Thin channel β-Ga2O3 MOSFETs with self-aligned refractory metal gates

We report the first demonstration of self-aligned gate (SAG) β-Ga2O3 metal-oxide-semiconductor field-effect transistors (MOSFETs) as a path toward eliminating source access resistance for low-loss power applications. The SAG process is implemented with a subtractively defined and etched refractory metal, such as Tungsten, combined with ion-implantation. We report experimental and modeled DC performance of a representative SAG device that achieved a maximum transconductance of 35 mS mm-1 and an on-resistance of ∼30 Ω mm with a 2.5 μm gate length. These results highlight the advantage of implant technology for SAG β-Ga2O3 MOSFETs enabling future power switching and RF devices with low parasitic resistance. © Not subject to copyright in the USA. Contribution of Wright-Patterson AFB

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment

Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors

Histone deacetylase inhibitors (HDACIs) represent a class of promising agents that can improve radiotherapy in cancer treatment. However, the full therapeutic potential of HDACIs as radiosensitizers has been restricted by limited efficacy in solid malignancies. In this study, we report the development of nanoparticle (NP) formulations of HDACIs that overcome these limitations, illustrating their utility to improve the therapeutic ratio of the clinically established first generation HDACI vorinostat and a novel second generation HDACI quisinostat. We demonstrate that NP HDACIs are potent radiosensitizers in vitro and are more effective as radiosensitizers than small molecule HDACIs in vivo using mouse xenograft models of colorectal and prostate carcinomas. We found that NP HDACIs enhance the response of tumor cells to radiation through the prolongation of γ-H2AX foci. Our work illustrates an effective method for improving cancer radiotherapy treatment

Nanoparticle delivery of chemosensitizers improve chemotherapy efficacy without incurring additional toxicity

We demonstrate proof of principle that nanoparticle delivery of chemosensitizers can improve efficacy of chemotherapy without increasing toxicity

Fault Tolerance in Protein Interaction Networks: Stable Bipartite Subgraphs and Redundant Pathways

As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model) motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all). We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair

Literacy outcomes for Deaf and Hard of Hearing primary school children: A cohort comparison study

Purpose: This study compared the language and literacy of two cohorts of children with severe-profound hearing loss, recruited 10 years apart, to determine whether outcomes had improved in line with the introduction of newborn hearing screening and access to improved hearing aid technology. Method: Forty-two deaf children, aged 5 -7 years with a mean unaided loss of 102 DB, were assessed on language, reading and phonological skills. Their performance was compared to that of a similar group of 32 deaf children assessed 10 years earlier, and also a group of 40 hearing children of similar single word reading ability. Results: English vocabulary was significantly higher in the new cohort, although it was still below chronological age. Phonological awareness and reading ability had not significantly changed over time. In both cohorts English vocabulary predicted reading but phonological awareness was only a significant predictor for the new cohort. Conclusions: The current results show that vocabulary knowledge of children with severe-profound hearing loss has improved over time but there has not been a commensurate improvement in phonological skills or reading. They suggest that children with severe-profound hearing loss will require continued support to develop robust phonological coding skills to underpin reading

Transverse momentum and centrality dependence of dihadron correlations in Au+Au collisions at sqrt(s_NN)=200 GeV: Jet-quenching and the response of partonic matter

Azimuthal angle \Delta\phi correlations are presented for charged hadrons from dijets for 0.4 < p_T < 10 GeV/c in Au+Au collisions at sqrt(s_NN) = 200 GeV. With increasing p_T, the away-side distribution evolves from a broad to a concave shape, then to a convex shape. Comparisons to p+p data suggest that the away-side can be divided into a partially suppressed "head" region centered at Delta\phi ~ \pi, and an enhanced "shoulder" region centered at Delta\phi ~ \pi +/- 1.1. The p_T spectrum for the "head" region softens toward central collisions, consistent with the onset of jet quenching. The spectral slope for the "shoulder" region is independent of centrality and trigger p_T, which offers constraints on energy transport mechanisms and suggests that the "shoulder" region contains the medium response to energetic jets.Comment: 420 authors from 58 institutions, 6 pages, 4 figures. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

High-pT pi^zero Production with Respect to the Reaction Plane in Au + Au Collisions at sqrt(s_NN) = 200 GeV

Measurements of the azimuthal anisotropy of high-\pT neutral pion neutral pion production in Au+Au collisions at sqrt(s_NN) = 200 GeV by the PHENIX experiment are presented. The data included in this paper were collected during the 2004 RHIC running period and represent approximately an order of magnitude increase in the number of analyzed events relative to previously published results. Azimuthal angle distributions of pi^0s detected in the PHENIX electromagnetic calorimeters are measured relative to the reaction plane determined event-by-event using the forward and backward beam-beam counters. Amplitudes of the second Fourier component (v_2) of the angular distributions are presented as a function of pi^0 transverse momentum p_T for different bins in collision centrality. Measured reaction plane dependent pi^0 yields are used to determine the azimuthal dependence of the pi^0 suppression as a function of p_T, R_AA (Delta phi,p_T). A jet-quenching motivated geometric analysis is presented that attempts to simultaneously describe the centrality dependence and reaction plane angle dependence of the pi^0 suppression in terms of the path lengths of hypothetical parent partons in the medium. This set of results allows for a detailed examination of the influence of geometry in the collision region, and of the interplay between collective flow and jet-quenching effects along the azimuthal axis.Comment: 344 authors, 35 pages text, RevTeX-4, 24 figures, 8 tables. Submitted to Physical Review