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1.
Nat Commun ; 13(1): 6620, 2022 Nov 04.
Article in English | MEDLINE | ID: mdl-36333309

ABSTRACT

As we approach the era of quantum advantage, when quantum computers (QCs) can outperform any classical computer on particular tasks, there remains the difficult challenge of how to validate their performance. While algorithmic success can be easily verified in some instances such as number factoring or oracular algorithms, these approaches only provide pass/fail information of executing specific tasks for a single QC. On the other hand, a comparison between different QCs preparing nominally the same arbitrary circuit provides an insight for generic validation: a quantum computation is only as valid as the agreement between the results produced on different QCs. Such an approach is also at the heart of evaluating metrological standards such as disparate atomic clocks. In this paper, we report a cross-platform QC comparison using randomized and correlated measurements that results in a wealth of information on the QC systems. We execute several quantum circuits on widely different physical QC platforms and analyze the cross-platform state fidelities.

2.
J Intellect Disabil Res ; 54(9): 860-74, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20712699

ABSTRACT

BACKGROUND: This paper describes the development of an Attitudes to Disability Scale for use with adults with physical or intellectual disabilities (ID). The aim of the research was to design a scale that could be used to assess the personal attitudes of individuals with either physical or ID. METHOD: The measure was derived following standard WHOQOL methodology as part of an international trial. In the pilot phase of the study, 12 centres from around the world carried out focus groups with people with physical disabilities, people with ID, with their carers, and with relevant professionals in order to identify themes relevant for attitudes to disability. Items generated from the focus groups were then tested in a pilot study with 1400 respondents from 15 different centres worldwide, with items being tested and reduced using both classical and modern psychometric methods. A field trial study was then carried out with 3772 respondents, again with the use of both classical and modern psychometric methods. RESULTS: The outcome of the second round of data collection and analysis is a 16-item scale that can be used for assessment of attitudes to disability in physically or intellectually disabled people and in healthy respondents. CONCLUSIONS: The Attitudes to Disability Scale is a new psychometrically sound scale that can be used to assess attitudes in both physically and intellectually disabled groups. The scale is also available in both personal and general forms and in a number of different language versions.


Subject(s)
Attitude to Health , Developmental Disabilities/psychology , Disability Evaluation , Intellectual Disability/psychology , Psychometrics/methods , Quality of Life , Adult , Aged , Cross-Cultural Comparison , Cultural Characteristics , Developmental Disabilities/ethnology , Female , Humans , Intellectual Disability/ethnology , Male , Middle Aged , Reproducibility of Results , Young Adult
3.
Qual Life Res ; 19(4): 571-84, 2010 May.
Article in English | MEDLINE | ID: mdl-20217246

ABSTRACT

PURPOSE: This paper describes the development of an add-on module for the World Health Organization WHOQOL measures of quality of life for use with adults with physical or intellectual disabilities. The add-on module, known as the WHOQOL-DIS, was derived following standard WHOQOL methodology and is designed to assess people with disabilities. RESULTS: In the pilot phase of the study, 12 centres from around the world carried out focus groups with people with physical disabilities, people with intellectual disabilities, with their carers, and with relevant professionals in order to identify gaps in the coverage of the WHOQOL-BREF that were relevant for their quality of life. Items generated from the focus groups were then tested in a pilot study with 1,400 respondents from 15 different centres worldwide, with items being tested and reduced using both classical and modern psychometric methods. A field trial study was then carried out with almost 3,800 respondents, again with the use of both classical and modern psychometric methods. CONCLUSIONS: The outcome of the two rounds of data collection and analysis is a 12-item module that can be used in conjunction with the WHOQOL-BREF or the WHOQOL-100 for assessment of quality of life in physically or intellectually disabled people. Further modifications are also proposed for the use of the WHOQOL-BREF with adults with intellectual disabilities, including simplification of wording of some of the items, the use of a three-point response scale, and the inclusion of smiley faces.


