Apparatus and Method for Restoring Eyelid Function

An apparatus is provided to restore eyelid function in a patient unable to voluntarily raise an eyelid. The apparatus includes a spiral torsion spring and pulley arrangement mounted in a housing that is implanted in the superior portion of the orbit of the eye. A wire connects the pulley to the eyelid. A spiral torsion spring provides the necessary spring force in tension to overcome the weight of the eyelid and draw the eyelid open. The natural muscles of eye closure are, however, sufficiently strong to overcome the spring tension thereby paying out wire from the pulley and closing the eye so as to provide normal blinking function. A position setting gear allows the biasing force of the spring to be selectively reduced sufficiently to allow the eye to remain closed for sleep or at other desired times. A method of treating ptosis is also disclosed

Combined analysis of microbial metagenomic and metatranscriptomic sequencing data to assess in situ physiological conditions in the premature infant gut.

Microbes alter their transcriptomic profiles in response to the environment. The physiological conditions experienced by a microbial community can thus be inferred using meta-transcriptomic sequencing by comparing transcription levels of specifically chosen genes. However, this analysis requires accurate reference genomes to identify the specific genes from which RNA reads originate. In addition, such an analysis should avoid biases in transcript counts related to differences in organism abundance. In this study we describe an approach to address these difficulties. Sample-specific meta-genomic assembled genomes (MAGs) were used as reference genomes to accurately identify the origin of RNA reads, and transcript ratios of genes with opposite transcription responses were compared to eliminate biases related to differences in organismal abundance, an approach hereafter named the "diametric ratio" method. We used this approach to probe the environmental conditions experienced by Escherichia spp. in the gut of 4 premature infants, 2 of whom developed necrotizing enterocolitis (NEC), a severe inflammatory intestinal disease. We analyzed twenty fecal samples taken from four premature infants (4-6 time points from each infant), and found significantly higher diametric ratios of genes associated with low oxygen levels in samples of infants later diagnosed with NEC than in samples without NEC. We also show this method can be used for examining other physiological conditions, such as exposure to nitric oxide and osmotic pressure. These study results should be treated with caution, due to the presence of confounding factors that might also distinguish between NEC and control infants. Nevertheless, together with benchmarking analyses, we show here that the diametric ratio approach can be applied for evaluating the physiological conditions experienced by microbes in situ. Results from similar studies can be further applied for designing diagnostic methods to detect NEC in its early developmental stages

The basis for limited specificity and MHC restriction in a T cell receptor interface

αβ Tcell receptors (TCRs) recognize peptides presented by major histocompatibility complex (MHC) proteins using multiple complementarity-determining region (CDR) loops. TCRs display an array of poorly understood recognition properties, including specificity, crossreactivity and MHC restriction. Here we report a comprehensive thermodynamic deconstruction of the interaction between the A6 TCR and the Tax peptide presented by the class I MHC HLA-A*0201, uncovering the physical basis for the receptor’s recognition properties. Broadly, our findings are in conflict with widely held generalities regarding TCR recognition, such as the relative contributions of central and peripheral peptide residues and the roles of the hypervariable and germline CDR loops in engaging peptide and MHC. Instead, we find that the recognition properties of the receptor emerge from the need to engage the composite peptide/MHC surface, with the receptor utilizing its CDR loops in a cooperative fashion such that specificity, crossreactivity and MHC restriction are inextricably linked

Sleep disturbance at pre-deployment is a significant predictor of post-deployment re-experiencing symptoms.

