A literature review of expert problem solving using analogy

We consider software project cost estimation from a problem solving perspective. Taking a cognitive psychological approach, we argue that the algorithmic basis for CBR tools is not representative of human problem solving and this mismatch could account for inconsistent results. We describe the fundamentals of problem solving, focusing on experts solving ill-defined problems. This is supplemented by a systematic literature review of empirical studies of expert problem solving of non-trivial problems. We identified twelve studies. These studies suggest that analogical reasoning plays an important role in problem solving, but that CBR tools do not model this in a biologically plausible way. For example, the ability to induce structure and therefore find deeper analogies is widely seen as the hallmark of an expert. However, CBR tools fail to provide support for this type of reasoning for prediction. We conclude this mismatch between experts’ cognitive processes and software tools contributes to the erratic performance of analogy-based prediction

An interactome-centered protein discovery approach reveals novel components involved in mitosome function and homeostasis in giardia lamblia

Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis. Live cell imaging revealed a highly immobilized array of 30–40 physically distinct mitosome organelles in trophozoites. We provide direct evidence for the single giardial dynamin-related protein as a contributor to mitosomal morphogenesis and homeostasis. To overcome inherent limitations that have hitherto severely hampered the characterization of these unique organelles we applied a novel interaction-based proteome discovery strategy using forward and reverse protein co-immunoprecipitation. This allowed generation of organelle proteome data strictly in a protein-protein interaction context. We built an initial Tom40-centered outer membrane interactome by co-immunoprecipitation experiments, identifying small GTPases, factors with dual mitosome and endoplasmic reticulum (ER) distribution, as well as novel matrix proteins. Through iterative expansion of this protein-protein interaction network, we were able to i) significantly extend this interaction-based mitosomal proteome to include other membrane-associated proteins with possible roles in mitosome morphogenesis and connection to other subcellular compartments, and ii) identify novel matrix proteins which may shed light on mitosome-associated metabolic functions other than Fe-S cluster biogenesis. Functional analysis also revealed conceptual conservation of protein translocation despite the massive divergence and reduction of protein import machinery in Giardia mitosomes

Degradation behaviors and mechanisms of MoS2 crystals relevant to bioabsorbable electronics

Monolayer molybdenum disulfide (MoS2) exhibits unique semiconducting and bioresorption properties, giving this material enormous potential for electronic/biomedical applications, such as bioabsorbable electronics. In this regard, understanding the degradation performance of monolayer MoS2 in biofluids allows modulation of the properties and lifetime of related bioabsorbable devices and systems. Herein, the degradation behaviors and mechanisms of monolayer MoS2 crystals with different misorientation angles are explored. High-angle grain boundaries (HAGBs) biodegrade faster than low-angle grain boundaries (LAGBs), exhibiting degraded edges with wedge and zigzag shapes, respectively. Triangular pits that formed in the degraded grains have orientations opposite to those of the parent crystals, and these pits grow into larger pits laterally. These behaviors indicate that the degradation is induced and propagated based on intrinsic defects, such as grain boundaries and point defects, because of their high chemical reactivity due to lattice breakage and the formation of dangling bonds. High densities of dislocations and point defects lead to high chemical reactivity and faster degradation. The structural cause of MoS2 degradation is studied, and a feasible approach to study changes in the properties and lifetime of MoS2 by controlling the defect type and density is presented. The results can thus be used to promote the widespread use of two-dimensional materials in bioabsorption applications

Spontaneous doping of the basal plane of MoS2 single layers through oxygen substitution under ambient conditions

The chemical inertness of the defect-free basal plane confers environmental stability to MoS2 single-layers, but it also limits their chemical versatility and catalytic activity. The stability of the pristine MoS2 basal plane against oxidation under ambient conditions is a widely accepted assumption in the interpretation of various studies and applications. However, single-atom level structural investigations reported here reveal that oxygen atoms spontaneously incorporate into the basal plane of MoS2 single layers during ambient exposure. Our scanning tunneling microscopy investigations reveal a slow oxygen substitution reaction, upon which individual sulfur atoms are one by one replaced by oxygen, giving rise to solid solution type 2D MoS2-xOx crystals. O substitution sites present all over the basal plane act as single-atomic active reaction centers, substantially increasing the catalytic activity of the entire MoS2 basal plane for the electrochemical H2 evolution reaction.Comment: 6 pages, 5 figure

EFFECTS OF SARILUMAB PLUS MTX ON CLINICAL, RADIOGRAPHIC, AND FUNCTIONAL ENDPOINTS IN PATIENTS WITH MODERATE-TO-SEVERE RHEUMATOID ARTHRITIS: RESULTS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, INTERNATIONAL STUDY

Pathophysiology and treatment of rheumatic disease

Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study

Pathophysiology and treatment of rheumatic disease