The SED of the TeV BLLac 1ES 1426+428 after correction for the TeV--IR absorption

The recent HEGRA detection and spectrum of 1ES 1426+428 at TeV energies, once corrected for absorption using present estimates of the diffuse extragalactic IR background, suggest that the high energy peak of the Spectral Energy Distribution (SED) could be much higher than the synchrotron one ($L_c/L_s>10$), and lie at energies above 8-10 TeV. To see if such an SED could be accounted for, we have applied a "finite injection time" SSC model, and present here some preliminary results. Within this model, we found the need of an external ("ambient") contribution to the energy density of seed photons, in order to account for both the high Compton dominance and the hard spectrum.Comment: 4 pages, 5 figures, to appear in the proceedings of the conference "Relativistic jets in the Chandra and XMM era", Bologna, 23-27/9/02 (New Astr. Rev.

Observation of cosmic ray positrons from 5 to 25 GeV

The positron data gathered in conjunction with electron data published elsewhere is reported. The basic recognition scheme was to look for low mass positive particles that cause a cascade in a 7 radiation length shower counter. The mass criteria is imposed by selecting particles that were accompanied by Cherenkov light but whose rigidity was below the proton Cherenkov threshold. Thus the proton Cherenkov threshold represents an upper limit to the range of the experiment

Absolute rigidity spectrum of protons and helium nuclei above 10 GV/c

Proton and helium nuclei differential spectra were gathered with a balloon borne magnet spectrometer. The data were fitted to the assumption that the differential flux can be represented by a power law in rigidity. In the rigidity range 10 to 25 GV/c the spectral indices were found to be -(2.74 plus or minus 0.04) for protons and -(2.71 plus or minus 0.05) for helium nuclei. A brief discussion is given by systematic errors

Potential glucose monitoring of blood plasma using hollow core photonic crystal fibre

The ratio (ζ) of surface tension to viscosity of liquids can be determined using hollow core photonic crystal fibres (HCPCF), and we show here techniques to determine ζ of glucose levels within fluids, of nano-litre quantities. We demonstrate an optically integrated micro-capillary viscometer, to determine the concentrations of nano-litre solutions based on properties of their flow within HC-PCF. The filling of the fibres with liquids within a given range of refractive index will induce a shift in the photonic band gap of the fibre, allowing guidance of light at wavelengths that were originally outside the bandgap of the HC-PCF

The New Mexico State University Satellite (NMSUSat) Mission

The New Mexico State University Satellite (NMSUSat) is part of the University Nanosat 3 program managed by the Air Force Research Laboratory and it is being developed at New Mexico State University. The planned Science Mission for the satellite is to perform Near Ultra Violet emission intensity measurements of the earth\u27s upper atmosphere over the night side of the earth. The Engineering Mission is to demonstrate techniques for distributed data relaying over the Internet and to conduct an energy storage experiment to assess the operational characteristics of double layer capacitors. The Educational Mission of the program to assist in the further development of the aerospace engineering concentration area in the College of Engineering and to develop multi-disciplinary capstone and design classes for students in engineering departments, computer science, and the engineering physics program. This paper will discuss the preliminary design for the satellite components and how the mission segments will be worked among the participating departments at New Mexico State University

Expression of a Degradation‐Resistant β‐Catenin Mutant in Osteocytes Protects the Skeleton From Mechanodeprivation‐Induced Bone Wasting

