Dinucleating Amino-Phenolate Platform for Zinc Catalysts: Impact on Lactide Polymerization.

We report imine- and amine-based dinucleating ligands bearing a bisphenol backbone and explore their coordination chemistry with zinc to form zinc alkyl, alkoxide, acetate, and amide complexes. Full characterization of the complexes shows that this ligand framework can support dinuclear and trinuclear complexes. We explore the reactivity of the zinc alkyl and alkoxide complexes as catalysts for the ring opening polymerization of lactide and compared this reactivity to analogous mononuclear complexes. We show that 1) The amine-based complexes are more reactive than the imine-based analogues; 2) The trinuclear zinc alkyl species show unusual control and reproducibility for lactide polymerization; and 3) The extent of bimetallic cooperation is hampered by the ability of the ligand framework to form trinuclear clusters.

Making Memories: Why Time Matters.

In the last decade advances in human neuroscience have identified the critical importance of time in creating long-term memories. Circadian neuroscience has established biological time functions via cellular clocks regulated by photosensitive retinal ganglion cells and the suprachiasmatic nuclei. Individuals have different circadian clocks depending on their chronotypes that vary with genetic, age, and sex. In contrast, social time is determined by time zones, daylight savings time, and education and employment hours. Social time and circadian time differences can lead to circadian desynchronization, sleep deprivation, health problems, and poor cognitive performance. Synchronizing social time to circadian biology leads to better health and learning, as demonstrated in adolescent education. In-day making memories of complex bodies of structured information in education is organized in social time and uses many different learning techniques. Research in the neuroscience of long-term memory (LTM) has demonstrated in-day time spaced learning patterns of three repetitions of information separated by two rest periods are effective in making memories in mammals and humans. This time pattern is based on the intracellular processes required in synaptic plasticity. Circadian desynchronization, sleep deprivation, and memory consolidation in sleep are less well-understood, though there has been considerable progress in neuroscience research in the last decade. The interplay of circadian, in-day and sleep neuroscience research are creating an understanding of making memories in the first 24-h that has already led to interventions that can improve health and learning.

Is 8:30 a.m. Still Too Early to Start School? A 10:00 a.m. School Start Time Improves Health and Performance of Students Aged 13-16.

While many studies have shown the benefits of later school starts, including better student attendance, higher test scores, and improved sleep duration, few have used starting times later than 9:00 a.m. Here we report on the implementation and impact of a 10 a.m. school start time for 13 to 16-year-old students. A 4-year observational study using a before-after-before (A-B-A) design was carried out in an English state-funded high school. School start times were changed from 8:50 a.m. in study year 0, to 10 a.m. in years 1-2, and then back to 8:50 a.m. in year 3. Measures of student health (absence due to illness) and academic performance (national examination results) were used for all students. Implementing a 10 a.m. start saw a decrease in student illness after 2 years of over 50% (p < 0.0005 and effect size: Cohen's d = 1.07), and reverting to an 8:50 a.m. start reversed this improvement, leading to an increase of 30% in student illness (p < 0.0005 and Cohen's d = 0.47). The 10:00 a.m. start was associated with a 12% increase in the value-added number of students making good academic progress (in standard national examinations) that was significant (<0.0005) and equivalent to 20% of the national benchmark. These results show that changing to a 10:00 a.m. high school start time can greatly reduce illness and improve academic performance. Implementing school start times later than 8:30 a.m., which may address the circadian delay in adolescents' sleep rhythms more effectively for evening chronotypes, appears to have few costs and substantial benefits.

Electrocatalytic reduction of CO2 with CCC-NHC pincer nickel complexes.

A CCC-NHC pincer Ni(ii)Cl complex was prepared according to the metallation/transmetallation methodology. It was fully characterized by electrochemical, NMR spectroscopic, theoretical, and X-ray crystallographic methods. The complex and its cation were evaluated for electrocatalytic reduction of CO2 under a variety of conditions and found to provide some of the fastest catalytic rates and highest substrate selectivities (CO2vs. H+) reported. Rates improved in the presence of water and, significantly, catalysis occurred at the first reduction potential, presumably at the Ni(i) state. Controlled potential electrolysis (CPE) was found to yield CO at 34% and formate at 47% Faradaic efficiency (FE).

Identifying the Best Times for Cognitive Functioning Using New Methods: Matching University Times to Undergraduate Chronotypes.

