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Ocular accommodation control and adaptive optics. The development of monocular and binocular adaptive optics instrumentation for the study of accommodation and convergence, and study of the monocular accommodative response to rapid changes in dioptric stimuli.
The relationship between accommodation and myopia has been under investigation for many years, and the effort to understand it is ongoing.
In this thesis, an introduction to the state of myopia research is given first, with particular reference to studies of accommodation and higher-order ocular aberrations, which feature in the subsequent chapters.
Following a brief introduction to the general technique of aberrometry and visual stimulus control using adaptive optics, the development of a monocular adaptive optics instrument for this purpose is described. The instrument is used to vary a dioptric stimulus and record the accommodation response in pilot studies and a detailed experiment, which has also been published elsewhere. It is found, among other things, that accommodation can respond to more than one different input level during its latency period, and that such inputs can be stored until components of the accommodation control system are free to process them. Indications of a minimum halting time for accommodation, of around 0.6 s, are presented.
In later chapters, the development and testing of a new, binocular adaptive optics apparatus will be found. As well as binocular aberrometry and adaptive optics control of stimulus aberrations, this instrument displaces images to allow for and stimulate ocular convergence in binocular accommodation experiments. It is the first instrument in the world with its combined functionalities.
Finally, the contribution of this thesis is summarised, and further instrumentation development and experiments are put forward for the continuation of this branch of accommodation and myopia research
A Dark Spot on a Massive White Dwarf
We present the serendipitous discovery of eclipse-like events around the
massive white dwarf SDSS J152934.98+292801.9 (hereafter J1529+2928). We
selected J1529+2928 for time-series photometry based on its spectroscopic
temperature and surface gravity, which place it near the ZZ Ceti instability
strip. Instead of pulsations, we detect photometric dips from this white dwarf
every 38 minutes. Follow-up optical spectroscopy observations with Gemini
reveal no significant radial velocity variations, ruling out stellar and brown
dwarf companions. A disintegrating planet around this white dwarf cannot
explain the observed light curves in different filters. Given the short period,
the source of the photometric dips must be a dark spot that comes into view
every 38 min due to the rotation of the white dwarf. Our optical spectroscopy
does not show any evidence of Zeeman splitting of the Balmer lines, limiting
the magnetic field strength to B<70 kG. Since up to 15% of white dwarfs display
kG magnetic fields, such eclipse-like events should be common around white
dwarfs. We discuss the potential implications of this discovery on transient
surveys targeting white dwarfs, like the K2 mission and the Large Synoptic
Survey Telescope.Comment: ApJ Letters, in pres
Decreased synthesis of serum carboxypeptidase N (SCPN) in familial SCPN deficiency
Serum carboxypeptidase N (SCPN) is the primary inactivator of the C3a, C4a, and C5a anaphylatoxins as well as an inactivator of bradykinin. Thus SCPN deficiency potentially could result in significant pathophysiologic consequences. Previous studies identified a deficient subject afflicted with frequent episodes of angioedema, and other family members also had SCPN deficiency. To delineate this abnormality further, the fractional catabolic rate (FRC) and enzyme synthesis were determined in three members of the afflicted kindred as well as in five normal persons following the infusion of homogeneous 125 I-SCPN. The mean FCR and synthesis rates for SCPN in the normal subjects were 1.3%/hr and 20,793 U/kg/hr, respectively. Reduced synthesis was concluded to be primarily responsible for the low SCPN levels in the afflicted kindred. The high FRC of SCPN discourages attempted maintenance therapy with infusions of enriched SCPN preparations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44847/1/10875_2004_Article_BF00915368.pd
Myosin-5 varies its steps along the irregular F-actin track
Molecular motors employ chemical energy to generate unidirectional mechanical output against a track. By contrast to the majority of macroscopic machines, they need to navigate a chaotic cellular environment, potential disorder in the track and Brownian motion. Nevertheless, decades of nanometer-precise optical studies suggest that myosin-5a, one of the prototypical molecular motors, takes uniform steps spanning 13 subunits (36 nm) along its F-actin track. Here, we use high-resolution interferometric scattering (iSCAT) microscopy to reveal that myosin takes strides spanning 22 to 34 actin subunits, despite walking straight along the helical actin filament. We show that cumulative angular disorder in F-actin accounts for the observed proportion of each stride length, akin to crossing a river on variably-spaced stepping stones. Electron microscopy revealed the structure of the stepping molecule. Our results indicate that both motor and track are soft materials that can adapt to function in complex cellular conditions
Multi-Dimensional Characterization of Battery Materials
Demand for low carbon energy storage has highlighted the importance of imaging techniques for the characterization of electrode microstructures to determine key parameters associated with battery manufacture, operation, degradation, and failure both for next generation lithium and other novel battery systems. Here, recent progress and literature highlights from magnetic resonance, neutron, X-ray, focused ion beam, scanning and transmission electron microscopy are summarized. Two major trends are identified: First, the use of multi-modal microscopy in a correlative fashion, providing contrast modes spanning length- and time-scales, and second, the application of machine learning to guide data collection and analysis, recognizing the role of these tools in evaluating large data streams from increasingly sophisticated imaging experiments
Processing blur of conflicting stimuli during the latency and onset of accommodation
