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Background: Approximately 12-15% of patients with intracranial aneurysms (IA) have affected first-degree relatives, and are considered to have familial intracranial aneurysms (FIA). Individuals with FIA are at higher risk for aneurysm formation and subarachnoid hemorrhage. THSD1 is the only gene to be associated with nonsyndromic FIA at this time. Our study aims to find rare DNA variants that are major risk factors for FIA in our cohort of patients. Methods: To date we have enrolled 37 affected and 31 unaffected people from 16 families. We have done exome or genome sequencing on at least 1 person from each of 12 families. Results: A rare p.(R686W) variant in THSD1 was found in 1/12 families, but did not cosegregate fully with disease. While less attractive as the primary cause of FIA, we cannot rule out the potential modifying effects of THSD1 p.(R686W) in this family. A second candidate, an extracellular matrix gene within a chromosomal region previously implicated by familial mapping studies, contains rare variants in 4/12 of our families. All four variants are predicted to be damaging. Conclusions: Alongside environmental risk factors, individual FIA families may also have complex rare variant contributions to their disease, such as digenic and multi-locus contributions.
The Fezzan Project completed its five-year fieldwork cycle in 2001. The geographical research team located numerous additional palaeolake sites within the Edeyen Ubari, using a combination of Remote Sensing technology and field visits. Additional samples were taken for analysis and dating from many lake edge locations, relating to both the large Pleistocene lake and to the numerous smaller Holocene lakes that have been identified by the team. The excavations at Old Germa were taken down through Garamantian occupation levels to the natural subsoil below the earliest cultural horizon. The earliest activity, represented by a few mudbrick walls and hearths built directly on the natural soil, is believed to date to c. 400-300 BC. Traces of several phases of Garamantian buildings were uncovered, along with numerous rubbish pits, which yielded a rich assemblage of finds, including, for the first time, examples of Garamantian figurines, small 3-D sculptures of humans and animals. Work on the various classes of finds (pottery, small finds, lithics and other stone artefacts, metallurgical evidence, etc.) complemented the excavation work. In addition, a small amount of further survey work was carried out on sites in the Wadi al-Ajal, along with a contour survey of Old Germa and standing building survey at a number of other sites.
Chagas disease is an important emerging disease in Texas that results in cardiomyopathy in about 30% of those infected with the parasite Trypanosoma cruzi. Between the years 2008 and 2012, about 1/6500 blood donors were T. cruzi antibody-confirmed positive. We found older persons and minority populations, particularly Hispanic, at highest risk for screening positive for T. cruzi antibodies during routine blood donation. Zip code analysis determined that T. cruzi is associated with poverty. Chagas disease has a significant disease burden and is a cause of substantial economic losses in Texas.
A subpopulation (~10%) of hot, luminous, massive stars have been revealed through spectropolarimetry to harbor strong (hundreds to tens of thousand Gauss), steady, large-scale (often significantly dipolar) magnetic fields. This review focuses on the role of such fields in channeling and trapping the radiatively driven wind of massive stars, including both in the strongly perturbed outflow from open field regions, and the wind-fed “magnetospheres” that develop from closed magnetic loops. For B-type stars with weak winds and moderately fast rotation, one finds “centrifugal magnetospheres”, in which rotational support allows magnetically trapped wind to accumulate to a large density, with quite distinctive observational signatures, e.g. in Balmer line emission. In contrast, more luminous O-type stars have generally been spun down by magnetic braking from angular momentum loss in their much stronger winds. The lack of centrifugal support means their closed loops form a “dynamical magnetosphere”, with trapped material falling back to the star on a dynamical timescale; nonetheless, the much stronger wind feeding leads to a circumstellar density that is still high enough to give substantial Balmer emission. Overall, this review describes MHD simulations and semi-analytic dynamical methods for modeling the magnetospheres, the magnetically channeled wind outflows, and the associated spin-down of these magnetic massive stars.
New poly(fluorene-thiophene) alternating copolymers are described in which either the dioctylfluorene or bithiophene units in poly(9,9-dioctylfluorene-alt-bithiophene) (F8T2) are replaced by other fluorene or thiophene-based groups, respectively. Improvements in solubility are realized when the bithiophene unit of F8T2 is replaced by dihexylterthiophene or dihexylpentathiophene units. Melting temperatures are also lowered by 50 – 100°C in these polymers when compared to F8T2. Replacement of the bithiophene unit of F8T2 with a dihexylpentathiophene unit also results in a significant improvement in hysteresis (< 2 V vs. 3.5 – 5 V for F8T2). Initial results are also reported on the thermal cleavage of the C8 side groups of F8T2, which yields an insoluble polymeric semiconductor film that continues to exhibit transistor switching characteristics as part of a bottom gate device.
