Synthesis and Oligonucleotide Incorporation of Fluorescent Cytosine Analogue tC: a Promising Nucleic Acid Probe

The tricyclic cytosine, tC, is a fluorescent base analogue with excellent properties for investigating intrinsic characteristics of nucleic acid as well as interactions between nucleic acids and other molecules. Its unique fluorescence properties and insignificant influence on overall structure and dynamics of nucleic acid after incorporation makes tC particularly interesting in fluorescence resonance energy transfer and anisotropy measurements. We here describe a straightforward synthesis of the standard monomer form of tC for DNA solid-phase synthesis, the tC phosphoramidite, and its subsequent incorporation into oligonucleotides. The total synthesis of the tC phosphoramidite takes approximately 8 days and its incorporation and the subsequent oligonucleotide purification an additional day

Developing Business Acumen in Chinese Business School Graduates

This study assessed the importance of knowledge, skills, abilities (i.e., KSAs) and competencies for managerial success in China’s market economy. Business students at a major Chinese university were surveyed over a five year period, initially in 2001 and later in 2006, five years after China’s entry into the World Trade Organization (WTO). Using Partial Least Squares (PLS), the explained variances in business acumen and social motivation skills were higher after China’s WTO entry. The results were reversed for communication skills. The results confirmed the predictive relevance of entrepreneurial behavior and adaptability in the model. Overall, the results suggest an enhanced appreciation for these KSAs after China’s WTO entry

Pricing in Retail Gasoline Markets

Although fuel costs represent over half of the per mile cost of driving an automobile, vehicle miles traveled are relatively inelastic with respect to changes in gasoline prices. Thus, when there are large increases in gasoline prices as there have been on occasion over the past few years, there have been concerns raised regarding the possibility of anti-competitive behavior on the part of gasoline retailers. The purpose of this paper is to examine price-cost margins for retail gasoline stations in local markets and to determine whether movements in these margins indicate the presence of such behavior. This study uses a unique proprietary data set from an extensive pricing survey that was collected twice weekly for 25 local markets in Oregon. Using a VAR specification, evidence of tacit collusion is tested for and found as indicated by downward price stickiness. Price leadership is observed in several markets, but this behavior is not found to have a significant impact on price-cost margins when compared with markets in which price leadership is not observed. This result supports the hypothesis that price leadership serves to signal price changes in the face of volatile costs in very competitive retail gasoline markets. Other factors, such as whether the firm was a known low-price firm, located in an isolated area, whether the firm was selling unbranded or branded gasoline, and whether the firm was located on an interstate exit, are found to be important and significant determinants of price-cost margins for retail gasoline stations

Conversation analysis of the two-chair self-soothing task in emotion-focused therapy

Despite an increasing recognition of the relevance and significance of self-compassion processes, little research has explored interventions that seek to enhance these in therapy. In this study, we used conversation analysis to examine the compassionate self-soothing task of emotion-focused therapy involving two-chair work, with seven clients. The analysis yielded a detailed description of interactional practices and processes involved in the accomplishment of self-soothing, drawing on Goffman’s concept of the participation frame. In this article we show how therapists and clients collaborate to move from the ordinary frame of therapeutic conversation to a self-soothing frame and back again. Furthermore, we show that in this movement between the frames, they make use of a number interactional practices: therapists' instructions to clients, specific ways of sequencing actions in interaction, explanations and justification of the importance of the self-soothing task, pronouns as a way to distinguish among addressees (e.g., clients versus soothing agents), corrections of clients’ talk, and response tokens (hm mm, yeah, good). These practices are used to help clients accomplish self-soothing in the form of self-praise, disclosing caring, and offering of helpful advice

Characterization of a K+-induced conformational switch in a human telomeric DNA oligonucleotide using 2-aminopurine fluorescence

Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucletotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a ‘basket’ topology of four antiparallel strands; in contrast, Tel22 in K(+) solutions consists of a mixture of unknown topologies. Our previous studies on the mechanism of folding of Tel22 and similar telomere analogs utilized changes in UV absorption between 270 and 325 nm that report primarily on G-quartet formation and stacking showed that quadruplex formation occurs within milliseconds upon mixing with an appropriate cation. In the current study, we assessed the dynamics and equilibria of folding of specific loops by using Tel22 derivatives in which the dA residues were serially substituted with the fluorescent reporter base, 2-aminopurine (2-AP). Tel22 folding induced by Na(+) or K(+) assessed by changes in 2-AP fluorescence consists of at least three kinetic steps with time constants spanning a range of ms to several hundred seconds. Na(+)-dependent equilibrium titrations of Tel22 folding could be approximated as a cooperative two-state process. In contrast, K(+)-dependent folding curves were biphasic, revealing that different conformational ensembles are present in 1 mM and 30 mM K(+). This conclusion was confirmed by (1)H NMR. Molecular dynamics simulations revealed a K(+) binding pocket in Tel22 located near dA1 that is specific for the so-called hybrid-1 conformation in which strand 1 is in a parallel arrangement. The possible presence of this topologically specific binding site suggests that K(+) may play an allosteric role in regulating telomere conformation and function by modulating quadruplex tertiary structure

