Spitz and wingless, emanating from distinct borders, cooperate to establish cell fate across the engrailed domain in the drosophila epidermis

A key step in development is the establishment of cell type diversity across a cellular field. Segmental patterning within the Drosophila embryonic epidermis is one paradigm for this process. At each parasegment boundary, cells expressing the Wnt family member Wingless confront cells expressing the homeoprotein Engrailed. The Engrailed-expressing cells normally differentiate as one of two alternative cell types. In investigating the generation of this cell type diversity among the 2-cell-wide Engrailed stripe, we previously showed that Wingless, expressed just anterior to the Engrailed cells, is essential for the specification of anterior Engrailed cell fate. In a screen for additional mutations affecting Engrailed cell fate, we identified anterior open/yan, a gene encoding an inhibitory ETS-domain transcription factor that is negatively regulated by the Rasl-MAP kinase signaling cascade. We find that Anterior Open must be inactivated for posterior Engrailed cells to adopt their correct fate. This is achieved by the EGF receptor (DER), which is required autonomously in the Engrailed cells to trigger the Ras1-MAP kinase pathway. Localized activation of DER is accomplished by restricted processing of the activating ligand, Spitz. Processing is confined to the cell row posterior to the Engrailed domain by the restricted expression of Rhomboid. These cells also express the inhibitory ligand Argos, which attenuates the activation of DER in cell rows more distant from the ligand source. Thus, distinct signals flank each border of the Engrailed domain, as Wingless is produced anteriorly and Spitz posteriorly. Since we also show that En cells have the capacity to respond to either Wingless or Spitz, these cells must choose their fate depending on the relative level of activation of the two pathways.Louise O’Keefe, Scott T. Dougan, Limor Gabay, Erez Raz, Ben-Zion Shilo and Stephen DiNard

Helium condensation in aerogel: avalanches and disorder-induced phase transition

We present a detailed numerical study of the elementary condensation events (avalanches) associated to the adsorption of $^4$He in silica aerogels. We use a coarse-grained lattice-gas description and determine the nonequilibrium behavior of the adsorbed gas within a local mean-field analysis, neglecting thermal fluctuations and activated processes. We investigate the statistical properties of the avalanches, such as their number, size and shape along the adsorption isotherms as a function of gel porosity, temperature, and chemical potential. Our calculations predict the existence of a line of critical points in the temperature-porosity diagram where the avalanche size distribution displays a power-law behavior and the adsorption isotherms have a universal scaling form. The estimated critical exponents seem compatible with those of the field-driven Random Field Ising Model at zero temperature.Comment: 16 pages, 14 figure

Band inversion driven by electronic correlations at the (111) LaAlO3_3/SrTiO3_3 interface

Quantum confinement at complex oxide interfaces establishes an intricate hierarchy of the strongly correlated $d$-orbitals which is widely recognized as a source of emergent physics. The most prominent example is the (001) LaAlO$_3$/SrTiO$_3$(LAO/STO) interface, which features a dome-shaped phase diagram of superconducting critical temperature and spin-orbit coupling (SOC) as a function of electrostatic doping, arising from a selective occupancy of $t_{2g}$ orbitals of different character. Here we study (111)-oriented LAO/STO interfaces - where the three $t_{2g}$ orbitals contribute equally to the sub-band states caused by confinement - and investigate the impact of this unique feature on electronic transport. We show that transport occurs through two sets of electron-like sub-bands, and the carrier density of one of the sets shows a non-monotonic dependence on the sample conductance. Using tight-binding modeling, we demonstrate that this behavior stems from a band inversion driven by on-site Coulomb interactions. The balanced contribution of all $t_{2g}$ orbitals to electronic transport is shown to result in strong SOC with reduced electrostatic modulation.Comment: 5 pages, 4 figures, (+ supplemental material

Generalized Forward-Backward Splitting

This paper introduces the generalized forward-backward splitting algorithm for minimizing convex functions of the form $F + \sum_{i=1}^n G_i$, where $F$ has a Lipschitz-continuous gradient and the $G_i$'s are simple in the sense that their Moreau proximity operators are easy to compute. While the forward-backward algorithm cannot deal with more than $n = 1$ non-smooth function, our method generalizes it to the case of arbitrary $n$. Our method makes an explicit use of the regularity of $F$ in the forward step, and the proximity operators of the $G_i$'s are applied in parallel in the backward step. This allows the generalized forward backward to efficiently address an important class of convex problems. We prove its convergence in infinite dimension, and its robustness to errors on the computation of the proximity operators and of the gradient of $F$. Examples on inverse problems in imaging demonstrate the advantage of the proposed methods in comparison to other splitting algorithms.Comment: 24 pages, 4 figure

Bimodal Phase Diagram of the Superfluid Density in LaAlO3/SrTiO3 Revealed by an Interfacial Waveguide Resonator