Stresses in WSi2 films prepared by chemical vapor deposition have been examined using an optically levered laser beam during typical processing cycles to 900 C. Initial heating produces tensile stress levels of 1.0 GPa at 500 C with crystallization into the inetastable hexagonal form. Cooling from this temperature results in room temperature stresses of 1.2 GPa. A large decrease in the tensile stress level accompanies the transformation into the stable tetragonal structure during heating from 500 C to 750 C. Films in this form are mechanically stable and respond elastically to further thermal cycling.
Films of TaSi2 sputtered from an intermetallic target and co-sputtered from elemental targets have also been investigated. Initial heating of films sputtered from the intermetallic target produces a tensile stress state during crystallization which is high but slightly less than observed during crystallization of WSi2. This high tensile state is not observed in films deposited in layers from elemental targets. The appearance of a metastable phase is not observed for intermediate anneals in either case. The initial crystallization results in the stable phase of hexagonal TaSi2. Fully annealed films are elastic below 920 C.
Polymeric materials are used as interlayer dielectrics for multichip modules. One of the central challenges for these structures is management of the large stresses induced by the differences in the thermal properties of the inorganic component structures and the organic film during processing.
Finite clement analysis has been used to model the stresses in the dielectric material in practical structures used in multilayer microelectronic architecture, such as interlayer vias and the associated internal metal patterns. Calculations have been performed on the stress field at the corner of square vias in benzocyclobutcne based interlayer dielectrics and related polymeric materials. The effects of the thermal and mechanical properties of the polymeric coating on the stress fields in metal patterns have been calculated and provide insight for design and process optimization.
This work reviews the dependence of reliability testing results on material processing and properties for polymeric materials used in high density interconnection technologies.Specific data are presented for CyclotenesTM 3022 resins containing divinylsiloxane bisbenzocyclobutene, (CAS 117732-87-3). Silane coupling agents discussed in this study are 3-aminopropyltriethoxysilane (CAS 01760-24-3)(APTES) and 3-methacryloxypropyl trimethoxysilane (CAS 02530-85-0) (MOP-TMS).
Wafer bending measurements have been used to study the glass transition temperature, Tg, of thin coatings of polystyrene and polycarbonate on Si wafers. The observed values of Tg agree with DSC and TMA measurements on bulk samples. The evolution of the substrate curvature has been used to examine the behavior of Tg in thin epoxy films and coatings derived from divinylsiloxane bisbenzocyclobutene, mixed stereo and positional isomers of 1, 3-bis(2-bicyclo[4.2.0]octa-1, 3, 5-trien-3-ylethenyl)-1, 1, 3, 3-tetramethyl disitoxane (CAS 117732–87–3). The dependence of the Tg of the epoxide coatings is studied as a function of the cross-linking. The evolution of the Tg in the benzocyclobutene coating is found to be a monotonie function of the level of conversion of the polymer network.
Measurements of the elastic modulus of fused silica, 6061-T6 and 7075-T651 aluminum alloys, GaAs, Ge, and Si samples are reported. A pulsed laser is used to generate surface acoustic waves in a sample and the wave velocity is measured using a knife-edge detection method. From the velocity of the surface waves the elastic modulus can be calculated. Extension of this work to thin films is discusssed.
Free-standing films of gold and aluminum have been fabricated using standard micro-machining techniques. LPCVD silicon nitride films are deposited onto (100) silicon wafers. Square and rectangular silicon nitride membranes are made by anisotropic etching of the silicon substrates. Then, metal films are deposited onto the silicon nitride membranes by means of evaporation. Finally, the sacrificial silicon nitride film is etched away by means of reactive plasma etching, resulting in well-defined, square and rectangular metal membranes.
Bulge testing of square windows allows one to determine the biaxial modulus of the film as well as the residual stress in it. Testing rectangular windows yields the plane-strain elastic modulus and the residual stress. Since deformation in rectangular membranes approaches plane-strain deformation, this geometry is ideal for studying the plastic properties of the metal films. Stress-strain curves can be readily determined from the load-deflection curves of rectangular membranes. The gold films have a biaxial modulus of 161±3 GPa and a plane-strain modulus of 105±5 GPa, slightly lower than the literature values for a (111) textured film. The yield stress of these films is approximately 231±17 MPa at 10−4% plastic strain. The elastic moduli of the aluminum films are 105±3 GPa and 76.4±0.7 GPa, respectively; the yield stress of these films is 187±30MPa.
The dependence of solid phase epitaxial growth in Si on uniaxial compression applied perpendicular to the amorphous-crystal interface is investigated. Long, thin pure Si bars of square cross section are ion-implanted to produce amorphous layers on the end faces. The bars are placed end-to-end and uniaxially loaded at temperature to partially regrow the amorphous layers. The resulting growth rates are measured ex situ by re-heating the samples on a hot stage and using time-resolved reflectivity to deduce interface depths. Preliminary results are that uniaxial compression is more effective than hydrostatic pressure for enhancing the growth rate, in qualitative but not quantitative agreement with previously made predictions.
