An efficient shooting algorithm for Evans function calculations in large systems

In Evans function computations of the spectra of asymptotically constant-coefficient linear operators, a basic issue is the efficient and numerically stable computation of subspaces evolving according to the associated eigenvalue ODE. For small systems, a fast, shooting algorithm may be obtained by representing subspaces as single exterior products \cite{AS,Br.1,Br.2,BrZ,BDG}. For large systems, however, the dimension of the exterior-product space quickly becomes prohibitive, growing as $\binom{n}{k}$, where $n$ is the dimension of the system written as a first-order ODE and $k$ (typically $\sim n/2$) is the dimension of the subspace. We resolve this difficulty by the introduction of a simple polar coordinate algorithm representing ``pure'' (monomial) products as scalar multiples of orthonormal bases, for which the angular equation is a numerically optimized version of the continuous orthogonalization method of Drury--Davey \cite{Da,Dr} and the radial equation is evaluable by quadrature. Notably, the polar-coordinate method preserves the important property of analyticity with respect to parameters.Comment: 21 pp., two figure

Learning with multiple representations: An example of a revision lesson in mechanics

We describe an example of learning with multiple representations in an A-level revision lesson on mechanics. The context of the problem involved the motion of a ball thrown vertically upwards in air and studying how the associated physical quantities changed during its flight. Different groups of students were assigned to look at the ball's motion using various representations: motion diagrams, vector diagrams, free-body diagrams, verbal description, equations and graphs, drawn against time as well as against displacement. Overall, feedback from students about the lesson was positive. We further discuss the benefits of using computer simulation to support and extend student learning.Comment: 10 pages, 5 figures, 2 tables http://iopscience.iop.org/0031-912

Perceptions and Barriers of Survivorship Care in Asia: Perceptions From Asian Breast Cancer Survivors.

PurposeWith the long-term goal to optimize post-treatment cancer care in Asia, we conducted a qualitative study to gather in-depth descriptions from multiethnic Asian breast cancer survivors on their perceptions and experiences of cancer survivorship and their perceived barriers to post-treatment follow-up.MethodsTwenty-four breast cancer survivors in Singapore participated in six structured focus group discussions. The focus group discussions were voice recorded, transcribed verbatim, and analyzed by thematic analysis.ResultsBreast cancer survivors were unfamiliar with and disliked the term "survivorship," because it implies that survivors had undergone hardship during their treatment. Cognitive impairment and peripheral neuropathy were physical symptoms that bothered survivors the most, and many indicated that they experienced emotional distress during survivorship, for which they turned to religion and peers as coping strategies. Survivors indicated lack of consultation time and fear of unplanned hospitalization as main barriers to optimal survivorship care. Furthermore, survivors indicated that they preferred receipt of survivorship care at the specialty cancer center.ConclusionBudding survivorship programs in Asia must take survivor perspectives into consideration to ensure that survivorship care is fully optimized within the community

Model-Independent Reionization Observables in the CMB

We represent the reionization history of the universe as a free function in redshift and study the potential for its extraction from CMB polarization spectra. From a principal component analysis, we show that the ionization history information is contained in 5 modes, resembling low-order Fourier modes in redshift space. The amplitude of these modes represent a compact description of the observable properties of reionization in the CMB, easily predicted given a model for the ionization fraction. Measurement of these modes can ultimately constrain the total optical depth, or equivalently the initial amplitude of fluctuations to the 1% level regardless of the true model for reionization.Comment: 4 pages, 5 figures, submitted to PRD (rapid communications

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a “driver” phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine–substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.Fil: Lui, Vivian Wai Yan. University of Pittsburgh; Estados UnidosFil: Peyser, Noah D.. University of Pittsburgh; Estados UnidosFil: Ng, Patrick Kwok-Shing. University Of Texas Md Anderson Cancer Center;Fil: Hritz, Jozef. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados Unidos. Masaryk University; República ChecaFil: Zeng, Yan. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Lu, Yiling. University Of Texas Md Anderson Cancer Center;Fil: Li, Hua. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Wang, Lin. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Gilbert, Breean R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: General, Ignacio. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Bahar, Ivet. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Ju, Zhenlin. University Of Texas Md Anderson Cancer Center;Fil: Wang, Zhenghe. Case Western Reserve University; Estados UnidosFil: Pendleton, Kelsey P.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Xiao, Xiao. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Du, Yu. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Vries, John K.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Hammerman, Peter S.. Harvard Medical School; Estados UnidosFil: Garraway, Levi A.. Harvard Medical School; Estados UnidosFil: Mills, Gordon B.. University Of Texas Md Anderson Cancer Center;Fil: Johnson, Daniel E.. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Grandis, Jennifer R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unido

