The Search for Stable, Massive, Elementary Particles

In this paper we review the experimental and observational searches for stable, massive, elementary particles other than the electron and proton. The particles may be neutral, may have unit charge or may have fractional charge. They may interact through the strong, electromagnetic, weak or gravitational forces or through some unknown force. The purpose of this review is to provide a guide for future searches - what is known, what is not known, and what appear to be the most fruitful areas for new searches. A variety of experimental and observational methods such as accelerator experiments, cosmic ray studies, searches for exotic particles in bulk matter and searches using astrophysical observations is included in this review.Comment: 34 pages, 8 eps figure

Optimal experience and personal growth. Flow and the consolidation of place identity

This study examined the relationship between flow experience and place identity, based on eudaimonistic identity theory (EIT) which prioritizes self-defining activities as important for an individual's identification of his/her goals, values, beliefs, and interests corresponding to one's own identity development or enhancement. This study focuses on place identity, the identity's features relating to a person's relation with her/his place. The study is also based on flow theory, according to which some salient features of an activity experience are important for happiness and well-being. Questionnaire surveys on Italian and Greek residents focused on their perceived flow and place identity in relation to their own specific local place experiences. The overall findings revealed that flow experience occurring in one's own preferred place is widely reported as resulting from a range of self-defining activities, irrespective of gender or age, and it is positively and significantly associated with one's own place identity. Such findings provide the first quantitative evidence about the link between flow experienced during meaningfully located self-defining activities and identity experienced at the place level, similarly to the corresponding personal and social levels that had been previously already empirically tested. Results are also discussed in terms of their implications for EIT's understanding and enrichment, especially by its generalization from the traditional, personal identity level up to that of place identity. More generally, this study has implications for maintaining or enhancing one's own place identity, and therefore people place relations, by means of facilitating a person's flow experience within psychologically meaningful place

Cell-specific occupancy of an extended repertoire of CREM and CREB binding loci in male germ cells

Background: CREB and CREM are closely related factors that regulate transcription in response to various stress, metabolic and developmental signals. The CREMτ activator isoform is selectively expressed in haploid spermatids and plays an essential role in murine spermiogenesis.Results: We have used chromatin immunoprecipitation coupled to sequencing (ChIP-seq) to map CREM and CREB target loci in round spermatids from adult mouse testis and spermatogonia derived GC1-spg cells respectively. We identify more than 9000 genomic loci most of which are cell-specifically occupied. Despite the fact that round spermatids correspond to a highly specialised differentiated state, our results show that they have a remarkably accessible chromatin environment as CREM occupies more than 6700 target loci corresponding not only to the promoters of genes selectively expressed in spermiogenesis, but also of genes involved in functions specific to other cell types. The expression of only a small subset of these target genes are affected in the round spermatids of CREM knockout animals. We also identify a set of intergenic binding loci some of which are associated with H3K4 trimethylation and elongating RNA polymerase II suggesting the existence of novel CREB and CREM regulated transcripts.Conclusions: We demonstrate that CREM and CREB occupy a large number of promoters in highly cell specific manner. This is the first study of CREM target promoters directly in a physiologically relevant tissue in vivo and represents the most comprehensive experimental analysis of CREB/CREM regulatory potential to date

A POU3F2-MITF-SHC4 Axis in Phenotype Switching of Melanoma Cells

Non

Coordinate regulation of RARgamma2, TBP, and TAF(II)135 by targeted proteolysis during retinoic acid-induced differentiation of F9 embryonal carcinoma cells