Molecular dynamics computer simulations of the growth processes and microstructural properties of amorphous carbon (a:C) and amorphous hydrogenated carbon (a:CH) ultra-thin films have been performed. Films 1 to 10 nm thick were grown on a diamond (100) surface using Brenner’s[1–2] bond-order potential for hydrocarbons. The stoichiometry, radial distribution function, chemical bonding (amount of sp2 and sp3 hybridization) and residual stress are presented.
Thermal stress influences adhesion of many coatings applied on tool substrates. Management of thermal stresses is important for improvement of coatings and tool life. We have shown that stresses can be controlled by developing a composite layer of diamond with carbides and nitrides such as TiC or TiN. We have modeled the thermal stresses in these composite diamond coatings using finite element analysis. The composite diamond coatings consist of a discontinuous layer of diamond with an embedded layer of TiC or TiN, and a top layer of continuous diamond. For comparison, a single layer of diamond coating has also been used. The thermal stresses in these coatings on WC(Co) and Si3N4 tool substrates were calculated. Results show that the thermal stresses at the interface between the coatings and the substrate are relaxed after introducing the composite layers. This stress relaxation is responsible for the improvement of the adhesion of composite coatings.
Using ion beam assisted deposition, 1.5–2.2 μm thick molybdenum and nickel films were prepared on silicon substrates. Some films were found to be strongly textured. By changing the rate of Ar+ bombardment during the deposition, the resulting in-plane film stresses could be changed from being strongly tensile to strongly compressive. Using nanoindentation, the hardness and elastic modulus were measured for all films, but no major influence of the film stress or different textures could be found. The elastic modulus of the Ni films was found to be close to its polycrystalline bulk value, and that of Mo was found to be about 70% of its polycrystalline bulk value.
Nanocrytslline composite films of Ag-Mo and Ag-Ni have been made by a co-deposition technique in UHV. The structure and composition have been studied by x-ray diffraction (XRD), transmission electron microscopy (TEM), and electron probe microanalysis (EPMA). For practical applications, the friction coefficient and wear rate were measured using a pin-on-plate machine for Ag-Mo composites deposited on steel. For fundamental studies, the hardness of the Ag-Ni composites deposited on oxidized Si wafers was measured using a nanoindenter. Experiments show that (1) reduction of friction and wear rate can be achieved using these nanocomposite coatings and (2) the hardness of the nanocomposites depends on the grain size. As the grain size of the Ag decreases from 100 to 10 nm, the hardness increases about 4 times.
Fracture behavior in Ni-10 wt.%P amorphous (10 µm thick) and overlay Y2O3 stabilized ZrO2 (0-1.0 µm thick) ceramic coatings on Al alloy substrates has been investigated using small punch (SP) testing and acoustic emission (AE) techniques. SP tests showed that coating cracks extensively propagate along both the radial and tangential directions under the biaxial stress condition. The formation of cracks was more profoundly found in Ni-P amorphous coatings than in amorphous/ceramic coatings. The cumulative AE events were well correlated with the severity of coating cracking independent of the type of coatings. Ceramic coatings with a thickness of 0.25 and 1.0 µm led to a decrease in the fracture toughness by 15–20%, compared with a uncoated alloy. The coating effect on the fracture toughness is discussed in light of residual stresses induced during coating processing and the presence of coating cracks.
The growth of hillocks and voids in metal films was studied. The applicability of a model involving fractals and kinetic equations was examined on the basis of whether there is independent justification for using scaling arguments in the model and whether there is reason to connect the evolution of hillocks with that of voids. Hillocks and voids were found to be self-similar across about three orders of magnitude of variation in spatial scale with the same fractal dimension. Voids and hillocks were found to have the same fractal dimension whether studied using atomic force microscopy (AFM) or scanning electron microscopy (SEM). The parameters obtained from these fractal analyses demonstrate quantitative internal consistency with an earlier time dependent study of thermal annealing effects on hillock distributions. Remarkably, area-perimeter data obtained from either a long-time study of a single void or a spatial average of a large number of different voids both yield quantitatively identical results.
Multilayer interconnection structures incorporating a novel polymeric dielectric derived from a bis-benzocyclobutene(bis-BCB) monomer have been fabricated. This paper discusses the processing conditions for the construction of these circuits and describes electrical characteristics of the dielectric layers. The relative dielectric constant of the BCB film was 2.7. Thermal cycling produced no significant change in the conductance of three level metal via chains through two layers of the polymer.