Serum levels of matrix metalloproteinases-2 and-9 and their tissue inhibitors in inflammatory neuromuscular disorders

We monitored serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) before and during intravenously applied immunoglobulin (IVIG) therapy in 33 patients with chronic immune-mediated neuropathies and myopathies and 15 controls. Baseline MMP-2 and TIMP-2 serum levels were lower and MMP-9 and TIMP-1 serum levels higher in all patients compared to age-matched controls. Eight days after IVIG treatment, MMP-2, TIMP-2, and TIMP-1 serum levels increased, while MMP-9 serum levels decreased, indicating tissue repair. After 60 days, MMP-9 levels increased, MMP-2 approached normal levels, while TIMP-1 and TIMP-2 serum levels were below day 8 levels, indicating relapsing tissue damage. Comparing the MMP/TIMP results with the clinical courses, IVIG treatment tended to change MMP/TIMP levels in a way that paralleled clinical improvement and relapse. In sum, during a distinct time period, IVIG therapy seems to be able to modulate VIMP-mediated tissue repair. Copyright (c) 2006 S. Karger AG, Basel

Electromagnetic channel capacity for practical purposes

We give analytic upper bounds to the channel capacity C for transmission of classical information in electromagnetic channels (bosonic channels with thermal noise). In the practically relevant regimes of high noise and low transmissivity, by comparison with know lower bounds on C, our inequalities determine the value of the capacity up to corrections which are irrelevant for all practical purposes. Examples of such channels are radio communication, infrared or visible-wavelength free space channels. We also provide bounds to active channels that include amplification.Comment: 6 pages, 3 figures. NB: the capacity bounds are constructed by generalizing to the multi-mode case the minimum-output entropy bounds of arXiv:quant-ph/0404005 [Phys. Rev. A 70, 032315 (2004)

Curves on Heisenberg invariant quartic surfaces in projective 3-space

This paper is about the family of smooth quartic surfaces $X \subset \mathbb{P}^3$ that are invariant under the Heisenberg group $H_{2,2}$. For a very general such surface $X$, we show that the Picard number of $X$ is 16 and determine its Picard group. It turns out that the general Heisenberg invariant quartic contains 320 smooth conics and that in the very general case, this collection of conics generates the Picard group.Comment: Updated references, corrected typo

A novel formulation technology for baculoviruses protects biopesticide from degradation by ultraviolet radiation

Biopesticides are biological pest control agents that are viewed as safer alternatives to the synthetic chemicals that dominate the global insecticide market. A major constraint on the wider adoption of biopesticides is their susceptibility to the ultraviolet (UV: 290–400 nm) radiation in sunlight, which limits their persistence and efficacy. Here, we describe a novel formulation technology for biopesticides in which the active ingredient (baculovirus) is micro-encapsulated in an ENTOSTAT wax combined with a UV absorbant (titanium dioxide, TiO2). Importantly, this capsule protects the sensitive viral DNA from degrading in sunlight, but dissolves in the alkaline insect gut to release the virus, which then infects and kills the pest. We show, using simulated sunlight, in both laboratory bioassays and trials on cabbage and tomato plants, that this can extend the efficacy of the biopesticide well beyond the few hours of existing virus formulations, potentially increasing the spray interval and/or reducing the need for high application rates. The new formulation has a shelf-life at 30 °C of at least 6 months, which is comparable to standard commercial biopesticides and has no phytotoxic effect on the host plants. Taken together, these findings suggest that the new formulation technology could reduce the costs and increase the efficacy of baculovirus biopesticides, with the potential to make them commercially competitive alternatives to synthetic chemicals

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

The unique ethical challenges of conducting research in the rehabilitation medicine population

BACKGROUND: The broad topic of research ethics is one which has been relatively well-investigated and discussed. Unique ethical issues have been identified for such populations as pediatrics, where the issues of consent and assent have received much attention, and obstetrics, with concerns such as the potential for research to cause harm to the fetus. However, little has been written about ethical concerns which are relatively unique to the population of patients seen by the practitioner of rehabilitation medicine. DISCUSSION: This paper reviews unique ethical concerns in conducting research in this population, including decision-making capacity, communication, the potential for subject overuse, the timing of recruitment, hope for a cure and therapeutic misconception and the nature of the health care provider-research subject relationship. SUMMARY: Researchers in the area of rehabilitation medicine should be aware of some of the unique ethical challenges posed by this patient population and should take steps to address any potential concerns in order to optimize subject safety and ensure that studies meet current ethical guidelines and standards

A prospective registry of emergency department patients admitted with infection

<p>Abstract</p> <p>Background</p> <p>Patients with infections account for a significant proportion of Emergency Department (ED) workload, with many hospital patients admitted with severe sepsis initially investigated and resuscitated in the ED. The aim of this registry is to systematically collect quality observational clinical and microbiological data regarding emergency patients admitted with infection, in order to explore in detail the microbiological profile of these patients, and to provide the foundation for a significant programme of prospective observational studies and further clinical research.</p> <p>Methods/design</p> <p>ED patients admitted with infection will be identified through daily review of the computerised database of ED admissions, and clinical information such as site of infection, physiological status in the ED, and components of management abstracted from patients' charts. This information will be supplemented by further data regarding results of investigations, microbiological isolates, and length of stay (LOS) from hospital electronic databases. Outcome measures will be hospital and intensive care unit (ICU) LOS, and mortality endpoints derived from a national death registry.</p> <p>Discussion</p> <p>This database will provide substantial insights into the characteristics, microbiological profile, and outcomes of emergency patients admitted with infections. It will become the nidus for a programme of research into compliance with evidence-based guidelines, optimisation of empiric antimicrobial regimens, validation of clinical decision rules and identification of outcome determinants. The detailed observational data obtained will provide a solid baseline to inform the design of further controlled trials planned to optimise treatment and outcomes for emergency patients admitted with infections.</p

Limit on Continuous Neutrino Emission from Neutron Stars

The timing data of the binary pulsar PSR1913+16, are used to establish an upper limit on the rate of continuous neutrino emission from neutron stars. Neutrino emission from each of the neutron stars of the binary system, increases the star binding energy and thus translates to a decrease in their masses. This in turn implies an increase with time of the binary period. Using the pulsar data we obtain an upper limit on the allowed rate of mass reduction : $| \dot{M}| <1.1 \times 10^{-12} yr^{-1} M$, where $M$ is the total mass of the binary. This constrains exotic nuclear equations of state that predict continuous neutrino emissions. The limit applies also to other channels of energy loss, e.g. axion emission. Continued timing measurements of additional binary pulsars, should yield a stronger limit in the future.Comment: 5 pages, Added a section on energy transport in the neutron star, JHEP publishe

Forward modelling of Kepler-band variability due to faculae and spots

Variability observed in photometric light curves of late-type stars (on time-scales longer than a day) is a dominant noise source in exoplanet surveys and results predominantly from surface manifestations of stellar magnetic activity, namely faculae and spots. The implementation of faculae in light-curve models is an open problem, with scaling typically based on spectra equivalent to hot stellar atmospheres or assuming a solar-derived facular contrast. We modelled rotational (single period) light curves of active G2, K0, M0, and M2 stars, with Sun-like surface distributions and realistic limb-dependent contrasts for faculae and spots. The sensitivity of light-curve variability to changes in model parameters such as stellar inclination, feature area coverage, spot temperature, facular region magnetic flux density, and active band latitudes is explored. For our light-curve modelling approach we used ACTRESS, a geometrically accurate model for stellar variability. ACTRESS generates two-sphere maps representing stellar surfaces and populates them with user-prescribed spot and facular region distributions. From this, light curves can be calculated at any inclination. Quiet star limb darkening and limb-dependent facular contrasts were derived from MURaM 3D magnetoconvection simulations using ATLAS9. 1D stellar atmosphere models were used for the spot contrasts. We applied ACTRESS in Monte Carlo simulations, calculating light-curve variability amplitudes in the Kepler band. We found that, for a given spectral type and stellar inclination, spot temperature and spot area coverage have the largest effect on variability of all simulation parameters. For a spot coverage of 1 per cent⁠, the typical variability of a solar-type star is around 2 parts per thousand. The presence of faculae clearly affects the mean brightness and light-curve shape, but has relatively little influence on the variability

Local Ca2+ signals couple activation of TRPV1 and ANO1 sensory ion channels

ANO1 (TMEM16A) is a Ca2+-activated Cl− channel (CaCC) expressed in peripheral somatosensory neurons that are activated by painful (noxious) stimuli. These neurons also express the Ca2+-permeable channel and noxious heat sensor TRPV1, which can activate ANO1. Here, we revealed an intricate mechanism of TRPV1-ANO1 channel coupling in rat dorsal root ganglion (DRG) neurons. Simultaneous optical monitoring of CaCC activity and Ca2+ dynamics revealed that the TRPV1 ligand capsaicin activated CaCCs. However, depletion of endoplasmic reticulum (ER) Ca2+ stores reduced capsaicin-induced Ca2+ increases and CaCC activation, suggesting that ER Ca2+ release contributed to TRPV1-induced CaCC activation. ER store depletion by plasma membrane–localized TRPV1 channels was demonstrated with an ER-localized Ca2+ sensor in neurons exposed to a cell-impermeable TRPV1 ligand. Proximity ligation assays established that ANO1, TRPV1, and the IP3 receptor IP3R1 were often found in close proximity to each other. Stochastic optical reconstruction microscopy (STORM) confirmed the close association between all three channels in DRG neurons. Together, our data reveal the existence of ANO1-containing multichannel nanodomains in DRG neurons and suggest that coupling between TRPV1 and ANO1 requires ER Ca2+ release, which may be necessary to enhance ANO1 activation