Introduction to the special section on cognitive bias modification in emotional disorders.

Cognitive models of anxiety disorders and unipolar depression have postulated that selective information processing plays an important role in the development and maintenance of emotional psychopathology. Cognitive bias modification (CBM) procedures have recently been developed to test this theoretical claim. The purpose of this special section is to introduce the central ideas underlying CBM and to bring together the research that exemplifies the theoretical and clinical potential of the CBM approach. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Heteronuclear 1H-31P statistical total correlation NMR spectroscopy of intact liver for metabolic biomarker assignment: application to galactosamine-induced hepatotoxicity

As part of our ongoing development of methods for enhanced biomarker information recovery from spectroscopic data we present the first example of a new hetero-nuclear statistical total correlation spectroscopy (HET-STOCSY) approach applied to intact tissue samples collected as part of a toxicological study. One-dimensional 1H and 31P-{1H} magic angle spinning (MAS) NMR spectra of intact liver samples after galactosamine (galN) treatment to rats and after cotreatment of galN plus uridine were collected at 275 K. Individual samples were also followed by 1H and 31P-{1H} MAS NMR through time generating time dependent modulations in metabolite signatures relating to toxicity. High-resolution 1H NMR spectra of urine and plasma and clinical chemical data were also collected to establish a biological framework in which to place these novel statistical heterospectroscopic data. In HET-STOCSY, calculation of the covariance between the 31P-{1H} and 1H NMR signals of phosphorus containing metabolites allows their molecular connectivities to be established and the construction of virtual two-dimensional heteronuclear correlation spectra that connect all protons on the molecule to the heteroatom. We show how HET-STOCSY applied to MAS NMR spectra of liver samples can be used to augment biomarker detection. This approach is generic and can be applied to correlate the covarying signals for any spin-active nuclei where there is parallel or serial collection of data.     

In Silico Study of the Acquired Resistance Caused by the Secondary Mutations of KRAS G12C Protein Using Long Time Molecular Dynamics Simulation and Markov State Model Analysis

Kirsten rat sarcoma viral oncogene homolog (KRAS) is a small GTPase protein which plays an important role in the treatment of KRAS mutant cancers. The FDA-approved AMG510 and MRTX849 (phase III clinical trials) are two potent KRASG12C-selective inhibitors that target KRAS G12C. However, the drug resistance caused by the second-site mutation in KRAS has emerged, and the mechanisms of drug resistance at atom level are still unclear. To clarify the mechanisms of drug resistance, we conducted long time molecular dynamics simulations (75 μs in total) to study the structural and energetic features of KRAS G12C and its four drug resistant variants to inhibitors. The combined binding free energy calculation and protein−ligand interaction fingerprint revealed that these second-site mutations indeed caused KRAS to produce different degrees of resistance to AMG510 and MRTX849. Furthermore, Markov State Models and 2D-free energy landscapes analysis revealed the difference in conformational changes of mutated KRAS bound with and without inhibitors. Furthermore, the comparative analysis of these systems showed that there were differences in their allosteric signal pathways. These findings provide the molecular mechanism of drug resistance, which helps to guide novel KRAS G12C inhibitor design to overcome drug resistance.     

Matrix multiplication on the Intel Touchstone Delta

Matrix multiplication is a key primitive in block matrix algorithms such as those found in LAPACK. We present results from our study of matrix multiplication algorithms on the Intel Touchstone Delta, a distributed memory message-passing architecture with a two-dimensional mesh topology. We analyze and compare three algorithms and obtain an implementation, BiMMeR, that uses communication primitives highly suited to the Delta and exploits the single node assembly-coded matrix multiplication. Our algorithm is completely general, i.e. able to deal with various data layouts as well as arbitrary mesh aspect ratios and matrix dimensions, and has achieved parallel efficiency of 86 %, with overall peak performance in excess of 8 Gflops on 256 nodes for an 8800 × 8800 matrix. We describe BiMMeR's design and implementation and present performance results that demonstrate scalability and robust behavior over varying mesh topologies.     

Using a Metabotype Framework to Deliver Personalized Nutrition Improves Dietary Quality and Metabolic Health Parameters: A 12-Week Randomized Controlled Trial

Scope

Effective strategies for tailoring dietary advice to individuals are urgently needed. The effectiveness of personalized nutrition advice delivered using a metabotype framework in improving dietary quality and metabolic health biomarkers compared to population-level advice is investigated.

