Limited mobility is something that affects approximately 6.8 million Americans. Approximately 1.7 million are using wheelchairs or scooters of some kind to enhance mobility. Everyday obstacles present a challenge to those in a wheelchair. Also, outdoor environments such as campsites, lakes, or even grass fields provide additional challenges for those with limited mobility. This project provides a solution to some of the limitations faced by those in wheelchairs. The wheels and tires of the wheelchair allow navigation through most terrains such as grass, gravel, and sand. Furthermore, as a wheelchair climbs or descends a hill it becomes unstable and the user risks tipping the wheelchair causing injury or even death. The self-leveling wheelchair uses an accelerometer to determine its angle of inclination and depending on user interface choices will display the angle or raise the seat with linear actuators to keep the seat level. This will keep the center of gravity towards the front of the chair when going up a hill and towards the back of the chair when going down a hill. This enhanced stability will give the user the confidence and ability to go places where most traditional wheelchairs can not. The chair has the ability to self-level at up to 45 degree and can provide a manual lift of 6 inches. The design presented in this report is patent pending.
The RING-type E3 ligase, Keep on Going (KEG), is required for early seedling establishment in Arabidopsis thaliana. Post-germination, KEG negatively regulates abscisic acid (ABA) signalling by targeting Abscisic Acid Insensitive 5 (ABI5) for ubiquitination and subsequent degradation. Previous reports suggest that the role of KEG during early seedling development is not limited to regulation of ABI5 abundance. Using a yeast two-hybrid screen, this study identified Calcineurin B-like Interacting Protein Kinase (CIPK) 26 as a KEG-interacting protein. In vitro pull-down and in planta bimolecular fluorescence complementation assays confirmed the interactions between CIPK26 and KEG. In planta experiments demonstrated that CIPK26 was ubiquitinated and degraded via the 26S proteasome. It was also found that turnover of CIPK26 was increased when KEG protein levels were elevated, suggesting that the RING-type E3 ligase is involved in targeting CIPK26 for degradation. CIPK26 was found to interact with the ABA signalling components ABI1, ABI2, and ABI5. In addition, CIPK26 was capable of phosphorylating ABI5 in vitro. Consistent with a role in ABA signalling, overexpression of CIPK26 increased the sensitivity of germinating seeds to the inhibitory effects of ABA. The data presented in this report suggest that KEG mediates the proteasomal degradation of CIPK26 and that CIPK26 is part of the ABA signalling network.
The visual systems flexibility in estimating depth is remarkable: We readily perceive 3-D structure under diverse conditions from the seemingly random dots of a "magic eye" stereogram to the aesthetically beautiful, but obviously flat, canvasses of the Old Masters. Yet, 3-D perception is often enhanced when different cues specify the same depth. This perceptual process is understood as Bayesian inference that improves sensory estimates. Despite considerable behavioral support for this theory, insights into the cortical circuits involved are limited. Moreover, extant work tested quantitatively similar cues, reducing some of the challenges associated with integrating computationally and qualitatively different signals. Here we address this challenge by measuring fMRI responses to depth structures defined by shading, binocular disparity, and their combination. We quantified information about depth configurations (convex "bumps" vs. concave "dimples") in different visual cortical areas using pattern classification analysis. We found that fMRI responses in dorsal visual area V3B/KO were more discriminable when disparity and shading concurrently signaled depth, in line with the predictions of cue integration. Importantly, by relating fMRI and psychophysical tests of integration, we observed a close association between depth judgments and activity in this area. Finally, using a cross-cue transfer test, we found that fMRI responses evoked by one cue afford classification of responses evoked by the other. This reveals a generalized depth representation in dorsal visual cortex that combines qualitatively different information in line with 3-D perception.
