Revisiting Mead on Pragmatic "Fusion": From Emotion to Function

A recent biography and re-issue of George H. Mead's Mind, Self, and Society emphasize the emergent meanings of his work and of self's cognitive and affective dimensions in interaction. Erving Goffman likewise posits an interaction order based on individual and social identity. Mead's metaphor of fusion furthers recognition of an emotional merging of selves with each other and with emerging community. He initially characterizes this experience as "precious" and illustrates its presence in interactional domains such as teamwork, religion, and patriotism. Among other scholars, Charles Taylor uses fusion to interpret aspects of the contemporary secular age. Application to terrorist identities finds that emotional fusion motivates actions that threaten the moral imperative informing presentation of selves that grounds public order. From a pragmatic perspective, selves in pluralistic contexts must subordinate emotional fusion to functional fusion within an interaction order that fosters a larger self and more inclusive community to address common issues

Interfacing Catholic Social Meanings, Sociology, Self, and Pedagogical Practices

What connects Catholic Social Tradition with Sociology? How do each inform the other and how do they, together, flow through and animate the sociologist? Within a student-driven learning community pedagogy, this course builds on the humanistic aspects of Sociology as a scientific perspective a la Peter Berger’s Invitation to Sociology. This foundation is then filtered through a social psychological understanding of self with a sense of vocation through which persons’ deepest passions meets humans’ greatest needs. Biographical vignettes of sociologists’ careers of study that address issues of racial and gender inequalities and psycho-social shifts in values over the life course exemplify linkage of social science and social justice. These portrayals of scientist-activists’ dedication to describing and explaining inequalities are complimented by case studies of sociologically-informed community activists struggling to change unjust structures and empower disadvantaged communities through initiatives that embody efforts to “live the Catholic Social Tradition.” Themes of humanistic social science, self and vocation, committed social scientists, and empowering community organizers for a more just society are then woven into an overview of Catholic Social Tradition around issues of globalization, spirituality, and justice. Finally, the course moves toward the universal issues developed within the larger Catholic social tradition—namely, common good, universal solidarity, personal dignity, and institutional subsidiarity—in an attempt to include other religious traditions and motivate all persons committed to a more just and peaceful social order

Minimal Informationally Complete Measurements for Pure States

We consider measurements, described by a positive-operator-valued measure (POVM), whose outcome probabilities determine an arbitrary pure state of a D-dimensional quantum system. We call such a measurement a pure-state informationally complete (PSI-complete) POVM. We show that a measurement with 2D-1 outcomes cannot be PSI-complete, and then we construct a POVM with 2D outcomes that suffices, thus showing that a minimal PSI-complete POVM has 2D outcomes. We also consider PSI-complete POVMs that have only rank-one POVM elements and construct an example with 3D-2 outcomes, which is a generalization of the tetrahedral measurement for a qubit. The question of the minimal number of elements in a rank-one PSI-complete POVM is left open.Comment: 2 figures, submitted for the Asher Peres festschrif

Compared to Australian Cultivars, European Summer Wheat (Triticum aestivum) Overreacts When Moderate Heat Stress Is Applied at the Pollen Development Stage

Heat stress frequently imposes a strong negative impact on vegetative and reproductive development of plants leading to severe yield losses. Wheat, a major temperate crop, is more prone to suffer from increased temperatures than most other major crops. With heat waves becoming more intense and frequent, as a consequence of global warming, a decrease in wheat yield is highly expected. Here, we examined the impact of a short-term (48 h) heat stress on wheat imposed during reproduction at the pollen mitosis stage both, at the physiological and molecular level. We analyzed two sets of summer wheat germplasms from Australia (Kukri, Drysdale, Gladius, and RAC875) and Europe (Epos, Cornetto, Granny, and Chamsin). Heat stress strongly affected gas exchange parameters leading to reduced photosynthetic and transpiration rates in the European cultivars. These effects were less pronounced in Australian cultivars. Pollen viability was also reduced in all European cultivars. At the transcriptional level, the largest group of heat shock factor genes (type A HSFs), which trigger molecular responses as a result of environmental stimuli, showed small variations in gene expression levels in Australian wheat cultivars. In contrast, HSFs in European cultivars, including Epos and Granny, were strongly downregulated and partly even silenced, while the high-yielding variety Chamsin displayed a strong upregulation of type A HSFs. In conclusion, Australian cultivars are well adapted to moderate heat stress compared to European summer wheat. The latter strongly react after heat stress application by downregulating photosynthesis and transpiration rates as well as differentially regulating HSFs gene expression pattern

