Dynamic wavelength control of laser pulse profiles at picosecond to nanosecond timescales.

We report on a novel combined laser pulse shaping and dynamic wavelength encoding capability based on a simple architecture implementing direct space to time mapping. There are several potential applications that can be enabled by the ability to control the instantaneous intensity or wavelength of an optical waveform on a picosecond-to-nanosecond timescale. To our knowledge, no known methods can access this temporal regime with a practical architecture. Here, we demonstrate an extension of the Space-Time Induced Linearly Encoded Transcription for Temporal Optimization (STILETTO) technique that can generate optical waveforms with a programmable instantaneous wavelength vs. time. We experimentally demonstrate the technique by generating self-gated spectrograms and show that it can encode dynamic wavelength vs time profiles at timescales not achievable by any other known method.

Programmable, direct space-to-time picosecond resolution pulse shaper with nanosecond record.

We demonstrate a novel, to the best of our knowledge, extension of optical arbitrary waveform generation capable of picosecond resolution over nanosecond duration. The method, called space-time induced linearly encoded transcription for temporal optimization, is based on direct space-to-time pulse shaping and is extended here to single-mode output with a programmable temporal profile. We develop the theory of operation and discuss ultimate limits on resolution, record length, and efficiency. We report on the results of an experimental demonstration showing ∼1ps resolution over 600 ps.

Single-shot optical recorder with sub-picosecond resolution and scalable record length on a semiconductor wafer.

We demonstrate a novel, single-shot recording technology for transient optical signals. A resolution of 0.4 ps over a record length of 54 ps was demonstrated. Here, a pump pulse crossing through a signal samples a diagonal "slice" of space-time, enabling a camera to record spatially the time content of the signal. Unlike related χ(2)-based cross-correlation techniques, here the signal is sampled through optically pumped carriers that modify the refractive index of a silicon wafer. Surrounding the wafer with birefringent retarders enables two time-staggered, orthogonally polarized signal copies to probe the wafer. Recombining the copies at a final crossed polarizer destructively interferes with them, except during the brief stagger window, where a differential phase shift is incurred. This enables the integrating response of the rapidly excited but persistent carriers to be optically differentiated. This sampling mechanism has several advantages that enable scaling to long record lengths, including making use of large, inexpensive semiconductor wafers, eliminating the need for phase matching, broad insensitivity to the spectral and angular properties of the pump, and overall hardware simplicity.

Conserving large populations of lions - the argument for fences has holes.

Packer et al. reported that fenced lion populations attain densities closer to carrying capacity than unfenced populations. However, fenced populations are often maintained above carrying capacity, and most are small. Many more lions are conserved per dollar invested in unfenced ecosystems, which avoid the ecological and economic costs of fencing.

Quality of life in children with Crohn disease.

OBJECTIVES: : Quality of life (QOL) is reportedly poor in children with Crohn disease (CD) but improves with increasing disease duration. This article aims to detail QOL in a cohort of Australian children with CD in relation to disease duration, disease activity, and treatment. MATERIALS AND METHODS: : QOL, assessed using the IMPACT-III questionnaire, and disease activity measures, assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), were available in 41 children with CD. For this cohort, a total of 186 measurements of both parameters were available. RESULTS: : QOL was found to be significantly lower, and disease activity significantly higher (F = 31.1, P = 0.00), in patients within 6 months of their diagnosis compared with those up to 2.5 years, up to 5 years, and beyond 5 years since diagnosis. Higher disease activity was associated with poorer QOL (r = -0.51, P = 0.00). Total QOL was highest in children on nil medications and lowest in children on enteral nutrition. The PCDAI (t = -6.0, P = 0.00) was a significant predictor of QOL, with the clinical history (t = -6.9, P = 0.00) and examination (t = -2.9, P = 0.01) sections of the PCDAI significantly predicting QOL. Disease duration, age, or sex was neither related to nor significant predictors of QOL, but height z score and type of treatment approached significance. CONCLUSIONS: : Children with CD within 6 months of their diagnosis have impaired QOL compared with those diagnosed beyond 6 months. These patients, along with those with growth impairment, ongoing elevated disease activity with abdominal pain, diarrhoea and/or perirectal and extraintestinal complications, may benefit from regular assessments of QOL as part of their clinical treatment.

