Four-dimensional modulation and coding: An alternate to frequency-reuse

Four dimensional modulation as a means of improving communication efficiency on the band-limited Gaussian channel, with the four dimensions of signal space constituted by phase orthogonal carriers (cos omega sub c t and sin omega sub c t) simultaneously on space orthogonal electromagnetic waves are discussed. "Frequency reuse' techniques use such polarization orthogonality to reuse the same frequency slot, but the modulation is not treated as four dimensional, rather a product of two-d modulations, e.g., QPSK. It is well known that, higher dimensionality signalling affords possible improvements in the power bandwidth sense. Four-D modulations based upon subsets of lattice-packings in four-D, which afford simplification of encoding and decoding are described. Sets of up to 1024 signals are constructed in four-D, providing a (Nyquist) spectral efficiency of up to 10 bps/Hz. Energy gains over the reuse technique are in the one to three dB range t equal bandwidth

Cardiac Gene Transfer of Short Hairpin RNA Directed Against Phospholamban Effectively Knocks Down Gene Expression but Causes Cellular Toxicity in Canines

Derangements in calcium cycling have been described in failing hearts, and preclinical studies have suggested that therapies aimed at correcting this defect can lead to improvements in cardiac function and survival. One strategy to improve calcium cycling would be to inhibit phospholamban (PLB), the negative regulator of SERCA2a that is upregulated in failing hearts. The goal of this study was to evaluate the safety and efficacy of using adeno-associated virus (AAV)-mediated cardiac gene transfer of short hairpin RNA (shRNA) to knock down expression of PLB. Six dogs were treated with self-complementary AAV serotype 6 (scAAV6) expressing shRNA against PLB. Three control dogs were treated with empty AAV6 capsid, and two control dogs were treated with scAAV6 expressing dominant negative PLB. Vector was delivered via a percutaneously inserted cardiac injection catheter. PLB mRNA and protein expression were analyzed in three of six shRNA dogs between days 16 and 26. The other three shRNA dogs and five control dogs were monitored long-term to assess cardiac safety. PLB mRNA was reduced 16-fold, and PLB protein was reduced 5-fold, with treatment. Serum troponin elevation and depressed cardiac function were observed in the shRNA group only at 4 weeks. An enzyme-linked immunospot assay failed to detect any T cells reactive to AAV6 capsid in peripheral blood mononuclear cells, heart, or spleen. Microarray analysis revealed alterations in cardiac expression of several microRNAs with shRNA treatment. AAV6-mediated cardiac gene transfer of shRNA effectively knocks down PLB expression but is associated with severe cardiac toxicity. Toxicity may result from dysregulation of endogenous microRNA pathways

High‐Frequency Dissolved Organic Carbon and Nitrate Measurements Reveal Differences in Storm Hysteresis and Loading in Relation to Land Cover and Seasonality

Storm events dominate riverine loads of dissolved organic carbon (DOC) and nitrate and are expected to increase in frequency and intensity in many regions due to climate change. We deployed three high‐frequency (15 min) in situ absorbance spectrophotometers to monitor DOC and nitrate concentration for 126 storms in three watersheds with agricultural, urban, and forested land use/land cover. We examined intrastorm hysteresis and the influences of seasonality, storm size, and dominant land use/land cover on storm DOC and nitrate loads. DOC hysteresis was generally anticlockwise at all sites, indicating distal and plentiful sources for all three streams despite varied DOC character and sources. Nitrate hysteresis was generally clockwise for urban and forested sites, but anticlockwise for the agricultural site, indicating an exhaustible, proximal source of nitrate in the urban and forested sites, and more distal and plentiful sources of nitrate in the agricultural site. The agricultural site had significantly higher storm nitrate yield per water yield and higher storm DOC yield per water yield than the urban or forested sites. Seasonal effects were important for storm nitrate yield in all three watersheds and farm management practices likely caused complex interactions with seasonality at the agricultural site. Hysteresis indices did not improve predictions of storm nitrate yields at any site. We discuss key lessons from using high‐frequency in situ optical sensors

Long-Term Systemic Myostatin Inhibition via Liver-Targeted Gene Transfer in Golden Retriever Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a lethal, X-linked recessive disease affecting 1 in 3,500 newborn boys for which there is no effective treatment or cure. One novel strategy that has therapeutic potential for DMD is inhibition of myostatin, a negative regulator of skeletal muscle mass that may also promote fibrosis. Therefore, our goal in this study was to evaluate systemic myostatin inhibition in the golden retriever model of DMD (GRMD). GRMD canines underwent liver-directed gene transfer of a self-complementary adeno-associated virus type 8 vector designed to express a secreted dominant-negative myostatin peptide (n =4) and were compared with age-matched, untreated GRMD controls (n =3). Dogs were followed with serial magnetic resonance imaging (MRI) for 13 months to assess cross-sectional area and volume of skeletal muscle, then euthanized so that tissue could be harvested for morphological and histological analysis. We found that systemic myostatin inhibition resulted in increased muscle mass in GRMD dogs as assessed by MRI and confirmed at tissue harvest. We also found that hypertrophy of type IIA fibers was largely responsible for the increased muscle mass and that reductions in serum creatine kinase and muscle fibrosis were associated with long-term myostatin inhibition in GRMD. This is the first report describing the effects of long-term, systemic myostatin inhibition in a large-animal model of DMD, and we believe that the simple and effective nature of our liver-directed gene-transfer strategy makes it an ideal candidate for evaluation as a novel therapeutic approach for DMD patients