Depression, Rational Identity and the Educational Imperative: Concordance-Finding in Tricky Diagnostic Moments

It is well-documented, within most medical and much health psychology, that many individuals find diagnoses of depression confusing or even objectionable. Within a corpus of research and practical clinical guidance dominated by the social-cognitive paradigm, the explanation for resistance to a depression diagnosis (or advice pertaining to it) within specific interactions is bordering on the canonical; patients misunderstand depression itself, often as an output of an associated social stigma that distorts public knowledge. The best way to overcome corollary resistance in situ is, logically thus, taken to be a clarification of the true (clinical) nature of depression. In this paper, exploring the diagnosis of depression in UK primary care contexts, the social-cognitive position embedded in contemporary medical reasoning around this matter is critically addressed. It is firstly highlighted how, even in a great deal of extant public health research, the link between an individual holding “correct” medical knowledge and being actively compliant with it is far from inevitable. Secondly, and with respect to concerns around direct communication in clinical contexts, a body of research emergent of Discursive Psychology and Conversation Analysis is explored so as to shed light on how non-cognitive concerns (not least those around the local interactional management of a patient’s social identity) that can inform the manner in which ostensibly “tricky” medical talk plays-out in practice, especially in cases where a mental illness is at stake. Finally, observations are drawn together in a formal Discursive Psychological analysis of a small but highly illustrative sample of three cases where a depression diagnosis is initially questioned or disputed by a patient in primary care but, following further in-consultation activity, concordance with the diagnosis is ultimately reached—a specific issue hitherto unaddressed in either DP or CA fields. These cases specifically reveal the coordinative attention of interlocutors to immediate concerns regarding how the patient might maintain a sense of being an everyday and rational witness to their own lives; indeed, the very act of challenging the diagnosis emerges as a means by which a patient can open up conversational space within the consultation to address such issues. While the veracity of the social-cognitive model is not deemed to be without foundation herein, it is concluded that attention to local interactional concerns might firstly be accorded, such that the practical social concerns and skills of practitioners and patients alike might not be overlooked in the endeavour to produce generally applicable theories

Creating and maintaining play connection in a toddler peer group

This study explores how one and two year old peers (henceforth toddlers) participate in joint play activities in a natural group-care setting. We focus on joint play activity between three toddler peers during one full day-care day in a Finnish toddler classroom. Questions guiding the analysis concern the sequential understanding of how play emerges within peer interaction and how toddler peers are able to build sustained co-participation in their joint play during the day. The analysis showed that joint play was fragmented and organized in short segments of dyadic or triadic interaction. Re-establishments of joint play and accumulation of significant play signals during the day were important practices for toddlers to constitute social organization and sustained co-participation in their multi-party peer play. The results strengthen our understanding of very young children as both more and less competent play companions in their peer groups and guide adults’ practice in relation to peer play in toddler classrooms.Peer reviewe

Lakeside Cemeteries in the Sahara: 5000 Years of Holocene Population and Environmental Change

Background: Approximately two hundred human burials were discovered on the edge of a paleolake in Niger that providea uniquely preserved record of human occupation in the Sahara during the Holocene (,8000 B.C.E. to the present). CalledGobero, this suite of closely spaced sites chronicles the rapid pace of biosocial change in the southern Sahara in response tosevere climatic fluctuation.Methodology/Principal Findings: Two main occupational phases are identified that correspond with humid intervals in theearly and mid-Holocene, based on 78 direct AMS radiocarbon dates on human remains, fauna and artifacts, as well as 9 OSLdates on paleodune sand. The older occupants have craniofacial dimensions that demonstrate similarities with mid-Holocene occupants of the southern Sahara and Late Pleistocene to early Holocene inhabitants of the Maghreb. Theirhyperflexed burials compose the earliest cemetery in the Sahara dating to ,7500 B.C.E. These early occupants abandon thearea under arid conditions and, when humid conditions return ,4600 B.C.E., are replaced by a more gracile people withelaborated grave goods including animal bone and ivory ornaments.Conclusions/Significance: The principal significance of Gobero lies in its extraordinary human, faunal, and archaeologicalrecord, from which we conclude the following:(1) The early Holocene occupants at Gobero (7700–6200 B.C.E.) were largely sedentary hunter-fisher-gatherers withlakeside funerary sites that include the earliest recorded cemetery in the Sahara.(2) Principal components analysis of craniometric variables closely allies the early Holocene occupants at Gobero with askeletally robust, trans-Saharan assemblage of Late Pleistocene to mid-Holocene human populations from the Maghreband southern Sahara.(3) Gobero was abandoned during a period of severe aridification possibly as long as one millennium (6200–5200 B.C.E).(4) More gracile humans arrived in the mid-Holocene (5200–2500 B.C.E.) employing a diversified subsistence economybased on clams, fish, and savanna vertebrates as well as some cattle husbandry.(5) Population replacement after a harsh arid hiatus is the most likely explanation for the occupational sequence at Gobero.(6) We are just beginnin