Governance and the loss of biodiversity.

Most of the world's biodiversity occurs within developing countries that require donor support to build their conservation capacity. Unfortunately, some of these countries experience high levels of political corruption, which may limit the success of conservation projects by reducing effective funding levels and distorting priorities. We investigated whether changes in three well surveyed and widespread components of biodiversity were associated with national governance scores and other socio-economic measures. Here we show that governance scores were correlated with changes in total forest cover, but not with changes in natural forest cover. We found strong associations between governance scores and changes in the numbers of African elephants and black rhinoceroses, and these socio-economic factors explained observed patterns better than any others. Finally, we show that countries rich in species and identified as containing priority areas for conservation have lower governance scores than other nations. These results stress the need for conservationists to develop and implement policies that reduce the effects of political corruption and, in this regard, we question the universal applicability of an influential approach to conservation that seeks to ban international trade in endangered species.

A novel size-selective airborne particle size fractionating instrument for health risk evaluation.

Health risks associated with the inhalation of airborne particles are known to be influenced by particle size. Studies have shown that certain nanoparticles, with diameters <100 nm, have increased toxicity relative to larger particles of the same substance. A reliable, size-resolving sampler able to collect a wide range of particle sizes, including particles with sizes in the nanometre range, would be beneficial in investigating health risks associated with the inhalation of airborne particles. A review of current aerosol samplers used for size-resolved collection of airborne particles highlighted a number of limitations. These could be overcome by combining an inertial deposition impactor with a diffusion collector in a single device. Verified theories of diffusion and inertial deposition suggested an optimal design and operational regime. The instrument was designed for analysing mass distribution functions. Calibration was carried out using a number of recognized techniques. The sampler was tested in the field by collecting size-resolved samples of lead containing aerosols present at workplaces in factories producing crystal glass. The mass deposited on each screen proved sufficient to be detected and measured by an appropriate analytical technique. Mass concentration distribution functions of lead were produced. The nanofraction of lead in air varied from 10 to 70% by weight of total lead.

Role of Macrophage Dopamine Receptors in Mediating Cytokine Production: Implications for Neuroinflammation in the Context of HIV-Associated Neurocognitive Disorders.

Despite the success of combination anti-retroviral therapy (cART), around 50% of HIV-infected individuals still display a variety of neuropathological and neurocognitive sequelae known as NeuroHIV. Current research suggests these effects are mediated by long-term changes in CNS function in response to chronic infection and inflammation, and not solely due to active viral replication. In the post-cART era, drug abuse is a major risk-factor for the development of NeuroHIV, and increases extracellular dopamine in the CNS. Our lab has previously shown that dopamine can increase HIV infection of primary human macrophages and increase the production of inflammatory cytokines, suggesting that elevated dopamine could enhance the development of HIV-associated neuropathology. However, the precise mechanism(s) by which elevated dopamine could exacerbate NeuroHIV, particularly in chronically-infected, virally suppressed individuals remain unclear. To determine the connection between dopaminergic alterations and HIV-associated neuroinflammation, we have examined the impact of dopamine exposure on macrophages from healthy and virally suppressed, chronically infected HIV patients. Our data show that dopamine treatment of human macrophages isolated from healthy and cART-treated donors promotes production of inflammatory mediators including IL-1ß, IL-6, IL-18, CCL2, CXCL8, CXCL9, and CXCL10. Furthermore, in healthy individuals, dopamine-mediated modulation of specific cytokines is correlated with macrophage expression of dopamine-receptor transcripts, particularly DRD5, the most highly-expressed dopamine-receptor subtype. Overall, these data will provide more understanding of the role of dopamine in the development of NeuroHIV, and may suggest new molecules or pathways that can be useful as therapeutic targets during HIV infection.

