Towards spectrally selective catastrophic response.

We study the large-amplitude response of classical molecules to electromagnetic radiation, showing the universality of the transition from linear to nonlinear response and breakup at sufficiently large amplitudes. We demonstrate that a range of models, from the simple harmonic oscillator to the successful Peyrard-Bishop-Dauxois type models of DNA, which include realistic effects of the environment (including damping and dephasing due to thermal fluctuations), lead to characteristic universal behavior: formation of domains of dissociation in driving force amplitude-frequency space, characterized by the presence of local boundary minima. We demonstrate that by simply following the progression of the resonance maxima in this space, while gradually increasing intensity of the radiation, one must necessarily arrive at one of these minima, i.e., a point where the ultrahigh spectral selectivity is retained. We show that this universal property, applicable to other oscillatory systems, is a consequence of the fact that these models belong to the fold catastrophe universality class of Thom's catastrophe theory. This in turn implies that for most biostructures, including DNA, high spectral sensitivity near the onset of the denaturation processes can be expected. Such spectrally selective molecular denaturation could find important applications in biology and medicine.

An extended core nanocoax pillar architecture for enhanced molecular detection.

Biosensors that incorporate nanomaterials and nanofabrication techniques enable molecular detection of chemical and biological macromolecules with a high degree of specificity and ultrasensitivity. Here, we present a novel fabrication process that yields a nanostructure capable of detecting biological macromolecules. The extended core nanocoax (ECC) structure builds on a previously reported nanocoaxial-based sensor. The fabrication of the device incorporates an extended inner pillar, with controllable extension above the annulus and into the surrounding solution. This new design eliminates structural constraints inherent in the original nanocoax architecture. We also provide results demonstrating improvement in biosensing capability. Specifically, we show the capability of the new architecture to detect the B subunit of the Vibrio cholerae toxin at improved sensitivity (100 pg/ml) in comparison to optical enzyme-linked immunosorbant assay (1 ng/ml) and previously reported coaxial nanostructures (2 ng/ml).

Variability in sleep disturbance, physical activity and quality of life by level of depressive symptoms in women with Type 2 diabetes.

AIMS: To examine (1) the prevalence of depressive symptoms in women with Type 2 diabetes, (2) the associations between depressive symptoms and the following dependent variables: sleep disturbance; physical activity; physical health-related; and global quality of life, and (3) the potential moderating effects of antidepressants and optimism on the relationship between depressive symptoms and dependent variables. METHODS: Participants in the Women's Health Initiative who had Type 2 diabetes and data on depressive symptoms (N=8895) were included in the analyses. In multivariable linear regression models controlling for sociodemographic, medical and psychosocial covariates, we examined the main effect of depressive symptoms, as well as the interactions between depressive symptoms and antidepressant use, and between depressive symptoms and optimism, on sleep disturbance, physical activity, physical health-related quality of life; and global quality of life. RESULTS: In all, 16% of women with Type 2 diabetes reported elevated depressive symptoms. In multivariable analyses, women with depressive symptoms had greater sleep disturbance (P<0.0001) and lower global quality of life (P<.0001). We found evidence of significant statistical interaction in the models for quality-of-life outcomes: the increased risk of poor physical health-related quality of life associated with antidepressant use was stronger in women without vs with depressive symptoms, and the association between greater optimism and higher global quality of life was stronger in women with vs without depressive symptoms. CONCLUSIONS: To improve health behaviours and quality of life in women with Type 2 diabetes, sociodemographic and medical characteristics may identify at-risk populations, while psychosocial factors including depression and optimism may be important targets for non-pharmacological intervention.

A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PURPOSE: Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. METHODS: Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. RESULTS: Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. CONCLUSION: Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. IMPLICATIONS FOR CANCER SURVIVORS: Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

Hot electron plasmon-protected solar cell.

