Localization and patterning of pannexin-1 in pre-diabetic murine corneal epithelial tissue after injury

Type II diabetes is a major cause of blindness according to the World Health Organization (WHO, 2018). Diabetics are at risk of developing corneal diseases such as recurrent abrasions, ulcers, and erosions due to dysfunctional wound healing. Corrective surgeries or corneal transplants may be considered as a treatment in some, but not all, cases. The purinoreceptor P2X7 has been shown to be involved in cell-cell communication and in the restructuring of cytoskeletal actin, a necessary process for cell migration in wound healing. P2X7 relies on the binding of extracellular ATP for activation. Panx1 is a transmembrane protein whose primary role is for the release of intracellular ATP into the extracellular space. In healthy corneal epithelium, Panx1 localizes to the wound edge and forms clusters with the P2X7, which augments the wound healing response. This thesis looks at the localization of Panx1 in pre-diabetic murine corneal tissue. It was found that Panx1 is less expressed and does not localize to the wound edge to the extent as control corneas, therefore, creating less clusters with P2X7. Furthermore, preliminary studies that inhibit Panx1 with probenecid reduce the communication between cells, which is hypothesized as critical for migration of the tissue sheet and proper wound healing.2019-12-17T00:00:00

Using Technical Performance Measures

All programs have requirements. For these requirements to be met, there must be a means of measurement. A Technical Performance Measure (TPM) is defined to produce a measured quantity that can be compared to the requirement. In practice, the TPM is often expressed as a maximum or minimum and a goal. Example TPMs for a rocket program are: vacuum or sea level specific impulse (lsp), weight, reliability (often expressed as a failure rate), schedule, operability (turn-around time), design and development cost, production cost, and operating cost. Program status is evaluated by comparing the TPMs against specified values of the requirements. During the program many design decisions are made and most of them affect some or all of the TPMs. Often, the same design decision changes some TPMs favorably while affecting other TPMs unfavorably. The problem then becomes how to compare the effects of a design decision on different TPMs. How much failure rate is one second of specific impulse worth? How many days of schedule is one pound of weight worth? In other words, how to compare dissimilar quantities in order to trade and manage the TPMs to meet all requirements. One method that has been used successfully and has a mathematical basis is Utility Analysis. Utility Analysis enables quantitative comparison among dissimilar attributes. It uses a mathematical model that maps decision maker preferences over the tradeable range of each attribute. It is capable of modeling both independent and dependent attributes. Utility Analysis is well supported in the literature on Decision Theory. It has been used at Pratt & Whitney Rocketdyne for internal programs and for contracted work such as the J-2X rocket engine program. This paper describes the construction of TPMs and describes Utility Analysis. It then discusses the use of TPMs in design trades and to manage margin during a program using Utility Analysis

Improved Constraints on the Gravitational Lens Q0957+561. I. Weak Lensing

Attempts to constrain the Hubble constant using the strong gravitational lens system Q0957+561 are limited by systematic uncertainties in the mass model, since the time delay is known very precisely. One important systematic effect is the mass sheet degeneracy, which arises because strong lens modeling cannot constrain the presence or absence of a uniform mass sheet $\kappa$, which rescales $H_0$ by the factor $(1-\kappa)$. In this paper we present new constraints on the mass sheet derived from a weak-lensing analysis of the Hubble Space Telescope imaging of a 6 arcmin square region surrounding the lensed quasar. The average mass sheet within a circular aperture (the strong lens model region) is constrained by integrating the tangential weak gravitational shear over the surrounding area. We find the average convergence within a $30"$ radius around the lens galaxy to be $\kappa(<30") = 0.166\pm0.056$ ($1\sigma$ confidence level), normalized to the quasar redshift. This includes contributions from both the lens galaxy and the surrounding cluster. We also constrain a few other low-order terms in the lens potential by applying a multipole aperture mass formalism to the gravitational shear in an annulus around the strong lensing region. Implications for strong lens models and the Hubble constant are discussed in an accompanying paper.Comment: 13 pages, 8 figures, accepted for publication in Ap

MetaQC: objective quality control and inclusion/exclusion criteria for genomic meta-analysis

