Film bulk acoustic resonators integrated on arbitrary substrates using a polymer support layer

The film bulk acoustic resonator (FBAR) is a widely-used MEMS device which can be used as a filter, or as a gravimetric sensor for biochemical or physical sensing. Current device architectures require the use of an acoustic mirror or a freestanding membrane and are fabricated as discrete components. A new architecture is demonstrated which permits fabrication and integration of FBARs on arbitrary substrates. Wave confinement is achieved by fabricating the resonator on a polyimide support layer. Results show when the polymer thickness is greater than a critical value, d, the FBARs have similar performance to devices using alternative architectures. For ZnO FBARs operating at 1.3–2.2 GHz, d is ~9 μm, and the devices have a Q-factor of 470, comparable to 493 for the membrane architecture devices. The polymer support makes the resonators insensitive to the underlying substrate. Yields over 95% have been achieved on roughened silicon, copper and glass

Film bulk acoustic resonator pressure sensor with self temperature reference

A novel film bulk acoustic resonator (FBAR) with two resonant frequencies which have opposite reactions to temperature changes has been designed. The two resonant modes respond differently to changes in temperature and pressure, with the frequency shift being linearly correlated with temperature and pressure changes. By utilizing the FBAR's sealed back trench as a cavity, an on-chip single FBAR sensor suitable for measuring pressure and temperature simultaneously is proposed and demonstrated. The experimental results show that the pressure coefficient of frequency for the lower frequency peak of the FBAR sensors is approximately −17.4 ppm kPa−1, while that for the second peak is approximately −6.1 ppm kPa−1, both of them being much more sensitive than other existing pressure sensors. This dual mode on-chip pressure sensor is simple in structure and operation, can be fabricated at very low cost, and yet requires no specific package, therefore has great potential for applications

Flexible surface acoustic wave resonators built on disposable plastic film for electronics and lab-on-a-chip applications

Flexible electronics are a very promising technology for various applications. Several types of flexible devices have been developed, but there has been limited research on flexible electromechanical systems (MEMS). Surface acoustic wave (SAW) devices are not only an essential electronic device, but also are the building blocks for sensors and MEMS. Here we report a method of making flexible SAW devices using ZnO nanocrystals deposited on a cheap and bendable plastic film. The flexible SAW devices exhibit two wave modes - the Rayleigh and Lamb waves with resonant frequencies of 198.1 MHz and 447.0 MHz respectively, and signal amplitudes of 18 dB. The flexible devices have a high temperature coefficient of frequency, and are thus useful as sensitive temperature sensors. Moreover, strong acoustic streaming with a velocity of 3.4 cm/s and particle concentration using the SAW have been achieved, demonstrating the great potential for applications in electronics and MEMS

Testing linear hypotheses in high-dimensional regressions

For a multivariate linear model, Wilk's likelihood ratio test (LRT) constitutes one of the cornerstone tools. However, the computation of its quantiles under the null or the alternative requires complex analytic approximations and more importantly, these distributional approximations are feasible only for moderate dimension of the dependent variable, say $p\le 20$. On the other hand, assuming that the data dimension $p$ as well as the number $q$ of regression variables are fixed while the sample size $n$ grows, several asymptotic approximations are proposed in the literature for Wilk's \bLa including the widely used chi-square approximation. In this paper, we consider necessary modifications to Wilk's test in a high-dimensional context, specifically assuming a high data dimension $p$ and a large sample size $n$. Based on recent random matrix theory, the correction we propose to Wilk's test is asymptotically Gaussian under the null and simulations demonstrate that the corrected LRT has very satisfactory size and power, surely in the large $p$ and large $n$ context, but also for moderately large data dimensions like $p=30$ or $p=50$. As a byproduct, we give a reason explaining why the standard chi-square approximation fails for high-dimensional data. We also introduce a new procedure for the classical multiple sample significance test in MANOVA which is valid for high-dimensional data.Comment: Accepted 02/2012 for publication in "Statistics". 20 pages, 2 pages and 2 table

Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope

The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 residues starting with M53 and ending with N58. G6 binding studies demonstrate the remarkable breadth of binding to 51p1 IGHV1-69 Abs with diverse CDR-H3, light chain, and antigen binding specificities. These studies detail the broad expression of the G6 cross-reactive idiotype (CRI) that further define its potential role in precision medicine

Unique structural solution from a VH3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among VH3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of VH3-30 antibodies and reveals that 3I14 represents a novel structural solution within the VH3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV

Mutations in influenza A virus neuraminidase and hemagglutinin confer resistance against a broadly neutralizing hemagglutinin stem antibody

Influenza A virus (IAV), a major cause of human morbidity and mortality, continuously evolves in response to selective pressures. Stem-directed, broadly neutralizing antibodies (sBnAbs) targeting influenza hemagglutinin (HA) are a promising therapeutic strategy, but neutralization escape mutants can develop. We used an integrated approach combining viral passaging, deep sequencing, and protein structural analyses to define escape mutations and mechanisms of neutralization escape in vitro for the F10 sBnAb. IAV was propagated with escalating concentrations of F10 over serial passages in cultured cells to select for escape mutations. Viral sequence analysis revealed three mutations in HA and one in neuraminidase (NA). Introduction of these specific mutations into IAV through reverse genetics confirmed their roles in resistance to F10. Structural analyses revealed that the selected HA mutations (S123G, N460S, and N203V) are away from the F10 epitope but may indirectly impact influenza receptor binding, endosomal fusion, or budding. The NA mutation E329K, which was previously identified to be associated with antibody escape, affects the active site of NA, highlighting the importance of the balance between HA and NA function for viral survival. Thus, whole genome population sequencing enables the identification of viral resistance mutations responding to antibody-induced selective pressure.IMPORTANCE Influenza A virus is a public health threat for which currently available vaccines are not always effective. Broadly neutralizing antibodies that bind to the highly-conserved stem region of influenza hemagglutinin (HA) can neutralize many influenza strains. To understand how influenza virus can become resistant or escape such antibodies, we propagated influenza A virus in vitro with escalating concentrations of antibody and analyzed viral populations with whole genome sequencing. We identified HA mutations near and distal to the antibody binding epitope that conferred resistance to antibody neutralization. Additionally, we identified a neuraminidase (NA) mutation that allowed the virus to grow in the presence of high concentrations of the antibody. Virus carrying dual mutations in HA and NA also grew under high antibody concentrations. We show that NA mutations mediate the escape of neutralization by antibodies against HA, highlighting the importance of a balance between HA and NA for optimal virus function

Asymmetry in Species Regional Dispersal Ability and the Neutral Theory

The neutral assumption that individuals of either the same or different species share exactly the same birth, death, migration, and speciation probabilities is fundamental yet controversial to the neutral theory. Several theoretical studies have demonstrated that a slight difference in species per capita birth or death rates can have a profound consequence on species coexistence and community structure. Whether asymmetry in migration, a vital demographic parameter in the neutral model, plays an important role in community assembly still remains unknown. In this paper, we relaxed the ecological equivalence assumption of the neutral model by introducing differences into species regional dispersal ability. We investigated the effect of asymmetric dispersal on the neutral local community structure. We found that per capita asymmetric dispersal among species could reduce species richness of the local community and result in deviations of species abundance distributions from those predicted by the neutral model. But the effect was moderate compared with that of asymmetries in birth or death rates, unless very large asymmetries in dispersal were assumed. A large difference in species dispersal ability, if there is, can overwhelm the role of random drift and make local community dynamics deterministic. In this case, species with higher regional dispersal abilities tended to dominate in the local community. However, the species abundance distribution of the local community under asymmetric dispersal could be well fitted by the neutral model, but the neutral model generally underestimated the fundamental biodiversity number but overestimated the migration rate in such communities