Offensive waste valorisation in the UK: Assessment of the potentials for absorbent hygiene product (AHP) recycling.

Offensive human waste refers to non-hazardous waste that contains body fluids from non-infectious humans, comprised of post-consumer Absorbent Hygiene Products (AHPs), swabs, dressings, bedding, gloves, and other materials. While this waste category requires more stringent handling, storage and disposal measures than general waste, its non-hazardous nature suggests that there are opportunities for waste valorisation. An inventory of 200 offensive human waste bags collected from various healthcare institutions in South-Eastern England show that about 76% of the waste is comprised of AHPs, most of which are adult incontinence pads and child nappies. Mixed plastics comprised of predominantly HDPE represent 9% of the waste. To evaluate the potentials for offensive human waste valorisation, small-scale separation tests involving artificially-soiled nappies and associated mixed plastic packaging wastes have been performed. Findings suggest that about 50% of the total superabsorbent polymer is recoverable from fluff pulp fractions, recoveries of which are unaffected by the presence of ionic species typically present in human waste. On the other hand, recovery of mixed plastic packaging is more challenging. Overall, however, findings suggest that viable AHP recycling is possible if recyclate materials are targeted towards non-food related markets outlets such as the construction and land remediation sectors.

Functions of FKBP12 and mitochondrial cyclophilin active site residues in vitro and in vivo in Saccharomyces cerevisiae.

Cyclophilin and FK506 binding protein (FKBP) accelerate cis-trans peptidyl-prolyl isomerization and bind to and mediate the effects of the immunosuppressants cyclosporin A and FK506. The normal cellular functions of these proteins, however, are unknown. We altered the active sites of FKBP12 and mitochondrial cyclophilin from the yeast Saccharomyces cerevisiae by introducing mutations previously reported to inactivate these enzymes. Surprisingly, most of these mutant enzymes were biologically active in vivo. In accord with previous reports, all of the mutant enzymes had little or no detectable prolyl isomerase activity in the standard peptide substrate-chymotrypsin coupled in vitro assay. However, in a variation of this assay in which the protease is omitted, the mutant enzymes exhibited substantial levels of prolyl isomerase activity (5-20% of wild-type), revealing that these mutations confer sensitivity to protease digestion and that the classic in vitro assay for prolyl isomerase activity may be misleading. In addition, the mutant enzymes exhibited near wild-type activity with two protein substrates, dihydrofolate reductase and ribonuclease T1, whose folding is accelerated by prolyl isomerases. Thus, a number of cyclophilin and FKBP12 "active-site" mutants previously identified are largely active but protease sensitive, in accord with our findings that these mutants display wild-type functions in vivo. One mitochondrial cyclophilin mutant (R73A), and also the wild-type human FKBP12 enzyme, catalyze protein folding in vitro but lack biological activity in vivo in yeast. Our findings provide evidence that both prolyl isomerase activity and other structural features are linked to FKBP and cyclophilin in vivo functions and suggest caution in the use of these active-site mutations to study FKBP and cyclophilin functions.

Early Mucosal Healing with Exclusive Enteral Nutrition is Associated with Improved Outcomes in Newly Diagnosed Children with Luminal Crohn's disease.

