Henri de Contenson: a personal memoir

It was May 1970 and Lebanon was warm and green from the plentiful spring rains; high summer with the onset of hot, humid days was still a month away. I was in Beirut for a couple of weeks, enjoying the hospitality of the Institut français d’Archéologie de Beyrouth as a visiting pensionnaire. My object was to examine collections of Neolithic material in the museums, to get to know members of the archaeological community in Lebanon, and to visit ancient sites. The stay at the Institut was tranq..

Retinal Architecture in ​\u3cem\u3eRGS9-\u3c/em\u3e and ​\u3cem\u3eR9AP\u3c/em\u3e-Associated Retinal Dysfunction (Bradyopsia)

Purpose To characterize photoreceptor structure and mosaic integrity in subjects with RGS9- and R9AP-associated retinal dysfunction (bradyopsia) and compare to previous observations in other cone dysfunction disorders such as oligocone trichromacy. Design Observational case series. Methods setting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA). study population: Six eyes of 3 subjects with disease-causing variants in RGS9 or R9AP. main outcome measures: Detailed retinal imaging using spectral-domain optical coherence tomography and confocal adaptive-optics scanning light ophthalmoscopy. Results Cone density at 100 μm from foveal center ranged from 123 132 cones/mm2to 140 013 cones/mm2. Cone density ranged from 30 573 to 34 876 cones/mm2 by 600 μm from center and from 15 987 to 16,253 cones/mm2 by 1400 μm from center, in keeping with data from normal subjects. Adaptive-optics imaging identified a small, focal hyporeflective lesion at the foveal center in both eyes of the subject with RGS9-associated disease, corresponding to a discrete outer retinal defect also observed on spectral-domain optical coherence tomography; however, the photoreceptor mosaic remained intact at all other observed eccentricities. Conclusions Bradyopsia and oligocone trichromacy share common clinical symptoms and cannot be discerned on standard clinical findings alone. Adaptive-optics imaging previously demonstrated a sparse mosaic of normal wave-guiding cones remaining at the fovea, with no visible structure outside the central fovea in oligocone trichromacy. In contrast, the subjects presented in this study with molecularly confirmed bradyopsia had a relatively intact and structurally normal photoreceptor mosaic, allowing the distinction between these disorders based on the cellular phenotype and suggesting different pathomechanisms

Design of General Purpose Minimal-Auxiliary Ising Machines

Ising machines are a form of quantum-inspired processing-in-memory computer which has shown great promise for overcoming the limitations of traditional computing paradigms while operating at a fraction of the energy use. The process of designing Ising machines is known as the reverse Ising problem. Unfortunately, this problem is in general computationally intractable: it is a nonconvex mixed-integer linear programming problem which cannot be naively brute-forced except in the simplest cases due to exponential scaling of runtime with number of spins. We prove new theoretical results which allow us to reduce the search space to one with quadratic scaling. We utilize this theory to develop general purpose algorithmic solutions to the reverse Ising problem. In particular, we demonstrate Ising formulations of 3-bit and 4-bit integer multiplication which use fewer total spins than previously known methods by a factor of more than three. Our results increase the practicality of implementing such circuits on modern Ising hardware, where spins are at a premium.Comment: 14 pages, 3 figures, submitted to IEEE International Conference on Rebooting Computing 202

The adolescent transition under energetic stress: Body composition tradeoffs among adolescent women in The Gambia

