Relationships between motion on isentropic surfaces from 3-H rawinsonde data and radar echoes

Vertical motion in insentropic surfaces obtained at 3-h intervals conducted on 11 and 12 May, 1974 is related to convection indicated by radar echoes. Temporal and spatial changes in vertical motion are shown and demonstrated to be associated with areas of convection. Large vertical motion was calculated, and it is shown that vertical motion changes as much as 20 cm s (-1) in a horizontal distance of 300 km. The rate of change of vertical motion is demonstrated to be as large a 8 cm s (-1)h(-1) from data taken at 3-h intervals, while data taken at 12-h intervals the same day displayed a maximum rate of change of 2 cm s(-1)n(-1). Radar observations confirmed that the intensity of convection varies as a result of the atmospheric variability as detected by 3-h data but is invisible in data taken at 12-h intervals

The Behaviour of Crude Oil Spilled on Snow

Field and laboratory studies of the behavior of isothermal and hot oil spills on snow are described. Alberta crude oil spilled at 0° C is readily absorbed by snow and contaminates an area of about 0.01 square metres per litre. A hot oil spill melts a channel in the snow and flows along the ground under the snow contaminating an area of about 0.024 square metres per litre. There may be considerable spreading of the oil during thaw. The flow regimes by which oil permeates into snow and the clean-up implications are discussed

TAILS N-terminomic and proteomic datasets of healthy human dental pulp

AbstractThe Data described here provide the in depth proteomic assessment of the human dental pulp proteome and N-terminome (Eckhard et al., 2015) [1]. A total of 9 human dental pulps were processed and analyzed by the positional proteomics technique TAILS (Terminal Amine Isotopic Labeling of Substrates) N-terminomics. 38 liquid chromatography tandem mass spectrometry (LC-MS/MS) datasets were collected and analyzed using four database search engines in combination with statistical downstream evaluation, to yield the by far largest proteomic and N-terminomic dataset of any dental tissue to date. The raw mass spectrometry data and the corresponding metadata have been deposited in ProteomeXchange with the PXD identifier <http://www.ebi.ac.uk/pride/archive/projects/PXD002264>; Supplementary Tables described in this article are available via Mendeley Data (10.17632/555j3kk4sw.1)

Towards third generation matrix metalloproteinase inhibitors for cancer therapy

The failure of matrix metalloproteinase (MMP) inhibitor drug clinical trials in cancer was partly due to the inadvertent inhibition of MMP antitargets that counterbalanced the benefits of MMP target inhibition. We explore how MMP inhibitor drugs might be developed to achieve potent selectivity for validated MMP targets yet therapeutically spare MMP antitargets that are critical in host protection

Effectiveness of structured patient-clinician communication with a solution focused approach (DIALOG+) in community treatment of patients with psychosis - a cluster randomised controlled trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations

LPS Responsiveness and Neutrophil Chemotaxis In Vivo Require PMN MMP-8 Activity

We identify matrix metalloproteinase (MMP)-8, the polymorphonuclear (PMN) leukocyte collagenase, as a critical mediator initiating lipopolysaccharide (LPS)-responsiveness in vivo. PMN infiltration towards LPS is abrogated in Mmp8-null mice. MMP-8 cleaves LPS-induced CXC chemokine (LIX) at Ser(4)∼Val(5) and Lys(79)∼Arg(80). LIX bioactivity is increased upon N-terminal cleavage, enhancing intracellular calcium mobilization and chemotaxis upon binding its cognate receptor, CXCR2. As there is no difference in PMN chemotaxis in Mmp8-null mice compared with wild-type mice towards synthetic analogues of MMP-8-cleaved LIX, MMP-8 is not essential for extravasation or cell migration in collagenous matrices in vivo. However, with biochemical redundancy between MMPs 1, 2, 9, and 13, which also cleave LIX at position 4∼5, it was surprising to observe such a markedly reduced PMN infiltration towards LPS and LIX in Mmp8-/- mice. This lack of physiological redundancy in vivo identifies MMP-8 as a key mediator in the regulation of innate immunity. Comparable results were found with CXCL8/IL-8 and CXCL5/ENA-78, the human orthologues of LIX. MMP-8 cleaves CXCL8 at Arg(5)-Ser(6) and at Val(7)-Leu(8) in CXCL5 to activate respective chemokines. Hence, rather than collagen, these PMN chemoattractants are important MMP-8 substrates in vivo; PMN-derived MMP-8 cleaves and activates LIX to execute an in cis PMN-controlled feed-forward mechanism to orchestrate the initial inflammatory response and promote LPS responsiveness in tissue

