Intersecting Flavor Branes

We consider an instance of the AdS/CFT duality where the bulk theory contains an open string tachyon, and study the instability from the viewpoint of the boundary field theory. We focus on the specific example of the AdS_5 X S^5 background with two probe D7 branes intersecting at general angles. For generic angles supersymmetry is completely broken and there is an open string tachyon between the branes. The field theory action for this system is obtained by coupling to N =4 super Yang-Mills two N =2 hyper multiplets in the fundamental representation of the SU(N) gauge group, but with different choices of embedding of the two N=2 subalgebras into N=4. On the field theory side we find a one-loop Coleman-Weinberg instability in the effective potential for the fundamental scalars. We identify a mesonic operator as the dual of the open string tachyon. By AdS/CFT, we predict the tachyon mass for small 't Hooft coupling (large bulk curvature) and confirm that it violates the AdS stability bound.Comment: 36 page

Human (α2→6) and Avian (α2→3) Sialylated Receptors of Influenza A Virus Show Distinct Conformations and Dynamics in Solution

Differential interactions between influenza A virus protein hemagglutinin (HA) and α2→3 (avian) or α2→6 (human) sialylated glycan receptors play an important role in governing host specificity and adaptation of the virus. Previous analysis of HA–glycan interactions with trisaccharides showed that, in addition to the terminal sialic acid linkage, the conformation and topology of the glycans, while they are bound to HA, are key factors in regulating these interactions. Here, the solution conformation and dynamics of two representative avian and human glycan pentasaccharide receptors [LSTa, Neu5Ac-α(2→3)-Gal-β(1→3)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc; LSTc, (Neu5Ac-α(2→6)-Gal-β(1→4)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc] have been explored using nuclear magnetic resonance and molecular dynamics simulation. Analyses demonstrate that, in solution, human and avian receptors sample distinct conformations, topologies, and dynamics. These unique features of avian and human receptors in solution could represent distinct molecular characteristics for recognition by HA, thereby providing the HA–glycan interaction specificity in influenza.Finlombardia SPAConselho Nacional de Pesquisas (Brazil)National Institutes of Health (U.S.) (R37 GM057073-13)Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology

Gluten-free diet in celiac disease—forever and for all?

The gluten-free diet is the only effective treatment available for celiac disease. However, it is difficult to adhere to and a closer look on the diet’s implementation and indications reveals several ambiguities: Not only is there controversy on the threshold of gluten that can be tolerated in the frame of a strict gluten-free diet, but it is also unclear whether the gluten-free diet is an appropriate treatment in patient subgroups with asymptomatic or potential celiac disease. Reports from a number of research groups suggest that a certain proportion of patients may effectively develop tolerance to gluten and thus become suitable for gluten reintroduction over time. In this review, we set out to create an overview about the current state of research as regards the definition of a strict gluten-free diet in terms of the gluten thresholds considered tolerable and the indication for a gluten-free diet in the absence of histological abnormalities or symptoms. Furthermore, we discuss the concept that a gluten-free diet must be followed for life by all patients

The low-FODMAP diet and the gluten-free diet in the management of functional abdominal bloating and distension

This review summarizes current knowledge on the role of low-FODMAP diet and gluten-free diet in functional abdominal bloating and distension, an emerging disorder of gut-brain interaction characterized by remarkable costs for healthcare systems and a significant impact on the patient’s quality of life. Ingested food plays a key role in the pathophysiology of disorders of gut-brain interaction as up to 84% of patients with irritable bowel syndrome (IBS) report food-triggered symptoms. Potential pathogenetic mechanisms of food-related symptoms in these patients are discussed, focusing on bloating and abdominal distension. These mechanisms provide the rationale for dietary treatment in patients with functional abdominal bloating and distension. The role of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) and gluten in functional abdominal bloating and distension is examined. Current literature evaluating the efficacy of the low-FODMAP diet and the gluten-free diet in abdominal bloating and distension is analyzed. Available evidence originates mainly from studies on patients with IBS, since clinical studies on selected cohorts of patients with only functional abdominal bloating and distension have been missing to date. Promising evidence on the potential efficacy of the low-FODMAP diet in functional abdominal bloating and distension is provided by the reduction of the bloating observed in patients with IBS. Regarding the gluten-free diet, there is insufficient evidence to recommend it to reduce bloating and abdominal distension. In conclusion, this review asserts the need for a close collaboration with experts in nutrition to optimize the management of these patients and reduce the risks associated with elimination diets

Beyond linear regression: A reference for analyzing common data types in discipline based education research

