYPOTHESIS: Chemical sympathectomy with 6-hydroxydopamine (HDA) increases middle ear bulla bone resorption in the Mongolian gerbil. BACKGROUND: Many diseases of the middle ear have pathologic processes linked to abnormal bone remodeling. Numerous factors controlling bone remodeling have been identified. An understanding of these factors and their role in pathologic remodeling is therefore essential. Sympathectomy, induced both surgically and pharmaceutically, is known to increase middle ear bone resorption, suggesting a role for the central nervous system in bone metabolism. This effect, however, may be confounded by hemodynamic changes induced by hemicranial surgical sympathectomy or by uncertainty in the action of pharmaceutical agents on the sympathetic nervous system. In this experiment, a third modality with unique properties, chemical sympathectomy with HDA, was used to quantify further the effect of sympathectomy on middle ear bone remodeling. METHODS: Eight gerbils designated experimental received intraperitoneal injections of HDA (75 mg/kg) for 1 week, whereas eight animals designated control received similar injections of saline. One week after injections, the animals were euthanized and bulla bone samples were analyzed histomorphometrically to determine osteoclastic activity. In addition, to assess for any direct effects on bone metabolism, the activity of HDA was determined in vitro using the calvarial calcium release assay. RESULTS: The in vitro study found HDA to have no direct stimulatory activity on calcium release. The in vivo study showed HDA to increase osteoclastic activity significantly in middle ear bone. CONCLUSION: HDA-induced sympathectomy increases bone resorption in gerbilline middle ear bone.

Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes.

The completion of the Arabidopsis thaliana genome sequence allows a comparative analysis of transcriptional regulators across the three eukaryotic kingdoms. Arabidopsis dedicates over 5% of its genome to code for more than 1500 transcription factors, about 45% of which are from families specific to plants. Arabidopsis transcription factors that belong to families common to all eukaryotes do not share significant similarity with those of the other kingdoms beyond the conserved DNA binding domains, many of which have been arranged in combinations specific to each lineage. The genome-wide comparison reveals the evolutionary generation of diversity in the regulation of transcription.

Sympathectomy, which induces membranous bone remodeling, has no effect on endochondral long bone remodeling in vivo.

Sympathectomy has been shown to induce resorption within the membranous middle ear bone of gerbils. It is unknown whether sympathectomy exerts a similar effect on endochondral long bone. In the present study, guanethidine sulfate (GS) and 6-hydroxydopamine (HDA) were administered to gerbils to induce sympathectomy. One week later, samples of middle ear bulla bone and radial long bone were harvested and assessed for osteoclastic activity. Histomorphometric analysis showed both pharmacologic sympathectomy with GS and chemical sympathectomy with HDA significantly increased the osteoclast counts and osteoclast surfaces of bulla bone samples but not radial long bone samples, respectively. In contrast, HDA but not GS increased the osteoclast profile area of both long bone and membranous bone samples when compared with vehicle-treated controls. Sympathectomy, induced both chemically and pharmacologically, thus has been shown to increase resorption in membranous bone but not endochondral long bone in the gerbilline model.

First place--resident basic science award 1999. Effects of leukotriene and cyclo-oxygenase inhibition on adaptive bone remodeling in the middle ear.

Abnormal bone remodeling is associated with important otolaryngologic diseases. In such diseases, the mechanisms of osteoclastic control underlie the pathologic processes. It is known that strain applied to auditory bullae induces bone resorption-an effect mediated by prostaglandins and blocked by cyclo-oxygenase inhibitors. It is also known that cyclo-oxygenase inhibition shunts arachidonic acid into alternate metabolic pathways, mainly the lipoxygenase pathway with leukotriene production. The role of these metabolites in adaptive bone remodeling is unknown. Using the gerbilline bulla as a model, we infused BW755c (dual lipoxygenase/cyclo-oxygenase inhibitor) and L-663,536 (5-lipoxygenase inhibitor) into animals undergoing middle ear pressurization. After 7 days, the bulla bones were harvested, and osteoclasts were quantified histomorphometrically. The results showed that neither treatment altered pressure-induced resorption. However, BW755c significantly increased resorption in unpressurized bone when compared with control values. Because BW775c blocks both lipoxygenase and cyclo-oxygenase pathways, the results suggest an alternate pathway in middle ear bone resorption.

Clinical efficacy of intravenous followed by oral azithromycin monotherapy in hospitalized patients with community-acquired pneumonia. The Azithromycin Intravenous Clinical Trials Group.

