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Cytochalasin D does not inhibit gravitropism in roots.

It is generally thought that sedimenting plastids are responsible for gravity sensing in higher plants. We directly tested the model generated by the current statolith hypothesis that the gravity sensing that leads to gravitropism results from an interaction between the plastids and actin microfilaments. We find that the primary roots of rice, corn, and cress undergo normal gravitropism and growth even when exposed to cytochalasin D, a disruptor of actin microfilaments. These results indicate that an interaction between amyloplasts and the actin cytoskeleton is not critical for gravity sensing in higher plants and weaken the current statolith hypothesis.

Actin Cytoskeleton↗

Demographics and social security.

"This paper considers the welfare implications of the interactions between demographic changes and social security in an overlapping generations model in which retirement decisions are endogenous. Both a pay-as-you-go system and an actuarially-fair system are examined." The geographical focus is on the United States.

Americas↗

Population age structure and the size of social security.

"This paper uses a general overlapping generations model to analyze social security. Rather than focusing on intertemporal price and income considerations, however, the paper focuses on the effect of contemporaneous (same period) prices and income. The analysis shows that the old-age dependency ratio acts as a shadow price for old-age benefits. With this new shadow price, the equilibrium price and quantity of social security benefits and the level of the payroll tax rate are determined in a demand-supply framework with individual utility maximization. Three explicit demand functions (intergenerational contracts) are analyzed. The model is tested using [U.S.] time series data for the social security Old-Age and Survivors (OASI) program."

Adult↗

Carpal instability.

The understanding of traumatic wrist instability continues to improve. Better definition of the role of ligaments, especially the interosseous ligaments, and use of computer-generated models of the wrist have shed new light on the nature of carpal kinematics. Nevertheless, a thorough patient history, a detailed physical examination, and plain radiographs remain the most important elements in the evaluation of wrist injuries. Wrist arthroscopy has supplanted most ancillary tests as the next step in diagnosis. Arthroscopy is also invaluable in the treatment of ligament injuries without significant instability. The management of static wrist instability remains challenging, and novel methods for reconstructing the scapholunate and lunotriquetral interosseous ligaments have been developed. These procedures are technically demanding, and long-term follow-up data are needed before they can become clinically useful.

Algorithms↗

Optimal time window for measurement of renal output parameters.

Although normalised residual activity (NORA) and output efficiency (OE) are usually measured at a fixed time t, their dependency on t may affect the prediction of mean transit time (MTT). This study aimed to evaluate their degree of dependency on t and to determine an optimal time of measurement by assessment of their relationship with MTT for various times t. A simulation model generated 232 cortical renograms by convolving one plasma disappearance curve with 232 created cortical retention functions. The results show that considerable changes are observed for NORA and OE, depending on the time of measurement t. The choice of this time significantly influences the predictive value of these parameters for estimating MTT. The optimal time for measurement of NORA and OE should be close to the MTT, at the moment when emptying takes place. In the clinical practice, it should be adapted to the clinical problem under investigation.

Journal Article↗

Effects of 2.45 GHz microwave exposures on the peroxidation status in Wistar rats.

One of the consequences of exposures to microwave (MW) radiations is the enhanced production of free O2, free radicals, peroxides and superoxides. The effects on the lipid peroxidation status (LPS) of whole body irradiation of 120 Wistar rats with 2.45 GHz MW at a power density of 6mWcm(-2) have been studied using the MW generator model ER6660E from Toshiba UK Ltd. The LPS in the rats was monitored for a period of 8 weeks post irradiation using thiobarbituric acid (TRA) method. The MW exposures caused an increase in the LPS from the mean control value of 4.18 x 10(-6)g 1(-1)to a maximum of 6.50 x 10(-6) g 1(-1) within the first 24 hrs, and then gradually reduced to control value after about a week. 1mg kg(-1) of ascorbic acid administered before irradiation caused a decrease in the LPS from the control value to a minimum of 2.86 x 10(-6)g 1(-1) within the first week. The value then gradually rose to a maximum of 3.96 x 10(-6)g 1(-1) within the monitoring period. 1 mg kg(-1) of a-tocopherol also administered before irradiation also caused a decrease in the LPS from the control value to a minimum of 2.10 x 10(-6) g 1(-1) within the first week. The value then gradually rose to a maximum of 3.94 x 10(-6) g 1(-1) within the monitoring period. The results obtained from this study demonstrate that MW exposures cause significant increase in the LPS and there are protective effects of the anti-oxidants ascorbic acid and alpha-tocopherol.