[This paper is part of the Focused Collection on Quantitative Methods in PER: A Critical Examination.] A common goal in discipline-based education research (DBER) is to determine how to improve student outcomes. Linear regression is a common technique used to test hypotheses about the effects of interventions on continuous outcomes (such as exam score) as well as control for student nonequivalence in quasirandom experimental designs. (In quasirandom designs, subjects are not randomly assigned to treatments. For example, when treatment is assigned by classroom, and observations are made on students, the design is quasirandom because treatment is assigned to classroom, not subject (students).) However, many types of outcome data cannot be appropriately analyzed with linear regression. In these instances, researchers must move beyond linear regression and implement alternative regression techniques. For example, student outcomes can be measured on binary scales (e.g., pass or fail), tightly bound scales (e.g., strongly agree to strongly disagree), or nominal scales (i.e., different discrete choices for example multiple tracks within a physics major), each necessitating alternative regression techniques. Here, we review extensions of linear modeling—generalized linear models (glms)—and specifically compare five glms that are useful for analyzing DBER data: logistic, binomial, proportional odds (also called ordinal; including censored regression), multinomial, and Poisson (including negative binomial, hurdle, and zero-inflated) regression. We introduce a diagnostic tool to facilitate a researcher’s identification of the most appropriate glm for their own data. For each model type, we explain when, why, and how to implement the regression approach. When: we provide examples of the types of research questions and outcome data that would motivate this regression approach, including citations to articles in the DBER literature. Why: we name which linear regression assumption is violated by the data type. How: we detail implementation and interpretation of this modeling approach in R, including R syntax and code, and how to discuss the regression output in research papers. Code accompanying each analysis can be found in the online github repository that is associated with this paper (https://github.com/ejtheobald/BeyondLinearRegression). This paper is not an exhaustive review of regression techniques, nor does it review nonregression-based analyses. Rather, it aims to compile and summarize regression techniques useful for the most common types of DBER data and provide examples, citations, and heavily annotated R code so that researchers can easily implement the technique in their work

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCG

Acquired Refractory Iron Deficiency Anemia

Anemia is a global health problem affecting one-third of the world population, and half of the cases are due to iron deficiency (ID). Iron deficiency anemia (IDA) is the leading cause of disability in several countries. Although multiple mechanisms may coexist, ID and IDA causes can be classified as i) insufficient iron intake for the body requirement, ii) reduced absorption, and iii) blood losses. Oral iron represents the mainstay of IDA treatment. IDA is defined as "refractory" when the hematologic response after 4 to 6 weeks of treatment with oral iron (an increase of >=1 g/dL of Hb) is absent. The cause of iron-refractory anemia is usually acquired and frequently related to gastrointestinal pathologies, although a rare genetic form called iron-refractory iron deficiency anemia (IRIDA) exists. In some pathological circumstances, either genetic or acquired, hepcidin increases, limiting the absorption in the gut, remobilization, and recycling of iron, thereby reducing iron plasma levels. Indeed, conditions with high hepcidin levels are often under-recognized as iron refractory, leading to inappropriate and unsuccessful treatments. This review provides an overview of the iron refractory anemia underlying conditions, from gastrointestinal pathologies to hepcidin dysregulation and iatrogenic or provoked conditions, and the specific diagnostic and treatment approach

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders

Orbital-optimized versus time-dependent density functional calculations of intramolecular charge transfer excited states

The performance of time-independent, orbital optimized calculations of excited states is assessed with respect to charge transfer excitations in organic molecules in comparison to the linear-response time-dependent density functional theory (TD-DFT) approach. A direct optimization method to converge on saddle points of the electronic energy surface is used to carry out calculations with the local density approximation (LDA) and the generalized gradient approximation (GGA) functionals PBE and BLYP for a set of 27 excitations in 15 molecules. The time-independent approach is fully variational and provides a relaxed excited state electron density from which the extent of charge transfer is quantified. The TD-DFT calculations are generally found to provide larger charge transfer distances compared to the orbital optimized calculations, even when including orbital relaxation effects with the Z-vector method. While the error on the excitation energy relative to theoretical best estimates is found to increase with the extent of charge transfer up to ca. $-2$ eV for TD-DFT, no correlation is observed for the orbital optimized approach. The orbital optimized calculations with the LDA and the GGA functionals provide a mean absolute error of $\sim$0.7 eV, outperforming TD-DFT with both local and global hybrid functionals for excitations with long-range charge transfer character. Orbital optimized calculations with the global hybrid functional B3LYP and the range-separated hybrid functional CAM-B3LYP on a selection of states with short- and long-range charge transfer indicate that inclusion of exact exchange has a small effect on the charge transfer distance, while it significantly improves the excitation energy, with the best performing functional CAM-B3LYP providing an absolute error typically around 0.15 eV.Comment: 42 pages, 8 figures; SI 4 pages, 2 figure