The purpose of this study was to evaluate intravenous (i.v.) azithromycin followed by oral azithromycin as a monotherapeutic regimen for community-acquired pneumonia (CAP). Two trials of i.v. azithromycin used as initial monotherapy in hospitalized CAP patients are summarized. Clinical efficacy is reported from an open-label randomized trial of azithromycin compared to cefuroxime with or without erythromycin. Bacteriologic and clinical efficacy results are also presented from a noncomparative trial of i.v. azithromycin that was designed to give additional clinical experience with a larger number of pathogens. Azithromycin was administered to 414 patients: 202 and 212 in the comparative and noncomparative trials, respectively. The comparator regimen was used as treatment for 201 patients; 105 were treated with cefuroxime alone and 96 were given cefuroxime plus erythromycin. In the comparative trial, clinical outcome data were available for 268 evaluable patients with confirmed CAP at the 10- to 14-day visit, with 106 (77%) of the azithromycin patients cured or improved and 97 (74%) of the comparator patients cured or improved. Mean i.v. treatment duration and mean total treatment duration (i.v. and oral) for the clinically evaluable patients were significantly (P < 0.05) shorter for the azithromycin group (3.6 days for the i.v. group and 8.6 days for the i.v. and oral group) than for the evaluable patients given cefuroxime plus erythromycin (4.0 days for the i.v. group and 10.3 days for the i.v. and oral group). The present comparative study demonstrates that initial therapy with i.v. azithromycin for hospitalized patients with CAP is associated with fewer side effects and is equal in efficacy to a 1993 American Thoracic Society-suggested regimen of cefuroxime plus erythromycin when the erythromycin is deemed necessary by clinicians.

When children tell their friends they have AIDS: possible consequences for psychological well-being and disease progression.

OBJECTIVE: Past research has demonstrated that self-disclosure of traumatic or secretive information produces observable health benefits. Self-disclosure has also been linked, albeit less consistently, to improved psychological health. The present study examined the physiological and psychological consequences of children's self-disclosure of their HIV/AIDS status to friends. METHODS: Data were collected twice, one year apart, from 64 caregiver-child dyads in which all of the children were infected with HIV. Dependent variables included the child's CD4%, self-concept, and level of behavioral problems. RESULTS: Children who had disclosed their HIV+ diagnosis to friends during the 1-year course of the study had a significantly larger increase in CD4% than children who had told their friends before the study or those children who had not yet disclosed their HIV+ diagnosis to friends. This effect remained significant when the child's age and level of medication (protease inhibitors) were statistically controlled. Self-disclosure to friends did not impact the child's behavior or self-concept. CONCLUSIONS: This is the first study to investigate the effect of self-disclosure in children. The results were consistent with previous studies showing the positive health consequences of self-disclosure in adults, and suggest potentially important implications for professional and familial care givers of HIV/AIDS individuals.

Effect of pharmacological sympathectomy on osteoclastic activity in the gerbilline auditory bulla in vivo.

Bone destruction causes hearing loss in various middle ear disorders. The mechanisms of such pathological remodeling are unknown. Unilateral surgical sympathectomy is known to induce resorption within mandibular and auditory bulla bone. Explanation of the cause of this effect, however, may be confounded by hemodynamic changes induced by hemicranial sympathectomy and by uncertainty as to the neuroanatomical origins of sympathetic fibers. In this study, gerbils were infused with guanethidine sulfate (GS) to evaluate the in vivo effects of systemic sympatholysis on auditory bone remodeling. In addition, to discount any direct osteolytic effect, GS was assessed of its bone resorbing activity in vitro by means of the calvarial calcium release assay. The in vitro study revealed GS to have no effect on calcium release. The in vivo study revealed GS to increase both the osteoclast surface and number. Guanethidine-induced sympathectomy has thus been shown to increase remodeling in gerbilline auditory bone, while no direct osteolytic effect could be measured in vitro.

Assessment of dysphagia with the use of pulse oximetry.

Recent anecdotal literature has shown a relation between arterial oxygen saturation (SpO2), as measured by pulse oximetry, and aspiration during eating. The present study was designed to determine whether bedside pulse oximetry has a role in the assessment of pharyngeal phase dysphagia. Forty-six adult patients with clinically suspected swallowing abnormalities underwent modified barium swallow to evaluate dysphagia. After determining baseline oxygen saturation by pulse oximetry, different consistencies of barium were sequentially ingested. Patients were monitored for radiographic evidence of penetration or aspiration, which was correlated with continuous SpO2 recording. Patients who exhibited aspiration or penetration without clearing had a significant decline in SpO2 compared with those patients who penetrated but cleared or in whom no penetration was observed. These relations were not associated with age, gender, or diagnosis. These preliminary data indicate that bedside pulse oximetry may be a useful tool in the evaluation of patients with dysphagia.

Atropine sulfate--a current review of a useful agent for controlling salivation during dental procedures.

After reading this article, the reader should be able to describe techniques for the control of saliva during dental procedures; discuss the problems associated with saliva contamination of an operative field; explain the clinical benefits, dosing guidelines, and contraindications for using atropine sulfate to temporarily reduce saliva flow during dental procedures.

A consensus map for loblolly pine (Pinus taeda L.). I. Construction and integration of individual linkage maps from two outbred three-generation pedigrees.

A consensus map for loblolly pine (Pinus taeda L.) was constructed from the integration of linkage data from two unrelated three-generation outbred pedigrees. The progeny segregation data from restriction fragment length polymorphism, random amplified polymorphic DNA, and isozyme genetic markers from each pedigree were recoded to reflect the two independent populations of parental meioses, and genetic maps were constructed to represent each parent. The rate of meiotic recombination was significantly greater for males than females, as was the average estimate of genome length for males (1983.7 cM [Kosambi mapping function (K)]) and females [1339.5 cM(K)]. The integration of individual maps allows for the synthesis of genetic information from independent sources onto a single consensus map and facilitates the consolidation of linkage groups to represent the chromosomes n = 12 of loblolly pine. The resulting consensus map consists of 357 unique molecular markers and covers approximately 1300 cM(K).