BACKGROUND: Exclusive Enteral Nutrition (EEN) induction in children with luminal Crohn's disease (CD) gives early mucosal healing (MH), but the long-term benefits of EEN-induced MH are just emerging. AIMS & METHODS: We prospectively followed an Australian cohort of newly diagnosed children with predominantly luminal CD who completed at least six weeks EEN and with paired clinical Pediatric Crohn's Disease Activity Index (PCDAI), biochemical (C-reactive protein; CRP) and endoscopic assessment at diagnosis and post EEN. All commenced immunomodulators (IMs) early (<3 months from diagnosis) and had a minimum of 1 year follow-up. Complete MH was a simple endoscopic score for Crohn's disease (SES-CD) of 0, and SES-CD≥1 was ascribed to active endoscopic disease (aED) and further divided into near complete MH (SES 1-3), mild active disease (SES-CD 4-10) and moderate to severe disease (SES-CD>10). The primary outcome was long-term supervised sustained remission (SR) on IMs alone without need for corticosteroids, infliximab (IFX) or surgery. RESULTS: A total of 54 eligible children (33 males) completing EEN induction were analysed. The median duration between pre and post EEN assessments was 60.5 days [interquartile range (IQR), 56-69.5]. Post EEN: clinical remission (PCDAI < 10) was observed in 45/54 (83%), and biochemical remission (PCDAI < 10 and CRP < 5 mg/dl) was observed in 39/54 (72%). Complete MH was observed in 18/54 (33%), near complete in 10/54(19%). SR was superior in those with complete MH vs. aED; 13/18, (72%) vs. 10/36 (28%), p = 0.003 at 1 year, 8/16, (50%) vs. 3/24, (8%), p = 0.008 at 2 years and (8/16, (50%) vs. 1/19, (6%), p = 0.005) at 3 years. Near-complete MH did not lead to superior SR. CONCLUSIONS: Only complete MH post EEN induction predicts more favourable SR for up to 3 years.

Temperature-sensitive mutants of the EcoRI endonuclease.

The EcoRI endonuclease is an important recombinant DNA tool and a paradigm of sequence-specific DNA-protein interactions. We have isolated temperature-sensitive (TS) EcoRI endonuclease mutants (R56Q, G78D, P90S, V97I, R105K, M157I, C218Y, A235E, M255I, T261I and L263F) and characterized activity in vivo and in vitro. Although the majority were TS for function in vivo, all of the mutant enzymes were stably expressed and largely soluble at both 30 degrees C and 42 degrees C in vivo and none of the mutants was found to be TS in vitro. These findings suggest that these mutations may affect folding of the enzyme at elevated temperature in vivo. Both non-conservative and conservative substitutions occurred but were not correlated with severity of the mutation. Of the 12 residues identified, 11 are conserved between EcoRI and the isoschizomer RsrI (which shares 50% identity), a further indication that these residues are critical for EcoRI structure and function. Inspection of the 2.8 A resolution X-ray crystal structure of the wild-type EcoRI endonuclease-DNA complex revealed that: (1) the TS mutations cluster in one half of the globular enzyme; (2) several of the substituted residues interact with each other; (3) most mutations would be predicted to disrupt local structures; (4) two mutations may affect the dimer interface (G78D and A235E); (5) one mutation (P90S) occurred in a residue that is part of, or immediately adjacent to, the EcoRI active site and which is conserved in the distantly related EcoRV endonuclease. Finally, one class of mutants restricted phage in vivo and was active in vitro, whereas a second class did not restrict and was inactive in vitro. The two classes of mutants may differ in kinetic properties or cleavage mechanism. In summary, these mutations provide insights into EcoRI structure and function, and complement previous genetic, biochemical, and structural analyses.

Seasonal independence of low prolactin concentration and high spontaneous eye blink rates in unipolar and bipolar II seasonal affective disorder.

Twenty-four subjects with seasonal affective disorder (SAD: bipolar II, n = 14; unipolar, n = 10) and 20 normal controls were assessed for early follicular basal serum prolactin (PRL) concentration in winter and summer. Luteal basal PRL concentration was assessed in winter. The PRL values represented the mean of three values derived during a 45-minute period. A subset of 17 subjects with SAD and 11 controls were also assessed for spontaneous eye blinking via a polygraphic recording in winter and summer. In winter, compared with controls, subjects with SAD were characterized by significantly lower follicular (10.1 vs 4.5 micrograms/L, respectively) and luteal (14.4 vs 7.4 micrograms/L, respectively) PRL values and by significantly higher eye blink rates (30 vs 61 blinks per 3 minutes, respectively). In summer, controls and subjects with SAD showed similar significant differences in follicular PRL values (9.3 vs 3.9 micrograms/L, respectively) and eye blink rates (25 vs 67 blinks per 3 minutes, respectively). No significant differences in PRL values or eye blink rates were found between the bipolar II and unipolar forms of SAD in either season. Results were discussed in terms of dopamine functioning.