We relate, by simple analytical centrifugation experiments, the density of colloidal fluids with the nature of their randomly packed solid sediments. We demonstrate that the most dilute fluids of colloidal hard spheres form loosely packed sediments, where the volume fraction of the particles approaches in frictional systems the random loose packing limit, ?RLP = 0.55. The dense fluids of the same spheres form denser sediments, approaching the so-called random close packing limit, ?RCP = 0.64. Our experiments, where particle sedimentation in a centrifuge is sufficiently rapid to avoid crystallization, demonstrate that the density of the sediments varies monotonically with the volume fraction of the initial suspension. We reproduce our experimental data by simple computer simulations, where structural reorganizations are prohibited, such that the rate of sedimentation is irrelevant. This suggests that in colloidal systems, where viscous forces dominate, the structure of randomly close-packed and randomly loose-packed sediments is determined by the well-known structure of the initial fluids of simple hard spheres, provided that the crystallization is fully suppressed.
When colloidal suspensions dry, stresses build up and cracks often occur -a phenomenon undesirable for important industries such as paint and ceramics. We demonstrate an effective method which can completely eliminate cracking during drying: by adding emulsion droplets into colloidal suspensions, we can systematically decrease the amount of cracking, and eliminate it completely above a critical droplet concentration. Since the emulsion droplets eventually also evaporate, our technique achieves an effective function while making little changes to the component of final product, and may therefore serve as a promising approach for cracking elimination. Furthermore, adding droplets also varies the speed of air invasion and provides a powerful method to adjust drying rate. With the effective control over cracking and drying rate, our study may find important applications in many drying- and cracking-related industrial processes.
The addition of sterically stabilized colloidal particles to a phase-separating microemulsion leads to dramatic changes in its demixing behavior, especially during the later stages. Our microemulsion is composed of reverse micelles of sodium dodecyl sulfate, pentanol, and water in a dodecane continuous phase which separates into micelle-rich and micelle-poor phases above a lower critical solution temperature. The poly(methyl methacrylate) particles preferentially partition into the less structured, micelle-poor phase. Nucleation of the minority phase or spinodal decomposition close to criticality continue to occur in the presence of particles, albeit with pronounced pretransitional clustering of particles when the micelle-poor phase is in the minority. The coalescence of micelle-poor droplets and the coarsening of micelle-rich domains are both strongly modified due to the presence of colloidal particles. We use our observations of the early stages of phase separation to understand these late stage changes.
People readily perceive smooth luminance variations as being due to the shading produced by undulations of a 3-D surface (shape-from-shading). In doing so, the visual system must simultaneously estimate the shape of the surface and the nature of the illumination. Remarkably, shape-from-shading operates even when both these properties are unknown and neither can be estimated directly from the image. In such circumstances humans are thought to adopt a default illumination model. A widely held view is that the default illuminant is a point source located above the observers head. However, some have argued instead that the default illuminant is a diffuse source. We now present evidence that humans may adopt a flexible illumination model that includes both diffuse and point source elements. Our model estimates a direction for the point source and then weights the contribution of this source according to a bias function. For most people the preferred illuminant direction is overhead with a strong diffuse component.
The modification of the glass transition in confined domains, particularly the length scales associated with cooperative motion, remains a mystery. Hard-sphere suspensions are confined between two surfaces to progressively smaller dimensions to probe the confinement effect on the growth of dynamic heterogeneities via confocal microscopy. The confinement length scale is defined as the critical spacing where deviations from bulk behaviors begin and is observed to occur at progressively larger gap spacings as the volume fraction is increased. However, dynamic length scales extracted from the four-point correlation function are on average smaller than the confinement length scale.
Using a system of modified silica particles and mixtures of water and 2,6-lutidine to form particle-stabilized emulsions, we show that subtle alterations to the hydration of the particle surface can cause major shifts in emulsion structure. We use fluorescence confocal microscopy, solid state nuclear magnetic resonance (NMR) and thermo-gravimetric analysis (TGA) to explore this sensitivity, along with other shifts caused by modifications to the silica surface chemistry. The silica particles are prepared by a variant of the Stöber procedure and are modified by the inclusion of 3-(aminopropyl)triethoxysilane and the dye fluorescein isothiocyanate. Treatment prior to emulsification consists of gently drying the particles under carefully controlled conditions. In mixtures of water and 2,6-lutidine of critical composition, the particles stabilize droplet emulsions and bijels. Decreasing particle hydration yields an inversion of the emulsions from lutidine-in-water (L/W) to water-in-lutidine (W/L), with bijels forming around inversion. So dependent is the emulsion behavior on particle hydration that microscopic differences in drying within a particle sample can cause differences in the wetting behavior of that sample, which helps to stabilize multiple emulsions. The formation of bijels at emulsion inversion is also crucially dependent on the surface modification of the silica.