Materials and results

A 12-week parallel randomized controlled trial is performed with 107 healthy adults. Individuals in the personalized group are classified into metabotypes using four markers (triacylglycerol, high-density lipoprotein [HDL]-cholesterol, total cholesterol [TC], and glucose) and received dietary advice from decision tree algorithms containing metabotypes characteristics and individual traits. Individuals in the control group received generic dietary advice based on national guidelines. The personalized approach results in higher dietary quality assessed by the Alternate Mediterranean Diet Score (effect size [95% confidence interval, CI], 0.77 [0.07, 1.48], 12% versus 3% increase) and significantly lower concentrations of triacylglycerol (−0.17 [−0.28, −0.06] log10 mmol L⁻¹), TC (−0.42 [−0.74, −0.10] mmol L⁻¹), low-density lipoprotein (LDL)-cholesterol (−0.34, [−0.60, −0.09] mmol L⁻¹), and lower triacylglycerol-glucose index (−0.40, [−0.67, −0.13]). Sixteen phosphatidylcholines and six lysophosphatidylcholines, predominately with chain lengths of 30–36 carbons, are lower in the personalized group.

Conclusions

Personalized nutrition advice delivered using the metabotype framework is effective to improve dietary quality, which could result in reduced CVD risk, and metabolic heath biomarkers.     

Enhancing traceability of wheat quality through the supply chain

With the growing global population, the need for food is expected to grow tremendously in the next few decades. One of the key tools to address such growing food demand is minimizing grain losses and optimizing food processing operations. Hence, several research studies are underway to reduce grain losses/degradation at the farm (upon harvest) and later during the milling and baking processes. However, less attention has been paid to changes in grain quality between harvest and milling. This paper aims to address this knowledge gap and discusses possible strategies for preserving grain quality (for Canadian wheat in particular) during unit operations at primary, process, or terminal elevators. To this end, the importance of wheat flour quality metrics is briefly described, followed by a discussion on the effect of grain properties on such quality parameters. This work also explores how drying, storage, blending, and cleaning, as some of the common post-harvest unit operations, could affect grain's end-product quality. Finally, an overview of the available techniques for grain quality monitoring is provided, followed by a discussion on existing gaps and potential solutions for quality traceability throughout the wheat supply chain.     

Investigating the nonlinear and conditional effects of trust—The new role of institutional contexts in online repurchase

Trust is paramount to developing and maintaining long-term relationships in all stages of the customer lifecycle, including the repurchase stage. This research goes beyond the simple finding documented in the extant trust literature that the effect of trust will diminish. It sheds light on the role of institutional contexts and develops a nuanced understanding of the boundary conditions under which trust operates in the repurchase stage, where knowledge-based trust becomes more predominant. Drawing on a different theoretical tenet, prospect theory, we find that customers exhibit distinctively different transaction intentions in the two perceptual conditions of high and low trust in institutional contexts. Specifically, the nonlinear relationship between trust and repeat online transaction intention is inverted U-shaped curvilinear when trust in institutional contexts is high, but is U-shaped when trust in institutional contexts is low. With data collected from both e-commerce and mobile banking contexts using two different measures of institutional contexts, we employed a new and advanced latent moderated structural (LMS) equations approach for analysis and provided robust results. Our findings largely confirm the hypotheses and offer theoretical, methodological, and practical implications.     

Negative Regulation of Innate Immune Signaling by Components of the Button Mushroom Agaricus bisporus

Scope: Mushrooms are valued as an edible and medical resource for millennia. As macrofungi, they possess conserved molecular components recognized by innate immune cells like macrophages, yet unlike pathogenic fungi, they do not trigger the immune system in the same way. That these well-tolerated foods both avoid immuno-surveillance and have positive health benefits, highlights the dearth of information on the interactions of mushroom-derived products with the immune system. Methods and results: Using powders produced from the common white button mushroom, Agaricus bisporus, it is observed that pre-treatment of mouse and human macrophages with mushroom powders attenuates innate immune signaling triggered by microbial ligands like LPS and  β-glucans, including NFκB activation and pro-inflammatory cytokine production. This effect of mushroom powders is observed at lower doses of TLR ligands, suggesting a model of competitive inhibition whereby mushroom compounds bind and occupy innate immune receptors, precluding activation by microbial stimuli. This effect is preserved following simulated digestion of the powders. Moreover, in vivo delivery of mushroom powders attenuates the development of colitis in a DSS-mouse model. Conclusion: This data highlights an important anti-inflammatory role for powdered A. bisporus mushrooms, which can be further utilized to develop complementary approaches to modulate chronic inflammation and disease.