University days generally start at fixed times in the morning, often early morning, without regard to optimal functioning times for students with different chronotypes. Research has shown that later starting times are crucial to high school students' sleep, health, and performance. Shifting the focus to university, this study used two new approaches to determine ranges of start times that optimize cognitive functioning for undergraduates. The first is a survey-based, empirical model (SM), and the second a neuroscience-based, theoretical model (NM). The SM focused on students' self-reported chronotype and times they feel at their best. Using this approach, data from 190 mostly first and second year university students were collected and analyzed to determine optimal times when cognitive performance can be expected to be at its peak. The NM synthesized research in sleep, circadian neuroscience, sleep deprivation's impact on cognition, and practical considerations to create a generalized solution to determine the best learning hours. Strikingly the SM and NM results align with each other and confirm other recent research in indicating later start times. They add several important points: (1) They extend our understanding by showing that much later starting times (after 11 a.m. or 12 noon) are optimal; (2) Every single start time disadvantages one or more chronotypes; and (3) The best practical model may involve three alternative starting times with one afternoon shared session. The implications are briefly considered.

Automated Calibration of Atmospheric Oxidized Mercury Measurements.

The atmosphere is an important reservoir for mercury pollution, and understanding of oxidation processes is essential to elucidating the fate of atmospheric mercury. Several recent studies have shown that a low bias exists in a widely applied method for atmospheric oxidized mercury measurements. We developed an automated, permeation tube-based calibrator for elemental and oxidized mercury, and we integrated this calibrator with atmospheric mercury instrumentation (Tekran 2537/1130/1135 speciation systems) in Reno, Nevada and at Mauna Loa Observatory, Hawaii, U.S.A. While the calibrator has limitations, it was able to routinely inject stable amounts of HgCl2 and HgBr2 into atmospheric mercury measurement systems over periods of several months. In Reno, recovery of injected mercury compounds as gaseous oxidized mercury (as opposed to elemental mercury) decreased with increasing specific humidity, as has been shown in other studies, although this trend was not observed at Mauna Loa, likely due to differences in atmospheric chemistry at the two locations. Recovery of injected mercury compounds as oxidized mercury was greater in Mauna Loa than in Reno, and greater still for a cation-exchange membrane-based measurement system. These results show that routine calibration of atmospheric oxidized mercury measurements is both feasible and necessary.

Lewis Acid Accelerated Aryl Ether Bond Cleavage with Nickel: Orders of Magnitude Rate Enhancement Using AlMe3.

Study of the kinetics of intramolecular aryl ether C-O bond cleavage by Ni was facilitated by access to a family of metal complexes supported by diphosphines with pendant aryl-methyl ethers. The nature of the aryl substituents was found to have little effect on the rate of cleavage. In contrast, soluble Lewis acidic additives accelerate the aryl ether cleavage dramatically. The effect of AlMe3 was studied in detail, and showed an increase in rate by several orders of magnitude. Low temperature NMR spectroscopy studies demonstrate quantitative coordination of ether to Al. From the Lewis acid-bound precursor, the activation parameters for ether cleavage are significantly lower. These findings provide a mechanistic basis for milder catalyst design for the activation of strong bonds.

Making long-term memories in minutes: a spaced learning pattern from memory research in education.

Memory systems select from environmental stimuli those to encode permanently. Repeated stimuli separated by timed spaces without stimuli can initiate Long-Term Potentiation (LTP) and long-term memory (LTM) encoding. These processes occur in time scales of minutes, and have been demonstrated in many species. This study reports on using a specific timed pattern of three repeated stimuli separated by 10 min spaces drawn from both behavioral and laboratory studies of LTP and LTM encoding. A technique was developed based on this pattern to test whether encoding complex information into LTM in students was possible using the pattern within a very short time scale. In an educational context, stimuli were periods of highly compressed instruction, and spaces were created through 10 min distractor activities. Spaced Learning in this form was used as the only means of instruction for a national curriculum Biology course, and led to very rapid LTM encoding as measured by the high-stakes test for the course. Remarkably, learning at a greatly increased speed and in a pattern that included deliberate distraction produced significantly higher scores than random answers (p < 0.00001) and scores were not significantly different for experimental groups (one hour spaced learning) and control groups (four months teaching). Thus learning per hour of instruction, as measured by the test, was significantly higher for the spaced learning groups (p < 0.00001). In a third condition, spaced learning was used to replace the end of course review for one of two examinations. Results showed significantly higher outcomes for the course using spaced learning (p < 0.0005). The implications of these findings and further areas for research are briefly considered.

