bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-board computer based control system for a portable Raman device with integrated chemical identification
Authors: Mobley Joel , Cullum Brian M. , Wintenberg Alan L. , Shane Frank S. , Maples Robert A. , Stokes David L. , Vo-Dinh Tuan
Published: May 2004

We report the development of a battery-powered portable chemical identification device for field use consisting of an acousto-optic tunable filter (AOTF)-based Raman spectrometer with integrated data processing and analysis software. The various components and custom circuitry are integrated into a self-contained instrument by control software that runs on an embedded single-board computer (SBC), which communicates with the various instrument modules through a 48-line bidirectional TTL bus. The user interacts with the instrument via a touch-sensitive liquid crystal display unit (LCD) that provides soft buttons for user control as well as visual feedback (e.g., spectral plots, stored data, instrument settings, etc.) from the instrument. The control software manages all operational aspects of the instrument with the exception of the power management module that is run by embedded firmware. The SBC-based software includes both automated and manual library searching capabilities, permitting rapid identification of samples in the field. The use of the SBC in tandem with the LCD touchscreen for interfacing and control provides the instrument with a great deal of flexibility as its function can be customized to specific users or tasks via software modifications alone. The instrument, as currently configured, can be operated as a research-grade Raman spectrometer for scientific applications and as a “black-box” chemical identification system for field use. The instrument can acquire 198-point spectra over a spectral range of 238–1620 cm−1, perform a library search, and display the results in less than 14 s. The operating modes of the instrument are demonstrated illustrating the utility and flexibility afforded the system by the SBC–LCD control module.
Performance evaluation of pulsed photothermal profiling of port wine stain in human skin
Authors: Li Bincheng , Majaron Boris , Viator John A. , Milner Thomas E. , Nelson J. Stuart
Published: May 2004

Treatment of port wine stain (PWS) birthmarks in human skin by pulsed laser irradiation requires the knowledge of the maximum epidermal temperature rise and PWS depth for an attending physician to select the optimal light dosage, irradiation wavelength, and cryogen spray cooling spurt duration on an individual patient basis. Pulsed photothermal radiometry (PPTR) is a promising technique to provide such information. In this article, computer simulations are performed to evaluate the performance of PPTR depth profiling of the laser-induced temperature rise in PWS. An iterative, non-negatively constrained conjugate gradient algorithm is used to reconstruct the laser-induced temperature profile from simulated PPTR signals. Human skin is assumed to contain an epidermal melanin layer and a single homogeneous PWS layer in the dermis. The influence of structural, experimental, and algorithm parameters on the temperature profile reconstruction are discussed. Accuracy of the maximum epidermal temperature rise and PWS depth determined from the reconstructed profiles is statistically analyzed. The simulations show that when the melanin and PWS layers are physically discrete, a good reconstruction can be obtained and the maximum epidermal temperature rise and PWS depth can be determined with accuracy sufficient for the intended clinical application. Measurements and reconstructions from PWS patients are performed and the results are in agreement with the simulations.
Lead-resistance effects in a constant voltage anemometer
Authors: Comte-Bellot Geneviève , Weiss Julien , Béra Jean-Christophe
Published: May 2004

Two effects of the lead resistances connecting the hot wire to a constant voltage anemometer (CVA) were analyzed and tested: one concerns the change in the sensitivity coefficient relating the anemometer output to velocity or temperature fluctuations, and the other the time constant of the hot wire determined by an in situ square-wave test technique. Small perturbations were assumed in both cases. The CVA output sensitivity was found to be reduced and the time constant increased with the lead resistance. Explicit formulas which involve the lead resistance, the cold wire resistance, and the wire overheat, as well as some characteristics of the CVA circuit, were established to take into account these effects. In the ranges tested, each effect can individually introduce as much as 10% error. Product of the two governs the overall response for the CVA. However, because the two effects change in opposite directions, interestingly, variation in the net response from their product is minimized. This feature may be very useful for many engineering applications of the CVA. Results of experiments conducted with the CVA in a subsonic jet are presented. They confirm the analysis and also establish that accurate measurements can be performed even with a large ratio of lead resistance to hot-wire resistance by applying the correction formulas developed with the analysis. Results from earlier experiments in a supersonic boundary layer also are presented.
Combined high-pressure cell–ultrahigh vacuum system for fast testing of model metal alloy catalysts using scanning mass spectrometry
Authors: Johansson M. , Hoffmann Jørgensen J. , Chorkendorff I.
Published: May 2004