Subject(s)
Disability Evaluation , Intellectual Disability , Psychometrics , Quality of Life , Sickness Impact Profile , World Health Organization , Adaptation, Psychological , Adult , Algorithms , Disabled Persons , Female , Focus Groups , Humans , Male , Middle Aged , Pilot Projects
4.
J Chem Phys ; 130(4): 044306, 2009 Jan 28.
Article in English | MEDLINE | ID: mdl-19191384

ABSTRACT

Zeeman quantum beat spectroscopy has been used to measure the 300 K rate constants for the angular momentum depolarization of OH(A (2)Sigma(+)) in the presence of Ar. We show that the beat amplitude at short times, in the absence of collisions, is well described by previously developed line strength theory for (1+1) laser induced fluorescence. The subsequent pressure dependent decay of the beat amplitude is used to extract depolarization rate constants and estimates of collisional depolarization cross sections. Depolarization accompanies both inelastic collisions, giving rise to rotational energy transfer, and elastic collisions, which change m(j) but conserve j. Previous experimental studies, as well as classical theory, suggest that elastic scattering contributes around 20% to the observed total depolarization rate at low j. Simulation of the experimental beat amplitudes, using theoretical calculations presented in the preceding paper, reveals that depolarization of OH(A) by Ar has a rate constant comparable to, if not larger than, that for energy transfer. This is consistent with a significant tilting or realignment of j(') away from j on collision. The experimental data are used to provide a detailed test of quantum mechanical and quasiclassical trajectory scattering calculations performed on a recently developed ab initio potential energy surface of Klos et al. [J. Chem. Phys. 129, 054301 (2008)]. The calculations and simulations account well for the observed cross sections at high N, but underestimate the experimental results by between 10% and 20% at low N, possibly due to remaining inaccuracies in the potential energy surface or perhaps to limitations in the dynamical approximations made, particularly the freezing of the OH(A) bond.

5.
Nanotechnology ; 19(45): 455307, 2008 Nov 12.
Article in English | MEDLINE | ID: mdl-21832772

ABSTRACT

We have registered the position and wavelength of a single InGaAs quantum dot using an innovative cryogenic laser lithography technique. This approach provides accurate marking of the location of self-organized dots and is particularly important for realizing any solid-state cavity quantum electrodynamics scheme where the overlap of the spectral and spatial characteristics of an emitter and a cavity is essential. We demonstrate progress in two key areas towards efficient single quantum dot photonic device implementation. Firstly, we show the registration and reacquisition of a single quantum dot with 50 and 150 nm accuracy, respectively. Secondly, we present data on the successful fabrication of a photonic crystal L3 cavity following the registration process.

6.
Infect Dis Obstet Gynecol ; 13(3): 145-50, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16126499

ABSTRACT

OBJECTIVE: To compare a real-time polymerase chain reaction (PCR) assay with broth culture for the detection of Trichomonas vaginalis using self-collected vaginal swabs. METHODS: Self-collected vaginal swabs were obtained from adolescent and young adult African-American women participating in HIV-1 prevention programs. T. vaginalis culture was performed using the InPouch TV System. Samples for the real-time PCR assay were collected using the BDProbeTec ET Culturette Direct Dry Swab system and tested in a laboratory-developed assay which targeted a repeated sequence of the genome. Discrepant samples that were culture negative and positive in the real-time PCR assay were tested in a confirmatory PCR which targeted a different region of the T. vaginalis genome, the18S ribosomal DNA gene. RESULTS: Of the 524 specimens tested by both culture and real-time PCR, 36 were culture positive and 54 were positive in the real-time PCR assay; 16 of the 18 discrepant specimens were also positive in the confirmatory PCR assay. Using a modified gold standard of positive by culture or positive in both PCR assays, the sensitivity of the real-time PCR assay was 100% and the specificity was 99.6%, whereas culture had a sensitivity of 69.2% and a specificity of 100%. CONCLUSIONS: The real-time PCR assay was sensitive and specific for the detection of T. vaginalis DNA from self-collected vaginal swab specimens. The ability to use the BDProbeTec dry swab system for the real-time PCR testing allowed for the detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and T. vaginalis from a single specimen.


