Size-tuneable nanometric MRI contrast agents for the imaging of molecular weight dependent transport processes

Purpose: To evaluate size-tuneable nanomeric glycol-chitosan-DTPA-Gd conjugates as MRI contrast agents for the imaging of molecular weight (MW) dependent transport processes. Material & Methods: Glycol chitosans (GC) – DTPA conjugates of precisely controlled MWs were synthesised and evaluated in mice against Gd-DTPA using times series of high-resolution MRI images of trunk, head, and xenograft flank tumours. All animal studies were approved by the local ethics committee and the UK authorities. Results: GC-DTPA modification ratio was one DTPA per 3.9 – 5.13 of GC monomers. GC-DTAPGd provided overall superior contrast compared to Gd-DTPA with the duration of the enhancement depending on MW (≥ 1h for 40kD). Kidneys showed early enhancement also in the renal pelvis suggesting renal elimination. Imaging of the head with GC-DTPA-Gd allowed detailed anatomical identification of specific blood vessels in particular with the high MW agent. Sequential high-resolution isotropic imaging of established A431 xenograft flank tumours with DTPA-Gd and GC-DTPA-Gd demonstrated that the initial delivery of the contrast agents was well correlated with blood supply. Subsequent tissue transport was primarily by diffusion and was limited by molecular weight. The data also highlight the role of heterogeneity in CA distribution that was again more prominent for the high MW agent. Conclusion: GC-DTPA-Gd with identical physical chemical properties but precisely controlled MW allow isotropic high-resolution three-dimensional imaging of molecular weight dependent transport processes which could potentially lead to clinical biomarkers for molecular weight dependent drug transport and support selection of suitable tumour models for pre-clinical development

Effects of coherence on speaker preference and rule-following

Rule-following is affected by multiple variables. A relevant aspect of rules regards whether they “make sense”, that is, the extent to which the instruction coheres with previously reinforced patterns of relational responding. The present study aimed to evaluate the influence of relational coherence upon rule-following. After mastering a particular set of conditional relations (e.g., A1B1, A2B2), the participants were exposed to two speakers, one of which would “state” relations that cohered (e.g., A1B1, A2B2) with the participant’s previous relational training and the other that would present relations that were incoherent (e.g., A1B2, A2B1). Then, rule-following was measured in a preference test in which the participant would have to choose which of the two speakers would provide instructions in each test trial. Results show that the participants preferred the coherent speaker to provide instructions and followed the rules presented by that speaker throughout the test. Coherence is discussed as a critical aspect of rule following and preference for particular narratives

Relating relational networks: An initial experimental analysis

Studying relating of relational networks is a complex and challenging task. The main objective of the present study was to demonstrate relating within and across relational networks based on same/opposite and bigger/smaller contextual cues and establish antecedent control. After nonarbitrary pretraining of the contextual cues, two nonsense stimulus classes were established based on comparative relations. Participants were trained to select stimuli from an array of options based on a symbolic rule that established a relation between two stimuli: one of Network 1 and one of Network 2. Training involved relating Network 1 to Network 2, and testing assessed relating Network 2 to Network 1. Seven of eight participants reached the mastery criterion in training and responded accordingly in test. In a final stage, reinforcing and punishing consequences were varied systematically in the presence of two novel stimuli and antecedent control was observed for all 7 participants. Experiment 2 replicated the results of Experiment 1 but using contextual cues taken from natural language, and Experiment 3 sought to understand the effects of pretraining relational responding using natural language. The mastery criteria were reached by four of seven participants in Experiment 2 and by all eight participants in Experiment 3. Future studies could develop and refine the methods employed here in analyzing the relating of relational networks, thus allowing for an increasingly sophisticated behavior-analytic account of human language and cognition

Simulated Atmospheric No3− Deposition Increases Soil Organic Matter By Slowing Decomposition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117243/1/eap20081882016.pd

Grappling with the Complexity of Behavioral Processes in Human Psychological Suffering: Some Potential Insights from Relational Frame Theory

Relational frame theory (RFT) has historically been considered the basic explanatory science behind acceptance and commitment therapy (ACT). However, some have argued that there has been an increasing separation between the two in recent years. The primary aim of the current article is to explore the extent to which RFT concepts, particularly those that have been proposed recently in the context of “up-dating” the theory, may be used to build stronger links between basic and applied behavior analyses in which there is a shared language of relatively precise technical terms. As an example of this strategy, we outline RFT process-based experimental and conceptual analyses of the impact of one of the most widely used sets of interventions employed in the ACT literature, defusion. In addition, we suggest a potential experimental methodology for analyzing the basic behavioral processes involved. Overall, the current article should be seen as part of a broader research agenda that aims to explore how RFT may be used to provide a functional-analytic abstractive treatment of the behavioral processes involved in human psychological suffering

Generalized contextual control based on nonarbitrary and arbitrary transfer of stimulus functions