Background and objectives: Life history theory predicts a shift in energy allocation from growth to reproductive function as a consequence of puberty. During adolescence, linear growth tapers off and, in females, ovarian steroid production increases. In this model, acquisition of lean mass is associated with growth while investment in adiposity is associated with reproduction. This study examines the chronological and developmental predictors of energy allocation patterns among adolescent women under conditions of energy constraint. Methodology: Fifty post-menarcheal adolescent women between 14 and 20 years old were sampled for weight and body composition at the beginning and end of 1 month in an energy-adequate season and 1 month in the subsequent energy-constrained season in a rural province of The Gambia. Results: Chronologically and developmentally younger adolescent girls gain weight in the form of lean mass in both energy-adequate and energy-constrained seasons, whereas older adolescents lose lean mass under conditions of energetic stress (generalized estimating equation (GEE) Wald chi-square comparing youngest tertile with older two tertiles 9.750, P = 0.002; GEE Wald chi-square comparing fast- with slow-growing individuals for growth rate 19.806, P < 0.001). When energy is limited, younger adolescents lose and older adolescents maintain fat (GEE Wald chi-square for interaction of age and season 6.568, P = 0.010; GEE Wald chi-square comparing fast- with slow-growing individuals for interaction of growth rate and season 7.807, P = 0.005). Conclusions and implications: When energy is constrained, the physiology of younger adolescents invests in growth while that of older adolescent females privileges reproductively valuable adipose tissue

Nigerian scam e-mails and the charms of capital

So-called '419' or 'advance-fee' e-mail frauds have proved remarkably successful. Global losses to these scams are believed to run to billions of dollars. Although it can be assumed that the promise of personal gain which these e-mails hold out is part of what motivates victims, there is more than greed at issue here. How is it that the seemingly incredible offers given in these unsolicited messages can find an audience willing to treat them as credible? The essay offers a speculative thesis in answer to this question. Firstly, it is argued, these scams are adept at exploiting common presuppositions in British and American culture regarding Africa and the relationships that are assumed to exist between their nations and those in the global south. Secondly, part of the appeal of these e-mails lies in the fact that they appear to reveal the processes by which wealth is created and distributed in the global economy. They thus speak to their readers’ attempts to map or conceptualise the otherwise inscrutable processes of that economy. In the conclusion the essay looks at the contradictions in the official state response to this phenomena

Growth and Morbidity of Gambian Infants are Influenced by Maternal Milk Oligosaccharides and Infant Gut Microbiota.

Human milk oligosaccharides (HMOs) play an important role in the health of an infant as substrate for beneficial gut bacteria. Little is known about the effects of HMO composition and its changes on the morbidity and growth outcomes of infants living in areas with high infection rates. Mother's HMO composition and infant gut microbiota from 33 Gambian mother/infant pairs at 4, 16, and 20 weeks postpartum were analyzed for relationships between HMOs, microbiota, and infant morbidity and growth. The data indicate that lacto-N-fucopentaose I was associated with decreased infant morbidity, and 3'-sialyllactose was found to be a good indicator of infant weight-for-age. Because HMOs, gut microbiota, and infant health are interrelated, the relationship between infant health and their microbiome were analyzed. While bifidobacteria were the dominant genus in the infant gut overall, Dialister and Prevotella were negatively correlated with morbidity, and Bacteroides was increased in infants with abnormal calprotectin. Mothers nursing in the wet season (July to October) produced significantly less oligosaccharides compared to those nursing in the dry season (November to June). These results suggest that specific types and structures of HMOs are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus

Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs.

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 &amp; PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders

Wall-Crossing in Coupled 2d-4d Systems

We introduce a new wall-crossing formula which combines and generalizes the Cecotti-Vafa and Kontsevich-Soibelman formulas for supersymmetric 2d and 4d systems respectively. This 2d-4d wall-crossing formula governs the wall-crossing of BPS states in an N=2 supersymmetric 4d gauge theory coupled to a supersymmetric surface defect. When the theory and defect are compactified on a circle, we get a 3d theory with a supersymmetric line operator, corresponding to a hyperholomorphic connection on a vector bundle over a hyperkahler space. The 2d-4d wall-crossing formula can be interpreted as a smoothness condition for this hyperholomorphic connection. We explain how the 2d-4d BPS spectrum can be determined for 4d theories of class S, that is, for those theories obtained by compactifying the six-dimensional (0,2) theory with a partial topological twist on a punctured Riemann surface C. For such theories there are canonical surface defects. We illustrate with several examples in the case of A_1 theories of class S. Finally, we indicate how our results can be used to produce solutions to the A_1 Hitchin equations on the Riemann surface C.Comment: 170 pages, 45 figure