Background: Insomnia is common in service members and associated with many mental and physical health problems. Recently, longitudinal data have been used to assess the impact of disturbed sleep on mental health outcomes. These studies have consistently shown relationships between sleep disturbance and development of mental illness. Objective: The present study examined the longitudinal relationship between sleep disturbance and PTSD symptomatology in a cohort of Marines and Navy Corpsmen deployed to Iraq and Afghanistan (n = 2,404) assessed prior to deployment, as well as at -3 and 6 months post-deployment. Additionally, we aimed to investigate the extent to which these relationships are moderated by combat-stress severity, and to what extent these findings are replicated in a second, separate cohort of Marines and Navy corpsmen (n = 938) assessed with identical measures prior to deployment and within 3 months of return. Method: The present study employed latent variable path models to examine the relationships between pre-deployment sleep disturbance and post-deployment re-experiencing symptoms. Initial cross-lagged path models were conducted on discovery and replication samples to validate the hypothesized predictive relationships. Follow up moderation path models were then conducted to include the effect of combat-stress severity on these relationships. Results: Initial cross-lagged models supported a significant relationship between pre-deployment sleep disturbance and future re-experiencing PTSD symptoms at all time points. Initial moderation models showed a small moderator effect of combat-stress severity, though the main predictive relationship between pre-deployment sleep disturbance and PTSD symptoms remained significant. The moderator effect was not significant in the replication sample. Conclusions: The results of this study support pre-deployment sleep disturbance as a risk factor for development of post-deployment PTSD symptoms. Interventions aimed at normalizing sleep may be important in preventive measures for PTSD

ProtoEXIST: Advanced Prototype CZT Coded Aperture Telescopes for EXIST

{\it ProtoEXIST1} is a pathfinder for the {\it EXIST-HET}, a coded aperture hard X-ray telescope with a 4.5 m$^2$ CZT detector plane a 90$\times$70 degree field of view to be flown as the primary instrument on the {\it EXIST} mission and is intended to monitor the full sky every 3 h in an effort to locate GRBs and other high energy transients. {\it ProtoEXIST1} consists of a 256 cm$^2$ tiled CZT detector plane containing 4096 pixels composed of an 8$\times$8 array of individual 1.95 cm $\times$ 1.95 cm $\times$ 0.5 cm CZT detector modules each with a 8 $\times$ 8 pixilated anode configured as a coded aperture telescope with a fully coded $10^\circ\times10^\circ$ field of view employing passive side shielding and an active CsI anti-coincidence rear shield, recently completed its maiden flight out of Ft. Sumner, NM on the 9th of October 2009. During the duration of its 6 hour flight on-board calibration of the detector plane was carried out utilizing a single tagged 198.8 nCi Am-241 source along with the simultaneous measurement of the background spectrum and an observation of Cygnus X-1. Here we recount the events of the flight and report on the detector performance in a near space environment. We also briefly discuss {\it ProtoEXIST2}: the next stage of detector development which employs the {\it NuSTAR} ASIC enabling finer (32$\times$32) anode pixilation. When completed {\it ProtoEXIST2} will consist of a 256 cm$^2$ tiled array and be flown simultaneously with the ProtoEXIST1 telescope

Earliest Cretaceous cocoons or plant seed structures from the Wealden Group, Hastings, UK

We thank Jason Hilton (University of Birmingham) and Alan Spencer (Imperial College) for discussion. RG is a member of the Interdisciplinary Centre for Ancient Life (UMRI). We are grateful for the reviews of both Jorge Genise, and Duncan McIlroy whose comments and guidance greatly improved the manuscript.Postprin

PACAP and Cocaine Reinstatement: A Neuropeptide Expressed by Corticostriatal Neurons that Regulates Nucleus Accumbens Astrocytes