Two experiments with human adults investigated the extent to which the transfer of function in accordance with nonarbitrary versus arbitrary stimulus relations may be brought under contextual control. Experiment 1 comprised four phases. Phase 1 consisted of multiple-exemplar training to establish discriminative functions for solid, dashed, or dotted lines. Phase 2 trained and tested two equivalence classes, each containing a 3D picture, a solid, a dashed, and a dotted form. During Phase 3, a discriminative function was established for each 3D picture. Phase 4 presented the solid, dashed, and dotted stimuli in two different frames, black or gray. The black frame cued function transfer based on nonarbitrary stimulus relations (Frame Physical); the gray frame cued function transfer based on equivalence relations (Frame Arbitrary). Testing and training with the frames was continued until contextual control was established; subsequently contextual control was demonstrated with novel equivalence classes with stimuli composed of the same forms. Experiment 2 replicated and extended Experiment 1 by demonstrating that such contextual control generalized to novel equivalence classes comprising novel forms and responses. The potential implications of the findings for developing increasingly precise experimental analyses of clinically relevant phenomena are considered (e.g., defusion)

March 1965

Turf and Lawn Grass Association Better turf through research and Educatio

Immune loss as a driver of coexistence during host-phage coevolution

Bacteria and their viral pathogens face constant pressure for augmented immune and infective capabilities, respectively. Under this reciprocally imposed selective regime, we expect to see a runaway evolutionary arms race, ultimately leading to the extinction of one species. Despite this prediction, in many systems host and pathogen coexist with minimal coevolution even when wellmixed. Previous work explained this puzzling phenomenon by invoking fitness tradeoffs, which can diminish an arms race dynamic. Here we propose that the regular loss of immunity by the bacterial host can also produce host-phage coexistence. We pair a general model of immunity with an experimental and theoretical case study of the CRISPR-Cas immune system to contrast the behavior of tradeoff and loss mechanisms in well-mixed systems. We find that, while both mechanisms can produce stable coexistence, only immune loss does so robustly within realistic parameter ranges

THE RESISTANCE TO FIBRINOLYTIC ACTIVITY OF THE HEMO- LYTIC STREPTOCOCCUS WITH SPECIAL REFERENCE TO PATIENTS WITH RHEUMATIC FEVER AND RHEUMATOID (ATROPHIC) ARTHRITIS'

Recently Tillett and Garner (1) have demonstrated that broth cultures of hemolytic streptococci of human origin rapidly liquefy the fibrinclot of human plasma. Cultures of other species of bacteria obtained from human beings fail to exhibit this property. Tillett, Edwards and Garner (2) further found that the plasma clot from patients convalescent from acute hemolytic streptococcal infections was highly resistant to the action of broth cultures of a human hemolytic streptococcus. The observations of Tillett and his coworkers were confirmed by Hadfield, Magee and Perry (3). Previously, we (4, 5, 6) have studied groups of patients with rheumatic fever and rheumatoid arthritis to determine what, if any, relationship exists between streptococcal infection and these diseases. In continuing these studies, we have determined the resistance to fibrinolysis of the blood plasma of patients with rheumatic fever and rheumatoid arthritis and of control groups of patients. METHODS OF STUDY All patients were studied while in the hospital. The methods employed in the determination of the resistance to fibrinolysis of blood plasma followed closely the method described by Tillett and his coworkers (1, 2). At weekly intervals 5 cc. of blood were collected. Potassium oxalate, 0.01 gram per 5 cc. of blood, was employed as an anticoagulant. The plasma was separated by centrifugalization and was used within two hours after its withdrawal. A hour cultures of this organism were grown in veal muscle infusion broth, adjusted to a pH of 7.2 and containing one per cent of peptone and 0.2 per cent of Na2HPO4. To 0.2 cc. of fresh oxalated plasma was added 0.8 cc. of sterile physiological salt solution. To this 0.5 cc. of a fresh broth culture of the CO strain of the hemolytic streptococcus was added and well mixed. Then 0.25 cc. of a 0.25 per cent sterile solution of CaCl2 was added and well mixed. The tubes were placed immediately in a water bath at 37.5°C. With repeated observations the times of solid coagulation and, finally, complete dissolution of the clot were recorded. All tests in which the plasma clot was resistant to dissolution after 24 hours' incubation were arbitrarily terminated. The classification of the degree of resistance of the plasma clot as suggested by Tillett, Edwards and Garner (2) was followed. The highest degree of resistance shown by a patient's plasma during the period of observation was utilized in the classification shown in RESULTS Determinations of the resistance to fibrinolysis of 520 samples of plasma from 135 individuals were made. Their ages varied between thirteen and seventy years. No correlation could be established between the age of the individual and the ability to develop resistance to fibrinolysis. The plasmas from groups of individuals without evidence of hemolytic streptococcal infection were studied. Samples of plasma from fourteen apparently normal laboratory workers were followed at frequent intervals for several months. A group of twenty-two patients with pulmonary tuberculosis, lobar pneumonia, herpes zoster and lung abscess were studied on fifty-one occasions. 11