Measurement of gravitational and thermal effects in a liquid-actuated torsion pendulum.

We describe a proof-of-principle experiment aiming to investigate the inverse-square law of gravitation at the centimeter scale. The sensor is a two-stage torsion pendulum, while actuation is accomplished by a variable liquid mass. The time-varying gravitational force is related to the level of the circulating fluid in one or two containers at a short distance from the test mass, with all moving mechanical parts positioned at a large distance. We provide a description of the apparatus and present the first results. We identified a systematic effect of thermal origin, producing offsets of few fNm in torque and of about 10 pN in force. When this effect is neutralized, the measurements agree well with the predictions of simulations. We also discuss the upcoming instrument upgradations and the expected sensitivity improvement that will allow us to perform measurements with adequate accuracy to investigate the unexplored regions of the α-λ parameter space of a Yukawa-like deviation from the Newtonian potential.

Size-dependent influence of NOx on the growth rates of organic aerosol particles.

Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.

The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis: The TRIO study.

Bisphosphonates are used to treat bone disease characterised by increased bone resorption by inhibiting the activity of mature osteoclasts, resulting in decreased bone turnover. Bisphosphonates may also reduce the population of osteoclast precursor cells. Our aims were to investigate the effect of bisphosphonates on i) osteoclast precursor cells and ii) circulating cytokine and cytokine receptor in postmenopausal women with osteoporosis compared with healthy premenopausal women. Participants were 62 postmenopausal women (mean age 66) from a 48-week parallel group trial of bisphosphonates. They received ibandronate 150mg/month (n=22), alendronate 70mg/week (n=19) or risedronate 35mg/week (n=21). Fasting blood was collected at baseline, weeks 1 and 48. At baseline, blood was also collected from 25 healthy premenopausal women (mean age 37) to constitute a control group. Peripheral blood mononuclear cells were extracted and stained for CD14, M-CSFR, CD11b and TNFRII receptors. Flow cytometry was used to identify cells expressing CD14+ and M-CSFR+ or CD11b+ or TNFRII+. RANKL and OPG were measured to evaluate potential mediation of the bisphosphonate effect. After 48weeks of treatment, there was a decrease in the percentage of cells expressing M-CSFR and CD11b receptors by 53% and 49% respectively (p<0.01). Cells expressing M-CSFR and CD11b were decreased with ibandronate and risedronate after 48weeks to the lower part of the premenopausal reference interval. These effects were not significantly different between each of the treatment groups. There was no significant effect on RANKL and OPG throughout the study period. Bisphosphonates inhibit bone resorption in the short-term by direct action on mature osteoclasts. There is also a later effect mediated in part by a reduction in the population of circulating osteoclast precursors.

New particle formation in the free troposphere: A question of chemistry and timing.

New particle formation (NPF) is the source of over half of the atmosphere's cloud condensation nuclei, thus influencing cloud properties and Earth's energy balance. Unlike in the planetary boundary layer, few observations of NPF in the free troposphere exist. We provide observational evidence that at high altitudes, NPF occurs mainly through condensation of highly oxygenated molecules (HOMs), in addition to taking place through sulfuric acid-ammonia nucleation. Neutral nucleation is more than 10 times faster than ion-induced nucleation, and growth rates are size-dependent. NPF is restricted to a time window of 1 to 2 days after contact of the air masses with the planetary boundary layer; this is related to the time needed for oxidation of organic compounds to form HOMs. These findings require improved NPF parameterization in atmospheric models.

Understanding the effects on HR-QoL of treatment for overactive bladder: a detailed analysis of EQ-5D clinical trial data for mirabegron.

BACKGROUND: Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB). DATA: Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4 mg was included as an active control in one study: (1) placebo, mirabegron 50 mg and 100 mg, and tolterodine 4 mg ER; (2) placebo, mirabegron 50 mg and 100 mg; (3) placebo, and mirabegron 25 mg and 50 mg. Data were collected at baseline, week 4, 8, and 12. METHODS: Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change. RESULTS: In modified ITT analyses, mirabegron 50 mg was superior to tolterodine 4 mg in changes from baseline utilities after 12 weeks (p < 0.05); similarly, AUC results showed mirabegron 50 mg to be superior to tolterodine (p < 0.05) and placebo (p < 0.05) with the benefit already apparent at 4 weeks (p < 0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms. CONCLUSION: Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4 mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.

