I went to John Darley\u27s funeral today

went to John\u27s funeral today few people there little to say guess janitors aren\u27t really people least not important anyway..

Isobutene formation from 3-hydroxy-3-methylbutyrate (3-HMB) by the Saccharomyces cerevisiae diphosphomevalonate decarboxylase (ScMDD) and directed enzyme evolution to improve enzyme function

Dependence on petroleum for energy and petrochemical products has led to high energy costs, a polluted environment, the depletion of a finite resource (oil), and the reliance on hostile nations for our energy security. Biofuels promise to alleviate some or all of these issues but remain costly and inefficient to produce, and difficult to integrate into our existing transportation infrastructure. A renewable fuel molecule capable of replacing petroleum for our fuel and chemical industries is desired. Isobutene is an important commercial chemical used for the synthesis of butyl rubber, terephthalic acid, specialty chemicals, and a gasoline performance additive known as alkylate. Currently, isobutene is produced from petroleum and hence is nonrenewable. Here we report that the Saccharomyces cerevisiae mevalonate diphosphate decarboxylase (ScMDD) can convert 3-hydroxy-3-methylbutyrate (3-HMB) to isobutene. Whole cells of Escherichia coli producing ScMDD formed isobutene from 3-HMB at a rate of 154 pmol h-1 g cells-1. His6-ScMDD was purified by nickel affinity chromatography and shown to produce isobutene from 3-HMB at a rate of 1.33 pmol min-1 mg-1 protein. In contrast, no isobutene was detected from control cells lacking ScMDD, and controls showed that both His6-ScMDD and 3-HMB were required for detectable isobutene formation in enzyme assays. ScMDD was subjected to error-prone PCR and 2 improved variants were characterized, ScMDD1 (I145F) and ScMDD2 (R74H). Whole cells of E. coli producing ScMDD1 and ScMDD2 produced isobutene from 3-HMB at rates of 3000 and 5888 pmol h-1 g cells-1 which are 19- and 38-fold increases compared to cells producing His6-ScMDD. Although ScMDD was shown to be amenable to manipulation in order to increase its activity on 3-HMB, we estimate that a 106 fold increase in activity is needed for commercial application. Two novel methods were designed to increase enzyme activity--a mevalonate selection and an isobutene biosensor. The mevalonate selection yielded one variant with a 3.9-fold increase in isopentenol production from mevalonate over wild-type, to 186.6 nmol min-1 g cells-1, as well as a 51.6% increase in isobutene-formation. The isobutene biosensor was built and confirmed to respond to isobutene, toluene, and isoprene with induction ratios of 1.64, 3.58, and 1.3, respectively

The Hand of Darkness

a glowing spindle speeding through the sky pushing its woven light then comes . . . the POWERFUL hand of darkness..

Winter D.O.A.

the earth bearing scars of careless surgery lies naked in the wind bleeding leaves which spurt from its wooden arteries. its liquid veins begin to clot writhing, it vomits the last warmth of life into the sky. chills and fevers heighten the agony and in the end a sterile sheet of snow is placed as shroud upon a weary, gnarled face.

Fall 1976

Lawn & Turf Seed Labeling--Are Changes Needed? (page 3) Weed Control: More Options Ahead (6) Problems and Solutions Associated with Heavily Used Turfgrass Areas (12) Past and Present Golf Course Maintenance (15) Tractor Safety Begins with ROPS (19

Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM-775)

Lysergic acid diethylamide (LSD) is perhaps one of the best-known psychoactive substances and many structural modifications of this prototypical lysergamide have been investigated. Several lysergamides were recently encountered as “research chemicals” or new psychoactive substances (NPS). Although lysergic acid morpholide (LSM-775) appeared on the NPS market in 2013, there is disagreement in the literature regarding the potency and psychoactive properties of LSM-775 in humans. The present investigation attempts to address the gap of information that exists regarding the analytical profile and pharmacological effects of LSM-775. A powdered sample of LSM-775 was characterized by X-ray crystallography, nuclear magnetic resonance stereoscopy (NMR), gas chromatography mass spectrometry (GC-MS), high mass accuracy electrospray MS/MS, HPLC diode array detection, HPLC quadrupole MS, and GC solid-state infrared analysis. Screening for receptor affinity and functional efficacy revealed that LSM-775 acts as a nonselective agonist at 5-HT1A and 5-HT2A receptors. Head twitch studies were conducted in C57BL/6J mice to determine whether LSM-775 activates 5-HT2A receptors and produces hallucinogen-like effects in vivo. LSM-775 did not induce the head twitch response unless 5-HT1A receptors were blocked by pretreatment with the antagonist WAY-100,635 (1 mg/kg, subcutaneous). These findings suggest that 5-HT1A activation by LSM-775 masks its ability to induce the head twitch response, which is potentially consistent with reports in the literature indicating that LSM-775 is only capable of producing weak LSD-like effects in humans

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

The Hand of Darkness

a glowing spindle speeding through the sky pushing its woven light then comes . . . the POWERFUL hand of darkness...</p