When an undulating surface bearing a painted texture is illuminated the resulting shading pattern produces in-phase modulations of the mean luminance (LM) and luminance amplitude (AM) of the texture. Experimentally, in-phase combinations of LM and AM (LM+AM) are seen as undulating surfaces whereas anti-phase combinations (LM-AM) are more ambiguous; being seen as undulating when presented alone but as flat when presented in a plaid with LM+AM. AM is a second-order cue and its influence on shape-from-shading can be explained with a bottom-up layer decomposition model containing second-order mechanisms. However, the role of second-order vision in layer decomposition has not been established. If second-order vision is involved in layer decomposition then the perceptual differences between LM+AM and LM-AM should depend on the properties of the carrier texture in a way that is consistent with the known properties of second-order vision. Here we find a preference for carrier frequencies 3 octaves above the modulation frequency and take this as an indication that second-order (filter-rectify-filter) mechanisms are involved in processing our LM/AM mixes. We introduce a modified model which takes into account the selectivity of second-order vision for carrier frequency.
A fit and well gentleman presented with scrotal swelling, 2 days after blunt force trauma to the lower left side of his chest. At the time of injury, a focused assessment with sonography for trauma (FAST) scan for intra-abdominal trauma was negative. He was discharged but returned with persistent pain and swelling of the scrotum 4 days after the injury. This swelling was due to a haematocele secondary to splenic laceration caused by the original trauma. He remained well and did not require further intervention; the scrotal swelling had resolved after 2 weeks. This case highlights that intra-abdominal injury is an important differential of acute scrotal swelling and that FAST negative needs to be treated with caution in order not to miss more subtle injuries.
A simple and versatile method for making chemically patterned anisotropic colloidal particles is proposed and demonstrated for two different types of patterning. Using a combination of thermo/mechanical stretching followed by a wet chemical treatment of a sterically stabilized latex, both patchy ellipsoidal particles with sticky interactions near the tips as well as particles with tunable fluorescent patterns could be easily produced. The potential of such model colloidal particles is demonstrated, specifically for the case of directed self-assembly.
The human visual system is sensitive to second-order modulations of the local contrast (CM) or amplitude (AM) of a carrier signal. Second-order cues are detected independently of first-order luminance signals; however, it is not clear why vision should benefit from second-order sensitivity. Analysis of the first- and second-order contents of natural images suggests that these cues tend to occur together, but their phase relationship varies. We have shown that in-phase combinations of LM and AM are perceived as a shaded corrugated surface whereas the anti-phase combination can be seen as corrugated when presented alone or as a flat material change when presented in a plaid containing the in-phase cue. We now extend these findings using new stimulus types and a novel haptic matching task. We also introduce a computational model based on initially separate first- and second-order channels that are combined within orientation and subsequently across orientation to produce a shading signal. Contrast gain control allows the LM + AM cue to suppress responses to the LM - AM when presented in a plaid. Thus, the model sees LM - AM as flat in these circumstances. We conclude that second-order vision plays a key role in disambiguating the origin of luminance changes within an image.
Observers performed three between- and two within-category perceptual decisions with hybrid stimuli comprising low and high spatial frequency (SF) images. We manipulated (a) attention to, and (b) congruency of information in the two SF bands. Processing difficulty of the different SF bands varied across different categorization tasks: house-flower, face-house, and valence decisions were easier when based on high SF bands, while flower-face and gender categorizations were easier when based on low SF bands. Larger interference also arose from response relevant distracters that were presented in the "preferred" SF range of the task. Low SF effects were facilitated by short exposure durations. The results demonstrate that decisions are affected by an interaction of task and SF range and that the information from the non-attended SF range interfered at the decision level. A further analysis revealed that overall differences in the statistics of image features, in particular differences of orientation information between two categories, were associated with decision difficulty. We concluded that the advantage of using information from one SF range over another depends on the specific task requirements that built on the differences of the statistical properties between the compared categories.
