104 research outputs found
Exploring the Effects of Implementation Intentions and Goal Formation on Anxiety and Communication Effectiveness when Discussing Difficult Interpersonal Topics
This study addressed the effects of two specific types of planning (i.e., goal intention and implementation intention formation) on interpersonal discussions of difficult topics (e.g., discussing the future of a relationship, discussing past romantic partners, discussing the current status of a relationship). Goal intentions specify a certain end point (e.g., I intend to reach x ), and implementation intentions (Gollwitzer, 1999) specify when, where, and how a goal will be achieved (e.g., If x, then y ). In addition, four personality traits (i.e., need for cognition, cognitive flexibility, self-efficacy, and trait dyadic communication apprehension) were examined in order to further understand the role of these traits in impacting planning and state anxiety, self-perceived communication effectiveness, message length, and motivation. Using Berger\u27s (1995a, 1997) Planning Theory as a guiding framework, this post-test only equivalent groups experimental design evaluated differences in state anxiety, self-perceived communication effectiveness, message length, and motivation among three conditions: implementation intention formation (n = 60), goal intention formation (n = 64), and a control group (n = 58). In Time 1, participants reported on a range of difficult topics that they perceived to be both anxiety-provoking and important. After this, each group was given an experimental manipulation, in which participants were guided through the formation of an implementation intention or a goal. The control group was a no message control group. In Time 2, which took place two weeks later, participants were asked to audio-record a message in which they talked about the difficult topic they reported on in Time 1. Results revealed that planning did not impact state anxiety, self-perceived communication effectiveness, or motivation. Individuals in the goal formation group formed messages with fewer words than did individuals in the control group. Self-efficacy interacted with the goal formation condition to impact message length, such that individuals with high self-efficacy recorded shorter messages than those in the control group. Taken together, it appears that planning had minimal impact on state anxiety associated with the discussion of difficult topics in interpersonal relationships
Stay or leave? The effects of communicative infidelity on relationship outcomes
The purpose of this study was to examine the effects of communicative infidelity (CI) motives on relationship outcomes. CI motives include jealousy, vengefulness, sexual self-esteem, sexual depression, and sexual preoccupation, while outcomes included forgiveness, reparation, voice, exit, loyalty, and neglect responses. Additionally, this study tested the relationship of commitment and satisfaction to relational outcomes. Participants were 215 undergraduate students currently involved in a romantic relationship. Participants were instructed to answer questions measuring their commitment and satisfaction levels, as well as read and respond to a CI scenario. Results indicated that commitment is positively related to voice responses and negatively related to neglect responses, while satisfaction is negatively related to neglect responses. Results also revealed that commitment and satisfaction are negatively related to forgiveness by minimizing. Additionally, significant differences were found in the ways that men and women respond following the discovery of a partner\u27s transgression. Specifically, men reported reacting to the discovery of a partner\u27s CI with more exit and neglect responses and less voice responses than women. Finally, both sexes rated all CI motives as relatively unacceptable
Indoleamine 2,3-Dioxygenase and Its Therapeutic Inhibition in Cancer
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8 + T effector cells and natural killer cells and induces CD4 + T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers. IDO1 and TDO are upregulated widely in neoplastic cells but also variably in stromal, endothelial, and innate immune cells of the tumor microenviroment and in tumor-draining lymph nodes. Pharmacological and genetic proofs in preclinical models of cancer have validated IDO1 as a cancer therapeutic target. IDO1 inhibitors have limited activity on their own but greatly enhance âimmunogenicâ chemotherapy or immune checkpoint drugs. IDO/TDO function is rooted in inflammatory programming, thereby influencing tumor neovascularization, MDSC generation, and metastasis beyond effects on adaptive immune tolerance. Discovery and development of two small molecule enzyme inhibitors of IDO1 have advanced furthest to date in Phase II/III human trials (epacadostat and navoximod, respectively). Indoximod, a tryptophan mimetic compound with a different mechanism of action in the IDO pathway has also advanced in multiple Phase II trials. Second generation combined IDO/TDO inhibitors may broaden impact in cancer treatment, for example, in addressing IDO1 bypass (inherent resistance) or acquired resistance to IDO1 inhibitors. This review surveys knowledge about IDO1 function and how IDO1 inhibitors reprogram inflammation to heighten therapeutic responses in cancer
