A Phos-Tag-Based Approach Reveals the Extent of Physiological Endoplasmic Reticulum Stress

Cellular response to endoplasmic reticulum (ER) stress or unfolded protein response (UPR) is a key defense mechanism associated with many human diseases. Despite its basic and clinical importance, the extent of ER stress inflicted by physiological and pathophysiological conditions remains difficult to quantitate, posing a huge obstacle that has hindered our further understanding of physiological UPR and its future therapeutic potential. Here we have optimized a Phos-tag-based system to detect the activation status of two proximal UPR sensors at the ER membrane. This method allowed for a quantitative assessment of the level of stress in the ER. Our data revealed quantitatively the extent of tissue-specific basal ER stress as well as ER stress caused by the accumulation of misfolded proteins and the fasting-refeeding cycle. Our study may pave the foundation for future studies on physiological UPR, aid in the diagnosis of ER-associated diseases and improve and facilitate therapeutic strategies targeting UPR in vivo

The psychophysics of number arise from resource-limited spatial memory

People can identify the number of objects in small sets rapidly and without error but become increasingly noisy for larger sets. However, the cognitive mechanisms underlying these ubiquitous psychophysics are poorly understood. We present a model of a limited-capacity visual system optimized to individuate and remember the location of objects in a scene which gives rise to all key aspects of number psychophysics, including error-free small number perception and scalar variability for larger numbers. We therefore propose that number psychophysics can be understood as an emergent property of primitive perceptual mechanisms --- namely, the process of identifying and representing individual objects in a scene. To test our theory, we ran two experiments: a change-localization task to measure participants' memory for the locations of objects (Experiment 1) and a numerical estimation task (Experiment 2). Our model accounts well for participants' performance in both experiments, despite only being optimized to efficiently encode where objects are present in a scene. Our results demonstrate that the key psychophysical features of numerical cognition do not arise from separate modules or capacities specific to number, but rather from lower-level constraints on perception which are manifested even in non-numerical tasks

Limited information-processing capacity in vision explains number psychophysics

Humans and other animals are able to perceive and represent the number of objects present in a scene, a core cognitive ability thought to underlie the development of mathematics. However, the perceptual mechanisms that underpin this capacity remain poorly understood. Here, we show that our visual sense of number derives from a visual system designed to efficiently encode the location of objects in scenes. Using a mathematical model, we demonstrate that an efficient but information-limited encoding of objects' locations can explain many key aspects of number psychophysics, including subitizing, Weber's law, underestimation, and effects of exposure time. In two experiments (N=100 each), we find that this model of visual encoding captures human performance in both a change-localization task and a number estimation task. In a third experiment (N=100), we find that individual differences in change-localization performance are highly predictive of differences in number estimation, both in terms of overall performance and inferred model parameters, with participants having numerically indistinguishable inferred information capacities across tasks. Our results therefore indicate that key psychophysical features of numerical cognition do not arise from separate modules or capacities specific to number, but rather as byproducts of lower-level constraints on perception

UPlan: Geographic Information System as Framework for Integrated Land Use Planning Model

A geographic information system (GIS) framework is appealing to model supply-side decisions because spatial relationships commonly used by developers to evaluate building sites, such as the proximity to transportation facilities, existing land uses, political boundaries, and environmentally sensitive areas, are defined precisely in the GIS layers. The GIS captures spatial synergisms that are lost in tabulations by traffic zone or larger forecasting districts. Further, the results are defined for individual parcels (grids). This method interfaces directly with the concerns of residents and other interest groups. Uncertainty and error in postmodel allocations from zones to parcels in existing land use models can significantly blur and degrade the relevance of forecasts made with existing models. The development patterns predicted by UPlan, a planning model, tend to be realistic and provide a basis for land use planning and evaluation. A GIS land use survey, supplemented with simulation model networks and census data, was used to calibrate the model. The calibrated UPlan model did a reasonably accurate job of allocating the various categories of land uses to predefined composite growth areas. The generalized UPlan model is applicable in a wide variety of rural, suburban, and urban settings. The model, as presented, was configured as a travel simulation integrated land use planning tool, but the method also can be used as the supply-side component within a comprehensive land use modeling framework

UPlan: Geographic Information System as Framework for Integrated Land Use Planning Model

A geographic information system (GIS) framework is appealing to model supply-side decisions because spatial relationships commonly used by developers to evaluate building sites, such as the proximity to transportation facilities, existing land uses, political boundaries, and environmentally sensitive areas, are defined precisely in the GIS layers. The GIS captures spatial synergisms that are lost in tabulations by traffic zone or larger forecasting districts. Further, the results are defined for individual parcels (grids). This method interfaces directly with the concerns of residents and other interest groups. Uncertainty and error in postmodel allocations from zones to parcels in existing land use models can significantly blur and degrade the relevance of forecasts made with existing models. The development patterns predicted by UPlan, a planning model, tend to be realistic and provide a basis for land use planning and evaluation. A GIS land use survey, supplemented with simulation model networks and census data, was used to calibrate the model. The calibrated UPlan model did a reasonably accurate job of allocating the various categories of land uses to predefined composite growth areas. The generalized UPlan model is applicable in a wide variety of rural, suburban, and urban settings. The model, as presented, was configured as a travel simulation integrated land use planning tool, but the method also can be used as the supply-side component within a comprehensive land use modeling framework

Quantitative study of dislocation densities of friction stir processed in-situ particles reinforced TiB2/AA6063 composites by X-ray line analysis

International audienc

Medical student career choice: Who is the influencer?

Background: While many factors influence medical student career choice, interactions with attending and resident physicians during clinical rotations are particularly important. To evaluate the influence of attending and resident physicians on medical students\u27 career choices, particularly for those pursuing surgical careers, we quantified their respective influence in the context of other known influences.Methods: Rising fourth-year medical students and new graduates were given an IRB-exempt, 14-item online survey. Descriptive statistics were performed on the demographic information. Chi-square analysis was used, as were Kruskal-Wallis and Mann-Whitney analyses on the Likert responses (α = 0.05).Results: Survey response was 24%. Students pursuing general surgery rated residents greater than or equal to attendings on 7 of 8 key mentoring characteristics. Of students choosing a different specialty than the one they intended to pursue upon entering medical school, the influence of residents was cited by 100% of the students pursuing general surgery, compared to 59% of the entire cohort. Identification of a role model and perceived personality fit were significantly more important than other factors (P \u3c 0.0001). Students pursuing general surgery rated the importance of identifying a role model and perceived personality fit greater than their peers.Conclusions: Residents have greater influences on medical students\u27 career choice compared to attendings. Students pursuing a surgical specialty, particularly general surgery, considered the influence of role models and perceived personality fit to be the most important factors in their specialty decision. These findings provide valuable insights to improve student experiences and career recruitment in surgical specialties, particularly general surgery