An apparatus for fabrication, surface analysis in ultrahigh vacuum, and testing of the catalytic activity of model metal alloy catalysts is described. Arrays of model catalysts are produced by electron-beam deposition of up to four metals simultaneously onto a substrate. The surface analysis techniques available are scanning electron microscopy, x-ray photoemission spectroscopy, ion scattering spectroscopy, Auger electron spectroscopy, sputter profiling, and temperature programmed desorption. The catalytic activity of the model catalysts is tested individually by scanning a combined gas delivery and gas sampling device over the sample surface. The gas sampled is analyzed with mass spectrometry. Experiments can be made at pressures up to 1 bar and temperatures up to 500 °C. It is shown that the lateral resolution is better than 0.2 mm and that up to 20 circular spots, 1 mm in diameter, can be studied on a substrate 10 mm in diameter. A high pressure cell with an all-metal sealed ultrahigh vacuum lock is also described as part of the work.
Differential thermocouples in megawatt plasma pulse measurements—computer simulations and preliminary results
Authors: Szymczyk W. , Werner Z. , Piekoszewski J.
Published: May 2004

Modern discharge plasma generators generate short pulses of plasma of high power (in megawatt range) and microsecond duration. Neither classical bolometers nor methods based on detection of electric current flow are applicable to power measurements in such machines. In our previous report [Z. Werner, J. Langner, J. Stanislawski, and J. Bialoskórski, J. Tech. Phys. 41, 55 (2000)] we presented several concepts, including differential thermocouple sensors. In this work we present the results of numerical simulations of the operation of such thermocouples, which help to find the limits within which the idea is useful and to optimize the detector design. Results of preliminary experiments are also presented.
Coaxially aligned electrodes for Stark-effect applied in resonators using a supersonic jet Fourier transform microwave spectrometer
Authors: Schnell Melanie , Banser Deike , Grabow Jens-Uwe
Published: May 2004

In this article, we present a setup for Stark-effect measurements using a Fourier transform-microwave (FTMW) spectrometer with coaxially oriented beam-resonator arrangement (COBRA). The open Fabry–Pérot-type arrangement of spherical mirrors provides the possibility to mount the reflectors electrically insulated. Since no electrical surface currents of the resonator are inhibited, the propagation of the microwave field remains unaffected. If the microwave antennas and the valve are mounted at the same mirror, the other reflector can be set to a static high voltage potential. Together with a number of coaxially arranged circular electrodes a homogeneous field along the resonator axis can be achieved, allowing accurate Stark-effect measurements with COBRA-FTMW spectrometers. The arrangement is suitable even at low frequencies, where a parallel plate arrangement for Stark-effect measurement would increasingly interfere with the microwave field. The design of the coaxially aligned electrodes for Stark-effect applied in resonators (CAESAR) arrangement has been supported by electrostatic calculations optimizing the geometry. The performance of the Stark-effect arrangement will be demonstrated by spectral examples of OCS and Ar-OCS.
Laser switch for stroboscopic read-out of magnetic flux
Authors: Ferrara Marco , Carelli Pasquale , Chiarello Fabio , Castellano Maria Gabriella , Torrioli Guido , Cosmelli Carlo
Published: May 2004

We have realized and tested a fast stroboscopic detector for magnetic flux measurements. The key element of our detector is a hysteretic dc superconducting quantum interference device (SQUID). Stroboscopic read-out of the magnetic flux coupled with the SQUID is accomplished by biasing the SQUID with fast current pulses. The shorter these pulses, the more stroboscopic and less invasive the measurement we are performing. In order to reduce the duration of the current pulses, we take advantage of the superconducting-normal transition induced by laser light in thin superconducting films. The interaction of laser light with superconducting thin films has been investigated thoroughly in the past and many applications have been proposed which rely on the fast typical times with which superconductivity is broken and a resistive behavior arises. We have measured a threshold resolution of 6.9mΦ0 at 4.2 K, and this value corresponds to the thermodynamic limit of the SQUID. The detector has been accurately characterized: An improved and more sensitive version might prove useful for quantum mechanics and quantum computation experiments, for example, in detecting the state of flux qubits.
Characterization of a liquid-xenon-jet laser-plasma extreme-ultraviolet source
Authors: Hansson B. A. M. , Hemberg O. , Hertz H. M. , Berglund M. , Choi H.-J. , Jacobsson B. , Janin E. , Mosesson S. , Rymell L. , Thoresen J. , Wilner M.
Published: May 2004