XBAT32, a member of the RING domain-containing ankyrin repeat subfamily of E3 ligases, was previously identified as a positive regulator of lateral root development. Arabidopsis (Arabidopsis thaliana) plants harboring a mutation in XBAT32 produce fewer lateral roots that wild-type plants. We found that xbat32 mutants produce significantly more ethylene than wild-type plants and that inhibition of ethylene biosynthesis or perception significantly increased xbat32 lateral root production. XBAT32 interacts with the ethylene biosynthesis enzymes AMINOCYCLOPROPANE-1-CARBOXYLIC ACID SYNTHASE4 (ACS4) and ACS7 in yeast-two-hybrid assays. XBAT32 is capable of catalyzing the attachment of ubiquitin to both ACS4 and ACS7 in in vitro ubiquitination assays. These results suggest that XBAT32 negatively regulates ethylene biosynthesis by modulating the abundance of ACS proteins. Loss of XBAT32 may promote the stabilization of ACSs and lead to increased ethylene synthesis and suppression of lateral root formation. XBAT32 may also contribute to the broader hormonal cross talk that influences lateral root development. While auxin treatments only partially rescue the lateral root defect of xbat32, they completely restore wild-type levels of xbat32 lateral root production when coupled with ethylene inhibition. Abscisic acid, an antagonist of ethylene synthesis/signaling, was also found to stimulate rather than inhibit xbat32 lateral root formation, and abscisic acid acts synergistically with auxin to promote xbat32 lateral root production.
Docetaxel is an effective chemotherapy drug to treat breast cancer but the underlying molecular mechanisms of drug resistance are not fully understood. DNA methylation is an epigenetic event, involved in the control of gene expression, which is known to play an important role in cancer and chemotherapy drug resistance. To investigate the role of DNA methylation in docetaxel resistance in breast cancer we used two human breast cancer cell lines (MCF-7 and MDA-MB-231) that were made resistant to docetaxel. Docetaxel-resistant sub-lines were treated with different concentrations of decitabine. Global methylation and DNA methyltransferase (DNMT) activity was measured using an ELISA-based assay. Quantitative real-time PCR was used to study DNMT gene expression. Cell viability was studied by MTT assay. Global methylation was increased in MCF-7 but not significantly changed in MDA-MB-231 docetaxel-resistant cells. Decreased DNMT activity and decreased DNMT1 and DNMT3b mRNA expression was associated with docetaxel resistance in both cell lines. To investigate how the components of the DNA methylation machinery may contribute towards docetaxel resistance, decitabine (5-aza-2-deoxycytidine), an inhibitor of DNA methylation, was used. Decitabine treatment decreased global methylation, DNMT activity and DNMT1, DNMT3a and DNMT3b mRNA expression in MDA-MB-231 docetaxel-resistant cells. In contrast, decitabine-treated MCF-7 docetaxel-resistant cells showed increased DNMT1, DNMT3a and DNMT3b mRNA expression indicating a cell line specific effect of decitabine. Decitabine treatment increased resistance in MCF-7 docetaxel-resistant cells and in the parental MCF-7 and MDA-MB231 docetaxel-sensitive cell lines, however, it did not alter response to docetaxel in MDA-MB-231 docetaxel-resistant cells. This study demonstrates that changes in the DNA methylation machinery are associated with resistance to docetaxel in breast cancer cells. The use of epigenetic therapies, as a strategy to overcome drug resistance, needs to be investigated more fully to determine their effectiveness in different cancers and for different chemotherapy drugs.