Metallomacrocycles as ligands: synthesis and characterisation of aluminium-bridged bisglyoximato complexes of palladium and iron.

Dialuminiummacrocycles based on bisglyoximato moieties were prepared and their coordination chemistry with Fe(II) and Pd(II) was investigated. The bridging aluminium centers were supported by several types of tetradentate diphenoxide diamine ligands. The nature of the ancillary ligands bound to aluminium was found to affect the overall geometry and symmetry of the metallomacrocycles. Enantiopure, chiral diphenoxide ligands based on the (R,R)-trans-1,2-diaminocyclohexane backbone afforded cleanly one metallomacrocycle isomer. The size and electronic properties of remote substituents on aluminium-bound ligands affected the binding mode and electronic properties of the central iron. A structurally characterized iron complex shows trigonal prismatic coordination mode, with phenoxide bridges between iron and aluminium. Increasing the size of the phenoxide substituents led to square bipyramidal coordination at iron. Employing p-NO(2)- instead of p-tBu-substituted phenoxide as supporting ligands for aluminium caused a 0.27 V positive shift of the Fe(III)/Fe(II) reduction potential. These results indicate that the present synthetic approach can be applied to a variety of metallomacrocycles based on bisglyoximato motifs to affect the chemistry at the central metal.

Nickel-mediated hydrogenolysis of C-O bonds of aryl ethers: what is the source of the hydrogen?

Mechanistic studies of the hydrogenolysis of aryl ethers by nickel were undertaken with (diphosphine)aryl methyl ethers. A Ni(0) complex containing Ni-arene interactions adjacent to the aryl-O bond was isolated. Heating led to aryl-O bond activation and generation of a nickel aryl methoxide complex. Formal ß-H elimination from this species produced a nickel aryl hydride which can undergo reductive elimination in the presence of formaldehyde to generate a carbon monoxide adduct of Ni(0). The reported complexes map out a plausible mechanism of aryl ether hydrogenolysis catalyzed by nickel. Investigations of a previously reported catalytic system using isotopically labeled substrates are consistent with the mechanism proposed in the stoichiometric system, involving ß-H elimination from a nickel alkoxide rather than cleavage of the Ni-O bond by H(2).

Modification of a commercial cavity ring-down spectroscopy NO2 detector for enhanced sensitivity.

Nitrogen dioxide (NO(2)) plays a central role in atmospheric chemistry, air pollution, and biogeochemical cycles. Many analytical techniques have been developed to detect NO(2), but only chemiluminescence-based instruments are commonly, commercially available. There remains a need for a fast, light, and simple method to directly measure NO(2). In this work we describe the modification and characterization of a small, commercially available cavity ring-down spectroscopy (CRDS) NO(2) detector suitable for surface and aircraft monitoring. A metal oxide scrubber was added to remove NO(2), and provide a chemical zero, improving the detection limit (3sigma of the background noise) from several parts per billion by volume (ppbv) to 0.06 ppbv, integrated over 60 s. Known interferences by water and particles were removed using Nafion tubing and a 1 microm Teflon filter, respectively. A 95% response time of 18+/-1 s was observed for a step change in concentration. The CRDS detector was run in parallel to an ozone chemiluminescence device with photolytic conversion of NO(2) to NO. The two instruments measured ambient air in suburban Maryland. A least-squares fit to the comparison data resulted a slope of 0.960+/-0.002 and R of 0.995, showing agreement within experimental uncertainty.

Proton bridging in the interactions of thrombin with small inhibitors.

