A study of acute respiratory disease in families exposed to different levels of Air pollution in the Great Salt Lake basin, Utah, 1971-1972 and 1972-1973.

The reported incidence of acute respiratory illness in families exposed to different concentrations of air pollution was studied during two consecutive school years. The purpose of the study was to determine the effect of increased exposure to sulfur dioxide and suspended particulate matter. In each of four study communities, the mothers of approximately 250 white families were contacted biweekly to obtain information regarding the occurrence of respiratory symptoms in each family member. Annual mean ambient sulfur dioxide concentrations in one community for the three years included in the study (1971-1973) were well above the current air quality standard of 80 micrograms/m3, while in the other three communities the annual sulfur dioxide concentrations were much lower (usually less than 40 micrograms/m3). Suspended particulate matter concentrations in high sulfur dioxide community were close to the limit designated by the annual standard (75 micrograms/m3) but actual exposures in the four communities probably were not excessive. Regression analyses of the data collected showed inconsistent associations between illness rates and educational attainment of the head of household, crowding in the home, bronchitis in parents or smoking of parents. However, once the effects of these factors were removed the adjusted rates showed little association with community of residence. It was concluded that the higher concentrations of sulfur dioxide in the Utah atmosphere could not be the cause of increases in acute respiratory illness in the exposed populations

Aluminum-implantation-induced deep levels in n-type 6H–SiC

Deep-level defect centers on the n-side of p+n junction diodes formed by low and elevated temperature aluminum-ion implantation into n-type 6H–SiC have been studied using deep-level transient spectroscopy. Two shallow Al-acceptor levels have been observed in the n region just beyond the implantation depth through their minority-carrier emission signatures. The dominant level is situated at 0.26 eV above the valence band and is accompanied by a shallower level of small intensity. Comparison with photoluminescence results suggests the dominant level (labeled Ak) and the shallower level (labeled Ah), are associated with the cubic and hexagonal lattice sites, respectively. Unlike previously reported results, which show many different implantation-induced donors within the implantation region, only one deep donor level at EC – 0.44 eV is found to occur in the postimplantation region, indicating that the various crystal damage sites occur with different spatial distributions. ©1998 American Institute of Physics.published_or_final_versio

Mergers and Mass Accretion Rates in Galaxy Assembly: The Millennium Simulation Compared to Observations of z~2 Galaxies

Recent observations of UV-/optically selected, massive star forming galaxies at z~2 indicate that the baryonic mass assembly and star formation history is dominated by continuous rapid accretion of gas and internal secular evolution, rather than by major mergers. We use the Millennium Simulation to build new halo merger trees, and extract halo merger fractions and mass accretion rates. We find that even for halos not undergoing major mergers the mass accretion rates are plausibly sufficient to account for the high star formation rates observed in z~2 disks. On the other hand, the fraction of major mergers in the Millennium Simulation is sufficient to account for the number counts of submillimeter galaxies (SMGs), in support of observational evidence that these are major mergers. When following the fate of these two populations in the Millennium Simulation to z=0, we find that subsequent mergers are not frequent enough to convert all z~2 turbulent disks into elliptical galaxies at z=0. Similarly, mergers cannot transform the compact SMGs/red sequence galaxies at z~2 into observed massive cluster ellipticals at z=0. We argue therefore, that secular and internal evolution must play an important role in the evolution of a significant fraction of z~2 UV-/optically and submillimeter selected galaxy populations.Comment: 5 pages, 4 figures, Accepted for publication in Ap

Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

<p>Abstract</p> <p>Background</p> <p>The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the <it>myelin protein zero (MPZ) </it>gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P₀) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P₀ex) is known, while the transmembrane and intracellular structure is unknown.</p> <p>Findings</p> <p>One novel missense mutation caused a milder late onset CMT type 2, while the second missense mutation caused a severe early onset phenotype compatible with Déjérine-Sottas syndrome.</p> <p>Conclusions</p> <p>The phenotypic variation caused by different missense mutations in the <it>MPZ </it>gene is likely caused by different conformational changes of the MPZ protein which affects the functional tetramers. Severe changes of the MPZ protein cause dysfunctional tetramers and predominantly uncompacted myelin, i.e. the severe phenotypes congenital hypomyelinating neuropathy and Déjérine-Sottas syndrome, while milder changes cause the phenotypes CMT type 1 and 2.</p

Non-surgical spinal decompression therapy: does the scientific literature support efficacy claims made in the advertising media?