We explore the superconducting phase diagram of the two-dimensional electron system at the LaAlO3/SrTiO3 interface by monitoring the frequencies of the cavity modes of a coplanar waveguide resonator fabricated in the interface itself. We determine the phase diagram of the superconducting transition as a function of temperature and electrostatic gating, finding that both the superfluid density and the transition temperature follow a dome shape, but that the two are not monotonically related. The ground state of this 2DES is interpreted as a Josephson junction array, where a transition from long- to short-range order occurs as a function of the electronic doping. The synergy between correlated oxides and superconducting circuits is revealed to be a promising route to investigate these exotic compounds, complementary to standard magneto-transport measurements.Comment: 5 pages, 4 figures and 10 pages of supplementary materia

Using Intervention Mapping to Develop an Efficacious Multicomponent Systems-Based Intervention to Increase Human Papillomavirus (HPV) Vaccination in a Large Urban Pediatric Clinic Network

Background: The CDC recommends HPV vaccine for all adolescents to prevent cervical, anal, oropharyngeal, vaginal, vulvar, and penile cancers, and genital warts. HPV vaccine rates currently fall short of national vaccination goals. Despite evidence-based strategies with demonstrated efficacy to increase HPV vaccination rates, adoption and implementation of these strategies within clinics is lacking. The Adolescent Vaccination Program (AVP) is a multicomponent systems-based intervention designed to implement five evidence-based strategies within primary care pediatric practices. The AVP has demonstrated efficacy in increasing HPV vaccine initiation and completion among adolescents 10-17 years of age. The purpose of this paper is to describe the application of Intervention Mapping (IM) toward the development, implementation, and formative evaluation of the clinic-based AVP prototype. Methods: Intervention Mapping (IM) guided the development of the Adolescent Vaccination Program (AVP). Deliverables comprised: a logic model of the problem (IM Step 1); matrices of behavior change objectives (IM Step 2); a program planning document comprising scope, sequence, theory-based methods, and practical strategies (IM Step 3); functional AVP component prototypes (IM Step 4); and plans for implementation (IM Step 5) and evaluation (IM Step 6). Results: The AVP consists of six evidence-based strategies implemented in a successful sequenced roll-out that (1) established immunization champions in each clinic, (2) disseminated provider assessment and feedback reports with data-informed vaccination goals, (3) provided continued medical and nursing education (with ethics credit) on HPV, HPV vaccination, message bundling, and responding to parent hesitancy, (4) electronic health record cues to providers on patient eligibility, and (5) patient reminders for HPV vaccine initiation and completion. Conclusions: IM provided a logical and systematic approach to developing and evaluating a multicomponent systems-based intervention to increase HPV vaccination rates among adolescents in pediatric clinics

Doing Biopolitics Differently? Radical Potential in the Post-2015 MDG and SDG Debates

Post print On institutional repository or subject-based repository after a 18 months embargo, withdraw

Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: implications for B-cell selection

Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked glycosylation motifs in silico and compared to 452 highly-mutated mAbs from RA patients and controls. Variable region N-linked motifs (N-X-S/T) were strikingly prevalent within ACPA (100%) compared to somatically hypermutated (SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from seropositive (39%) and seronegative RA (7%). When normalized for SHM, ACPA still had significantly higher frequency of N-linked motifs compared to all studied mAbs including highly-mutated HIV broadly-neutralizing and malaria-associated mAbs. The Fab glycans of ACPA-mAbs were highly sialylated, contributed to altered charge, but did not influence antigen binding. The analysis revealed evidence of unusual B-cell selection pressure and SHM-mediated decreased in surface charge and isoelectric point in ACPA. It is still unknown how these distinct features of anti-citrulline immunity may have an impact on pathogenesis. However, it is evident that they offer selective advantages for ACPA+ B cells, possibly also through non-antigen driven mechanisms

A temperature-controlled device for volumetric measurements of Helium adsorption in porous media

We describe a set-up for studying adsorption of helium in silica aerogels, where the adsorbed amount is easily and precisely controlled by varying the temperature of a gas reservoir between 80 K and 180 K. We present validation experiments and a first application to aerogels. This device is well adapted to study hysteresis, relaxation, and metastable states in the adsorption and desorption of fluids in porous media

A Framework for Generalising the Newton Method and Other Iterative Methods from Euclidean Space to Manifolds

The Newton iteration is a popular method for minimising a cost function on Euclidean space. Various generalisations to cost functions defined on manifolds appear in the literature. In each case, the convergence rate of the generalised Newton iteration needed establishing from first principles. The present paper presents a framework for generalising iterative methods from Euclidean space to manifolds that ensures local convergence rates are preserved. It applies to any (memoryless) iterative method computing a coordinate independent property of a function (such as a zero or a local minimum). All possible Newton methods on manifolds are believed to come under this framework. Changes of coordinates, and not any Riemannian structure, are shown to play a natural role in lifting the Newton method to a manifold. The framework also gives new insight into the design of Newton methods in general.Comment: 36 page