Subject(s)
DNA, Protozoan/analysis , Polymerase Chain Reaction/methods , Trichomonas Vaginitis/diagnosis , Trichomonas vaginalis/isolation & purification , Vagina/parasitology , Adolescent , Adult , Black or African American , Animals , Female , Humans , Sensitivity and Specificity , Trichomonas vaginalis/genetics
7.
Mol Ecol ; 11(2): 191-5, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11856421

ABSTRACT

Fungal cultivars of fungus-growing ants (Attini, Formicidae) are carried by dispersing queens from parent to offspring nest. This vertical cultivar transmission between generations is thought to result in long-term ant-fungus coevolution and selection for beneficial cultivar traits that maximize harvests and thus colony productivity. In contrast to this traditional view of vertical cultivar transmission, frequent horizontal cultivar transmission between ant species is implicated by a phylogenetic analysis of 72 cultivars propagated by two fungus-growing ant species coexisting sympatrically in central Panama. The two ant species are specialized on the same group of closely related cultivars, but in six of 12 cultivar clades identifiable within this group, cultivars from both ant species were united in the same clade. Five of these 'mixed' clades were supported by bootstrap values of about 90% or higher. In one instance, colonies from the two ant species cultivated the same, genetically identical, cultivar clone. These phylogenetic patterns indicate that: (i) cultivar exchanges between the two ant species occur routinely throughout ecological time; and that (ii) coevolutionary processes between ants and their fungi are more diffuse than previously assumed. Because the two ant species are specialized on a narrow group of closely related cultivars that they regularly exchange among each other, but not with other sympatric ant species, cultivar exchanges are constrained, most likely, by ant preferences for their own cultivar group or by stringent selection against transitions of ant lineages to distantly related cultivars.


Subject(s)
Ants/physiology , Fungi/genetics , Animals , Biological Evolution , Fungi/classification , Fungi/growth & development , Panama , Phylogeny , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length
8.
J Neuroimmunol ; 120(1-2): 103-11, 2001 Nov 01.
Article in English | MEDLINE | ID: mdl-11694325

ABSTRACT

The monoclonal Lewis rat skeletal muscle cell line, LE1, responded to the acetylcholine receptor (AChR)-reactive antibody mAb35 by up-regulating levels of mRNA for inducible nitric oxide synthase (iNOS/NOS-II), followed by levels of NO. Interferon-gamma (IFN-gamma) and interleukin-1 (IL-1) were also each capable of inducing iNOS message, and synergistically with mAb35. Finally, myocyte-derived NO was implicated as a possible source of immunomodulation in experimental autoimmune myasthenia gravis (EAMG), as shown by the ability of the culture fluids from IFN-gamma-activated LE1 cells to inhibit the proliferation of AChR-reactive T cells.


Subject(s)
Antibodies, Monoclonal/pharmacology , Cytokines/pharmacology , Muscle, Skeletal/drug effects , Myasthenia Gravis, Autoimmune, Experimental/immunology , Nitric Oxide/biosynthesis , Receptors, Cholinergic/drug effects , Up-Regulation/drug effects , Adjuvants, Immunologic/pharmacology , Animals , Cell Division/drug effects , Cell Division/immunology , Cells, Cultured/drug effects , Cells, Cultured/immunology , Cells, Cultured/metabolism , Cytokines/immunology , Cytokines/metabolism , Dose-Response Relationship, Drug , Drug Synergism , Enzyme Inhibitors/pharmacology , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interferon-gamma/pharmacology , Interleukin-1/immunology , Interleukin-1/metabolism , Interleukin-1/pharmacology , Muscle, Skeletal/immunology , Muscle, Skeletal/metabolism , Myasthenia Gravis, Autoimmune, Experimental/metabolism , Myasthenia Gravis, Autoimmune, Experimental/physiopathology , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/genetics , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Rats, Inbred Lew , Receptors, Cholinergic/immunology , Receptors, Cholinergic/metabolism , Stem Cells/drug effects , Stem Cells/immunology , Stem Cells/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Up-Regulation/immunology
10.
Surgery ; 130(2): 256-64, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11490358