<p>Abstract</p> <p>Background</p> <p>Traction therapy has been utilized in the treatment of low back pain for decades. The most recent incarnation of traction therapy is non-surgical spinal decompression therapy which can cost over $100,000. This form of therapy has been heavily marketed to manual therapy professions and subsequently to the consumer. The purpose of this paper is to initiate a debate pertaining to the relationship between marketing claims and the scientific literature on non-surgical spinal decompression.</p> <p>Discussion</p> <p>Only one small randomized controlled trial and several lower level efficacy studies have been performed on spinal decompression therapy. In general the quality of these studies is questionable. Many of the studies were performed using the VAX-D^®unit which places the patient in a prone position. Often companies utilize this research for their marketing although their units place the patient in the supine position.</p> <p>Summary</p> <p>Only limited evidence is available to warrant the routine use of non-surgical spinal decompression, particularly when many other well investigated, less expensive alternatives are available.</p

Tube Models for Rubber-Elastic Systems

In the first part of the paper we show that the constraining potentials introduced to mimic entanglement effects in Edwards' tube model and Flory's constrained junction model are diagonal in the generalized Rouse modes of the corresponding phantom network. As a consequence, both models can formally be solved exactly for arbitrary connectivity using the recently introduced constrained mode model. In the second part, we solve a double tube model for the confinement of long paths in polymer networks which is partially due to crosslinking and partially due to entanglements. Our model describes a non-trivial crossover between the Warner-Edwards and the Heinrich-Straube tube models. We present results for the macroscopic elastic properties as well as for the microscopic deformations including structure factors.Comment: 15 pages, 8 figures, Macromolecules in pres

Novel human liver-tropic AAV variants define transferable domains that markedly enhance the human tropism of AAV7 and AAV8

Recent clinical successes have intensified interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. The liver is a key clinical target, given its critical physiological functions and involvement in a wide range of genetic diseases. Here, we report the bioengineering of a set of next-generation AAV vectors, named AAV-SYDs (where “SYD” stands for Sydney, Australia), with increased human hepato-tropism in a liver xenograft mouse model repopulated with primary human hepatocytes. We followed a two-step process that staggered directed evolution and domain-swapping approaches. Using DNA-family shuffling, we first mapped key AAV capsid regions responsible for efficient human hepatocyte transduction in vivo. Focusing on these regions, we next applied domain-swapping strategies to identify and study key capsid residues that enhance primary human hepatocyte uptake and transgene expression. Our findings underscore the potential of AAV-SYDs as liver gene therapy vectors and provide insights into the mechanism responsible for their enhanced transduction profile

Aluminum and electron-irradiation induced deep-levels in n-type and p-type 6H-SiC

Two deep levels, located at Ev+0.26eV and Ec-0.44eV, in Al-implanted n-type samples and one at Ev+0.48eV in p-type samples have been observed by the deep level transient spectroscopy. The level of Ev+0.26eV is identified as the shallower aluminum-acceptor. The 1.7 MeV electron-irradiation, used as a probe to distinguish the implantation induced deep-levels, induces at least six electron traps in the n-SiC and one hole-trap in the p-type material. The peak positions of these deep-levels in DLTS spectra are quite different from those induced by Al-implantation. This result suggests that various damages are formed after heavy ion (Al) and light particle (e') irradiation.published_or_final_versio

Attenuation of Heparan Sulfate Proteoglycan Binding Enhances In Vivo Transduction of Human Primary Hepatocytes with AAV2

Use of the prototypical adeno-associated virus type 2 (AAV2) capsid delivered unexpectedly modest efficacy in an early liver-targeted gene therapy trial for hemophilia B. This result is consistent with subsequent data generated in chimeric mouse-human livers showing that the AAV2 capsid transduces primary human hepatocytes in vivo with low efficiency. In contrast, novel variants generated by directed evolution in the same model, such as AAV-NP59, transduce primary human hepatocytes with high efficiency. While these empirical data have immense translational implications, the mechanisms underpinning this enhanced AAV capsid transduction performance in primary human hepatocytes are yet to be fully elucidated. Remarkably, AAV-NP59 differs from the prototypical AAV2 capsid by only 11 aa and can serve as a tool to study the correlation between capsid sequence/structure and vector function. Using two orthogonal vectorological approaches, we have determined that just 2 of the 11 changes present in AAV-NP59 (T503A and N596D) account for the enhanced transduction performance of this capsid variant in primary human hepatocytes in vivo, an effect that we have associated with attenuation of heparan sulfate proteoglycan (HSPG) binding affinity. In support of this hypothesis, we have identified, using directed evolution, two additional single amino acid substitution AAV2 variants, N496D and N582S, which are highly functional in vivo. Both substitution mutations reduce AAV2's affinity for HSPG. Finally, we have modulated the ability of AAV8, a highly murine-hepatotropic serotype, to interact with HSPG. The results support our hypothesis that enhanced HSPG binding can negatively affect the in vivo function of otherwise strongly hepatotropic variants and that modulation of the interaction with HSPG is critical to ensure maximum efficiency in vivo. The insights gained through this study can have powerful implications for studies into AAV biology and capsid development for preclinical and clinical applications targeting liver and other organs