Effects of aging on cholinergic neuromuscular transmission in isolated small intestine of ad libitum fed and calorically-restricted rats.

BACKGROUND: Age-associated losses of enteric neurons have been described. In rat ileum, myenteric neurons lost during aging have been reported to be predominantly cholinergic, and caloric restriction (CR) has been shown to protect against these losses. Cholinergic myenteric neurons include excitatory motor neurons, so the aim of this work was to determine whether neuronal loss in ad libitum (AL)-fed animals is reflected in dysfunctional cholinergic neuromuscular transmission, and if CR reduces any such dysfunction. METHODS: Effects of electrical field stimulation (EFS) and applied acetylcholine (ACh) were examined in the longitudinal muscle of isolated ileal segments from 6-month-old rats and from 13- and 24-month-old rats fed either AL or CR diets. KEY RESULTS: Contractile responses to EFS were abolished by atropine and potentiated by the acetylcholinesterase inhibitor, eserine. Frequency-response relationships were not significantly different amongst the three age-groups. Sensitivity to applied ACh, however, was three-fold lower in the oldest animals (P < 0.05). Eserine potentiated responses to ACh; there were no statistically significant differences amongst the sensitivities to ACh in its presence. No significant differences between AL- and CR-fed animals were measured, although variability was less in CR-fed than in AL-fed groups. CONCLUSIONS & INFERENCES: The cholinergic system supplying the rat ileum longitudinal muscle did not appear to be impaired in old age. Decreased sensitivity to applied ACh in old tissues may have been due to increased acetylcholinesterase activity. Caloric restriction had no significant effect on responses to EFS or applied ACh. The implications of these results are discussed.

Diadenosine tetraphosphate protects sympathetic terminals from 6-hydroxydopamine-induced degeneration in the eye.

AIMS: To examine diadenosine tetraphosphate (Ap(4)A) for its ability to protect the eye from neurodegeneration induced by subconjunctival application of 6-hydroxydopamine (6-OHDA). METHODS: Intraocular neurodegeneration of anterior structures was induced by subconjunctival injections of 6-OHDA. Animals were pre-treated with topical corneal applications of Ap(4)A or saline. RESULTS: 6-OHDA caused miosis, abnormal pupillary light reflexes, a precipitous drop in intraocular pressure and loss of VMAT2-labelled (vesicle monoamine transporter-2, a marker for sympathetic neurones) intraocular neurones. Pre-treatment with Ap(4)A prevented all of these changes from being induced by 6-OHDA, demonstrably preserving the sympathetic innervation of the ciliary processes. This neuroprotective action of Ap(4)A was not shared with the related compounds adenosine, ATP or diadenosine pentaphosphate. P2-receptor antagonists showed that the effects of Ap(4)A were mediated via a P2-receptor. CONCLUSION: Ap4A is a natural component of tears and aqueous humour, and its neuroprotective effect indicates that one of its physiological roles is to maintain neurones within the eye. Ap(4)A can prevent the degeneration of intraocular nerves, and it is suggested that this compound may provide the basis for a therapeutic intervention aimed at preventing or ameliorating the development of glaucoma associated with neurodegenerative diseases. Furthermore, subconjunctival application of 6-OHDA provides a useful model for studying diseases that cause ocular sympathetic dysautonomia.

Efficient LED light distribution cavities using low loss, angle-selective interference transflectors.