A liquid-xenon-jet laser-plasma source for extreme-ultraviolet (EUV) and soft-x-ray generation has been characterized. Being a source candidate for EUV lithography (EUVL), we especially focus on parameters important for the integration of the source in EUVL systems. The deep-ultraviolet (DUV) out-of-band radiation (λ=120–400 nm) was quantified, to within a factor of two, using a flying-circus tool together with a transmission-grating spectrograph resulting in a total DUV conversion efficiency (CE) of ∼0.33%/2πsr. The size and the shape of the xenon plasma was investigated using an in-band-only EUV microscope, based on a spherical Mo/Si multilayer mirror and a charge-coupled device detector. Scalability of the source size from 20–270 μm full width at half maximum was shown. The maximum repetition-rate sustainable by the liquid-xenon-jet target was simulated by a double-pulse experiment indicating feasibility of >17 kHz operation. The xenon-ion energy distribution from the plasma was determined in a time-of-flight experiment with a Faraday-cup detector showing the presence of multi-kilo-electron-volt ions. Sputtering of silicon witness plates exposed to the plasma was observed, while a xenon background of >1 mbar was shown to eliminate the sputtering. It is concluded that the source has potential to meet the requirements of future EUVL systems.
Excited-state spectroscopy on a nearly closed quantum dot via charge detection
Authors: Elzerman J. M. , Hanson R. , Willems van Beveren L. H. , Vandersypen L. M. K. , Kouwenhoven L. P.
Published: May 2004

We demonstrate a method for measuring the discrete energy spectrum of a quantum dot connected very weakly to a single lead. A train of voltage pulses applied to a metal gate induces tunneling of electrons between the quantum dot and a reservoir. The effective tunnel rate depends on the number and nature of the energy levels in the dot made accessible by the pulse. Measurement of the charge dynamics thus reveals the energy spectrum of the dot, as demonstrated for a dot in the few-electron regime.
Role of electron–phonon coupling in thermal conductance of metal–nonmetal interfaces
Authors: Majumdar Arun , Reddy Pramod
Published: May 2004

We theoretically show that the thermal conductance associated with electron–phonon coupling in a metal near a metal–nonmetal interface can be estimated as hep=Gkp, where G is the volumetric electron–phonon coupling constant and kp is the phonon or lattice thermal conductivity of the metal. The expression suggests hep≈1/T at temperatures comparable to the Debye temperature of the metal. The predicted values of hep fall within the range of conductance values experimentally observed (0.3–1 GW/m2 K), suggesting that it cannot be ignored, and could even play a dominant role at high temperatures. Predictions of the total thermal conductance, that include both electron–phonon and phonon–phonon interfacial conductances, show reasonable agreement in its temperature dependence with experimental data for TiN/MgO interfaces.
Hydrogen-induced reversible changes in drain current in Sc2O3/AlGaN/GaN high electron mobility transistors
Authors: Kang B. S. , Mehandru R. , Kim S. , Ren F. , Fitch R. C. , Gillespie J. K. , Moser N. , Jessen G. , Jenkins T. , Dettmer R. , Via D. , Crespo A. , Gila B. P. , Abernathy C. R. , Pearton S. J.
Published: May 2004

Pt contacted AlGaN/GaN high electron mobility transistors with Sc2O3 gate dielectrics show reversible changes in drain–source current upon exposure to H2-containing ambients, even at room temperature. The changes in current (as high as 3 mA for relatively low gate voltage and drain–source voltage) are approximately an order of magnitude larger than for Pt/GaN Schottky diodes and a factor of 5 larger than Sc2O3/AlGaN/GaN metal–oxide–semiconductor (MOS) diodes exposed under the same conditions. This shows the advantage of using a transistor structure in which the gain produces larger current changes upon exposure to hydrogen-containing ambients. The increase in current is the result of a decrease in effective barrier height of the MOS gate of 30–50 mV at 25 °C for 10% H2/90% N2 ambients relative to pure N2 and is due to catalytic dissociation of the H2 on the Pt contact, followed by diffusion to the Sc2O3/AlGaN interface.
Nanoparticle ring formation in evaporating micron-size droplets
Authors: Govor L. V. , Reiter G. , Bauer G. H. , Parisi J.
Published: May 2004