A solar cell based on a hot electron plasmon protection effect is proposed and made plausible by simulations, non-local modeling of the response, and quantum mechanical calculations. In this cell, a thin-film, plasmonic metamaterial structure acts as both an efficient photon absorber in the visible frequency range and a plasmonic resonator in the IR range, the latter of which absorbs and protects against phonon emission the free energy of the hot electrons in an adjacent semiconductor junction. We show that in this structure, electron-plasmon scattering is much more efficient than electron-phonon scattering in cooling-off hot electrons, and the plasmon-stored energy is recoverable as an additional cell voltage. The proposed structure could become a prototype of a new generation of high efficiency solar cells.

Spectroscopic evidence for negative electronic compressibility in a quasi-three-dimensional spin-orbit correlated metal.

Negative compressibility is a sign of thermodynamic instability of open or non-equilibrium systems. In quantum materials consisting of multiple mutually coupled subsystems, the compressibility of one subsystem can be negative if it is countered by positive compressibility of the others. Manifestations of this effect have so far been limited to low-dimensional dilute electron systems. Here, we present evidence from angle-resolved photoemission spectroscopy (ARPES) for negative electronic compressibility (NEC) in the quasi-three-dimensional (3D) spin-orbit correlated metal (Sr1-xLax)3Ir2O7. Increased electron filling accompanies an anomalous decrease of the chemical potential, as indicated by the overall movement of the deep valence bands. Such anomaly, suggestive of NEC, is shown to be primarily driven by the lowering in energy of the conduction band as the correlated bandgap reduces. Our finding points to a distinct pathway towards an uncharted territory of NEC featuring bulk correlated metals with unique potential for applications in low-power nanoelectronics and novel metamaterials.

Nanoscope based on nanowaveguides.

The far field spatial resolution of conventional optical lenses is of the order of the wavelength of light, due to loss in the far field of evanescent, near electromagnetic field components. We show that subwavelength details can be restored in the far field with an array of divergent nanowaveguides, which map the discretized, subwavelength image of an object into a magnified image observable with a conventional optical microscope. We demonstrate in simulations that metallic nanowires, nanocoaxes, and nanogrooves can be used as such nanowaveguides. Thus, an optical microscope capable of subwavelength resolution - a nanoscope - can be produced, with possible applications in a variety of fields where nanoscale optical imaging is of value.

Phase II trial of temsirolimus in patients with metastatic breast cancer.

Preclinical models suggested that activating mutations of the PIK3CA gene are associated with sensitivity to inhibitors of the mammalian target of rapamycin (mTOR). In breast cancers, PIK3CA mutations are associated with estrogen receptor (ER) positivity. We therefore performed an open-label single arm phase II study of the rapamycin analog, temsirolimus, at a dose of 25 mg weekly, in women with pretreated breast cancers that were positive for ER, PR, or HER2. Archived formalin-fixed paraffin embedded tumor was collected for immunohistochemical evaluation of components of the PI3K/Akt/mTOR pathway and PIK3CA mutation analysis. Thirty-one patients were enrolled. There were no major objective responses; however, three patients had stable disease for over 24 weeks. Twenty-three tumor samples were available for mutational analysis. There were five tumors with PIK3CA mutations; no association was found between prolonged stable disease and PIK3CA mutation or any immunohistochemical marker. There was a trend toward improved progression free survival (PFS) for patients with positive nuclear staining for phospho-Akt308. One patient remains on study four and a half years after starting therapy; her tumor did not have a PIK3CA mutation. We conclude that single agent temsirolimus has minimal activity in a population of women with heavily pretreated breast cancer. We found no evidence that either absence of immunohistochemical staining for PTEN or mutations in the hotspot domains of PIK3CA in the primary tumor were associated with clinical benefit.

Enhanced ductile behavior of tensile-elongated individual double-walled and triple-walled carbon nanotubes at high temperatures.