Genomic meta-analysis to combine relevant and homogeneous studies has been widely applied, but the quality control (QC) and objective inclusion/exclusion criteria have been largely overlooked. Currently, the inclusion/exclusion criteria mostly depend on ad-hoc expert opinion or naïve threshold by sample size or platform. There are pressing needs to develop a systematic QC methodology as the decision of study inclusion greatly impacts the final meta-analysis outcome. In this article, we propose six quantitative quality control measures, covering internal homogeneity of coexpression structure among studies, external consistency of coexpression pattern with pathway database, and accuracy and consistency of differentially expressed gene detection or enriched pathway identification. Each quality control index is defined as the minus log transformed P values from formal hypothesis testing. Principal component analysis biplots and a standardized mean rank are applied to assist visualization and decision. We applied the proposed method to 4 large-scale examples, combining 7 brain cancer, 9 prostate cancer, 8 idiopathic pulmonary fibrosis and 17 major depressive disorder studies, respectively. The identified problematic studies were further scrutinized for potential technical or biological causes of their lower quality to determine their exclusion from meta-analysis. The application and simulation results concluded a systematic quality assessment framework for genomic meta-analysis

Listening in the dark: why we need stories of people living with severe and enduring anorexia nervosa

A bold step forward in our approach to Severe and Enduring Anorexia Nervosa invites new paradigms for research and practice. It provides an opportunity for us to explore fault lines, both in our communities of practice and the social structures that inform them. This paper serves to question the medical metaphors on which treatment has been based, in favour of alternative perspectives that resonate more clearly with the lived experience of those for whom it has failed. We invite the consideration of alternative metaphors, which can disrupt the notion of heroic patients (and therapists), mediate against acts of self-silencing and sensitising us to more radical acts of listening. Beyond the randomised trials and manuals it is time for us to listen to the realities of suffering, the minutiae of resistance and the life that can still be lived

On the Perception of Religious Group Membership from Faces

BACKGROUND: The study of social categorization has largely been confined to examining groups distinguished by perceptually obvious cues. Yet many ecologically important group distinctions are less clear, permitting insights into the general processes involved in person perception. Although religious group membership is thought to be perceptually ambiguous, folk beliefs suggest that Mormons and non-Mormons can be categorized from their appearance. We tested whether Mormons could be distinguished from non-Mormons and investigated the basis for this effect to gain insight to how subtle perceptual cues can support complex social categorizations. METHODOLOGY/PRINCIPAL FINDINGS: Participants categorized Mormons' and non-Mormons' faces or facial features according to their group membership. Individuals could distinguish between the two groups significantly better than chance guessing from their full faces and faces without hair, with eyes and mouth covered, without outer face shape, and inverted 180°; but not from isolated features (i.e., eyes, nose, or mouth). Perceivers' estimations of their accuracy did not match their actual accuracy. Exploration of the remaining features showed that Mormons and non-Mormons significantly differed in perceived health and that these perceptions were related to perceptions of skin quality, as demonstrated in a structural equation model representing the contributions of skin color and skin texture. Other judgments related to health (facial attractiveness, facial symmetry, and structural aspects related to body weight) did not differ between the two groups. Perceptions of health were also responsible for differences in perceived spirituality, explaining folk hypotheses that Mormons are distinct because they appear more spiritual than non-Mormons. CONCLUSIONS/SIGNIFICANCE: Subtle markers of group membership can influence how others are perceived and categorized. Perceptions of health from non-obvious and minimal cues distinguished individuals according to their religious group membership. These data illustrate how the non-conscious detection of very subtle differences in others' appearances supports cognitively complex judgments such as social categorization

Vicious circle: systemic autoreactivity in Ro52/TRIM21-deficient mice

Dysregulated innate responses, particularly excessive activation of interferon (IFN) pathways, have been implicated in the development of autoimmune pathologies. Autoreactivity frequently targets IFN-inducible genes such as the Ro autoantigens, which ubiquitinate and inhibit interferon regulatory factors (IRFs). A new study validates the role of these common autoantigens in preventing autoimmunity. The findings reveal that injury-induced systemic autoimmune disease is exacerbated in the absence of Ro52/Trim21 and is driven by the IL-23–Th17 pathway

Cohesin Proteins Promote Ribosomal RNA Production and Protein Translation in Yeast and Human Cells

Cohesin is a protein complex known for its essential role in chromosome segregation. However, cohesin and associated factors have additional functions in transcription, DNA damage repair, and chromosome condensation. The human cohesinopathy diseases are thought to stem not from defects in chromosome segregation but from gene expression. The role of cohesin in gene expression is not well understood. We used budding yeast strains bearing mutations analogous to the human cohesinopathy disease alleles under control of their native promoter to study gene expression. These mutations do not significantly affect chromosome segregation. Transcriptional profiling reveals that many targets of the transcriptional activator Gcn4 are induced in the eco1-W216G mutant background. The upregulation of Gcn4 was observed in many cohesin mutants, and this observation suggested protein translation was reduced. We demonstrate that the cohesinopathy mutations eco1-W216G and smc1-Q843Δ are associated with defects in ribosome biogenesis and a reduction in the actively translating fraction of ribosomes, eiF2α-phosphorylation, and 35S-methionine incorporation, all of which indicate a deficit in protein translation. Metabolic labeling shows that the eco1-W216G and smc1-Q843Δ mutants produce less ribosomal RNA, which is expected to constrain ribosome biogenesis. Further analysis shows that the production of rRNA from an individual repeat is reduced while copy number remains unchanged. Similar defects in rRNA production and protein translation are observed in a human Roberts syndrome cell line. In addition, cohesion is defective specifically at the rDNA locus in the eco1-W216G mutant, as has been previously reported for Roberts syndrome. Collectively, our data suggest that cohesin proteins normally facilitate production of ribosomal RNA and protein translation, and this is one way they can influence gene expression. Reduced translational capacity could contribute to the human cohesinopathies

Localized Waves: A not-so-short Review

In the FIRST PART we present simple introductions to gaussian and Bessel waves, and to the Localized Waves (LW), pulses or beams, showing the important properties of the latter, and their applications whenever a role is played by a wave-equation (electromagnetism, optics, acoustics, seismology, geophysics, gravitation, elementary particle physics,...). The First Part ends with a historical APPENDIX, recalling how the geometrical methods of Special Relativity (SR) had predicted the most interesting LWs, i.e., the X-shaped pulses; and presenting a bird's-eye view of the experiments performed with evanescent waves (and/or tunnelling photons), and with the "localized Superluminal solutions". In the SECOND PART, after some more theoretical introduction, we develop a Generalized "Bidirectional Decomposition", and obtain several luminal and Superluminal non-diffracting solutions; we get a space-time focusing of X-Shaped pulses; and deal with chirped optical X-shaped pulses in material media. Finally, in the THIRD PART we investigate also the subluminal LWs, which, among the others, allow to emphasize the role of SR, in its extended, or rather non-restricted, formulation. We study in particular the topic of zero-speed waves, endowed with a static envelope: Namely, we show how localized wavefields can be constructed with high transverse localization, and with a longitudinal intensity pattern that assumes any desired shape within a chosen interval of the propagation axis. Such "Frozen Waves" promise to have even more applications. In between, we do not forget to briefly treat the case of not axially-symmetric solutions, in terms of higher order Bessel beams.Comment: 121 pages, with 41 Figures (source file in LaTeX). It is a preliminary version of Chap.4 in vol.156 of AIEP (2009

The choice for EU theorists: Establishing a common framework for analysis

European Union (EU) studies have entered a highly contentious and, arguably, creative phase. A range of theoretical perspectives, seemingly quite highly differentiated from one another, now compete for influence and lsquospacersquo. However, the questions remain: is EU studies developing theories which are truly competing theories? Or is it developing theories that do not compete so much as they aim to explain distinctly different pieces of the EU puzzle? This paper responds directly to these two questions, while reviewing recent literature on EU governance. It argues, first, that we lack theories of EU governance that are true rivals; and, second, that leading models explain different outcomes at different levels in a multi-level system of governance. The result is somewhat phoney debates between compatible theories masquerading as rivals, and between lsquocomparative politicsrsquo and lsquointernational relationsrsquo approaches. Above all, perhaps, we find middle range theories posing as general or lsquometa-theoriesrsquo. In the absence of a plausible general theory of EU governance, theorists must choose precisely which type of outcome theywish to explain