Indoleamine 2,3-Dioxygenase and Its Therapeutic Inhibition in Cancer
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8 + T effector cells and natural killer cells and induces CD4 + T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers. IDO1 and TDO are upregulated widely in neoplastic cells but also variably in stromal, endothelial, and innate immune cells of the tumor microenviroment and in tumor-draining lymph nodes. Pharmacological and genetic proofs in preclinical models of cancer have validated IDO1 as a cancer therapeutic target. IDO1 inhibitors have limited activity on their own but greatly enhance âimmunogenicâ chemotherapy or immune checkpoint drugs. IDO/TDO function is rooted in inflammatory programming, thereby influencing tumor neovascularization, MDSC generation, and metastasis beyond effects on adaptive immune tolerance. Discovery and development of two small molecule enzyme inhibitors of IDO1 have advanced furthest to date in Phase II/III human trials (epacadostat and navoximod, respectively). Indoximod, a tryptophan mimetic compound with a different mechanism of action in the IDO pathway has also advanced in multiple Phase II trials. Second generation combined IDO/TDO inhibitors may broaden impact in cancer treatment, for example, in addressing IDO1 bypass (inherent resistance) or acquired resistance to IDO1 inhibitors. This review surveys knowledge about IDO1 function and how IDO1 inhibitors reprogram inflammation to heighten therapeutic responses in cancer
Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase
Tryptophan (Trp) catabolizing enzymes play an important and complex role in the development of cancer. Significant evidence implicates them in a range of inflammatory and immunosuppressive activities. Whereas inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) have been reported and analyzed in the clinic, fewer inhibitors have been described for tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase-2 (IDO2) which also have been implicated more recently in cancer, inflammation and immune control. Consequently the development of dual or pan inhibitors of these Trp catabolizing enzymes may represent a therapeutically important area of research. This is the first report to describe the development of dual and pan inhibitors of IDO1, TDO and IDO2
The Lantern Vol. 67, No. 1, Fall 1999
⢠I Write Poetry ⢠So Many Poems Start This Way... ⢠Mantra 99 for A. Joe ⢠Indecision ⢠Last Night ⢠My Body Cut Off at the Back ⢠Brittany Sestina ⢠The Hearth ⢠To Jane ⢠Attention ⢠Chemistry ⢠Recombination ⢠Buried ⢠Going Home ⢠Bound for Happiness ⢠Stumble ⢠Punk Rock ⢠Ghost Spray and a Slingshot ⢠Distant Voices ⢠Beyond the Gear Shift ⢠Damn It ⢠Poppy Hands ⢠Waist Deep ⢠The Lie ⢠Paying Your Dueshttps://digitalcommons.ursinus.edu/lantern/1155/thumbnail.jp
A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma
<p>Abstract</p> <p>Background</p> <p>Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab.</p> <p>Methods</p> <p>In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365), 82 pretreated or treatment-naĂŻve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated.</p> <p>Results</p> <p>Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014) and indoleamine 2,3-dioxygenase (p = 0.012), and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs) between baseline and 3 weeks after start of treatment (p = 0.005). Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma.</p> <p>Conclusions</p> <p>Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with ipilimumab clinical activity. The observed pharmacodynamic changes in gene expression warrant further analysis to determine whether treatment-emergent changes in gene expression may be associated with clinical efficacy. Further studies are required to determine the predictive value of these and other potential biomarkers associated with clinical response to ipilimumab.</p
Multimaterial 4D Printing with Tailorable Shape Memory Polymers
We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PÎźSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures
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