X-ray photoelectron spectroscopy (XPS) is widely used to determine the chemical and electronic states of atoms within a material. However, it is often complex to interpret the O 1s region in metal ...oxides, where an ∼531 eV binding energy feature appears between lattice oxygen (∼530 eV) and oxygen-containing surface species (∼532 eV). This feature has been vaguely ascribed to oxygen vacancies or oxygen deficient regions for many decades. This work employs full-potential density functional theory to calculate the binding energies of the O 1s electrons under two- and three-dimensional periodic boundary conditions as a probe of expected XPS spectra. ZnO is used as an example system. Both bulk crystal regions containing a range of oxygen defects and slabs with a range of surface terminations and functionalizations have been considered. The slabs considered are mostly {1010} and {1120} surfaces that are not expected to be reconstructed from the cleaved bulk structure. The resulting O 1s binding energies show no signature for oxygen defects in bulk regions. Furthermore, the 531 eV binding energy feature often ascribed to oxygen vacancies or oxygen deficient regions can instead be readily explained by the O 1s electrons from water molecules strongly bound to the exposed ZnO surface (i.e., chemisorbed, as distinct from more loosely bound water) or surface oxygen passivated with hydrogen. This work will rectify many misinterpretations of XPS data of the O 1s region in metal oxides, provide guidance for precisely understanding the oxygen states of a material, and subsequently enable the real origin of material properties to be revealed.
Understanding the influence of surface properties (roughness, grooves, discrete textures/dimples) on the performance of hydrodynamically lubricated contacts has been the aim of numerous studies. A ...variety of different numerical models have been employed by many researchers in order to find optimal texturing parameters (shape, size, distribution) for best performance enhancement in terms of load carrying capacity, film thickness, friction and wear. However, the large number of different modeling techniques and complexity in the patterns make finding the optimum texture a challenging task and have led to contrary conclusions. This article outlines the research effort on surface texturing worldwide, reviews the key findings and, in particular, provides a comparative summary of different modeling techniques for fluid flow, cavitation and micro-hydrodynamic effects.
•This article facilitates the application of textures for hydrodynamic contacts.•Functions of surface textures, texture design and modeling techniques are discussed.•Textures must be designed for a given application and range of operating conditions.•Robust models allow the evaluation of texture designs prior to being manufactured.•The three major challenges in numerical modeling are discussed.
The successes with chimeric antigen receptor (CAR) T cell therapy in early clinical trials involving patients with pre-B cell acute lymphoblastic leukaemia (ALL) or B cell lymphomas have ...revolutionized anticancer therapy, providing a potentially curative option for patients who are refractory to standard treatments. These trials resulted in rapid FDA approvals of anti-CD19 CAR T cell products for both ALL and certain types of B cell lymphoma - the first approved gene therapies in the USA. However, growing experience with these agents has revealed that remissions will be brief in a substantial number of patients owing to poor CAR T cell persistence and/or cancer cell resistance resulting from antigen loss or modulation. Furthermore, the initial experience with CAR T cells has highlighted challenges associated with manufacturing a patient-specific therapy. Understanding the limitations of CAR T cell therapy will be critical to realizing the full potential of this novel treatment approach. Herein, we discuss the factors that can preclude durable remissions following CAR T cell therapy, with a primary focus on the resistance mechanisms that underlie disease relapse. We also provide an overview of potential strategies to overcome these obstacles in an effort to more effectively incorporate this unique therapeutic strategy into standard treatment paradigms.
Graves' Disease Smith, Terry J; Hegedüs, Laszlo
New England journal of medicine/The New England journal of medicine,
2016-Oct-20, Volume:
375, Issue:
16
Journal Article
This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor ...(IGF-IR) and the IGF-I binding proteins. The IGF/IGF-IR pathway plays important and diverse roles in tissue development and function. It regulates cell cycle progression, apoptosis, and the translation of proteins. Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. In contrast, activating antibodies directed at IGF-IR have been detected in patients with Graves' disease, where the receptor is overexpressed by multiple cell types. The frequency of IGF-IR+ B and T cells is substantially increased in patients with that disease. Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. IGF-IR has been targeted in efforts directed toward drug development for cancer, employing both small-molecule and monoclonal antibody approaches. These have been generally well-tolerated. Recognizing the broader role of IGF-IR in regulating both normal and pathological immune responses may offer important opportunities for therapeutic intervention in several allied diseases that have proven particularly difficult to treat.