The Effect of Arc Proximity on Hydrothermal Activity Along Spreading Centers: New Evidence From the Mariana Back Arc (12.7°N-18.3°N)

Back-arc spreading centers (BASCs) form a distinct class of ocean spreading ridges distinguished by steep along-axis gradients in spreading rate and by additional magma supplied through subduction. These characteristics can affect the population and distribution of hydrothermal activity on BASCs compared to mid-ocean ridges (MORs). To investigate this hypothesis, we comprehensively explored 600 km of the southern half of the Mariana BASC. We used water column mapping and seafloor imaging to identify 19 active vent sites, an increase of 13 over the current listing in the InterRidge Database (IRDB), on the bathymetric highs of 7 of the 11 segments. We identified both high and low (i.e., characterized by a weak or negligible particle plume) temperature discharge occurring on segment types spanning dominantly magmatic to dominantly tectonic. Active sites are concentrated on the two southernmost segments, where distance to the adjacent arc is shortest (48 mm/yr), and tectonic extension is pervasive. Re-examination of hydrothermal data from other BASCs supports the generalization that hydrothermal site density increases on segments <90 km from an adjacent arc. Although exploration quality varies greatly among BASCs, present data suggest that, for a given spreading rate, the mean spatial density of hydrothermal activity varies little between MORs and BASCs. The present global database, however, may be misleading. On both BASCs and MORs, the spatial density of hydrothermal sites mapped by high-quality water-column surveys is 2–7 times greater than predicted by the existing IRDB trend of site density versus spreading rate

Therapeutic Neonatal Hepatic Gene Therapy in Mucopolysaccharidosis VII Dogs

Dogs with mucopolysaccharidosis VII (MPS VII) were injected intravenously at 2–3 days of age with a retroviral vector (RV) expressing canine β-glucuronidase (cGUSB). Five animals received RV alone, and two dogs received hepatocyte growth factor (HGF) before RV in an attempt to increase transduction efficiency. Transduced hepatocytes expanded clonally during normal liver growth and secreted enzyme with mannose 6-phosphate. Serum GUSB activity was stable for up to 14 months at normal levels for the RV-treated dogs, and for 17 months at 67-fold normal for the HGF/RV-treated dog. GUSB activity in other organs was 1.5–60% of normal at 6 months for two RV-treated dogs, which was likely because of uptake of enzyme from blood by the mannose 6-phosphate receptor. The body weights of untreated MPS VII dogs are 50% of normal at 6 months. MPS VII dogs cannot walk or stand after 6 months, and progressively develop eye and heart disease. RV- and HGF/RV-treated MPS VII dogs achieved 87% and 84% of normal body weight, respectively. Treated animals could run at all times of evaluation for 6–17 months because of improvements in bone and joint abnormalities, and had little or no corneal clouding and no mitral valve thickening. Despite higher GUSB expression, the clinical improvements in the HGF/RV-treated dog were similar to those in the RV-treated animals. This is the first successful application of gene therapy in preventing the clinical manifestations of a lysosomal storage disease in a large animal

Acute Effects of Dry Needling on Myofascial Trigger Points in the Triceps Surae of Ballet Dancers: A Pilot Randomized Controlled Trial

# Background There is convincing evidence that dancers suffer injuries to the triceps surae musculature. Research on the immediate effects of dry needling (DN) is limited, and it is important to understand the acute effects of this treatment prior to performance. # Purpose The purpose of this pilot study was to assess the immediate effects of DN on myofascial trigger points in terms of skin surface temperature, pain, active and passive range of motion, and torque production in the triceps surae of ballet dancers. # Study Design Randomized, double-blinded pilot study # Methods Professional ballet dancers that fit inclusion and exclusion criteria (n=11) were randomly assigned to an experimental or control group. The dancers had three pre-determined standard point (SP) measurement spots that were used as a baseline for surface temperature comparisons. The dancers were also palpated for trigger point (TP) spots. Both SP and TP spots were marked for future measurements. The experimental group received DN, while the control group received sham DN (SHAM) to their bilateral calves at the TP spots. Immediately prior to and following treatment, both DN and SHAM groups were tested for skin surface temperature, pain, range of motion, and plantar flexion torque by blinded assessors. Paired t-tests and independent t-tests were performed to examine for differences between groups. # Results The surface temperature for the TP was higher than the SP measurements prior to intervention (Right calf p= .014; Left calf p= .031). There were no significant changes in VAS scale reported pain and ROM. The plantar flexion torque measurements showed an increase in the DN group of the left calf at the angular velocity of 60 degrees/sec. # Conclusion This was a unique pilot study examining the acute effects of DN on professional ballet dancers. The results were limited due to low sample size. However, the methodology for this study and surface temperature results invites future research. # Level of evidence Level 1

The practical politics of sharing personal data

The focus of this paper is upon how people handle the sharing of personal data as an interactional concern. A number of ethnographic studies of domestic environments are drawn upon in order to articulate a range of circumstances under which data may be shared. In particular a distinction is made between the in situ sharing of data with others around you and the sharing of data with remote parties online. A distinction is also drawn between circumstances of purposefully sharing data in some way and circumstances where the sharing of data is incidental or even unwitting. On the basis of these studies a number of the organisational features of how people seek to manage the ways in which their data is shared are teased out. The paper then reflects upon how data sharing practices have evolved to handle the increasing presence of digital systems in people’s environments and how these relate to the ways in which people traditionally orient to the sharing of information. In conclusion a number of ways are pointed out in which the sharing of data remains problematic and there is a discussion of how systems may need to adapt to better support people’s data sharing practices in the future