Animals↗

Portable/transport ventilators.

Portable ventilators are often used with patients who require long-term breathing support. Current-generation models are compact and lightweight and offer some of the same features that once were available only on costly intensive care ventilators. As technological advances continue to prolong life for critically ill patients and make life possible for both children and adults with otherwise fatal conditions, portable ventilators are helping to make these patients more comfortable and more mobile. They ease the transport of patients within the hospital, and they allow some difficult-to-ventilate patients, especially infants, to receive ventilation at home. In this article, we evaluate three portable/transport ventilators from three suppliers, rating them separately for (1) home care and long-term care applications and (2) in-hospital transport applications. Our ratings place special emphasis on ventilator performance, alarm effectiveness, ease of use, and portability. We found that all the units provide at least satisfactory ventilation, but that their other characteristics vary considerably. For home care and long-term care, we rate two units Acceptable--but one of them is suitable for use only if certain steps related to its alarm volume are taken. The third unit is Not Recommended because of significant drawbacks associated with its ease of use, alarms, and portability. For in-hospital transport, we rate one unit Preferred because it has many features beneficial for transporting critically ill patients. A second unit is Acceptable, while the third is Not Recommended, again because of its many drawbacks.

Ambulatory Care↗

Osteocytes: a proposed multifunctional bone cell.

Most cell types are ascribed a single function. The osteoclast holds the unique distinction of performing only one function in the body - that of resorbing bone. The osteoblast has been ascribed the major function of bone matrix production. Other less well-defined cell types include progenitor cells and the nebulous cell type that can support osteoclast formation upon stimulation with various bone resorbing cytokines. Obviously, these cells could have other functions. The definition of an osteocyte is descriptive of its location - cells surrounded by mineralized matrix - not its function. For this year's Sun Valley Workshop on osteocytes, several proposed functions will be presented. First, a general consensus exists that osteocytes are most likely sensitive to mechanotransduction and translate mechanical strain into biochemical signals. Consensus does not exist on the nature of the mechanical strain, the form of the biochemical signals, the target cell(s), or the viability status of the osteocyte. Second, it is also proposed that this cell is incredibly adaptable and expresses plasticity in response to mechanical stimuli. In other words, this cell can readjust its responses to strain in the presence of other bone agents such as hormones and bone factors. Third, it will also be presented that osteocytes maintain systemic mineral homeostasis by regulating mineral release and deposition over the enormous surface area over which these cells interface with the surrounding matrix. Although osteocytes are terminally differentiated osteoblasts, they appear to have separate and distinct properties from their predecessors. Bone cell biologists loaded with an arsenal of bone anabolic and catabolic factors are examining the expression and effects of these factors on osteocytes. Engineers trained in mathematical modeling have generated new models of strain and connectivity to be tested. The unique morphology of osteocytes suggests that the cytoskeleton in these cells may function differently from osteoblasts and other cell types. Osteocytes may consist of different subpopulations; some that possess receptors for parathyroid hormone (PTH) and others that only express receptors for carboxyl terminal PTH suggesting different functions and responses. Osteocytes may respond rapidly to strain through glutamate receptor-like mechanisms, through calcium influxes, through gap junctions, and less rapidly through the production of small molecules and factors. Strain may take the form of substrate stretching and/or fluid flow. Osteocytes may communicate with other osteocytes and/or bone surface cells such as lining cells, stromal cells, osteoblasts, and/or osteoclasts and their precursors. The viability status of the osteocyte may determine the type of signals sent from these cells. If the cells are deprived of oxygen or nutrients, the apoptotic cells may send signals for initiation of resorption. If the cells and/or their dendritic process are ripped or torn by microdamage, they may send signals of both resorption and formation. If the majority of these theories are correct, then the osteocyte is the 'smart' cell that can direct or orchestrate the bone resorbing and bone forming cells even in its death and dying.