Thrombin is the pivotal serine protease enzyme in the blood cascade system. Phe-Pro-Arg-chloromethylketone (PPACK), phosphate, and phosphonate ester inhibitors form a covalent bond with the active-site Ser of thrombin. PPACK, a mechanism-based inhibitor, and the phosphate/phosphonate esters form adducts that mimic intermediates formed in reactions catalyzed by thrombin. Therefore, the dependence of the inhibition of human alpha-thrombin on the concentration of these inhibitors, pH, and temperature was investigated. The second-order rate constant (ki/Ki) and the inhibition constant (Ki) for inhibition of human alpha-thrombin by PPACK are (1.1 +/- 0.2) x 10(7) M(-1) s(-1) and (2.4 +/- 1.3) x 10(-8) M, respectively, at pH 7.00 in 0.05 M phosphate buffer and 0.15 M NaCl at 25.0 +/- 0.1 degrees C, in good agreement with previous reports. The activation parameters at pH 7.00 in 0.05 M phosphate buffer and 0.15 M NaCl are as follows: DeltaH = 10.6 +/- 0.7 kcal/mol, and DeltaS = 9 +/- 2 cal mol(-1) degrees C(-1). The pH dependence of the second-order rate constants of inhibition is bell-shaped. Values of pKa1 and pKa2 are 7.3 +/- 0.2 and 8.8 +/- 0.3, respectively, at 25.0 +/- 0.1 degrees C. A phosphate and a phosphonate ester inhibitor gave higher values, 7.8 and 8.0 for pKa1 and 9.3 and 8.6 for pKa2, respectively. They inhibit thrombin more than 6 orders of magnitude less efficiently than PPACK does. The deuterium solvent isotope effect for the second-order rate constant at pH 7.0 and 8.3 at 25.0 +/- 0.1 degrees C is unity within experimental error in all three cases, indicating the absence of proton transfer in the rate-determining step for the association of thrombin with the inhibitors, but in a 600 MHz 1H NMR spectrum of the inhibition adduct at pH 6.7 and 30 degrees C, a peak at 18.10 ppm with respect to TSP appears with PPACK, which is absent in the 1H NMR spectrum of a solution of the enzyme between pH 5.3 and 8.5. The peak at low field is an indication of the presence of a short-strong hydrogen bond (SSHB) at the active site in the adduct. The deuterium isotope effect on this hydrogen bridge is 2.2 +/- 0.2 (phi = 0.45). The presence of an SSHB is also established with a signal at 17.34 ppm for a dealkylated phosphate adduct of thrombin.

Structure of human prostasin, a target for the regulation of hypertension.

Prostasin (also called channel activating protease-1 (CAP1)) is an extracellular serine protease implicated in the modulation of fluid and electrolyte regulation via proteolysis of the epithelial sodium channel. Several disease states, particularly hypertension, can be affected by modulation of epithelial sodium channel activity. Thus, understanding the biochemical function of prostasin and developing specific agents to inhibit its activity could have a significant impact on a widespread disease. We report the expression of the prostasin proenzyme in Escherichia coli as insoluble inclusion bodies, refolding and activating via proteolytic removal of the N-terminal propeptide. The refolded and activated enzyme was shown to be pure and monomeric, with kinetic characteristics very similar to prostasin expressed from eukaryotic systems. Active prostasin was crystallized, and the structure was determined to 1.45 A resolution. These apoprotein crystals were soaked with nafamostat, allowing the structure of the inhibited acyl-enzyme intermediate structure to be determined to 2.0 A resolution. Comparison of the inhibited and apoprotein forms of prostasin suggest a mechanism of regulation through stabilization of a loop which interferes with substrate recognition.

The effects of tea polyphenolic compounds on hair loss among rodents.

The objective of this study was to examine the effects of polyphenolic compounds, present in noncommercially available green tea, on hair loss among rodents. In an experimental study, we randomly assigned 60 female Balb/black mice, which had developed spontaneous hair loss on the head, neck and dorsal areas into two equal groups; A (experimental) and B (control). Group A received 50% fraction of polyphenol extract from dehydrated green tea in their drinking water for six months. Group B received regular drinking water. Both groups were fed regular rodent diets (Purina Rodent Chow 5001) and housed individually in polycarbonate cages. The results showed that 33% of the mice in experimental Group A, who received polyphenol extract in their drinking water, had significant hair regrowth during six months of treatment (p = 0.014). No hair growth was observed among mice in the control group, which received regular water.

Bright ideas to market your department.

Nobody can do everything discussed in this article. Choose several ideas and try them. Increase your profile by letting more people in the hospital know who you are, what you do, when you do it, and how you do it. Get noticed and develop a reputation as the "go to" department. It will be worth the effort and increase your stature within the hospital. It may also help you get more staff and assume additional duties. Most of all, it will increase the respect of your department, and promote a more smoothly operating asset management system.