Webs of Proximity and Just-in-Time Information

Disciplinary webs of proximity frequently overlap at the periphery of a topic where interests intersect for problem-solving. Failure to account for disciplinary differences can result in dis-ease – tension that interferes with meaning-making. This can be especially problematic in just-in-time information settings. An unexpected social media case study involving severe weather reporting and algorithm-driven system censorship makes evident the role of a constellation of pragmatic factors that can enhance or hinder just-in-time information delivery. Employing webs of proximity, we probe the severe weather censorship event with complementary bodies of knowledge and disciplinary perspectives. Intersectionalities are discussed through lenses of proximity and epidata. Entanglements of commonality between differing web plots are represented in a negotiation vestibule. The possibility of the communication channel itself being noise is presented. The vestibule highlights opportunities for negotiation points to attempt functional meaning-making

Storm Warnings: Time Sensitive Proximity

Weather-predictive tasks during high risk severe weather events are carried out for the common good of the community by virtual teams of weather professionals. Severe weather predictors are responsible for producing the early warnings that inform people in harms way and potentially save lives. Should we be concerned with the use of “other-generated” information from social media used by these professionals? Teams extend understanding of an event by looking to external sources of situationally relevant information such as storm spotters, publicly generated photos and comments posted to online social media (OSM), and communication with community partners. Situationally relevant OSM, specifically Twitter, provides insight to the information behavior of the team. Here we examine the role of proximity and how it impacts decisions on potentially life-saving information sharing in time sensitive information environments: proximity within the team (shared knowledge state) and proximity to the event (hashtag) specifically are addressed

Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy

Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy. Fractional clearances of uncharged dextran 40 and anionic proteins were performed in an attempt to elucidate the defect in glomerular barrier function responsible for heavy proteinuria in diabetic nephropathy. Notwithstanding urinary albumin excretion (UalbV) at 3634 ± 608 µg/min, the fractional clearance for dextran molecules with Einstein-Stokes radii (r) between 22 and 36 Å was depressed in 12 patients with advanced diabetic nephropathy, which suggests a reduction in mean glomerular pore size or density. Equivalent restriction to transglomerular passage of dextrans with a r < 36 Å in 7 patients with minimal change nephropathy was associated with a similarly enhanced proteinuria (UalbV, 3333 ± 759 µg/min). The dissociation between fractional clearances for neutral and anionic macromolecules in both disorders is consistent with loss of glomerular electrostatic charge. In diabetic nephropathy, however, the fractional clearances for large dextrans and test proteins considerably exceeded corresponding values in minimal change nephropathy when r ≥ 36 Å. Furthermore, the fractional clearances for test proteins were two orders of magnitude smaller than that for equivalent-sized dextrans in minimal change nephropathy, whereas this difference was much less in diabetic nephropathy. Thus, a selective increase in transglomerular passage of large molecules and a progressive loss of ability to discriminate between large molecules of different configuration distinguish the glomerular capillary wall in diabetic nephropathy from that in minimal change nephropathy.Protéinurie et caractéristiques fonctionnelles de la barrière glomérulaire dans la néphropathie diabétique. Les clearances fractionnelles de dextran 40 neutre et de protéines anioniques ont été mesurées afin d'étudier le défaut de la fonction de la barrière glomérulaire responsable de la protéinurie massive au cours de la néphropathie diabétique. Malgré une excrétion urinaire d'albumine (UalbV) de 3634 ± 608 µg/min, la clearance fractionnelle pour les molécules de dextran dont le rayon d'Einstein-Stokes (r) était compris entre 22 et 36 Å était abaissé chez 12 malades atteints de néphropathie diabétique avancée, ce qui suggère une diminution de la taille moyenne ou de la densité des pores. Une diminution équivalente de la restriction au franchissement du glomérule de dextran r < 36 Å chez 7 malades atteints de néphropathie à modifications minimes était associée à une protéinurie du même ordre (UalbV, 3333 ± 759 /µg/min). La dissociation entre les clearances fractionnelles des macromolécules neutres et anioniques dans les deux affections est compatible avec une perte des charges électrostatiques glomérulaires. Dans la néphropathie diabétique, cependant les clearances fractionnelles des dextrans de grande taille et des protéines étudiées était plus élevé que les valeurs obtenues dans les néphropathies à modifications minimes quand r ≥ 36 Å. De plus, les clearances fractionnelles pour les protéines étudiées sont plus es petit de deux ordres de grandeur que les clearances fractionnelles pour les dextrans de taille équivalente dans la néphropathie à modifications minimes, alors que cette différence était bien moindre dans la néphropathie diabétique. Ainsi une augmentation sélective du passage transglomérulaire des grosses molécules et une perte progressive de la capacité de discriminer entre les grosses molécules selon leur configuration différencie la paroi du capillaire glomérulaire de la néphropathie diabétique de celle de la néphropathie à modifications minimes

Epigenetic suppression of hippocampal calbindin-D28k by ΔFosB drives seizure-related cognitive deficits.