Gene disruption with PCR products in Saccharomyces cerevisiae.

We describe here the generation of gene disruption constructs using PCR amplification of selectable markers with primers that provide homology to the target gene of interest. We find that regions of homology as short as 38 to 50 bp suffice to mediate homologous recombination in yeast. We describe applications of this technology to three specific yeast genes that would have been difficult to disrupt with current methods. By dispensing with the need to either clone the gene of interest or engineer a standard disruption construct, this method should facilitate analysis of sequenced genes of unknown function, which will soon include the entire yeast genome.

Effect of phototherapy on spontaneous eye blink rate in subjects with seasonal affective disorder.

Eye blink rate was measured in four subjects with seasonal affective disorder and in four control subjects before and after phototherapy. The subjects with seasonal disorder blinked twice as often as the control subjects before therapy but no differently after phototherapy.

Nitroimidazoles with antibacterial activity against Neisseria gonorrhoeae.

Nitroimidazoles have been prepared which show interesting activity against the bacterium, Neisseria gonorrhoeae, in addition to the activities usually shown by nitroimidazoles against protozoa and anaerobic bacteria. The compounds were prepared by alkylation of 1-methyl-2-mercaptoimidazole, followed by nitration. Optimum activity occurs with a 5-nitro group and a free carboxyl at the end of the group attached to the sulfur. The linkage between the sulfur atom and the carboxyl group can be alkylene or phenoxyalkylene. These compounds have only weak activity against other aerobic or facultative bacteria.

Antidromic excitation of motoneurons by intramuscular electrical stimulation.

The terminal branches of motoneurons can be excited by electrical current pulses delivered via needles inserted intramuscularly. Observations are reported which indicate that tungsten semi-microelectrodes suitably positioned in a muscle belly can excite antidromically a large proportion of the alpha-motoneurons of that muscle, at stimulus strengths weak enough to avoid spread of excitation to motor units of adjacent muscles. Some gamma-motoneurons and afferent axons can also be excited by intramuscular stimulation. This technique of antidromic excitation will find application in electrophysiological studies on motoneurons of small muscles, such as intrinsic hand and foot musculature, where the individual muscle nerves are too fragile to be dissected and mounted on stimulating electrodes in the conventional manner.

Prenatal screening of pregnant mothers for parenting difficulties: final results from the Queen Mary Child Care Unit.

This paper reports the results of 10 years of research into the prenatal identification of mothers likely to have major parenting problems. Previous published research reported the development of a set of criteria for determining risk status. These criteria were used to classify into four levels of risk a sample of mothers who were consecutive enrollments for prenatal care. The sample was monitored through various social agencies for 2 years. Results of this monitoring indicate the predictive validity of the risk code in an unselected sample. The value of prenatal identification of the 'at risk' is discussed together with the procedures adopted for implementing routine screening in the maternity hospital. The issue of causation, as distinct from prediction, is addressed.

Heat-loss response to a thermal challenge in seasonal affective disorder.

This study extends earlier findings of poorly facilitated postexercise heat loss during the winter in seasonal affective disorder (SAD). While depressed in the winter, 19 SAD subjects exhibited a significantly impaired postexercise heat loss relative to 10 control subjects. During the summer while euthymic, SAD subjects did not significantly differ from control subjects in postexercise heat loss. Since thermoregulatory heat loss is a highly dopamine-dependent process, these results support earlier findings of poorly facilitated dopamine availability in SAD during the winter and suggest a centrally mediated effect of light in SAD.

Management of massive abdominal wall defects.

Patients with acute losses of large portions of the anterior abdominal wall are discussed. Management is divided into the acute or immediate phase in which initial wound control is paramount, and then a subacute period in which coverage with skin is accomplished. Many weeks later during the chronic phase, reconstructive procedures are done if needed. Methods of handling these defects are presented.