Drug addiction involves heightened relapse vulnerability arising from persistent drug-induced neuro-adaptations, including a) hypofrontality which is thought to reflect reduced firing of cortical afferents to the nucleus accumbens (NAcc) and b) altered glutamate homeostasis in NAcc that likely involves reduced glutamate release and uptake by astrocytes. An important question is whether these forms of pathological plasticity are functionally linked such that reduced corticostriatal firing may result in aberrant regulation of astrocytes in the NAcc. To begin to evaluate this possibility, we first determined whether neurons regulate system xc- (Sxc) activity, a mechanism of non-vesicular glutamate release by astrocytes. We found that the rate of Sxc activity in astrocyte cultures was significantly increased in cells exposed to neuronal conditioned media achieved using neuronal inserts. These experiments demonstrate that releasable neuronal factors significantly upregulate Sxc activity. We hypothesize that the pituitary adenylyl cyclase activating peptide (PACAP) may be the neuronal factor regulating glutamate release by astrocytes involving Sxc. First we determined that PACAP mimics a neuronal insert in that it significantly upregulates Sxc activity in astrocytes. Next, we verified the expression of PACAP in neurons from the prefrontal cortex (PFC) projecting to NAcc. Together, these data support the hypothesis that reduced corticostriatal firing may result in decreased PACAP release in NAcc which could potentially blunt Sxc activity in NAcc astrocytes. To determine whether this would impact relapse vulnerability, we microinjected PACAP into the NAcc and found that this significantly reduced cocaine-primed reinstatement, suggesting that increased PACAP signaling, consistent with other approaches capable of increasing Sxc activity, may blunt relapse vulnerability. In order to determine whether reduced PACAP signaling is sufficient to increase relapse vulnerability, we microinjected the PAC1R inhibitor PACAP6-38 into the NAcc. Preliminary data indicate that this is sufficient to produce an increase in cocaine reinstatement. Collectively, these studies demonstrate that neuropeptide PACAP is a powerful regulator of cocaine-related behaviors, likely through the modulation of glutamate homeostasis as maintained by astrocytes. As a result, an unrecognized consequence of hypofrontality may be impairing neuron-astrocyte interactions in a manner that determines the magnitude of relapse vulnerability

1D Potts, Yang-Lee Edges and Chaos

It is known that the (exact) renormalization transformations for the one-dimensional Ising model in field can be cast in the form of a logistic map f(x) = 4 x (1 - x) with x a function of the Ising couplings. Remarkably, the line bounding the region of chaotic behaviour in x is precisely that defining the Yang-Lee edge singularity in the Ising model. In this paper we show that the one dimensional q-state Potts model for q greater than or equal to 1 also displays such behaviour. A suitable combination of Potts couplings can again be used to define an x satisfying f(x) = 4 x (1 -x). The Yang-Lee zeroes no longer lie on the unit circle in the complex z = exp (h) plane, but their locus is still reproduced by the boundary of the chaotic region in the logistic map.Comment: 6 pages, no figure

Renewed investigations at Taung; 90 years after the discovery of Australopithecus africanus

2015 marked the 90th anniversary of the description of the first fossil ofAustralopithecus africanus, commonly known as the Taung Child, which was unearthed during blasting at the Buxton-Norlim Limeworks (referred to as the BNL) 15 km SE of the town of Taung, South Africa. Subsequently, this site has been recognized as a UNESCOWorld Heritage site on the basis of its importance to southern African palaeoanthropology. Some other sites such as Equus Cave and Black Earth Cave have also been investigated; but the latter not since the 1940s. These sites indicate that the complex of palaeontological and archaeological localities at the BNL preserve a time sequence spanning the Pliocene to the Holocene. The relationship of these various sites and how they fit into the sequence of formation of tufa, landscapes and caves at the limeworks have also not been investigated or discussed in detail since Peabody’s efforts in the 1940s. In this contribution we mark the 90th anniversary of the discovery and description of the Taung Child by providing a critical review of previous work at Taung based on our recent preliminary work at the site. This includes a reassessment of the Taung Child Type Site, as well as renewed excavations at Equus Cave and the lesser-known locality and little-investigated Black Earth Cave. Preliminary results suggest that much of our previous understandings of the BNL’s formational history and site formation processes need to be reassessed. Only through detailed analysis on the BNLas a whole can we understand this complex depositional environment.Australian Research Council Future Fellowship grant FT120100399 Palaeontological Scientific Trust (PAST) National Geographic grants (8774-10 and 3212)JNC2016https://www.wits.ac.za/esi/palaeontologia-africana