Journal Article↗

Reactive nitrogen intermediate production and tolerance variability in different mouse strains after in vivo treatment with lipopolysaccharide from Salmonella abortus equi.

Lipopolysaccharide (LPS) stimulation in animal models generates a large number of immune factors including cytokines and mediators. It also acts as a potent inducer of macrophage reactive oxygen intermediates and reactive nitrogen intermediates (RNI). RNI as stable metabolites of nitric oxide (NO) are produced by cells stimulated with LPS and cytokines. In this study, LPS from Salmonella abortus equi was investigated as an inducer of RNI in untreated controls and test groups of white Naval Medical Research Institute (NMRI) mice. Animals were humanely killed at 30, 60, 120 and 180 min after LPS injection, and plasma RNI was measured by Griess microassay. In a further experiment, host tolerance against bacterial LPS was evaluated by sequential intravenous injection of LPS concentrations of 4, 1 and 0.5 mg/kg at 24 h intervals in NMRI and with the same schedule but via subcutaneous injection in Balb/c mice. Statistical analysis of RNI values using analysis of variance test indicated that in vivo LPS stimulation induced high levels of NO in murine hosts (p<0.001). Comparison of RNI levels at different times after administration revealed the largest amount of RNI at 180 min after inoculation. Analysis of the time course until maximum RNI induction indicated that NMRI mice had the longest delay, suggesting a difference in tolerance of NMRI and Balb/c mice to LPS stimulation dependent on LPS concentration, dose, and route of inoculation.

Animals↗

Clustering algorithms and other exploratory methods for microarray data analysis.

OBJECTIVES: We introduce methods for the exploratory analysis of microarray data, especially focusing on cluster algorithms. Benefits and problems are discussed. METHODS: We describe application and suitability of unsupervised learning methods for the classification of gene expression data. Cluster algorithms are treated in more detail, including assessment of cluster quality. RESULTS: When dealing with microarray data, most cluster algorithms must be applied with caution. As long as the structure of the true generating models of such data is not fully understood, the use of simple algorithms seems to be more appropriate than the application of complex black-box algorithms. New methods explicitly targeted to the analysis of microarray data are increasingly being developed in order to increase the amount of useful information extracted from the experiments. CONCLUSIONS: Unsupervised methods can be a helpful tool for the analysis of microarray data, but a critical choice of the algorithm and a careful interpretation of the results are required in order to avoid false conclusions.

Algorithms↗

Bioinformatics meets clinical informatics.

The field of bioinformatics has exploded over the past decade. Hopes have run high for the impact on preventive, diagnostic, and therapeutic capabilities of genomics and proteomics. As time has progressed, so has our understanding of this field. Although the mapping of the human genome will certainly have an impact on health care, it is a complex web to unweave. Addressing simpler "Single Nucleotide Polymorphisms" (SNPs) is not new, however, the complexity and importance of polygenic disorders and the greater role of the far more complex field of proteomics has become more clear. Proteomics operates much closer to the actual cellular level of human structure and proteins are very sensitive markers of health. Because the proteome, however, is so much more complex than the genome, and changes with time and environmental factors, mapping it and using the data in direct care delivery is even harder than for the genome. For these reasons of complexity, the expected utopia of a single gene chip or protein chip capable of analyzing an individual's genetic make-up and producing a cornucopia of useful diagnostic information appears still a distant hope. When, and if, this happens, perhaps a genetic profile of each individual will be stored with their medical record; however, in the mean time, this type of information is unlikely to prove highly useful on a broad scale. To address the more complex "polygenic" diseases and those related to protein variations, other tools will be developed in the shorter term. "Top-down" analysis of populations and diseases is likely to produce earlier wins in this area. Detailed computer-generated models will map a wide array of human and environmental factors that indicate the presence of a disease or the relative impact of a particular treatment. These models may point to an underlying genomic or proteomic cause, for which genomic or proteomic testing or therapies could then be applied for confirmation and/or treatment. These types of diagnostic and therapeutic requirements are most likely to be introduced into clinical practice through traditional forms of clinical practice guidelines and clinical decision support tools. The opportunities created by bioinformatics are enormous, however, many challenges and a great deal of additional research lay ahead before this research bears fruit widely at the care delivery level.