A survey of owners' perceptions of fear of fireworks in a sample of dogs and cats in New Zealand

AIMS: To establish reliable information regarding the behavioural responses of dogs and cats to fireworks in New Zealand; record interventions used by owners, and their perceived efficacies; and establish the prevalence of firework-related injury, and quantify owners' attitudes towards fireworks. METHODS: A questionnaire targeting dog and cat owners was distributed via the Auckland Society for the Prevention of Cruelty to Animals (SPCA) Animals Voice magazine and 25 veterinary clinics. The questionnaire covered demographics of animals, fear of fireworks, severity of the fear, and behaviours exhibited. Also included were treatments tried, source and perceived efficacy, prevalence of injury, and owners' attitudes towards the sale of fireworks for private use. RESULTS: From a total of 8,966 questionnaires distributed, 1,007 valid questionnaires were returned, representing 3,527 animals. Of these 1,635 (46%) animals displayed a level of fear of fireworks recognisable to their owners. Owners of dogs identified a significantly higher fear response than owners of cats but the duration of these fear responses did not differ between species. Fear of fireworks frequently resulted in dogs exhibiting active fear behaviours, whereas cats were more likely to exhibit hiding and cowering behaviours. A significantly increased severity and duration of fear response over time in dogs and cats was associated with owners who comforted them when they displayed a fearful response. Only 141/890 (15.8%) of owners sought professional treatment from a veterinarian, animal behaviourist or animal trainer for their animals, with variable efficacy. Six percent (51/923) of animals had received physical injuries from fireworks. The majority (837/1,007; 83%) of respondents, regardless of whether they owned a fearful animal or not, supported a ban on the sale of fireworks for private use. CONCLUSIONS: The results provide valuable information that is, as yet, unsubstantiated in New Zealand, although potential biases exist due to the non-random selection of respondents. Differences between dogs and cats were likely due to differing responses to fear-provoking stimuli between the species. Owner-reported increase in fearful response over time for comforted animals may indicate a negative impact on the longer-term psychological welfare of their animal. CLINICAL RELEVANCE: The greater the awareness of effective treatment plans for animals that suffer from a fear of fireworks, the greater the possibility that this fear can be reduced. Wider dissemination of effective owner behaviour and treatment programmes for firework fears is needed to improve levels of professional treatment for dogs and cats

De novo DNA methylation controls neuronal maturation during adult hippocampal neurogenesis

Adult neurogenesis enables the life-long addition of functional neurons to the hippocampus and is regulated by both cell-intrinsic molecular programs and behavioral activity. De novo DNA methylation is crucial for embryonic brain development, but its role during adult hippocampal neurogenesis has remained unknown. Here, we show that de novo DNA methylation is critical for maturation and functional integration of adult-born neurons in the mouse hippocampus. Bisulfite sequencing revealed that de novo DNA methyltransferases target neuronal enhancers and gene bodies during adult hippocampal neural stem cell differentiation, to establish neuronal methylomes and facilitate transcriptional up-regulation of neuronal genes. Inducible deletion of both de novo DNA methyltransferases Dnmt3a and Dnmt3b in adult neural stem cells did not affect proliferation or fate specification, but specifically impaired dendritic outgrowth and synaptogenesis of newborn neurons, thereby hampering their functional maturation. Consequently, abolishing de novo DNA methylation modulated activation patterns in the hippocampal circuitry and caused specific deficits in hippocampus-dependent learning and memory. Our results demonstrate that proper establishment of neuronal methylomes during adult neurogenesis is fundamental for hippocampal function