Recent advances in solid state light source efficiency and luminance present the technical challenge of distributing light from very small point sources to large areas, with area distribution ratios having orders of magnitude greater than previously addressed. Broad adoption of LEDs in lighting and liquid crystal displays is in part contingent on addressing this fundamental light distribution issue. Here we present new materials based on giant birefringent nanotechnology which address these deficiencies allowing us to guide light in air via a novel light distribution system. Resulting from controlled in-plane and out-of-plane x,y,z refractive indices of adjacent layers, these multilayer interference films possess both angle selective and polarization selective reflectance. The angle selectivity can be tuned in both azimuth and polar angle, relieving a key constraint of prior materials. Our work has been done on a physically large scale enabling demonstration of large light management systems of industrial and practical relevance.

Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy.

OBJECTIVE: To document the effects of long-term daily corticosteroid treatment on a variety of orthopedic outcomes in boys with Duchenne muscular dystrophy. METHODS: We reviewed the charts of 159 boys with genetically confirmed dystrophinopathies followed at the Ohio State University Muscular Dystrophy Clinic between 2000 and 2003. Charts were reviewed for ambulation status, type and duration of steroid treatment (if any), and orthopedic complications including presence and location of long bone fractures, vertebral compression fractures, and the presence and degree of scoliosis. RESULTS: The cohort consisted of 143 boys (16 boys with Becker dystrophy were excluded); 75 had been treated with steroids for at least 1 year, whereas 68 boys had never been treated or had received only a brief submaximal dose. The mean duration of daily steroid treatment was 8.04 years. Treated boys ambulated independently 3.3 years longer than the untreated group (p < 0.0001) and had a lower prevalence of scoliosis than the untreated group (31 vs 91%; p < 0.0001). The average scoliotic curve was also milder in the treated group (11.6 degrees) compared with the untreated group (33.2 degrees; p < 0.0001). Vertebral compression fractures occurred in 32% of the treated group, whereas no vertebral fractures were discovered in the steroid naive group (p = 0.0012). Long bone fractures were 2.6 times greater in steroid-treated patients. CONCLUSIONS: Although boys with Duchenne muscular dystrophy on long-term corticosteroid treatment have a significantly decreased risk of scoliosis and an extension of more than 3 years' independent ambulation, they are at increased risk of vertebral and lower limb fractures compared with untreated boys.

Particle-physics implications of a recent test of the gravitational inverse-square law.

We use data from our recent search for violations of the gravitational inverse-square law to constrain dilaton, radion, and chameleon exchange forces as well as arbitrary vector or scalar Yukawa interactions. We test the interpretation of the PVLAS Collaboration effect and a conjectured "fat-graviton" scenario and constrain the gamma_{5} couplings of pseuodscalar bosons and arbitrary power-law interactions.

Tests of the gravitational inverse-square law below the dark-energy length scale.

We conducted three torsion-balance experiments to test the gravitational inverse-square law at separations between 9.53 mm and 55 microm, probing distances less than the dark-energy length scale lambda(d)=[4 -root](variant Planck's over 2pic/rho(d) approximately 85 microm. We find with 95% confidence that the inverse-square law holds (|alpha|

Active membrane transport and receptor proteins from bacteria.

A general strategy for the expression of bacterial membrane transport and receptor genes in Escherichia coli is described. Expression is amplified so that the encoded proteins comprise 5-35% of E. coli inner membrane protein. Depending upon their topology, proteins are produced with RGSH6 or a Strep tag at the C-terminus. These enable purification in mg quantities for crystallization and NMR studies. Examples of one nutrient uptake and one multidrug extrusion protein from Helicobacter pylori are described. This strategy is successful for membrane proteins from H. pylori, E. coli, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Microbacterium liquefaciens, Brucella abortus, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides, Streptomyces coelicolor and Rhodobacter sphaeroides.

Second autologous transplant with cyclosporin/interferon alpha-induced graft versus host disease for patients who have failed first-line consolidation.