Mechanical stimulation is a key regulator of bone mass, maintenance, and turnover. Wnt signaling is a key regulator of mechanotransduction in bone, but the role of β‐catenin—an intracellular signaling node in the canonical Wnt pathway—in disuse mechanotransduction is not defined. Using the β‐catenin exon 3 flox (constitutively active [CA]) mouse model, in conjunction with a tamoxifen‐inducible, osteocyte‐selective Cre driver, we evaluated the effects of degradation‐resistant β‐catenin on bone properties during disuse. We hypothesized that if β‐catenin plays an important role in Wnt‐mediated osteoprotection, then artificial stabilization of β‐catenin in osteocytes would protect the limbs from disuse‐induced bone wasting. Two disuse models were tested: tail suspension, which models fluid shift, and botulinum‐toxin (botox)‐induced muscle paralysis, which models loss of muscle force. Tail suspension was associated with a significant loss of tibial bone mass and density, reduced architectural properties, and decreased bone formation indices in uninduced (control) mice, as assessed by dual‐energy X‐ray absorptiometry (DXA), micro‐computed tomography (µCT), and histomorphometry. Activation of the βcatCA allele in tail‐suspended mice resulted in little to no change in those properties; ie, these mice were protected from bone loss. Similar protective effects were observed among botox‐treated mice when the βcatCA was activated. RNAseq analysis of altered gene regulation in tail‐suspended mice yielded 35 genes, including Wnt11, Gli1, Nell1, Gdf5, and Pgf, which were significantly differentially regulated between tail‐suspended β‐catenin stabilized mice and tail‐suspended nonstabilized mice. Our findings indicate that selectively targeting/blocking of β‐catenin degradation in bone cells could have therapeutic implications in mechanically induced bone disease

Principal components of thermal regimes in mountain river networks

Description of thermal regimes in flowing waters is key to understanding physical processes, enhancing predictive abilities, and improving bioassessments. Spatially and temporally sparse data sets, especially in logistically challenging mountain environments, have limited studies on thermal regimes, but inexpensive sensors coupled with crowd-sourced data collection efforts provide efficient means of developing large data sets for robust analyses. Here, thermal regimes are assessed using annual monitoring records compiled from several natural resource agencies in the northwestern United States that spanned a 5-year period (2011–2015) at 226 sites across several contiguous montane river networks. Regimes were summarized with 28 metrics and principal component analysis (PCA) was used to determine those metrics which best explained thermal variation on a reduced set of orthogonal axes. Four principal components (PC) accounted for 93.4&thinsp;% of the variation in the temperature metrics, with the first PC (49&thinsp;% of variance) associated with metrics that represented magnitude and variability and the second PC (29&thinsp;% of variance) associated with metrics representing the length and intensity of the winter season. Another variant of PCA, T-mode analysis, was applied to daily temperature values and revealed two distinct phases of spatial variability – a homogeneous phase during winter when daily temperatures at all sites were &lt;3&thinsp;∘C and a heterogeneous phase throughout the year's remainder when variation among sites was more pronounced. Phase transitions occurred in March and November, and coincided with the abatement and onset of subzero air temperatures across the study area. S-mode PCA was conducted on the same matrix of daily temperature values after transposition and indicated that two PCs accounted for 98&thinsp;% of the temporal variation among sites. The first S-mode PC was responsible for 96.7&thinsp;% of that variance and correlated with air temperature variation (r=0.92), whereas the second PC accounted for 1.3&thinsp;% of residual variance and was correlated with discharge (r=0.84). Thermal regimes in these mountain river networks were relatively simple and responded coherently to external forcing factors, so sparse monitoring arrays and small sets of summary metrics may be adequate for their description. PCA provided a computationally efficient means of extracting key information elements from the temperature data set used here and could be applied broadly to facilitate comparisons among more diverse stream types and develop classification schemes for thermal regimes.</p

Induction of Lrp5 HBM-causing mutations in Cathepsin-K expressing cells alters bone metabolism