The aim of this study was to develop a self-administered scale based on the special features of smartphone. The reliability and validity of the Smartphone Addiction Inventory (SPAI) was demonstrated.
...A total of 283 participants were recruited from Dec. 2012 to Jul. 2013 to complete a set of questionnaires, including a 26-item SPAI modified from the Chinese Internet Addiction Scale and phantom vibration and ringing syndrome questionnaire. There were 260 males and 23 females, with ages 22.9 ± 2.0 years. Exploratory factor analysis, internal-consistency test, test-retest, and correlation analysis were conducted to verify the reliability and validity of the SPAI. Correlations between each subscale and phantom vibration and ringing were also explored.
Exploratory factor analysis yielded four factors: compulsive behavior, functional impairment, withdrawal and tolerance. Test-retest reliabilities (intraclass correlations = 0.74-0.91) and internal consistency (Cronbach's α = 0.94) were all satisfactory. The four subscales had moderate to high correlations (0.56-0.78), but had no or very low correlation to phantom vibration/ringing syndrome.
This study provides evidence that the SPAI is a valid and reliable, self-administered screening tool to investigate smartphone addiction. Phantom vibration and ringing might be independent entities of smartphone addiction.
The evolution of territoriality reflects the balance between the benefit and cost of monopolising a resource. While the benefit of territoriality is generally intuitive (improved access to ...resources), our understanding of its cost is less clear. This paper combines: 1. a review of hypotheses and meta-analytic benchmarking of costs across diverse taxa; and 2. a new empirical test of hypotheses using a longitudinal study of free-living male territorial lizards. The cost of territoriality was best described as a culmination of multiple factors, but especially costs resulting from the time required to maintain a territory (identified by the meta-analysis) or those exacerbated by a territory that is large in size (identified by the empirical test). The meta-analysis showed that physiological costs such as energetic expenditure or stress were largely negligible in impact on territory holders. Species that used territories to monopolise access to mates appeared to incur the greatest costs, whereas those defending food resources experienced the least. The single largest gap in our current understanding revealed by the literature review is the potential cost associated with increased predation. There is also a clear need for multiple costs to be evaluated concurrently in a single species. The empirical component of this study showcases a powerful analytical framework for evaluating a range of hypotheses using correlational data obtained in the field. More broadly, this paper highlights key factors that should be considered in any investigation that attempts to account for the evolutionary origin or ecological variation in territorial behaviour within and between species.
Thyroid eye disease (TED), a vision-threatening and disfiguring autoimmune process, has thwarted our efforts to understand its pathogenesis and develop effective and safe treatments. Recent ...scientific advances have facilitated improved treatment options.
Review historically remote and recent advances in understanding TED.
PubMed was scanned using search terms including thyroid-associated ophthalmopathy, thyroid eye disease, Graves' orbitopathy, autoimmune thyroid disease, and orbital inflammation.
Strength of scientific evidence, size, scope, and controls of clinical trials/observations.
Glucocorticoid steroids are widely prescribed systemic medical therapy. They can lessen inflammation-related manifestations of TED but fail to reliably reduce proptosis and diplopia, 2 major causes of morbidity. Other current therapies include mycophenolate, rituximab (anti-CD20 B cell-depleting monoclonal antibody), tocilizumab (interleukin-6 receptor antagonist), and teprotumumab (IGF-I receptor inhibitor). Several new therapeutic approaches have been proposed including targeting prostaglandin receptors, vascular endothelial growth factor, mTOR, and cholesterol pathways. Of potentially greater long-term importance are attempts to restore immune tolerance.
Despite their current wide use, steroids may no longer enjoy first-tier status for TED as more effective and better tolerated medical options become available. Multiple current and emerging therapies, the rationales for which are rooted in theoretical and experimental science, promise better options. These include teprotumumab, rituximab, and tocilizumab. Restoration of immune tolerance could ultimately become the most effective and safe medical management for TED.