Actin polymerization as a key innate immune effector mechanism to control Salmonella infection.

Salmonellosis is one of the leading causes of food poisoning worldwide. Controlling bacterial burden is essential to surviving infection. Nucleotide-binding oligomerization domain-like receptors (NLRs), such as NLRC4, induce inflammasome effector functions and play a crucial role in controlling Salmonella infection. Inflammasome-dependent production of IL-1β recruits additional immune cells to the site of infection, whereas inflammasome-mediated pyroptosis of macrophages releases bacteria for uptake by neutrophils. Neither of these functions is known to directly kill intracellular salmonellae within macrophages. The mechanism, therefore, governing how inflammasomes mediate intracellular bacterial-killing and clearance in host macrophages remains unknown. Here, we show that actin polymerization is required for NLRC4-dependent regulation of intracellular bacterial burden, inflammasome assembly, pyroptosis, and IL-1β production. NLRC4-induced changes in actin polymerization are physically manifested as increased cellular stiffness, and leads to reduced bacterial uptake, production of antimicrobial molecules, and arrested cellular migration. These processes act in concert to limit bacterial replication in the cell and dissemination in tissues. We show, therefore, a functional link between innate immunity and actin turnover in macrophages that underpins a key host defense mechanism for the control of salmonellosis.Financial support for this work was provided by a Cambridge International Scholarship (to S.M.M.), European Research Council Starting Investigator Grant “LightTouch” 282060 (to J.R.G.), Biotechnology and Biological Sciences Research Council (BBSRC) Grants BB/H003916/1 and BB/K006436/1 and BBSRC Research Development Fellowship BB/ H021930/1 (to C.E.B.)This is the accepted manuscript. The final version is available from PNAS at http://www.pnas.org/content/111/49/17588.abstract

The dynamics of genome replication using deep sequencing

Peer reviewedPublisher PD

Minimal Scalar Sector of 3-3-1 Models without Exotic Electric Charges

We study the minimal set of Higgs scalars, for models based on the local gauge group $SU(3)_c \otimes SU(3)_L \otimes U(1)_X$ which do not contain particles with exotic electric charges. We show that only two Higgs $SU(3)_L$ triplets are needed in order to properly break the symmetry. The exact tree-level scalar mass matrices resulting from symmetry breaking are calculated at the minimum of the most general scalar potential, and the gauge bosons are obtained, together with their couplings to the physical scalar fields. We show how the scalar sector introduced is enough to produce masses for fermions in a particular model which is an $E_6$ subgroup. By using experimental results we constrain the scale of new physics to be above 1.3 TeV.Comment: LaTeX, 22 pages, 1 figure include

Development of a clinical prototype of a miniature hand-held optical coherence tomography probe for prematurity and pediatric ophthalmic imaging

We report a novel design and operation of a highly integrated miniature handheld OCT probe, with high-speed angiography function that can be used in clinical settings for young children and infants, providing rapid, non-invasive structural and angiographic imaging of the retina and choroid. The imaging system is operated at 200 kHz, with 3D OCT and OCTA scan time of 0.8 and 3.2 seconds, respectively, and the scanning angle on the pupil is ± 36°, covering the full perifoveal region. Operator assisting features of the direct-view iris camera and on-probe display are integrated into the hand-held probe, and the fixation target can display animations to attract the attention of young subjects. Compared to conventional OCT systems, the high-speed hand-held OCT system significantly improves the operator's experience and scanning efficiency, which is important for imaging infants. Imaging results indicate a significant reduction in total time consumption in pediatric ophthalmic imaging sessions, as well as the image quality of OCT angiography.</p