Computational Biology↗

[The use of CAD/CAM techniques in the repair of complex orbital fractures and the reposition of enophthalmos].

OBJECTIVE: To reconstruct the three-dimensional (3 D) imaging and computer-generated models of the complex orbital fractures, and to develop a Computer-Aided Design/Computer-Aided Manufacture (CAD/CAM) system for orbital fracture repair. METHODS: We carried out study on 12 patients with orbital fractures from August 2003 to March 2004 in the Ninth People's Hospital. Before the orbital fracture repair, helical computer tomography scanning was applied to acquire the 3 D imaging data of the patient's orbits. The 3 D imaging data were then transferred to a CAD/CAM interactive program for image processing, which then designed and produced a stereolithography model mathematically. Using the designed software, the repair of orbital fractures could be planned with the computer. At the same time, the orbital cubane was calculated. Then the operation was performed and the effect of the therapy was evaluated. RESULTS: Using the CAD/CAM system of orbital fracture repair, the 3 D image of the orbit could be reconstructed, and the orbital cubane could be calculated accurately. The preoperative surgical plan was put into reality. After the orbital fracture repair, all cases received excellent appearance and function. This system had proved to run smoothly and accurately, and could easily be controlled. CONCLUSIONS: The CAD/CAM system of the orbital fracture repair may be proved as one of the most useful clinical tools for orbital surgery.

Adult↗

Neurotoxins and degeneration in the central nervous system.

Numerous examples exist where neurotoxins have been shown to induce selective death of certain groups of nerve cells. While the peripheral nerves are particularly vulnerable, neurotoxins are also capable of generating models of the major degenerative disorders of the central nervous system: dementia of Alzheimer's type, Parkinsonism, and amyotrophic lateral sclerosis. Important organic toxins, in this context, include certain pyridines, amines, aminoacids, nitriles, hexacarbons, and sulphides. Inorganic toxins include free radicals and certain metals. Toxins may also be classified according to their origin--exogenous or endogenous. This review will not consider neurological damage that can result from exposure to alcohol, or neurological adverse reactions to medications.

Animals↗

Simulation of carboxymyoglobin photodissociation.

Computer-generated models of the structures of deoxymyoglobin and CO-bound myoglobin show that the CO molecule is not packed so tightly by the amino acid residues of the distal pocket to prevent its motion away from the iron atom upon photodissociation. A simulation of low temperature photodissociation by energy minimization techniques shows that the CO moves to a position approximately 4 A away from the iron atom due to the van der Waals forces. The final position of the CO molecule requires far larger motion of the carbon atom than the oxygen atom and thereby suggests that the isotope dependence of the molecular tunneling is a consequence of the orientation of the photodissociated CO.

Computer Simulation↗

Prognostic discrimination among younger patients with chronic granulocytic leukemia: relevance to bone marrow transplantation.

To obtain information relevant to the question of bone marrow transplantation, we examined the prognostic significance of disease features recorded at the time of diagnosis among 625 patients, aged 5 to 45, with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia. The actuarial death rate for this population was 5% during the first year after diagnosis, 12% during the second year, and averaged 22.5% per year during the next eight years. Multivariable regression analysis of features recorded in nearly all cases indicated that sex, spleen size, hematocrit, platelet count, and percentage of circulating blasts were significant prognostic indicators. Analyses of additional data available in 113 to 421 cases suggested that serum lactic dehydrogenase activity, percentage of blasts in marrow, nucleated RBCs in blood, and percentage of basophils plus eosinophils might also provide useful prognostic information. A Cox model, generated with five variables representing features recorded regularly (the first five listed), permitted segregation of these patients into three groups with significantly different survival patterns. The high-risk group exhibited an actuarial mortality of 30% during the first two years after diagnosis and an annual risk of 30% thereafter. In contrast, the most favorable group had a two-year actuarial mortality of 9% and an average risk thereafter of 17% per year, with a median survival of 5 1/2 years. We conclude that it should be possible to classify potential candidates for bone marrow transplantation according to risk with conventional therapy. Such information may be useful in making decisions regarding early v deferred marrow transplantation.

