Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from freeDNAwere present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase.

Negative change and job outcomes : the impact of subjective fit in public sector health care organization

There is an ongoing level of organizational-wide change (such as empowerment and downsizing) occurring within the Australian health care sector. However, there is a paucity of empirical evidence on how public and nonprofit sector nurses cope with these organizational-wide change initiatives and their consequences on individual and work outcomes. This will be the primary aim of the current paper. To this end, a path model is developed base on an integration of existing theoretical perspectives on occupational stress, change management, and person-organizational fit. Data were collected from 252 public and not-for-profit sector nurses. The path analysis suggests that public and nonprofit nurses experience positive and negative change initiatives. Negative change initiatives resulted in an increase in the level of administrative-related stressors. Nurses with more congruent values report less experience with administrative stressors. As nurses experienced more administrative stressors, they tend to report more job dissatisfaction. Nurses whose values were more congruent during organizational change reported higher level of psychological wellbeing. Nurses who were had higher level of psychological wellbeing were found to have higher job satisfaction, which subsequently led to a higher level of organizational commitment.

Variation in risk seeking behavior in a natural experiment following a large negative wealth shock induced by a natural disaster

An ongoing challenge in behavioral economics is to understand the variations observed in risk attitudes as a function of their environmental context. Of particular interest is the effect of wealth on risk attitudes. The research in this area has however faced two constraints: the difficulty to study the causal effects of large changes in wealth, and the causal effects of losses on risk behavior. The present paper address this double limitation by providing evidence of the variation of risk attitude after large losses using a natural disaster (Brisbane floods) as the setting for a natural experiment.

Grameen Bank's social performance disclosure : responding to a negative assessment by Wall Street Journal in late 2001

Purpose – The aim of this paper is to establish a linkage between negative global media news towards Grameen Bank (GB), the largest microfinance organisation in the developing world, and the extent and type of annual report social performance disclosures by GB, over the nine-year period 1997-2005. Design/methodology/approach – Content analysis instruments are utilised to analyse GB annual report social disclosure. Findings – The study finds that GB's community poverty alleviation disclosures account for the highest proportion of total social disclosures in the period 1997-2005. The results of this study are particularly significant in relation to poverty alleviation – the issue attracting severe criticism from the Wall Street Journal (WSJ?) late in 2001. The community poverty alleviation disclosures by GB are significantly greater over the four years following the negative news in the WSJ than in the four years before. The results suggest that GB responds to a negative media story or legitimacy threatening news via annual report social disclosures in an attempt to re-establish its legitimacy. Originality/value – This paper contributes to the literature because in the past there has been no research published linking global media attention to the social disclosure practices of major organisations in developing countries

Effects of family environment on negative symptoms and quality of life of psychotic patients

This study tested the hypothesis that negative symptoms and quality of life for patients with functional psychoses are associated with family environment. Fifty-seven first-admission patients with functional psychoses were assessed at hospital admission for severity of psychopathology and premorbid adjustment. Relatives residing with patients rated the family environment at admission and one month after discharge on the Family Environment Scale. Patients made the same ratings after discharge. Six months later, patients were reassessed on severity of psychopathology, negative symptoms, and quality of life. Multiple regression analyses showed that higher levels of positive emotional expressiveness in the family predicted milder and fewer negative symptoms and better quality of life at follow-up. The prediction was statistically independent of the initial severity of psychopathology or premorbid adjustment

Determining process model precision and generalization with weighted artificial negative events

Process mining encompasses the research area which is concerned with knowledge discovery from event logs. One common process mining task focuses on conformance checking, comparing discovered or designed process models with actual real-life behavior as captured in event logs in order to assess the “goodness” of the process model. This paper introduces a novel conformance checking method to measure how well a process model performs in terms of precision and generalization with respect to the actual executions of a process as recorded in an event log. Our approach differs from related work in the sense that we apply the concept of so-called weighted artificial negative events towards conformance checking, leading to more robust results, especially when dealing with less complete event logs that only contain a subset of all possible process execution behavior. In addition, our technique offers a novel way to estimate a process model’s ability to generalize. Existing literature has focused mainly on the fitness (recall) and precision (appropriateness) of process models, whereas generalization has been much more difficult to estimate. The described algorithms are implemented in a number of ProM plugins, and a Petri net conformance checking tool was developed to inspect process model conformance in a visual manner.

A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura

Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.