The prognosis for patients with non-Hodgkin's lymphoma (NHL) and advanced Hodgkin's disease (HD) who relapse following autologous transplant is poor. We report on a pilot study designed to evaluate the feasibility of using Cyclosporin A and interferon alpha to induce autologous GVHD following a second autologous transplant for relapsed lymphoma. In all, 10 patients entered the study with median age 46.5 years. Diagnosis was NHL (n=7) or Hodgkin's lymphoma (n=3). All had relapsed from a prior autologous transplant. The second transplant was well tolerated by all patients. Histological changes consistent with cutaneous GVHD developed in 30% of patients at a median of 22.5 days from transplant and settled spontaneously in all cases. Five patients have died (four from progressive disease) at a median 7 months from second transplant. Five patients are still alive and in complete remission at a median of 20 months from transplant. Median overall survival for the group is 13.5 months and median relapse-free survival has not been reached at 42 months. This is a well-tolerated regimen for use in this poor-risk group of patients with lymphoma. The overall survival and event-free survival are encouraging, however further studies are necessary.

Simple model of errors in chirped fiber gratings.

A simple etalon based model is presented to show the origin of the wavelength-dependent ripples in the group delay and phase, and in the intensity of optical signals reflected from chirped fiber gratings. The simplicity of the model allows intuitive understanding of the effects, and quantitative predictions. We derive accurate scaling laws that allow the experimenter to make quantitative connections between the grating writing process parameters and grating performance.

Laser flash photolysis of bismaleimides.

Bismaleimides containing between 2 and 12 methylene spacer units have been synthesized and characterized using laser flash photolysis spectroscopy. In the case of the monofunctional N-methylmaleimide, the 1,4-biradical was observed only at maleimide concentrations high enough to effectively quench the triplet state, indicating that the 1,4-biradical is Formed from self-quenching of the triplet excited state. The transient spectral features and the transient lifetimes of bismaleimides containing 2 and 9 methylene spacer units closely resemble those of N-methylmaleimide and are attributed to triplet-state transients. N,N'-Alkylenebismaleimides with 3 and 6 methylene spacer groups exhibit a transient with a very short lifetime attributed to a singlet 1,4-biradical species formed from intramolecular interaction. The absence of triplet spectra in these latter bismaleimides indicate that the 1,4-biradical is formed directly from the excited singlet state. The large difference in the lifetime of the 1,4-biradical formed in monofunctional maleimide solutions and bismaleimide solutions is reflective of differences in the biradical spin-state multiplicity. The bismaleimide with a 12 methylene spacer group exhibits transient spectra corresponding to both a triplet state of the maleimide and a 1,4-biradical formed by exo interaction of two maleimide groups. As a demonstration of the ability of acrylate monomers to react with the short-lived singlet biradicals, it is shown that the photopolymerization of a multifunctional acrylate monomer is readily initiated by the 1,4-biradical formed from the bismaleimides with 3 and 6 methylene spacer groups, presumably by direct reaction of the biradical with the acrylate.

Achieving geodetic motion for LISA test masses: ground testing results.

The low-frequency resolution of space-based gravitational wave observatories such as LISA (Laser Interferometry Space Antenna) hinges on the orbital purity of a free-falling reference test mass inside a satellite shield. We present here a torsion pendulum study of the forces that will disturb an orbiting test mass inside a LISA capacitive position sensor. The pendulum, with a measured torque noise floor below 10 fN m/square root of Hz from 0.6 to 10 mHz, has allowed placement of an upper limit on sensor force noise contributions, measurement of the sensor electrostatic stiffness at the 5% level, and detection and compensation of stray dc electrostatic biases at the millivolt level.

Analysis of pancreatic polypeptide cDNA from the house musk shrew, Suncus murinus, suggests a phylogenetically closer relationship with humans than for other small laboratory animal species.

Pancreatic polypeptide was isolated and sequenced from endocrine cells of the pancreas from an insectivore, the house musk shrew, Suncus murinus. The primary sequence was APLEPAYPGD(10)NATPEQMAQY(20)AAELRKYINM(30)VTRPRYamide. This is the first polypeptide hormone to be characterised from this species and is typical of the primary sequences of pancreatic polypeptide of other animals, being a C-terminal-amidated peptide with 36 residues. Comparison with several vertebrate sequences shows that it has more in common with the human form than do the forms from common laboratory animals such as rabbits, rats, mice and guinea-pigs.