The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer\u27s disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. We demonstrate that ΔFosB, a highly stable transcription factor, is induced in the hippocampus in mouse models of AD and seizures, in which it binds and triggers histone deacetylation at the promoter of the calbindin gene (Calb1) and downregulates Calb1 transcription. Notably, increasing DG calbindin levels, either by direct virus-mediated expression or inhibition of ΔFosB signaling, improves spatial memory in a mouse model of AD. Moreover, levels of ΔFosB and calbindin expression are inversely related in the DG of individuals with temporal lobe epilepsy (TLE) or AD and correlate with performance on the Mini-Mental State Examination (MMSE). We propose that chronic suppression of calbindin by ΔFosB is one mechanism through which intermittent seizures drive persistent cognitive deficits in conditions accompanied by recurrent seizures

The role of perceived benefits and costs in patients’ medical decisions

Background  Many decisions can be understood in terms of actors’ valuations of benefits and costs. The article investigates whether this is also true of patient medical decision making. It aims to investigate (i) the importance patients attach to various reasons for and against nine medical decisions; (ii) how well the importance attached to benefits and costs predicts action or inaction; and (iii) how such valuations are related to decision confidence. Methods  In a national random digit dial telephone survey of U.S. adults, patients rated the importance of various reasons for and against medical decisions they had made or talked to a health‐care provider about during the past 2 years. Participants were 2575 English‐speaking adults age 40 and older. Data were analysed by means of logistic regressions predicting action/inaction and linear regressions predicting confidence. Results  Aggregating individual reasons into those that may be regarded as benefits and those that may be regarded as costs, and weighting them by their importance to the patient, shows the expected relationship to action. Perceived benefits and costs are also significantly related to the confidence patients report about their decision. Conclusion  The factors patients say are important in their medical decisions reflect a subjective weighing of benefits and costs and predict action/inaction although they do not necessarily indicate that patients are well informed. The greater the difference between the importance attached to benefits and costs, the greater patients’ confidence in their decision.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102701/1/hex739.pd

Contemporary visions of progress in ecology and thoughts for the future

Although ecological research is progressing rapidly, the answers to certain key questions continue to elude us. This paper considers several of the contemporary challenges facing ecology. (1) Terminology is voluminous and often poorly defined, resulting in inefficient communication. (2) The concept of scale affects our inferences about system structure and function, requiring us to continue an almost heuristic investigation of breaks, domains, and integration. New tools that more explicitly incorporate scalar issues will need to be developed for progress to take place in the field of ecology. (3) Increasingly, it is expected that applied questions will be solved in less than a year. This demand for solutions from ecologists often produces short-term and inadequate responses. (4) How can ecologists improve communication between subdisciplines, with undergraduate students, and with the public? How will ecology be done in the future, and by whom? We provide some background to these observations and questions, and offer some potential solutions from the viewpoint of young practicing ecologists

Structure-based Protocol for Identifying Mutations that Enhance Protein–Protein Binding Affinities

The ability to manipulate protein binding affinities is important for the development of proteins as biosensors, industrial reagents, and therapeutics. We have developed a structure-based method to rationally predict single mutations at protein-protein interfaces that enhance binding affinities. The protocol is based on the premise that increasing buried hydrophobic surface area and/or reducing buried hydrophilic surface area will generally lead to enhanced affinity if large steric clashes are not introduced and buried polar groups are not left without a hydrogen bond partner. The procedure selects affinity enhancing point mutations at the protein-protein interface using three criteria: 1) the mutation must be from a polar amino acid to a non-polar amino acid or from a non-polar amino acid to a larger non-polar amino acid, 2) the free energy of binding as calculated with the Rosetta protein modeling program should be more favorable than the free energy of binding calculated for the wild type complex and 3) the mutation should not be predicted to significantly destabilize the monomers. The Rosetta energy function emphasizes short-range interactions: steric repulsion, Van der Waals forces, hydrogen bonding, and an implicit solvation model that penalizes placing atoms adjacent to polar groups. The performance of the computational protocol was experimentally tested on two separate protein complexes; Gαi1 from the heterotrimeric G-protein system bound to the RGS14 GoLoco motif, and the E2, UbcH7, bound to the E3, E6AP from the ubiquitin pathway. 12 single-site mutations that were predicted to be stabilizing were synthesized and characterized in the laboratory. 9 of the 12 mutations successfully increased binding affinity with 5 of these increasing binding by over 1.0 kcal/mol. To further assess our approach we searched the literature for point mutations that pass our criteria and have experimentally determined binding affinities. Of the 8 mutations identified, 5 were accurately predicted to increase binding affinity, further validating the method as a useful tool to increase protein-protein binding affinities