Inpatients had mostly negative experiences of seclusion during short term treatment in a mental health facility

Design Semi-structured interviews. Setting 2 open, acute care units of a large tertiary mental health facility in Queensland, Australia. Patients 12 patients (58% men) who were 18–52 years of age and were secluded in the previous 7 days (mean duration 3.4 h). Methods Semi-structured, thematically organised interviews were audiotaped and transcribed. Transcripts were checked for errors against the audiotaped versions and were analysed using the process of meaning categorisation. Themes were identified and coded to produce categories. All members of the research team agreed on the final categorisations. These broad categories were further analysed, and themes were used to reflect patients' experiences of seclusion. Main findings 5 recurrent themes emerged. (1) Patients described the use of seclusion. Some patients thought that seclusion was used inappropriately and that the seclusion period was of more benefit to …

International assessments of science learning : their positive and negative contributions to science education

The establishment and continuity of two international comparative assessments of science learning—the IEA’s TIMSS project and the OECD’s PISA project—have meant that there are now high-status reference points for other national and more local approaches to assessing the efficacy of science teaching and learning. Both projects, albeit with very different senses of what the outcome of science learning should be, have contributed positively and negatively to the current state of assessment of school science. The TIMSS project looks back at the science that is commonly included in the curricula of the participating countries. It is thus not about established school science nor about innovations in it. PISA is highly innovative looking, prospectively forward to see how students can use their science learning in everyday life situations. In this chapter some of these positives and negatives are discussed.

A coordinated voltage control approach for coordination of OLTC, voltage regulator and DG to regulate voltage in a distribution feeder

Integration of small-scale electricity generators, known as Distributed Generation (DG), into the distribution networks has become increasingly popular at the present. This tendency together with the falling price of synchronous-type generator has potential to give the DG a better chance in participating in the voltage regulation process together with other devices already available in the system. The voltage control issue turns out to be a very challenging problem for the distribution engineers since existing control coordination schemes would need to be reconsidered to take into account the DG operation. In this paper, we propose a control coordination technique, which is able to utilize the ability of the DG as a voltage regulator, and at the same time minimizes interaction with other active devices, such as On-load Tap Changing Transformer (OLTC) and voltage regulator. The technique has been developed based on the concept of control zone, Line Drop Compensation (LDC), as well as the choice of controller's parameters. Simulations carried out on an Australian system show that the technique is suitable and flexible for any system with multiple regulating devices including DG.

Heat of formation of the hydroperoxyl radical HOO via negative ion studies

We present a determination of Delta(f)H(298)(HOO) based upon a negative. ion thermodynamic cycle. The photoelectron spectra of HOO- and DOO- were used to measure the molecular electron affinities (EAs). In a separate experiment, a tandem flowing afterglow-selected ion flow tube (FA-SIFT) was used to measure the forward and reverse rate constants for HOO- + HCdropCH reversible arrow HOOH + HCdropC(-) at 298 K, which gave a value for Delta(acid)H(298)(HOO-H). The experiments yield the following values: EA(HOO) = 1.078 +/- 0.006 eV; T-0((X) over tilde HOO - (A) over tilde HOO) = 0.872 +/- 0.007 eV; EA(DOO) = 1.077 +/- 0.005 eV; T-0((X) over tilde DOO - (A) over tilde DOO) = 0.874 +/- 0.007 eV; Delta(acid)G(298)(HOO-H) = 369.5 +/- 0.4 kcal mol(-1); and Delta(acid)H(298)(HOO-H) = 376.5 +/- 0.4 kcal mol(-1). The acidity/EA thermochemical cycle yields values for the bond enthalpies of DH298(HOO-H) = 87.8 +/- 0.5 kcal mol(-1) and Do(HOO-H) = 86.6 +/- 0.5 kcal mol(-1). We recommend the following values for the heats of formation of the hydroperoxyl radical: Delta(f)H(298)(HOO) = 3.2 +/- 0.5 kcal mol(-1) and Delta(f)H(0)(HOO) = 3.9 +/- 0.5 kcal mol(-1); we recommend that these values supersede those listed in the current NIST-JANAF thermochemical tables.

Negative affectivity and responses to work stressors : an experimental study

An experiment tested the hypothesis that individuals high in negative affectivity (NA) show increased stress reactivity to stressors. There were three predictor variables: NA (measured 1 week prior to experimental participation), and two manipulated variables—demand (high/low) and behavioral control (high/low). First-year psychology students (n=256) were randomly allocated to one of the four experimental conditions. Measures obtained were initial and post-task negative mood, coping strategies, task satisfaction, and performance (subjective and objective). Participants with high levels of NA reported more post-task negative mood in response to high demand conditions, compared to participants with low NA. A similar pattern of results emerged for task satisfaction, particularly in response to high demand-low behavioral control situations. Mediation analyses suggested this was because participants with high NA used more emotion-focused coping strategies. The study provides support for the stress reactivity role of NA in the stressor-strain process.