Adolescent↗

Focused encephalography.

Focused encephalography is a diagnostic procedure performed after computed tomography (CT) that can be specifically focused on diagnostic problems not solved by CT. The authors have used the procedure in 20 cases, and it has proved to be quick, risk-free, and without serious side effects. It provides useful supplementary diagnostic information, and can be especially helpful when CT is not available or when the CT scanner is an early-generation model.

Brain Diseases↗

Age correlation between mates and average consanguinity in age-structured human populations.

When population geneticists wish to determine the genetic consequences of some aspect of mating behavior, it is often necessary to compare observed levels of consanguinity to the level expected when mating is random with respect to the factor being studied. Expectations under random mating are often derived from discrete generation models that ignore age structure. Observed frequencies of consanguineous matings are due to processes that are continuous in time and are affected by variables that are functions of age structure. The extent to which this discrepancy between the models and reality might distort conclusions drawn from comparisons of observed and expected behavior has received insufficient attention. One potential source of error is the tendency for people to choose mates whose ages differ from their own by a certain amount; this tendency influences the frequency of consanguineous matings. Age correlation between mates should therefore also affect average consanguinity between mates and average inbreeding in the population. Expected levels of consanguinity might then differ depending on whether or not age structure has been taken into account. Hajnal developed a model that predicts the frequencies of consanguineous matings in age-structured populations. Hajnal's model is extended here to include relationships that are defined by lineal descent as well as by common ancestry, and to allow calculation of the frequencies of consanguineous matings in the absence of age correlation between mates. The extended model is then used to determine the effect of age correlation between mates on average consanguinity under various sets of conditions. The magnitude of this effect depends on the degree to which the increased frequency of some types of consanguineous matings is offset by the decrease in other types of matings. There is a fairly wide range of conditions under which this compensation is nearly complete and therefore under which the overall effect of age correlation is small. But the size of this effect is sensitive to many factors, especially the distribution of age differences between mates and the variances of ages at maternity and paternity. Under some conditions, age correlation between mates will have a substantial effect on average consanguinity.

Age Factors↗

Vocal mimicry of computer-generated sounds and vocal labeling of objects by a bottlenosed dolphin, Tursiops truncatus.

A bottlenosed dolphin (Tursiops truncatus) was trained to mimic computer-generated "model" sounds, using a whistle mode of vocalization. Prior to training, the whistle sounds of this dolphin were limited to a few stereotyped forms, none of which resembled the model sounds. After training, high-fidelity imitations were obtained of model sounds having (a) moderately or widely swept, slow-rate frequency modulation (1-2 Hz), (b) narrowly or moderately swept frequency modulation at moderate to rapid rates (3-11 Hz), (c) square-wave frequency transitions, and (d) unmodulated (pure-tone) waveforms. New models, not heard previously, could be mimicked immediately, often with good fidelity, including mimicry of amplitude variation that had not been explicitly reinforced during training. Subsets of familiar models were mimicked with high reliability in repeated tests. In additional training, control of the mimic response was transferred from the acoustic model to objects shown the dolphin (e.g., a ball or a hoop) so that, in effect, the dolphin gave unique vocal labels to those objects. In a test of accuracy and reliability of labeling, correct vocal labels were given on 91% of 167 trials comprised of five different objects presented in random order. The dolphin's ability for vocal mimicry compared favorably with that of the more versatile mimic birds, and it contrasted sharply with the apparent lack of vocal mimicry ability in terrestrial mammals other than humans. The ability to label objects vocally was similar to abilities shown for some birds and similar, in principle, to abilities of great apes trained in visual languages to label objects through gestures or other visual symbols.

Animals↗