Next-Generation cDNA Screening for Oncogene and Resistance Phenotypes

There is a pressing need for methods to define the functional relevance of genetic alterations identified by next-generation sequencing of cancer specimens. We developed new approaches to efficiently construct full-length cDNA libraries from small amounts of total RNA, screen for transforming and resistance phenotypes, and deconvolute by next-generation sequencing. Using this platform, we screened a panel of cDNA libraries from primary specimens and cell lines in cytokine-dependent murine Ba/F3 cells. We demonstrate that cDNA library-based screening can efficiently identify DNA and RNA alterations that confer either cytokine-independent proliferation or resistance to targeted inhibitors, including RNA alterations and intergenic fusions. Using barcoded next-generation sequencing, we simultaneously deconvoluted cytokine-independent clones recovered after transduction of 21 cDNA libraries. This approach identified multiple gain-of-function alleles, including KRAS G12D, NRAS Q61K and an activating splice variant of ERBB2. This approach has broad applicability for identifying transcripts that confer proliferation, resistance and other phenotypes in vitro and potentially in vivo

Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes mellitus and is associated with considerable morbidity and high mortality. There is increasing evidence to suggest that dysregulation of the epigenome is involved in diabetic nephropathy. We assessed whether epigenetic modification of DNA methylation is associated with diabetic nephropathy in a case-control study of 192 Irish patients with type 1 diabetes mellitus (T1D). Cases had T1D and nephropathy whereas controls had T1D but no evidence of renal disease. METHODS: We performed DNA methylation profiling in bisulphite converted DNA from cases and controls using the recently developed Illumina Infinium(R) HumanMethylation27 BeadChip, that enables the direct investigation of 27,578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14,495 genes. RESULTS: Singular Value Decomposition (SVD) analysis indicated that significant components of DNA methylation variation correlated with patient age, time to onset of diabetic nephropathy, and sex. Adjusting for confounding factors using multivariate Cox-regression analyses, and with a false discovery rate (FDR) of 0.05, we observed 19 CpG sites that demonstrated correlations with time to development of diabetic nephropathy. Of note, this included one CpG site located 18 bp upstream of the transcription start site of UNC13B, a gene in which the first intronic SNP rs13293564 has recently been reported to be associated with diabetic nephropathy. CONCLUSION: This high throughput platform was able to successfully interrogate the methylation state of individual cytosines and identified 19 prospective CpG sites associated with risk of diabetic nephropathy. These differences in DNA methylation are worthy of further follow-up in replication studies using larger cohorts of diabetic patients with and without nephropathy

Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry

Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1) in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC) stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors), but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of patients for clinical trials

Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition

Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment of myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements of the cytokine receptor subunit cytokine receptor–like factor 2 (CRLF2), and other tumors with constitutive JAK2 signaling. In this study, we identify G935R, Y931C, and E864K mutations within the JAK2 kinase domain that confer resistance across a panel of JAK inhibitors, whether present in cis with JAK2 V617F (observed in MPNs) or JAK2 R683G (observed in B-ALL). G935R, Y931C, and E864K do not reduce the sensitivity of JAK2-dependent cells to inhibitors of heat shock protein 90 (HSP90), which promote the degradation of both wild-type and mutant JAK2. HSP90 inhibitors were 100–1,000-fold more potent against CRLF2-rearranged B-ALL cells, which correlated with JAK2 degradation and more extensive blockade of JAK2/STAT5, MAP kinase, and AKT signaling. In addition, the HSP90 inhibitor AUY922 prolonged survival of mice xenografted with primary human CRLF2-rearranged B-ALL further than an enzymatic JAK2 inhibitor. Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe