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Supplementary figure 1: Replication of recombinant adenoviruses in MCF7 breast cancer cells. Supplementary figure 2: Telomerase expression in normal human cells and cancer cell lines. Supplementary figure 3: Labeling mixtures of HCT116 colon cancer cells and WBCs. Supplementary figure 4: Imaging the mixture of HCT116 colon cancer cells and WBCs. Supplementary figure 5: Imaging the mixture of MCF7 breast cancer cells and WBCs.

Korn’s first inequality states that there exists a constant such that the ${\mathcal {L}}^{2}$ L 2 -norm of the infinitesimal displacement gradient is bounded above by this constant times the ${\mathcal {L}}^{2}$ L 2 -norm of the infinitesimal strain, i.e., the symmetric part of the gradient, for all infinitesimal displacements that are equal to zero on the boundary of a body ℬ. This inequality is known to hold when the ${\mathcal {L}}^{2}$ L 2 -norm is replaced by the ${\mathcal {L}}^{p}$ L p -norm for any $p\in (1,\infty )$ p ∈ ( 1 , ∞ ) . However, if $p=1$ p = 1 or $p=\infty $ p = ∞ the resulting inequality is false. It was previously shown that if one replaces the ${\mathcal {L}}^{\infty}$ L ∞ -norm by the $\operatorname{BMO}$ BMO -seminorm (Bounded Mean Oscillation) then one maintains Korn’s inequality. (Recall that ${\mathcal {L}}^{\infty}({\mathcal {B}})\subset \operatorname{BMO}({\mathcal {B}}) \subset {\mathcal {L}}^{p}({\mathcal {B}})\subset {\mathcal {L}}^{1}({ \mathcal {B}})$ L ∞ ( B ) ⊂ BMO ( B ) ⊂ L p ( B ) ⊂ L 1 ( B ) , $1< p 1 < p < ∞ .) In this manuscript it is shown that Korn’s inequality is also maintained if one replaces the ${\mathcal {L}}^{1}$ L 1 -norm by the norm in the Hardy space ${\mathcal {H}}^{1}$ H 1 , the predual of $\operatorname{BMO}$ BMO . One caveat: the results herein are only applicable to the pure-displacement problem with the displacement equal to zero on the entire boundary of ℬ.

Free-space optical communication (FSOC) systems require precise pointing, acquisition, and tracking to send and receive optical beams for effective operation. In a lens-assisted beam steering (LABS) system, light is steered by controlling the emission location in a focal plane. The emitted light is directed into the scene by a lens, like a camera but operating in reverse. In this paper, we demonstrate a novel free-space optical communications link using a micro-opto-electro-mechanical-system (MOEMS) based photonic integrated circuit (PIC) for LABS between multiple receive locations. The MOEMS PIC operates via selective electrical actuation of an array of small grating switches (30 μm x 30 μm footprint, 100 μm pitch). Data rates up to 10 Gbps and a 3 dB optical bandwidth covering the infrared C and L bands (1530 nm to 1625 nm) are measured over a 1 m free-space link distance. Eye diagrams indicate a quality communications link for data rates up to 10 Gbps and bit-error-rates < 10-10 are measured for on-off keying (OOK) modulation. A measured beam profile is propagated into the far-field via simulation, and used to calculate link budgets for example CubeSat crosslink and downlink scenarios. Link budget calculations indicate potential > 1 Gbps CubeSat FSOC crosslinks for link lengths > 1000 km and 1 W of input optical power, using identical 90 mm transmit and receive apertures and a commercially-available fiber-coupled InGaAs avalanche photodiode (APD) receive detector.

In this manuscript two BMO estimates are obtained, one for Linear Elasticity and one for Nonlinear Elasticity. It is first shown that the BMO-seminorm of the gradient of a vector-valued mapping is bounded above by a constant times the BMO-seminorm of the symmetric part of its gradient, that is, a Korn inequality in BMO. The uniqueness of equilibrium for a finite deformation whose principal stresses are everywhere nonnegative is then considered. It is shown that when the second variation of the energy, when considered as a function of the strain, is uniformly positive definite at such an equilibrium solution, then there is a BMO-neighborhood in strain space where there are no other equilibrium solutions.

In this note two results are established for energy functionals that are given by the integral of W ( x , ∇ u ( x ) ) W({\mathbf x},\nabla {\mathbf u}({\mathbf x})) over Ω ⊂ R n \Omega \subset {\mathbb R}^n with ∇ u ∈ B M O ( Ω ; R N × n ) \nabla {\mathbf u}\in \mathrm {BMO}(\Omega ;{\mathbb R}^{N\times n}) , the space of functions of Bounded Mean Oscillation of John and Nirenberg. A version of Taylor’s theorem is first shown to be valid provided the integrand W W has polynomial growth. This result is then used to demonstrate that every Lipschitz-continuous solution of the corresponding Euler-Lagrange equations at which the second variation of the energy is uniformly positive is a strict local minimizer of the energy in W 1 , B M O ( Ω ; R N ) W^{1,\mathrm {BMO}}(\Omega ;{\mathbb R}^N) , the subspace of the Sobolev space W 1 , 1 ( Ω ; R N ) W^{1,1}(\Omega ;{\mathbb R}^N) for which the weak derivative ∇ u ∈ B M O ( Ω ; R N × n ) \nabla {\mathbf u}\in \mathrm {BMO}(\Omega ;{\mathbb R}^{N\times n}) .

The uniqueness of equilibrium for a compressible, hyperelastic body subject to dead-load boundary conditions is considered. It is shown, for both the displacement and mixed problems, that there cannot be two solutions of the equilibrium equations of Finite (Nonlinear) Elasticity whose nonlinear strains are uniformly close to each other. This result is analogous to the result of Fritz John (Comm. Pure Appl. Math. 25, 617-634, 1972) who proved that, for the displacement problem, there is a most one equilibrium solution with uniformly small strains. The proof in this manuscript utilizes Geometric Rigidity; a new straightforward extension of the Fefferman-Stein inequality to bounded domains; and, an appropriate adaptation, for Elasticity, of a result from the Calculus of Variations. Specifically, it is herein shown that the uniform positivity of the second variation of the energy at an equilibrium solution implies that this mapping is a local minimizer of the energy among deformations whose gradient is sufficiently close, in $BMO\cap\, L^1$, to the gradient of the equilibrium solution., 39 pages

Background: Tumor-induced osteomalacia (TIO) is a rare cause of FGF23-mediated hypophosphatemia in which mesenchymal tumors produce ectopic FGF23, leading to renal phosphate wasting, decreased 1,25-dihydroxy-vitamin D and hypophosphatemia. Clinical features include muscle weakness, fractures and bone pain. Entheses are sites where tendons, ligaments, fasciae and joint capsules attach to bones. Calcifications in entheses, called enthesophytes, are frequent in adults with X-linked hypophosphatemia (XLH), the most common genetic form of FGF23-mediated hypophosphatemia. One study reported 68% of XLH patients having enthesopathies at an average of 18 different insertion sites per person (Polisson, NEJM, 1985). However, the prevalence of enthesophytes in patients with TIO is not known. Methods: Skeletal surveys of 66 patients with TIO were reviewed by a single radiologist for the presence of enthesophytes, which were then grouped into the following sites: occiput, axial, upper extremities, pelvis/femur, tibia/fibula and feet. The data presented are from the 59 patients (33 men, 26 women) for whom near-complete skeletal surveys were available; feet radiographs were not available in 9 subjects. Descriptive statistics and regression analyses were performed, including analyses of concurrent intact FGF23 and phosphate levels. Data are presented as mean ± SD. Results: At the time of the skeletal survey, the age of the subjects was 48.7 ± 14.4 years; 78% were over 40 years. The estimated duration of TIO was 6.6 ± 5.3 years. Mean phosphate level was 1.7 ± 0.5 mg/dL (normal 2.5-4.5 mg/dL) and intact FGF23 was 743 ± 1213 pg/mL (normal < 50 pg/mL). Enthesophytes were identified in 51/59 patients (86.4%) with a mean of 4.5 ± 3.7 enthesophytes per patient (range 0-14). The most frequently affected site was the feet (35/50, 70%) followed by occiput (30/59, 51%), pelvis/femur (28/59, 48%), axial (22/59, 37%), upper extremities (18/59, 31%), tibia/fibula (18/59, 17%). In many subjects, more than one enthesophyte was seen within each region - the total number of enthesophytes in the cohort were: feet – 84, pelvis/femur -74, upper extremities – 40, occiput – 30, axial – 23, tibia/fibula – 16. Multiple linear regression demonstrated a significant positive relationship between number of enthesopathies with age and duration of TIO (p < 0.001). Intact FGF23 and phosphate did not significantly correlate with enthesophyte number. Conclusions: Similar to XLH, these data demonstrate that enthesopathies are a common feature of tumor-induced osteomalacia, increasing with both age and duration of disease. The underlying mechanism of enthesophytes in the general population is unclear and may be related to mechanical forces and/or inflammation. The additional factors of chronic hypophosphatemia and elevated FGF23 likely contribute to this mechanism.

The uniqueness of absolute minimizers of the energy of a compressible, hyperelastic body subject to a variety of dead-load boundary conditions in two and three dimensions is herein considered. Hypotheses under which a given solution of the corresponding equilibrium equations is the unique absolute minimizer of the energy are obtained. The hypotheses involve uniform polyconvexity and pointwise bounds on derivatives of the stored-energy density when evaluated on the given equilibrium solution. In particular, an elementary proof of the uniqueness result of Fritz John (Commun. Pure Appl. Math. 25:617–634, 1972) is obtained for uniformly polyconvex stored-energy densities.

The 1960s is seen as a decade of great turbulence in the United States and globally and in fact, it was an unusually rebellious decade, particularly in the United States, Western Europe, and China. However, two caveats are in order. First of all, historical change is not neatly divided into tight ten-year packages with specific beginnings and ends. Certainly in the United States, and much of Europe, the 1960s arguably started with the election of President John F. Kennedy in late 1960 and includes the first few years of the 1970s as well. The focus here is on the 1960s in the USA. Rebellion around the world was often more massive and militant; however, just as the rebellions within the USA were energized by these international rebellions, so too were many of those rebellions energized by rebellions in the USA, the so-called belly of the beast of powerful world capitalism.

Circulating tumor cells (CTC) have become an important biomarker for early cancer diagnosis, prognosis, and treatment monitoring. Recently, a replication-competent recombinant adenovirus driven by a human telomerase gene (hTERT) promoter was shown to detect live CTCs in blood samples of patients with cancer. Here, we report a new class of adenoviruses containing regulatory elements that repress the hTERT gene in normal cells. Compared with the virus with only the hTERT core promoter, the new viruses showed better selectivity for replication in cancer cells than in normal cells. In particular, Ad5GTSe, containing three extra copies of a repressor element, displayed a superior tropism for cancer cells among leukocytes and was thus selected for CTC detection in blood samples. To further improve the efficiency and specificity of CTC identification, we tested a combinatory strategy of microfiltration enrichment using flexible micro spring arrays and Ad5GTSe imaging. Our experiments showed that this method efficiently detected both cancer cells spiked into healthy blood and potential CTCs in blood samples of patients with breast and pancreatic cancer, demonstrating its potential as a highly sensitive and reliable system for detection and capture of CTCs of different tumor types. Mol Cancer Ther; 14(3); 835–43. ©2015 AACR.

Silicon photonics offers the possibility of a reduction in size weight and power for many optical systems, and could open up the ability to build optical systems with complexities that would otherwise be impossible to achieve. Silicon photonics is an emerging technology that has already been inserted into commercial communication products. This technology has also been applied to analog signal processing applications. MIT Lincoln Laboratory in collaboration with groups at MIT has developed a toolkit of silicon photonic devices with a focus on the needs of analog systems. This toolkit includes low-loss waveguides, a high-speed modulator, ring resonator based filter bank, and all-silicon photodiodes. The components are integrated together for a hybrid photonic and electronic analog-to-digital converter. The development and performance of these devices will be discussed. Additionally, the linear performance of these devices, which is important for analog systems, is also investigated.

Recently, Lehmich et al. (Math. Mech. Solids 19, 369–375, 2014) obtained necessary and sufficient conditions for the function C↦h(detC) to be convex on strictly positive-definite, symmetric n×n matrices C. In this note an alternate proof of their result is provided.

Plus que tout autre groupe de San Francisco au milieu des années 1960, les Grateful Dead représentent la quintessence du rock psychédélique. Dans cet article, j’analyse la manière dont leur type d’improvisation, qu’on a appelé « jamming » – quoiqu’il incorpore des techniques typiques du jazz – se révèle être une transformation des façons de jouer de la musique. Ce style amena le groupe à composer un nouveau genre de musique, le rock psychédélique. Un changement dans la conscience sous-tend cette mutation du jeu et de la composition, auquel correspond un changement ontologique qui est l’un des traits distinctifs de la contre-culture des années 1960. More than any other of the San Francisco bands from the mid 1960’s, the Grateful Dead have been identified as the quintessential psychedelic rock band. In this paper, I discuss how their mode of improvising, what has been called jamming, while incorporating the traditional jazz modes of improvisation is actually a transformation in a style of playing music. Playing in this new style eventually led the band to compose a new kind of music—psychedelic rock. Underlying the transformation in the way they played and in the songs they composed is a shift in consciousness with a corresponding shift in ontology that is one of the markers of the 1960’s counterculture.

Consider a cylinder (not necessarily of circular cross-section) that is composed of a hyperelastic material and which is stretched parallel to its axis of symmetry. Suppose that the elastic material that constitutes the cylinder is homogeneous, transversely isotropic, and incompressible and that the deformed length of the cylinder is prescribed, the ends of the cylinder are free of shear, and the sides are left completely free. In this paper it is shown that mild additional constitutive hypotheses on the stored-energy function imply that the unique absolute minimizer of the elastic energy for this problem is a homogeneous, isoaxial deformation. This extends recent results that show the same result is valid in 2-dimensions. Prior work on this problem had been restricted to a local analysis: in particular, it was previously known that homogeneous deformations are strict (weak) relative minimizers of the elastic energy as long as the underlying linearized equations are strongly elliptic and provided that the load/displacement curve in this class of deformations does not possess a maximum.

Irregular mappings that are weak solutions of the energy–momentum equations are presented. One example is discontinuous at a countable number of points while the other is C1, but not C2. These mappings are not solutions of the usual Euler–Lagrange equations.

The proposal of new negotiation formulae in the midst of stalemated conflicts can help to reframe the problem and restart dialogue. They can also unleash new controversy. The Moroccan Initiative for Negotiating an Autonomy Statute for the Sahara Region is a formulaic proposal advanced by Morocco to describe the broad outlines for Sahrawi autonomy under Moroccan sovereignty. It has been the subject of debate within the international community since it was first introduced in April 2007. Until now, however, discussion of its efficacy as a formulaic basis for a negotiated resolution to the Western Sahara dispute has largely outweighed serious consideration of how the proposal relates to current understandings of international law concerning self-determination and free association. Like Western Sahara, the Cook Islands, Niue, Aceh, New Caledonia, and Bougainville are cases of non-self-governing territories and other high autonomy arrangements where there has been recognition of the need to substitute, as the basis for ending the conflict, a comprehensive negotiated political status, in place of frequently unworkable or unattractive alternatives such as a contentious referendum on independence, open-ended talks, or continued armed conflict. In light of the lessons learned from actual state practice and international responses in the foregoing cases, an assessment of the present Moroccan proposal demonstrates that with some improvements, it may offer a viable new starting point for negotiations. The result of using this plan as a formula to restart negotiations can be the attainment for Western Sahara of a full measure of self-government ‐ in a manner consistent with international law ‐ by means of free association.

An optical modulator in silicon based on a diode structure has been operated in both forward and reverse bias. This modulator achieves near state-of-the-art performance in both modes, thereby making this device ideal for comparing the two modes of operation. In reverse bias, the device has a V?L of 4.0 V·cm and a bandwidth of 26 GHz. In forward bias, the device is very sensitive, a V?L as low as 0.0025 V·cm has been achieved, but the bandwidth is only 100 MHz. A new geometry for a reverse-bias device is proposed, and it is predicted to achieve a V?L of 0.5 V·cm.

When a rectangular bar is subjected to uniaxial tension, the bar usually deforms (approximately) homogeneously and isoaxially until a critical load is reached. A bifurcation, such as the formation of shear bands or a neck, may then be observed. One approach is to model such an experiment as the in-plane extension of a two-dimensional, homogeneous, isotropic, incompressible, hyperelastic material in which the length of the bar is prescribed, the ends of the bar are assumed to be free of shear and the sides are left completely free. It is shown that standard constitutive hypotheses on the stored-energy function imply that no such bifurcation is possible in this model due to the fact that the homogeneous isoaxial deformation is the unique absolute minimizer of the elastic energy. Thus, in order for a bifurcation to occur either the material must cease to be elastic or the stored-energy function must violate the standard hypotheses. The fact that no local bifurcations can occur under the assumptions used herein was known previously, since these assumptions prohibit the load on the bar from reaching a maximum value. However, the fact that the homogeneous deformation is the absolute minimizer of the energy appears to be a new result.

Let $${A=\{{\bf x} \in \mathbb{R}^n : a 0}$$ , be the region occupied by an incompressible, nonlinearly hyperelastic material in its reference configuration. Deformations $${{\bf u} : {\it A} \rightarrow \mathbb{R}^n}$$ are therefore isochoric maps and so satisfy the incompressibility constraint $${\rm det}\nabla{\bf u} =1.$$ The displacement and the mixed displacement/zero-traction boundary-value problems are considered. Here a displacement boundary condition of the form $${\bf u} ({\bf x} ) =\sigma {\bf x}$$ is prescribed on one of the boundary components (where σ > 0 is a given constant) and the displacement on the remaining boundary component is either prescribed in the same form (in the case of the pure displacement boundary-value problem) or left unspecified (in the case of the mixed boundary-value problem). In this paper isoperimetric arguments are used to prove that the radially symmetric solutions to these problems are global energy minimisers in various classes of (possibly non-symmetric) isochoric deformations of the region A.

In this paper the tame estimate of Moser [Ann. Scuola Norm. Sup. Pisa (3), 20 (1966), pp. 265–315] is used to extend the standard regularity estimate of Agmon, Douglis, and Nirenberg [Comm. Pure Appl. Math., 17 (1964), pp. 35–92] for systems of strongly elliptic equations in linearized elasticity so that the components of the elasticity tensor need only lie in the Sobolev space $W^{m,p}(\Omega)$ for $p>n/m$, rather than $p>n$, when one obtains $W^{m+1,p}$-regularity of the solution. This improvement is necessary if one wants to prove global continuation results in such spaces for the equations of nonlinear elasticity.

Consider an incompressible, hyperelastic material occupying the unit ball B⊂ℝn in its reference state. Suppose that the deformation u:B→ℝn is specified on the boundary by $$\mathbf{u}({\mathbf{x}})=\lambda{\mathbf{x}}\quad\mbox{for}\ {\mathbf{x}}\in \partial B,$$ where λ>1 is a given constant.

Although there is an extensive literature on the linearization instability of the nonlinear system of partial differential equations that governs an elastic material, there are very few results that prove that a second branch of solutions actually bifurcates from a known solution branch when the known branch becomes unstable. In this paper the implicit function theorem in a Banach space setting is used to prove that the quasistatic compression of a rectangular elastic rod between rigid frictionless plates leads to the buckling of the rod as is observed in experiment and as first predicted by Euler.

It is still not known if the radial cavitating minimizers obtained by Ball [J.M. Ball, Discontinuous equilibrium solutions and cavitation in nonlinear elasticity, Phil. Trans. R. Soc. Lond. A 306 (1982) 557–611] (and subsequently by many others) are global minimizers of any physically reasonable nonlinearly elastic energy. We therefore consider in this paper the related problem of obtaining necessary conditions for these radial solutions to be minimizers with respect to nonradial perturbations. A standard blowup argument applied to either an inner or an outer variation yields an apparently new inequality that, for most constitutive relations, has yet to be verified. However, in the special case of a compressible neo-Hookean material, W( F) = μ |F| 2 + h(detF), we show that the inequality produced by an outer variation clearly holds whilst that produced by an inner variation is a well-known inequality (first proven by Brezis, Coron, and Lieb [H. Brezis, J.-M. Coron, E.H. Lieb, Harmonic maps with defects, Comm. Math. Phys. 107 (1986) 649–705] ) which arises in the theory of nematic liquid crystals

In adenovirus particles, the viral nucleoprotein is organized into a highly compacted core structure. Upon delivery to the nucleus, the viral nucleoprotein is very likely to be remodeled to a form accessible to the transcription and replication machinery. Viral protein VII binds to intra-nuclear viral DNA, as do at least two cellular proteins, SET/TAF-Ibeta and pp32, components of a chromatin assembly complex that is implicated in template remodeling. We showed previously that viral DNA-protein complexes released from infecting particles were sensitive to shearing after cross-linking with formaldehyde, presumably after transport of the genome into the nucleus. We report here the application of equilibrium-density gradient centrifugation to the analysis of the fate of these complexes. Most of the incoming protein VII was recovered in a form that was not cross-linked to viral DNA. This release of protein VII, as well as the binding of SET/TAF-Ibeta and cellular transcription factors to the viral chromatin, did not require de novo viral gene expression. The distinct density profiles of viral DNA complexes containing protein VII, compared to those containing SET/TAF-Ibeta or transcription factors, were consistent with the notion that the assembly of early viral chromatin requires both the association of SET/TAF-1beta and the release of protein VII.

Consider a three-dimensional, homogeneous, compressible, hyperelastic bodythat occupies a cylindrical domain in its reference configuration.We identify a variety of hypotheses on the structure of the stored-energy function under which there exists an axisymmetric, homogeneous deformation that globally minimizes the energy. For certain classes of energy functions the uniqueness of this minimizer is also established. The primary boundary condition considered is the extension of the cylinder via the prescription of its deformedaxial length, but the biaxial extension of the curved surface is also briefly considered. In particular, the results contained in this paper give conditions on the stored-energy function under which material instabilities, such as necking or the formation of shear bands, are not energy favorable.

Reported here is a method for trimming the resonant frequency of microring resonators by permanent thermal modification of a waveguide cladding. This method would use in-situ heaters, avoiding the need for highly specialized equipment.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. © 2015 Reppe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

We experimentally investigate integrated photonic microring resonator filters as frequency windows in CHERPe transmitters. The impact of filter-order on optical loss, power handling, modulation extinction ratio enhancement, and waveform distortion is assessed.

Consider a nonlinearly elastic body which occupies the region $\Omega \subset {\mathbb{R}} ^m$ ($m=2,3$) in its reference state and which is held in tension under prescribed boundary displacements on $\partial \Omega$. Let ${\bf x}_0 \in \Omega$ be any fixed point in the body. It is known from variational arguments that, for sufficiently large boundary displacements, there may exist discontinuous weak solutions of the equilibrium equations corresponding to a hole forming at ${\bf x}_0$ in the deformed body (this is the phenomenon of cavitation). For each $\epsilon >0$, define the regularized domains $\Omega _\epsilon = \Omega \backslash \overline{B_\epsilon ({\bf x}_0)}$ which contain a preexisting hole of radius $\epsilon >0$ centered on ${\bf x}_0$. Now consider the corresponding mixed displacement/traction problem on $\Omega _\epsilon$ in which the boundary $\partial \Omega$ is subject to the same boundary displacements and the deformed cavity surface (i.e., the image of $\partial B_\epsilon$) is requi...

The objective of the current study was to determine whether survivors of non-Hodgkin lymphoma are meeting select American Cancer Society (ACS) health-related guidelines for cancer survivors, as well as to examine relationships between these lifestyle factors and health-related quality of life (HRQoL) and posttraumatic stress (PTS).A cross-sectional sample of 566 survivors of NHL was identified from the tumor registries of 2 large academic medical centers. Respondents were surveyed regarding physical activity, fruit and vegetable intake, body weight, tobacco use, HRQoL using the Medical Outcomes Study Short Form-36, and PTS using the Posttraumatic Stress Disorder CheckList-Civilian form. Lifestyle cluster scores were generated based on whether individuals met health guidelines and multiple linear regression analysis was used to evaluate relationships between lifestyle behaviors and HRQoL scores and PTS scores.Approximately 11% of participants met all 4 ACS health recommendations. Meeting all 4 healthy recommendations was related to better physical and mental QoL (standardized regression coefficient [β], .57 [P.0001] and β, .47 [P = .002]) and to lower PTS scores (β, -0.41; P = .01).Survivors of NHL who met more ACS health-related guidelines appeared to have better HRQoL and less PTS. Unfortunately, many survivors are not meeting these guidelines, which could impact their overall well-being and longevity.

Objective: This study reports the results of treatment for supraglottic laryngeal cancer with nine different treatment modalities with long-term follow-up. Study Design: Retrospective study of 653 patients with supraglottic laryngeal squamous cell cancer treated from April 1955 to January 1999. Methods: The study population included previously untreated patients with cancer of the supraglottic larynx treated with curative intent by one of nine treatment modalities and who were eligible for 5-year follow-up. The treatment modalities included subtotal supraglottic laryngectomy (SSL), SSL with neck dissection (SSL/ND), total laryngectomy (TL), TL/ND, radiation therapy (RT), SSL/RT, SSL/ND/RT, TL/RT, and TL/ND/RT. Multiple diagnostic, treatment, and follow-up parameters were studied using standard statistical analysis to determine significance. Results: None of the nine treatment modalities produced a survival advantage, either overall or within the stages. Overall disease specific survival (DSS) by treatment modality included SSL 88.9%, SSL/ND 75.8%, TL 83.3%, TL/ND 66.7%, RT 47.2%, SSL/RT 68.9%, SSL/ND/RT 68.1%, TL/RT 59.3%, and TL/ND/RT 46.7%. Improved DSS and cumulative disease specific survival rates were associated with patients under the age of 65 years (P = .0001), early stage disease, N0 disease (P = .0001), clear resection margins (P = .0094), and no recurrence (P = .0001). Posttreatment function showed that 90% of patients were functional in everyday life, 90.7% were eating satisfactorily, 91.4% were breathing naturally, and 83% of SSL patients, 85.7% of RT patients, and 52.8% of TL patients had “good” voices. Laryngeal preservation was accomplished in 86.1% of SSL patients and 72.7% of RT patients (P = .0190). Conclusions: No treatment modality produced a survival advantage. Because SSL produced the best rate of laryngeal preservation, we recommend its use in treating the primary in eligible patients. The importance of clear resection margins is stressed. Patients with N+ disease should have the neck treated. Patients with N0 disease may be observed safely with no loss of survival advantage. Because of the pattern of recurrence and the high rates of distant metastasis and second primary cancers, follow-up for a period of not less than 8 years is recommended.

Objectives/Hypothesis: The best therapeutic approach for the treatment of stage IV glottic carcinoma is controversial. Study Design : A retrospective study. Methods: A retrospective study of Tumor Research Project data was performed using patients with stage IV glottic squamous cell carcinoma treated with curative intent by five different treatment modalities from 1955 to 1998 at Washington University School of Medicine and Barnes-Jewish Hospital (St. Louis, MO). Results: Ninety-six patients with stage IV glottic carcinoma were treated by five modalities: total laryngectomy (TL) (n = 13), total laryngectomy with neck dissection (TL/ND) (n = 18), radiation therapy alone (RT) (n = 7) (median dose, 69.5 Gy), total laryngectomy combined with radiation therapy (TL/RT) (n = 10), and total laryngectomy and neck dissection combined with radiation therapy (TL/ND/RT) (n = 48). The overall 5-year observed survival (OS) rate was 39%, and the 5-year disease-specific survival (DSS) rate was 45%. The 5-year DSS rates for the individual treatment modalities included the following: TL, 58.3%; TL/ND, 42.9%; RT, 50.0%; TL/RT, 30.0%; and TL/ ND/RT, 43.9%. There was no significant difference in DSS for any individual treatment modality (P = .759). The overall locoregional control rate was 69% (66 of 96). The overall recurrence rate was 39% with recurrence at the primary site and in the neck at 19% and 17%, respectively. Recurrence was not related to treatment modality. The 5-year DSS after treatment of locally recurrent cancer (salvage rate) was 30% (3 of 10) and for recurrent neck disease (28 of 67) was 42%. The incidence of delayed regional metastases was 28%; of distant metastasis, 12%; and of second primary cancers, 9%. There was no statistically significant difference in survival between node-negative (NO) necks initially treated (5-y DSS, 31%) versus NO necks observed and later treated if necessary (5-y DSS, 44%) (P = .685). Conclusion: The five treatment modalities had statistically similar survival, recurrence, and complication rates. The overall 5-year DSS for patients with stage IV glottic carcinoma was 45%, and the OS was 39%. The cumulative disease-specific survival (CDSS) was 0.4770 with a mean survival of 10.1 years and a median survival of 3.9 years. Patients younger than age 55 years had better survival (DSS) than patients 56 years of age or older (P = .0002). Patients with early T stage had better survival than patients with more advanced T stage (P = .04). Tumor recurrence at the primary site (P = .0001) and in the neck (P = .014) and distant metastasis (P = .0001) had a deleterious effect on survival. Tumor recurrence was not related to treatment modality. Patients with clear margins of resection had a statistically significant improved survival (DSS and CDSS) compared with patients with close or involved margins (P = .0001). Post-treatment quality of life was not significantly related to treatment modality. Patients whose NO neck was treated with observation and appropriate treatment for subsequent neck disease had statistically similar survival compared with patients whose NO neck was treated prophylactically at the time of treatment of the primary. A minimum of 7 years of follow-up is recommended for early identification of recurrent disease, second primary tumors, and distant metastasis. None of the standard treatment modalities currently employed has a statistical advantage regarding survival, recurrence, complications, or quality of life. Glottic carcinoma, stage IV, radiation therapy, surgery, combined therapy.

Purpose To assess the clinical features, prognostic factors, results, and complications of treatment of carcinomas of the paranasal sinus. Methods and materials The records of 106 patients (72 men and 34 women) with paranasal sinus carcinoma treated with curative intent at Washington University between January 1960 and August 1998 were analyzed. Patient age ranged from 29 to 91 years (median, 64 years). Most tumors originated in the maxillary (76%) or ethmoid (18%) sinus. Most tumors were locally advanced at presentation. All patients underwent radiotherapy (RT), combined with surgery in 65%; 2% received chemotherapy. Results Follow-up ranged from 1.7 months to 24 years (median 5 years). The 5-year local tumor control, locoregional tumor control, disease-free survival (DFS), and overall survival rate was 58%, 39%, 33%, and 27%, respectively. A statistically significant improvement in DFS was noted with the addition of surgical resection to RT (35% vs. 29%, p = 0.05). Nodal status at presentation emerged as a statistically significant predictor for locoregional tumor control and DFS in multivariate analysis. Distant metastases occurred in 29% of patients. Conclusion This review of a large, single-institution experience of paranasal sinus carcinoma patients who underwent RT showed that locoregional tumor progression and recurrence remain predominant patterns of failure despite aggressive local treatment with combined surgery and RT. DFS improved slightly with combined modality treatment. The overall survival rates remained suboptimal, suggesting a need for more accurate determination of tumor extent, as well as more effective locoregional and systemic therapies.

We present a 'flip chip' technique for testing electronic self-assembled monolayers (SAMs). Metal–SAM–metal junctions with contact areas of approximately (25 nm)2 and smaller have been created and tested. While the approach is similar in spirit to conductive atomic force microscope measurements, it requires only straightforward optical lithography to create the test chips and a simple gravitational-force flexure to close the junction with sub-angstrom scale precision. The junction is formed in a vertical manner, in which the SAM is grown on one or both metal electrodes, and the circuit is closed via the pressure-induced flexing of one chip into another. This method of creating a junction is rapid and facilitates multiple measurements per chip set. We have investigated the electrical transport characteristics of a variety of SAMs using this technique, including aliphatic alkanethiols and aromatic dithiols. Results are consistent with junction contact areas , and elucidate information regarding the role of pressure and defects on SAM transport.

Wild-type early activity of the adenovirus 5 E1b gene promoter requires readthrough transcription originating from the adjacent upstream E1a gene. This unusual mode of viral transcription activation was identified by genetic manipulation of the mouse β maj -globin gene transcription termination sequence ( GGT ) inserted into the E1a gene. To facilitate further study of the mechanism of readthrough activation, the activities of GGT and a composite termination sequence CT were tested in recombinant adenoviruses containing luciferase reporters driven by the E1b promoter. There was a strict correlation between readthrough and substantial downstream gene expression, indicating that interference with downstream transcription was not a unique property of GGT . Blockage of readthrough transcription of E1a had no apparent effect on early expression of the major late promoter, the next active promoter downstream of E1b. A test for epistatic interaction between termination sequence insertions and E1a enhancer mutations suggested that readthrough activation and E1a enhancer activation of the E1b promoter are mechanistically distinct. In addition, substitution of the human cytomegalovirus major immediate-early promoter for the E1b promoter suppressed the requirement for readthrough. These results suggest that readthrough activation is a “local” effect of a direct interaction between the invading transcription elongation complex and the E1b promoter. DNase I hypersensitivity footprinting provided evidence that this interaction altered an extensive E1b promoter DNA-protein complex that was assembled in the absence of readthrough transcription.

We report here the properties of viral DNA–protein complexes that purify with cellular chromatin following formaldehyde cross-linking of intact cells early after infection. The cross-linked viral DNA fractionated into shear-sensitive (S) and shear- resistant (R) components that were separable by sedimentation, which allowed independent characterization. The R component had the density and sedimentation properties expected for DNA–protein complexes and contained intact viral DNA. It accounted for about 50% of the viral DNA recovered at 1.5 h after infection but less than 20% by 4.5 h. The proportion of R component was independent of multiplicity of infection, even at less than one particle per cell. Viral hexon and protein VII, but not protein VI, were detected in the fractions containing the R component. These properties are consistent with those of partially uncoated virions associated with the nuclear envelope. A substantial proportion of the S component viral DNA had the same density as cellular chromatin. Protein VII was the most abundant viral protein present in gradient fractions that contained the S component. Complexes containing USF transcription factor cross-linked to the adenovirus major late promoter were detected by viral chromatin immunoprecipitation of the fractions containing S component. The S component probably contained uncoated nuclear viral DNA that assembles into early viral transcription complexes.