High-bone-mass (HBM)-causing missense mutations in the low density lipoprotein receptor-related protein-5 (Lrp5) are associated with increased osteoanabolic action and protection from disuse- and ovariectomy-induced osteopenia. These mutations (e.g., A214V and G171V) confer resistance to endogenous secreted Lrp5/6 inhibitors, such as sclerostin (SOST) and Dickkopf homolog-1 (DKK1). Cells in the osteoblast lineage are responsive to canonical Wnt stimulation, but recent work has indicated that osteoclasts exhibit both indirect and direct responsiveness to canonical Wnt. Whether Lrp5-HBM receptors, expressed in osteoclasts, might alter osteoclast differentiation, activity, and consequent net bone balance in the skeleton, is not known. To address this, we bred mice harboring heterozygous Lrp5 HBM-causing conditional knock-in alleles to Ctsk-Cre transgenic mice and studied the phenotype using DXA, μCT, histomorphometry, serum assays, and primary cell culture. Mice with HBM alleles induced in Ctsk-expressing cells (TG) exhibited higher bone mass and architectural properties compared to non-transgenic (NTG) counterparts. In vivo and in vitro measurements of osteoclast activity, population density, and differentiation yielded significant reductions in osteoclast-related parameters in female but not male TG mice. Droplet digital PCR performed on osteocyte enriched cortical bone tubes from TG and NTG mice revealed that ~8–17% of the osteocyte population (depending on sex) underwent recombination of the conditional Lrp5 allele in the presence of Ctsk-Cre. Further, bone formation parameters in the midshaft femur cortex show a small but significant increase in anabolic action on the endocortical but not periosteal surface. These findings suggest that Wnt/Lrp5 signaling in osteoclasts affects osteoclastogenesis and activity in female mice, but also that some of the changes in bone mass in TG mice might be due to Cre expression in the osteocyte population

Sclerostin neutralization unleashes the osteoanabolic effects of Dkk1 inhibition

The WNT pathway has become an attractive target for skeletal therapies. High-bone-mass phenotypes in patients with loss-of-function mutations in the LRP5/6 inhibitor Sost (sclerosteosis), or in its downstream enhancer region (van Buchem disease), highlight the utility of targeting Sost/sclerostin to improve bone properties. Sclerostin-neutralizing antibody is highly osteoanabolic in animal models and in human clinical trials, but antibody-based inhibition of another potent LRP5/6 antagonist, Dkk1, is largely inefficacious for building bone in the unperturbed adult skeleton. Here, we show that conditional deletion of Dkk1 from bone also has negligible effects on bone mass. Dkk1 inhibition increases Sost expression, suggesting a potential compensatory mechanism that might explain why Dkk1 suppression lacks anabolic action. To test this concept, we deleted Sost from osteocytes in, or administered sclerostin neutralizing antibody to, mice with a Dkk1-deficient skeleton. A robust anabolic response to Dkk1 deletion was manifest only when Sost/sclerostin was impaired. Whole-body DXA scans, μCT measurements of the femur and spine, histomorphometric measures of femoral bone formation rates, and biomechanical properties of whole bones confirmed the anabolic potential of Dkk1 inhibition in the absence of sclerostin. Further, combined administration of sclerostin and Dkk1 antibody in WT mice produced a synergistic effect on bone gain that greatly exceeded individual or additive effects of the therapies, confirming the therapeutic potential of inhibiting multiple WNT antagonists for skeletal health. In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue

Clcn7F318L/+ as a new mouse model of Albers-Schönberg disease

Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2). More than 25 different CLCN7 mutations have been identified in patients affected with Albers-Schönberg disease, but only one mutation (Clcn7G213R) has been introduced in mice to create an animal model of this disease. Here we describe a mouse with a different osteopetrosis-causing mutation (Clcn7F318L). Compared to Clcn7+/+ mice, 12-week-old Clcn7F318L/+ mice have significantly increased trabecular bone volume, consistent with Clcn7F318L acting as a dominant negative mutation. Clcn7F318L/F318L and Clcn7F318L/G213R mice die by 1 month of age and resemble Clcn7 knockout mice, which indicate that p.F318L mutant protein is non-functional and p.F318L and p.G213R mutant proteins do not complement one another. Since it has been reported that treatment with interferon gamma (IFN-G) improves bone properties in Clcn7G213R/+ mice, we treated Clcn7F318L/+ mice with IFN-G and observed a decrease in osteoclast number and mineral apposition rate, but no overall improvement in bone properties. Our results suggest that the benefits of IFN-G therapy in patients with Albers-Schönberg disease may be mutation-specific