BACKGROUND: Treatment of mouse F9 embryonal carcinoma cells with all-trans retinoic acid (T-RA) induces differentiation into primitive endodermal type cells. Differentiation requires the action of the receptors for all trans, and 9cis-retinoic acid (RAR and RXR, respectively) and is accompanied by growth inhibition, changes in cell morphology, increased apoptosis, proteolytic degradation of the RARγ2 receptor, and induction of target genes. RESULTS: We show that the RNA polymerase II transcription factor TFIID subunits TBP and TAF(II)135 are selectively depleted in extracts from differentiated F9 cells. In contrast, TBP and TAF(II)135 are readily detected in extracts from differentiated F9 cells treated with proteasome inhibitors showing that their disappearance is due to targeted proteolysis. This regulatory pathway is not limited to F9 cells as it is also seen when C2C12 myoblasts differentiate into myotubes. Targeting of TBP and TAF(II)135 for proteolysis in F9 cells takes place coordinately with that previously reported for the RARγ2 receptor and is delayed or does not take place in RAR mutant F9 cells where differentiation is known to be impaired or abolished. Moreover, ectopic expression of TAF(II)135 delays proteolysis of the RARγ2 receptor and impairs primitive endoderm differentiation at an early stage as evidenced by cell morphology, induction of marker genes and apoptotic response. In addition, enhanced TAF(II)135 expression induces a novel differentiation pathway characterised by the appearance of cells with an atypical elongated morphology which are cAMP resistant. CONCLUSIONS: These observations indicate that appropriately timed proteolysis of TBP and TAF(II)135 is required for normal F9 cell differentiation. Hence, in addition to transactivators, targeted proteolysis of basal transcription factors also plays an important role in gene regulation in response to physiological stimuli

On the abundance of non-cometary HCN on Jupiter

Using one-dimensional thermochemical/photochemical kinetics and transport models, we examine the chemistry of nitrogen-bearing species in the Jovian troposphere in an attempt to explain the low observational upper limit for HCN. We track the dominant mechanisms for interconversion of N2-NH3 and HCN-NH3 in the deep, hightemperature troposphere and predict the rate-limiting step for the quenching of HCN at cooler tropospheric altitudes. Consistent with other investigations that were based solely on time-scale arguments, our models suggest that transport-induced quenching of thermochemically derived HCN leads to very small predicted mole fractions of hydrogen cyanide in Jupiter's upper troposphere. By the same token, photochemical production of HCN is ineffective in Jupiter's troposphere: CH4-NH3 coupling is inhibited by the physical separation of the CH4 photolysis region in the upper stratosphere from the NH3 photolysis and condensation region in the troposphere, and C2H2-NH3 coupling is inhibited by the low tropospheric abundance of C2H2. The upper limits from infrared and submillimeter observations can be used to place constraints on the production of HCN and other species from lightning and thundershock sources.Comment: 56 pages, 0 tables, 6 figures. Submitted to Faraday Discussions [in press

Problematic practice in integrated impact assessment: the role of consultants and predictive computer models in burying uncertainty

It is well known in impact assessment that predictive model outputs will be as credible as their inputs and that model assumptions will drive outputs. What is less well known is how the practice of integrated impact assessment with its pervasive use of predictive computer models and multiple teams of consultants can influence evidence relied upon in deliberations over the impacts and benefits of major projects. This paper draws on an integrated impact assessment of a major energy infrastructure project in Australia known as Basslink to examine the epistemic implications of current practice. It will be argued that what has become standard procedure can serve to diminish the disclosure of prediction uncertainty

TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation

Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-β gene (Ifnb1) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results in high, sustained expression of Ifnb1 at late stages of toll-like receptor-mediated activation in macrophages but not in fibroblasts. In macrophages, TRIM33 is recruited by PU.1 to a conserved region, the Ifnb1 Control Element (ICE), located 15 kb upstream of the Ifnb1 transcription start site. ICE constitutively interacts with Ifnb1 through a TRIM33-independent chromatin loop. At late phases of lipopolysaccharide activation of macrophages, TRIM33 is bound to ICE, regulates Ifnb1 enhanceosome loading, controls Ifnb1 chromatin structure and represses Ifnb1 gene transcription by preventing recruitment of CBP/p300. These results characterize a previously unknown mechanism of macrophage-specific regulation of Ifnb1 transcription whereby TRIM33 is critical for Ifnb1 gene transcription shutdown

Aristotle's Peculiarly Human Psychology

For Aristotle, human cognition has a lot in common both with non-human animal cognition and with divine cognition. With non-human animals, humans share a non-rational part of the soul and non-rational cognitive faculties (DA 427b6–14, NE 1102b29 and EE 1219b24–6). With gods, humans share a rational part of the soul and rational cognitive faculties (NE 1177b17– 1178a8). The rational part and the non-rational part of the soul, however, coexist and cooperate only in human souls (NE 1102b26–9, EE 1219b28–31). In this chapter, I show that a study of this cooperation helps to uncover some distinctive aspects of human cognition and desire