ABSTRACT

BACKGROUND: Catecholamines are significantly elevated in inflammatory responses and play a regulatory role in sepsis. Nitric oxide (NO), also a key inflammatory mediator in sepsis, is produced in large amounts by the inducible nitric oxide synthase (iNOS) in the liver. The purpose of this study was to test the hypothesis that catecholamines play a role in the regulation of NO production by hepatocytes. METHODS: Primary hepatocytes were isolated from healthy male Sprague-Dawley rats and either cultured with normal medium or stimulated with cytomix (interleukin-1 beta, interferon-gamma, and tumor necrosis factor-alpha) in the presence or absence of epinephrine or norepinephrine at varying concentrations. Total RNA was isolated 6 hours after treatment and analyzed by Northern blotting for iNOS mRNA. Protein extracts were obtained at 12 hours and were analyzed by Western immunoblotting for iNOS. Cell culture supernatants were analyzed for NO, determined as the stable end-product NO(2)(-), at 24 hours. RESULTS: Epinephrine and norepinephrine significantly decreased NO(2)(-) levels in stimulated hepatocytes but had no effect on iNOS mRNA or protein levels. The decrease in NO(2)(-) was reproduced by the adenylate cyclase stimulator, forskolin. The catecholamine-induced decrease in NO(2)(-) was completely reversed by the protein kinase A inhibitor Rp-8-Br-cyclic adenosine monophosphate. CONCLUSIONS: Catecholamines decrease hepatocyte production of NO in response to cytokine stimulation. This effect seems to be due to post-translational events and appears to be mediated in part by cyclic adenosine monophosphate.


Subject(s)
Cytokines/pharmacology , Epinephrine/pharmacology , Hepatocytes/metabolism , Nitric Oxide/biosynthesis , Sympathomimetics/pharmacology , 8-Bromo Cyclic Adenosine Monophosphate/analogs & derivatives , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Adenoviridae/genetics , Animals , Antineoplastic Agents/pharmacology , Biopterins/metabolism , Cell Survival/physiology , Cells, Cultured , Cyclic AMP-Dependent Protein Kinase Type II , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Enzyme Inhibitors/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Gene Transfer Techniques , Hepatocytes/cytology , Hepatocytes/immunology , Interferon-gamma/pharmacology , Interleukin-1/pharmacology , Male , Nitrates/metabolism , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Nitrites/metabolism , Norepinephrine/pharmacology , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Stimulation, Chemical , Thionucleotides/pharmacology , Tumor Necrosis Factor-alpha/pharmacology
11.
J Neurosci ; 21(11): 3968-85, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11356885

ABSTRACT

Rotational and translational vestibulo-ocular reflexes (RVOR and TrVOR) function to maintain stable binocular fixation during head movements. Despite similar functional roles, differences in behavioral, neuroanatomical, and sensory afferent properties suggest that the sensorimotor processing may be partially distinct for the RVOR and TrVOR. To investigate the currently poorly understood neural correlates for the TrVOR, the activities of eye movement-sensitive neurons in the rostral vestibular nuclei were examined during pure translation and rotation under both stable gaze and suppression conditions. Two main conclusions were made. First, the 0.5 Hz firing rates of cells that carry both sensory head movement and motor-like signals during rotation were more strongly related to the oculomotor output than to the vestibular sensory signal during translation. Second, neurons the firing rates of which increased for ipsilaterally versus contralaterally directed eye movements (eye-ipsi and eye-contra cells, respectively) exhibited distinct dynamic properties during TrVOR suppression. Eye-ipsi neurons demonstrated relatively flat dynamics that was similar to that of the majority of vestibular-only neurons. In contrast, eye-contra cells were characterized by low-pass filter dynamics relative to linear acceleration and lower sensitivities than eye-ipsi cells. In fact, the main secondary eye-contra neuron in the disynaptic RVOR pathways (position-vestibular-pause cell) that exhibits a robust modulation during RVOR suppression did not modulate during TrVOR suppression. To explain these results, a simple model is proposed that is consistent with the known neuroanatomy and postulates differential projections of sensory canal and otolith signals onto eye-contra and eye-ipsi cells, respectively, within a shared premotor circuitry that generates the VORs.


Subject(s)
Fixation, Ocular/physiology , Models, Neurological , Motion , Reflex, Vestibulo-Ocular/physiology , Vestibular Nuclei/physiology , Action Potentials/physiology , Animals , Computer Simulation , Eye Movements/physiology , Feedback , Head Movements/physiology , Macaca mulatta , Neurons/classification , Neurons/physiology , Predictive Value of Tests , Pursuit, Smooth/physiology , Rotation , Signal Processing, Computer-Assisted , Vestibular Nuclei/cytology , Vision, Binocular/physiology
12.
Naturwissenschaften ; 87(11): 491-3, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11151668

ABSTRACT

Fungi cultivated by fungus-growing ants (Attini: Formicidae) are passed on between generations by transfer from maternal to offspring nest (vertical transmission within ant species). However, recent phylogenetic analyses revealed that cultivars are occasionally also transferred between attine species. The reasons for such lateral cultivar transfers are unknown. To investigate whether garden loss may induce ants to obtain a replacement cultivar from a neighboring colony (lateral cultivar transfer), pairs of queenright colonies of two Cyphomyrmex species were set up in two conjoined chambers; the garden of one colony was then removed to simulate the total crop loss that occurs naturally when pathogens devastate gardens. Garden-deprived colonies regained cultivars through one of three mechanisms: joining of a neighboring colony and cooperation in a common garden; stealing of a neighbor's garden; or aggressive usurpation of a neighbor's garden. Because pathogens frequently devastate attine gardens under natural conditions, garden joining, stealing and usurpation emerge as critical behavioral adaptations to survive garden catastrophes.


Subject(s)
Ants/physiology , Fungi/physiology , Animals , Feeding Behavior , Female , Social Behavior , Species Specificity
14.
Int J Cancer ; 81(6): 889-96, 1999 Jun 11.
Article in English | MEDLINE | ID: mdl-10362135

ABSTRACT

The role of nitric oxide (NO) in tumor biology remains controversial and poorly understood. While a few reports indicate that the presence of NO in tumor cells or their micro-environment is detrimental for tumor-cell survival, and consequently their metastatic ability, a large body of data suggests that NO promotes tumor progression. The purpose of this study was to identify the source of NO in the spontaneously metastasizing C3-L5 murine mammary-adenocarcinoma model, the role of tumor-derived NO in tumor-cell invasiveness, and the mechanisms underlying the invasion-stimulating effects of tumor-derived NO. The source of NO was established by immunocytochemical localization of NO synthase (NOS) enzymes in C3-L5 cells in vitro and transplanted tumors in vivo. An in vitro transwell Matrigel invasion assay was used to test the invasiveness of C3-L5 cells in the presence or the absence of NO blocking agents or iNOS inducers (IFN-gamma and LPS). The mechanisms underlying the invasion-stimulating effects of tumor-derived NO were examined by measuring mRNA expression of matrix metalloproteinases (MMP)-2 and -9, and tissue inhibitors of metalloproteinases (TIMP) 1, 2 and 3 in C3-L5 cells in various experimental conditions. Results showed that C3-L5 cells expressed high level of eNOS protein in vitro, and in vivo, both in primary and in metastatic tumors. C3-L5 cells also expressed iNOS mRNA and protein when cultured in the presence of IFN-gamma and LPS. Constitutively produced NO promoted tumor-cell invasiveness in vitro by down-regulating TIMP 2 and TIMP 3. In addition, there was up-regulation of MMP-2, when extra NO was induced by IFN-gamma and LPS. In conclusion, NO produced by C3-L5 cells promoted tumor-cell invasiveness by altering the balance between MMP-2 and its inhibitors TIMP-2 and 3. Thus, our earlier observations of anti-tumor and anti-metastatic effects of NO inhibitors in vivo in this tumor model can be explained, at least in part, by reduced tumor-cell invasiveness.


Subject(s)
Adenocarcinoma/pathology , Lung Neoplasms/secondary , Mammary Neoplasms, Experimental/pathology , Nitric Oxide Synthase/biosynthesis , Nitric Oxide/physiology , Adenocarcinoma/enzymology , Adenocarcinoma/physiopathology , Adenocarcinoma/secondary , Animals , Enzyme Induction , Female , Gene Expression Regulation, Neoplastic/drug effects , Interferon-gamma/pharmacology , Lipopolysaccharides/pharmacology , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Mammary Neoplasms, Experimental/enzymology , Mammary Neoplasms, Experimental/physiopathology , Mice , Mice, Inbred C3H , NG-Nitroarginine Methyl Ester/pharmacology , Neoplasm Invasiveness , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitric Oxide Synthase Type III , Recombinant Proteins , Tissue Inhibitor of Metalloproteinase-3/genetics , Tumor Cells, Cultured , omega-N-Methylarginine/pharmacology
15.
J Neurophysiol ; 80(4): 2222-8, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9772275

ABSTRACT

A common goal of the translational vestibuloocular reflex (TVOR) and the rotational vestibuloocular reflex (RVOR) is to stabilize visual targets on the retinae during head movement. However, these reflexes differ significantly in their dynamic characteristics at both sensory and motor levels, implying a requirement for different central processing of canal and otolith signals. Semicircular canal afferents carry a signal proportional to angular head velocity, whereas primary otolith afferents modulate approximately in phase with linear head acceleration. Behaviorally, the RVOR exhibits a robust response down to approximately 0.01 Hz, yet the TVOR is only significant above approximately 0.5 Hz. Several hypotheses were proposed to address central processing in the TVOR pathways. All rely on a central filtering process that precedes a "neural integrator" shared with the RVOR. We propose an alternative hypothesis for the convergence of canal and otolith signals that does not impose the requirement for additional low-pass filters for the TVOR. The approach is demonstrated using an anatomically based, simple model structure that reproduces the general dynamic characteristics of the RVOR and TVOR at both ocular and central levels. Differential dynamic processing of otolith and canal signals is achieved by virtue of the location at which sensory information enters a shared but distributed neural integrator. As a result, only the RVOR is provided with compensation for the eye plant. Hence canal and otolith signals share a common central integrator, as in previous hypotheses. However, we propose that the required additional filtering of otolith signals is provided by the eye plant.


Subject(s)
Brain/physiology , Models, Neurological , Otolithic Membrane/physiology , Semicircular Canals/physiology , Signal Transduction/physiology , Animals , Humans , Reflex, Vestibulo-Ocular/physiology , Rotation
16.
Otolaryngol Head Neck Surg ; 119(3): 231-43, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9743079

ABSTRACT

Vestibular adaptation can be induced optically or by chemical or physical injury to the vestibular apparatus or the brain stem. In searching for the sites or mechanisms of vestibular adaptation, neurophysiologists often rely on comparing central resting (background) activities and central modulations (sensitivity) during vestibular stimulation, before and after motor learning or vestibular compensation. It is assumed that adapted central sites must exhibit modulation changes that parallel vestibulo-ocular reflex changes. Using model simulations and analysis, we will show that such presumptions may be misleading. First, using a simple schematic of interconnected cells or nuclei, one can show that modulation depth and background "tone" can be modified (or fixed) independently, using weightings on direct or indirect afferent projections. That is, if synaptic weights along all stimulus pathways are altered, one may fix or strongly modify central premotor characteristics in a manner apparently unrelated to global reflex changes. In the vestibulo-ocular reflex, the dominant premotor pathways contain position-vestibular-pause cells and eye-head-velocity cells (which are behaviorally similar to floccular-target neurons). Several experiments have reported negligible changes in the velocity sensitivity of position-vestibular-pause cells, despite large gain changes in the vestibulo-ocular reflex induced by training with visual-vestibular conflict. On the other hand, the modulation changes on floccular-target neurons (position-vestibular-pause) can be much larger than the changes in reflex gain. Using a bilateral vestibulo-ocular reflex model, we show that overall increases or decreases in reflex gain can be expressed (even overexpressed) in one particular subgroup of premotor neurons. Nevertheless, such observations are theoretically compatible with synaptic changes on all primary projections in a widely interconnected central network. Hence, stable neural responses during reflex adaptation are not sufficient to exclude a potential site of sensory-motor adaptation. Similarly, modified neural responses (as in cerebellum) need not necessarily imply a direct role in supporting the adapted state. Model predictions should help to design additional experimental protocols, to test hypotheses, and to refine diagnostic measures of recovery after vestibular lesions.