The accommodative response (AR) to changes in dioptric accommodative stimulus (AS) during the latency period and onset of accommodation was investigated. Participants monocularly observed one period of a square wave in AS, with a 2-D baseline and mean, and amplitude 1 D or 2 D; the period of the square wave ranged from 0.10 s to 1.00 s; both increases and decreases were used for the first step in AS. At periods of 0.30 s and longer, accommodation was found to respond to both levels of the stimulus. Rapid retinal monitoring appeared to be taking place for such stimuli. The amplitudes of peaks in AR did not usually depend on whether a particular level of AS occurred first or second, but for 8/40 conditions, a significant difference was found, with a stronger response when the level of AS occurred second. Null or incorrect responses were also observed in many trials, possibly linked with the natural microfluctuations of accommodation. Minimum response times to the changes in AS were observed, which increased with decreasing period of the AS. The time interval between peaks in the AR decreased with decreasing period of the AS. The findings were consistent with a parallel processing model previously proposed for saccades, where input from a later change in stimulus may enter an element of the control system when that element has finished processing an earlier change. More than one change in stimulus may therefore be passing through the multi-element control system at a time
The democratic interface: technology, political organization, and diverging patterns of electoral representation
Democracies are experiencing historic disruptions affecting how people engage with core institutions such as the press, civil society organizations, parties, and elections. These processes of citizen interaction with institutions operate as a democratic interface shaping self-government and the quality of public life. The electoral dimension of the interface is important, as its operation can affect all others. This analysis explores a growing left-right imbalance in the electoral connection between citizens, parties, elections, and government. This imbalance is due, in part, to divergent left-right preferences for political engagement, organization, and communication. Support on the right for clearer social rules and simpler moral, racial and nationalist agendas are compatible with hierarchical, leader-centered party organizations that compete more effectively in elections. Parties on the left currently face greater challenges engaging citizens due to the popular meta-ideology of diversity and inclusiveness and demands for direct or deliberative democracy. What we term connective parties are developing technologies to perform core organizational functions, and some have achieved electoral success. However, when connective parties on the left try to develop shared authority processes, online and offline, they face significant challenges competing with more conventionally organized parties on the right
Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans
Rare hematopoietic stem and progenitor cell (HSPC) pools outside the bone marrow (BM) contribute to blood production in stress and disease but remain ill-defined. Although non-mobilized peripheral blood (PB) is routinely sampled for clinical management, the diagnosis and monitoring potential of PB HSPCs remains untapped, as no healthy PB HSPC baseline has been reported. Here we comprehensively delineate human extramedullary HSPC compartments comparing spleen, PB and mobilized PB (mPB) to BM using single-cell RNA-seq and/or functional assays.
We uncover HSPC features shared by extramedullary tissues and others unique to PB. First, in contrast to actively dividing BM HSPCs, we find no evidence of substantial ongoing hematopoiesis in extramedullary tissues at steady state, but report increased splenic HSPC proliferative output during stress erythropoiesis. Second, extramedullary stem cells/multipotent progenitors (HSC/MPPs) from spleen, PB and mPB share a common transcriptional signature and increased abundance of lineage-primed subsets compared to BM. Third, healthy PB HSPCs display a unique bias towards erythroid-megakaryocytic differentiation. At HSC/MPP level, this is functionally imparted by a subset of phenotypic CD71+ HSC/MPPs, exclusively producing erythrocytes and megakaryocytes, highly abundant in PB but rare in other adult tissues. Finally, the unique erythroid-megakaryocytic-skewing of PB is perturbed with age, in essential thrombocythemia and in beta-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are non-proliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction
Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans.
Rare hematopoietic stem and progenitor cell (HSPC) pools outside the bone marrow (BM) contribute to blood production in stress and disease but remain ill-defined. Although nonmobilized peripheral blood (PB) is routinely sampled for clinical management, the diagnosis and monitoring potential of PB HSPCs remain untapped, as no healthy PB HSPC baseline has been reported. Here we comprehensively delineate human extramedullary HSPC compartments comparing spleen, PB, and mobilized PB to BM using single-cell RNA-sequencing and/or functional assays. We uncovered HSPC features shared by extramedullary tissues and others unique to PB. First, in contrast to actively dividing BM HSPCs, we found no evidence of substantial ongoing hematopoiesis in extramedullary tissues at steady state but report increased splenic HSPC proliferative output during stress erythropoiesis. Second, extramedullary hematopoietic stem cells/multipotent progenitors (HSCs/MPPs) from spleen, PB, and mobilized PB share a common transcriptional signature and increased abundance of lineage-primed subsets compared with BM. Third, healthy PB HSPCs display a unique bias toward erythroid-megakaryocytic differentiation. At the HSC/MPP level, this is functionally imparted by a subset of phenotypic CD71+ HSCs/MPPs, exclusively producing erythrocytes and megakaryocytes, highly abundant in PB but rare in other adult tissues. Finally, the unique erythroid-megakaryocytic-skewing of PB is perturbed with age in essential thrombocythemia and β-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are nonproliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction
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