We report exceptional ductile behavior in individual double-walled and triple-walled carbon nanotubes at temperatures above 2000 degrees C, with tensile elongation of 190% and diameter reduction of 90%, during in situ tensile-loading experiments conducted inside a high-resolution transmission electron microscope. Concurrent atomic-scale microstructure observations reveal that the superelongation is attributed to a high temperature creep deformation mechanism mediated by atom or vacancy diffusion, dislocation climb, and kink motion at high temperatures. The superelongation in double-walled and triple-walled carbon nanotubes, the creep deformation mechanism, and dislocation climb in carbon nanotubes are reported here for the first time.

Field-enhanced diamagnetism in the pseudogap state of the cuprate Bi2Sr2CaCu2O(8+delta) superconductor in an intense magnetic field.

In hole-doped cuprates, Nernst experiments imply that the superconducting state is destroyed by spontaneous creation of vortices which destroy phase coherence. Using torque magnetometry on Bi2Sr2CaCu2O(8+delta), we uncover a field-enhanced diamagnetic signal M above the transition temperature Tc that increases with applied field to 32 Tesla and scales just like the Nernst signal. The magnetization results above Tc distinguish M from conventional amplitude fluctuations and strongly support the vortex scenario for the loss of phase coherence at Tc.

Coexistence of superconductivity and antiferromagnetism probed by simultaneous nuclear magnetic resonance and electrical transport in (TMTSF)2PF6 system.

We report simultaneous NMR and electrical transport experiments in the pressure range near the boundary of the antiferromagnetic spin density wave (SDW) insulator and the metallic/superconducting (SC) phase in (TMTSF)2PF6. Measurements indicate a tricritical point separating a line of second-order SDW/metal transitions from a line of first-order SDW/metal(SC) transitions with coexistence of macroscopic regions of SDW and metal(SC) order, with little mutual interaction but strong hysteretic effects. NMR results quantify the fraction of each phase.

Magic angle effects and angular magnetoresistance oscillations as dimensional crossovers.

Interference effects between velocity and density of states, which occur as electrons move along open orbits in the extended Brillouin zone in anisotropic conductors, result in a change of wave functions' dimensionality at magic angle (MA) directions of a magnetic field. In particular, these 1D-->2D dimensional crossovers result in the appearance of sharp minima in a resistivity component rho perpendicular (H,alpha), perpendicular to conducting layers. This explains the main qualitative features of MA and angular magnetoresistance oscillations' phenomena observed due to the existence of quasi-one-dimensional sheets of Fermi surface in (TMTSF)2X, (DMET-TSeF)2X, and kappa-(ET)2Cu(NCS)(2) conductors.

Magnetic determination of H(c2) under accurate alignment in (TMTSF)2ClO4.

Cantilever magnetometry has been used to measure the upper critical magnetic field H(c2) of the quasi-one-dimensional molecular organic superconductor (TMTSF)2ClO4. From simultaneous resistivity and torque magnetization experiments conducted under precise field alignment, H(c2) at low temperature is shown to reach 5 T, nearly twice the Pauli paramagnetic limit imposed on spin singlet superconductors. These results constitute the first thermodynamic evidence for a large H(c2) in this system and provide support for spin triplet pairing in this unconventional superconductor.

Interference commensurate oscillations in quasi-one-dimensional conductors.

We suggest an analytical theory to describe angular magnetoresistance oscillations recently discovered in the quasi-one-dimensional conductor (TMTSF)2PF6 [see Phys. Rev. B 57, 7423 (1998)]] and define the positions of the oscillation minima. The origin of these oscillations is related to interference effects resulting from Bragg reflections which occur as electrons move along quasiperiodic and periodic ("commensurate") electron trajectories in the extended Brillouin zone. We reproduce via calculations existing experimental data and predict some novel effects.

Intersubband transport in quantum wells in strong magnetic fields mediated by single- and two-electron scattering.

We show theoretically that in quantum wells subjected to a strong magnetic field the intersubband current peaks at magnetic field values, which reveal the underlying specific intersubband scattering mechanism. We have designed and grown a superlattice structure in which such current oscillations are clearly visible, and in which the transition from the purely single-electron to the mixed single- and two-electron scattering regimes can be observed by tuning the applied voltage bias. The measurements were conducted in ultrahigh magnetic fields (up to 45 T) to obtain the full spectrum of the current oscillations.

The health-related quality of life and survival of small-cell lung cancer patients: results of a companion study to CALGB 9033.

The purposes of this study were 2-fold: to evaluate the impact of the schedule dependency of etoposide (3-day IV short course vs. a 21-day oral prolonged course) with cisplatin on the quality of life of small-cell lung cancer (SCLC) patients; and to examine the effect of baseline quality of life variables on long-term survival, after adjustment for known demographic and clinical prognostic factors. Participants were 70 patients enrolled in the cancer and leukemia group B (CALGB) protocol 9033. Quality of life was assessed at baseline, 6 and 12 weeks by: the EORTC QLQ-30, the Centers for epidemiology studies--Depression short form, the medical outcomes study (MOS) social support questionnaire, and a scale of sleep quality. Contrary to expectations, study results suggested no significant differences in the patients' life quality and treatment response based on whether they received etoposide in a 3-day IV vs. a 21-day oral regimen. The use of the baseline variables in predicting overall survival indicated that patients who were non-white and with liver involvement had decreased survival. Brain involvement, being male, and higher depressive symptoms were also found to be borderline significant in predicting decreased survival in this patient population.

Critical field enhancement near a superconductor-insulator transition.

We have discovered a phenomenon where the orbital pair breaking effect is reduced, if not eliminated. It appears as a striking enhancement in the upper critical field H(c2) for (TMTSF)2PF6 and a strong upward curvature in the critical field versus temperature in the region of pressure-temperature phase space near the superconductor-spin density wave insulator boundary. A simple model based on self-consistently dividing the superconductor into layers explains the observations remarkably well and provides a unique way around orbital frustration and toward higher critical fields.

Triplet superconductivity in an organic superconductor probed by NMR Knight shift.

The nature of the superconducting state in quasi-one-dimensional organic conductors has remained controversial since its discovery. Here we present results of (77)Se NMR Knight shift (K(s)) experiments in (TMTSF)(2)PF(6) under 7 kbar of pressure with a magnetic field aligned along the most conducting a axis. We find no noticeable shift in K(s) upon cooling through the superconducting transition. Since K(s) directly probes the spin susceptibility chi(s), the fact that chi(s) remains unchanged through the superconducting transition strongly suggests spin-triplet superconductivity.

Promoting adherence and retention to clinical trials in special populations: a women's health initiative workshop.

This paper describes a Women's Health Initiative workshop on promoting adherence and retention in randomized clinical trials among ethnic minority women, participants of lower socioeconomic status, and older women. Workshop objectives were: (1) to increase knowledge of demographic and cultural characteristics of diverse groups, (2) to increase awareness of how diversity can affect interactions in clinical research, (3) to explore how research staff behavior can influence adherence and retention, and (4) to increase knowledge of strategies to enhance adherence and retention in special populations. The workshop emphasized the importance of understanding beliefs, values, and experiences that are common in diverse groups of individuals, while at the same time recognizing and respecting individual differences that result from varying life circumstances and experiences. We discuss strategies to increase cultural competence, reduce stereotypes and discrimination, and create a culturally relevant and sensitive research environment.

Involving minority and underrepresented women in clinical trials: the National Centers of Excellence in Women's Health.

Recent attention to reducing health disparities among population groups has focused on the need to include in clinical studies, especially clinical trials, participants who represent the diversity of the populations to which study results will be applied. While scientists generally applaud the goal of broadening the characteristics of participants in clinical trials, they are faced with multiple challenges as they seek to include historically underrepresented populations in their research. This article examines the historical and sociocultural context of participation by underrepresented groups, especially women and minorities, in clinical trials, identifies major barriers and challenges facing researchers, and suggests strategies for meeting these challenges. The article draws upon the experiences of the investigators affiliated with the National Centers of Excellence of Women's Health (CoEs).