We investigate the 3D structure and drying dynamics of complex mixtures of emulsion droplets and colloidal particles, using confocal microscopy. Air invades and rapidly collapses large emulsion droplets, forcing their contents into the surrounding porous particle pack at a rate proportional to the square of the droplet radius. By contrast, small droplets do not collapse, but remain intact and are merely deformed. A simple model coupling the Laplace pressure to Darcys law correctly estimates both the threshold radius separating these two behaviors, and the rate of large-droplet evacuation. Finally, we use these systems to make novel hierarchical structures.
To quantify gene expression levels, appropriate controls have to be used to adjust for experimental variation. Endogenous control genes are widely used as they are stably expressed independent of cell cycle and experimental conditions, however, they can be altered upon drug treatment. DNA methylation is widely studied in chemotherapy drug resistance and the DNA methylation inhibitor decitabine showed promising results reversing drug resistance in cancer. We aimed to investigate the effect of different decitabine concentrations on the expression of selected endogenous control genes (GAPDH, 18S rRNA, PPIA, RPL13A, OAZ1) in two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) compared to untreated cells. In MCF-7 cells, 18S rRNA remained stable, however, GAPDH, PPIA and OAZ1 gene expression was increased after treatment. RPL13A was stably expressed at 8 muM decitabine but was increased at lower drug concentrations. In MDA-MB-231 cells, GAPDH levels remained relatively stable following decitabine treatment and so was PPIA expression at low decitabine concentrations. Decitabine increased 18S rRNA, RPL13A and OAZ1 gene expression. In this study, we observed cell line specific effects of decitabine and suggest that 18S rRNA is most suitable to use in MCF-7 cells, while GAPDH is recommended to use in MDA-MB-231 cells during decitabine treatment.
Immunonutrition, containing arginine as a key component, has been shown to enhance the immune system and significantly reduce infectious complications in patients undergoing upper gastrointestinal surgery. Arginine, however, may also influence tumour cell behaviour. The aim of this study was to investigate the effects of arginine on tumour cell growth, invasion and modulation of expression of genes involved in these aspects of cell behaviour.
In stereo vision, regions with ambiguous or unspecified disparity can acquire perceived depth from unambiguous regions. This has been called stereo capture, depth interpolation or surface completion. We studied some striking induced depth effects suggesting that depth interpolation and surface completion are distinct stages of visual processing. An inducing texture (2-D Gaussian noise) had sinusoidal modulation of disparity, creating a smooth horizontal corrugation. The central region of this surface was replaced by various test patterns whose perceived corrugation was measured. When the test image was horizontal 1-D noise, shown to one eye or to both eyes without disparity, it appeared corrugated in much the same way as the disparity-modulated (DM) flanking regions. But when the test image was 2-D noise, or vertical 1-D noise, little or no depth was induced. This suggests that horizontal orientation was a key factor. For a horizontal sine-wave luminance grating, strong depth was induced, but for a square-wave grating, depth was induced only when its edges were aligned with the peaks and troughs of the DM flanking surface. These and related results suggest that disparity (or local depth) propagates along horizontal 1-D features, and then a 3-D surface is constructed from the depth samples acquired. The shape of the constructed surface can be different from the inducer, and so surface construction appears to operate on the results of a more local depth propagation process.
Ornithine decarboxylase (ODC), the first enzyme in the biosynthesis of polyamines, has increased activity in breast cancer tissue compared with benign and normal tissues. The ODC gene contains a single nucleotide polymorphism in which a guanine is substituted for an adenine. This study investigated whether the ODC +316 G > A polymorphism (rs2302615) was associated with the risk of developing breast cancer. A case-control study involving 121 controls, without breast cancer, 46 patients with breast cancer but without a family history, and 130 breast cancer cases with a family history of breast cancer was conducted. A nested PCR-restriction fragment length polymorphism procedure and the TaqMan 5 nuclease assay was used to genotype individuals. Risk was significantly lower for heterozygote (GA genotype) individuals [odds ratio (OR) = 0.39, 95% confidence interval (CI) 0.17-0.86, P = 0.018], or individuals with at least one A allele (OR = 0.44, 95% CI 0.21-0.92, P = 0.027), without family history. This protective effect of having at least one copy of the variant A allele was not as strong, however, in those with a family history of the disease. In sporadic breast cancer, the presence of at least one A allele is protective against the disease. The influence of this polymorphism may be less important in individuals with an inherited breast cancer predisposition.