Subject(s)
Adaptation, Physiological/physiology , Models, Biological , Reflex, Vestibulo-Ocular/physiology , Vestibule, Labyrinth/physiology , Brain Stem/physiology , Cerebellum/physiology , Vestibule, Labyrinth/innervation
17.
J Nucl Cardiol ; 4(6): 539-49, 1997.
Article in English | MEDLINE | ID: mdl-9456195

ABSTRACT

Human clinical investigation plays a central role in contemporary nuclear cardiology. It is a complex expensive endeavor triggering multiple responsibilities not otherwise encountered by physicians in clinical practice. Clinical investigators, drug and device manufacturers, hospitals and universities, governmental agencies, research subjects, patient advocacy groups, and investors all have a legitimate interest in the conduct and the outcome of clinical research. Past abuses of research subjects in many countries including those unknowingly exposed to radioactive isotopes have raised ethical concerns that are now addressed by overlapping laws, regulations, guidelines, and institutional policies that have evolved to guide the research enterprise. The policies underlying this legal and regulatory structure include protection of research subjects, protection of the integrity of research design and research data, and protection of the public and private purse. Knowledge of these laws and regulations is essential for physicians participating in clinical investigations to protect their professional and personal interests. This article reviews legal issues relevant to physicians conducting human clinical trials in the United States.


Subject(s)
Clinical Trials as Topic/legislation & jurisprudence , Conflict of Interest , Human Experimentation , Humans , Informed Consent , United States
18.
J Biomed Mater Res ; 28(5): 647-53, 1994 May.
Article in English | MEDLINE | ID: mdl-8027105

ABSTRACT

Previous studies suggested that surface topographic configurations of 1-3 microns influence cellular behavior and tissue response. They did not address which specific aspect of the configurations elicits the cellular response. We therefore investigated the effect of the orientation of several surface configurations. Seven different textures on polydimethyl siloxane (silicone; Dow Corning Silastic) specimens were used to test the question of whether orientation into (down) or out of the surface (up) affected cellular response to a material. The textures were smooth and photoetched configurations of 2 microns up, 2 microns down, 5 microns up, 5 microns down, 10 microns up, and 10 microns down. The response of cultured fibroblasts on these surfaces was compared with that of a standard tissue culture material, polyethylene terepthalate (Thermanox). The cell density was measured over a 12-day period with the use of a colorimetric assay. The uptake of methylene blue was measured daily and compared as an absorbance in a destaining agent. Cells on the 2 and 5 microns up arrays showed increased rates of proliferation and cell density as compared with their down counterparts. This would indicate that textures of 2 and 5 microns have a significant influence on cell growth, and that the surface with hills has a greater effect than the surface with wells. In contrast, the 10 microns up and 10 microns down arrays did not prove to be statistically different from smooth ones. This indicates that the orientation effect is related to the configuration size and that this configuration size is not viewed differently from smooth silicone by the cells. The presented data are in agreement with results of this laboratory and others that fibroblasts recognize the dimensions of surface configurations and react accordingly. Specifically, they appear to react to the uppermost surface area presented to them, but conclusive data can only be obtained from a study of the focal adhesions.


Subject(s)
Fibroblasts/cytology , Silicones , Surface Properties , Adult , Cell Division , Cells, Cultured , Humans , Male
20.
J Med Chem ; 35(22): 4061-8, 1992 Oct 30.
Article in English | MEDLINE | ID: mdl-1433212

ABSTRACT

Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.


Subject(s)
Hydroxamic Acids/chemical synthesis , Interleukin-1/biosynthesis , Lipoxygenase Inhibitors/chemical synthesis , Vinyl Compounds/chemical synthesis , Animals , Humans , Hydroxamic Acids/chemistry , Hydroxamic Acids/pharmacology , In Vitro Techniques , Lipoxygenase Inhibitors/chemistry , Lipoxygenase Inhibitors/pharmacology , Rats , Glycine max , Structure-Activity Relationship , Tumor Cells, Cultured , Vinyl Compounds/chemistry , Vinyl Compounds/pharmacology
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