Luminance variations are ambiguous: they can signal changes in surface reflectance or changes in illumination. Layer decomposition-the process of distinguishing between reflectance and illumination changes-is supported by a range of secondary cues including colour and texture. For an illuminated corrugated, textured surface the shading pattern comprises modulations of luminance (first order, LM) and local luminance amplitude (second-order, AM). The phase relationship between these two signals enables layer decomposition, predicts the perception of reflectance and illumination changes, and has been modelled based on early, fast, feed-forward visual processing (Schofield et al., 2010). However, while inexperienced viewers appreciate this scission at long presentation times, they cannot do so for short presentation durations (250 ms). This might suggest the action of slower, higher-level mechanisms. Here we consider how training attenuates this delay, and whether the resultant learning occurs at a perceptual level. We trained observers to discriminate the components of plaid stimuli that mixed in-phase and anti-phase LM/AM signals over a period of 5 days. After training, the strength of the AM signal needed to differentiate the plaid components fell dramatically, indicating learning. We tested for transfer of learning using stimuli with different spatial frequencies, in-plane orientations, and acutely angled plaids. We report that learning transfers only partially when the stimuli are changed, suggesting that benefits accrue from tuning specific mechanisms, rather than general interpretative processes. We suggest that the mechanisms which support layer decomposition using second-order cues are relatively early, and not inherently slow.
We introduce confocal differential dynamic microscopy (ConDDM), a new technique yielding information comparable to that given by light scattering but in dense, opaque, fluorescent samples of micron-sized objects that cannot be probed easily with other existing techniques. We measure the correct wave vector q-dependent structure and hydrodynamic factors of concentrated hard-sphere-like colloids. We characterize concentrated swimming bacteria, observing ballistic motion in the bulk and a new compressed-exponential scaling of dynamics, and determine the velocity distribution; by contrast, near the coverslip, dynamics scale differently, suggesting that bacterial motion near surfaces fundamentally differs from that of freely swimming organisms.
In disordered colloidal systems, we experimentally measure the normal modes with the covariance matrix method and clarify the origin of low-frequency quasilocalization at the single-particle level. We observe important features from both jamming and glass simulations: There is a plateau in the density of states [D(?)] which is suppressed upon compression, as predicted by jamming; within the same systems, we also find that the low-frequency quasilocalization originates from the large vibrations of defective structures coupled with transverse excitations, consistent with a recent glass simulation. The coexistence of these features demonstrates an experimental link between jamming and glass. Extensive simulations further show that such a structural origin of quasilocalization is universally valid for various temperatures and volume fractions.
The perception of shape from shading (SFS) has been an active research topic for more than two decades, yet its quantitative description remains poorly specified. One obstacle is the variability typically found between observers during SFS tasks. In this study, we take a different view of these inconsistencies, attributing them to uncertainties associated with human SFS. By identifying these uncertainties, we are able to probe the underlying computation behind SFS in humans. We introduce new experimental results that have interesting implications for SFS. Our data favor the idea that human SFS operates in at least two distinct modes. In one mode, perceived slant is linear to luminance or close to linear with some perturbation. Whether or not the linear relationship is achieved is influenced by the relative contrasts of edges bounding the luminance variation. This mode of operation is consistent with collimated lighting from an oblique angle. In the other mode, recovered surface height is indicative of a surface under lighting that is either diffuse or collimated and frontal. Shape estimates under this mode are partially accounted for by the "dark-is-deep" rule (height ? luminance). Switching between these two modes appears to be driven by the sign of the edges at the boundaries of the stimulus. Linear shading was active when the boundary edges had the same contrast polarity. Dark-is-deep was active when the boundary edges had opposite contrast polarity. When both same-sign and opposite-sign edges were present, observers preferred linear shading but could adopt a combination of the two computational modes.
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