Self-assembly process of CoPt3 particles into a ring pattern (ring diameter ranging from 0.6 to 1.5 μm, particle diameter 6 nm) results from phase separation in the thin film of a binary mixture, giving rise to a bilayer structure and subsequent decomposition of the top layer into droplets. Evaporation of the droplet leads to a shrinking of its contact line, and the particles located at the contact line follow its motion and self-assemble along the line.
Quantitative microwave evanescent microscopy of dielectric thin films using a recursive image charge approach
Authors: Gao Chen , Hu Bo , Zhang Pu , Huang Mengming , Liu Wenhan , Takeuchi I.
Published: May 2004

A recursive image charge approach has been successfully developed for quantitative microwave microscopy of dielectric thin films using the scanning evanescent microwave microscope. With this approach and the recursion-to-circulation algorithm, frequency shift of the microscope as functions of the thickness of the film, dielectric constants of the film and the substrate can be efficiently computed in a circulation way.
Vacancy ordering in reduced barium titanate
Authors: Woodward David I. , Reaney Ian M. , Yang Gaiying Y. , Dickey Elizabeth C. , Randall Clive A.
Published: May 2004

A crystal structure is proposed for reduced barium titanate, BaTiO3−δ, δ≈0.33, formed during the degradation of Ni–BaTiO3 X7R multilayer ceramic capacitors. High-resolution transmission electron microscopy and selected-area electron diffraction have been used in combination with computer simulations to show that oxygen vacancies accrete on every third pseudocubic {111} plane, resulting in a cell with space group P3m1. Additionally, from electron energy loss spectroscopy, it is proposed that Ti4+ is reduced to Ti3+ as a mechanism of charge compensation within oxygen-deficient octahedra.
Influence of buffer layers on metalorganic vapor phase epitaxy grown GaN on Si(001)
Authors: Schulze F. , Dadgar A. , Bläsing J. , Krost A.
Published: May 2004

GaN layers grown by metalorganic vapor phase epitaxy on Si(001) substrates were investigated by x-ray analysis and scanning electron microscopy. Several sample series were grown changing the AlN/GaN buffer layer deposition temperature, sequence, and thickness. By variation of the buffer layer structure, two different growth orientations could be realized. First, GaN grows c-axis oriented on the Si(001) substrates with two rotational alignments. Second, the r plane (101̄2) of the hexagonal GaN-structure is oriented parallel to the surface. In the latter case, four rotational in-plane alignments are observed. By a miscut (2°–6° off) of the Si substrates one of these alignments is preferred.
Surface plasmon resonant interference nanolithography technique
Authors: Luo Xiangang , Ishihara Teruya
Published: May 2004

We demonstrate a promising nanofabrication method, used to fabricate fine patterns beyond the diffraction limit, by employing surface plasmon polariton (SPP) resonance. Sub-100 nm lines were patterned photolithographically using surface plasmon polaritonic interference in the optical near field excited by a wavelength of 436 nm. The unperforated metallic mask approach which has corrugated surfaces on both sides is proposed for arbitrary patterning. The corrugated surface of the metallic mask on the illuminated side collects light through SPP coupling, and SPP on the exit side of metallic mask redistributes the light into nanoscale spatial distribution, which can be used to fabricate nanostructures. Preliminary numerical simulations support the experimental results.
High-speed and high-current density C60 diodes
Authors: Ma Liping , Ouyang Jianyong , Yang Yang
Published: May 2004

A high-performance organic diode is demonstrated by using C60 sandwiched between a cathode and an anode using metals with different diffusivity and donor ability. In this letter, copper (Cu) and aluminum (Al) are selected as the cathode and anode, respectively. C60 is used as the organic electron-acceptor for its high stability and high carrier mobility. The as-prepared diode shows poor performance. However, after heat treatment, the Cu/C60 interface becomes an Ohmic contact through Cu diffusion and charge-transfer processes, allowing highly efficient electron injection from the Cu electrode. On the other hand, a rectified C60/Al contact is formed, prohibiting efficient electron injection from the Al electrode into C60. Hence, a high-performance organic diode is formed through a heat treatment process, not by the selection of metals with different work functions. Due to the high mobility of C60, the device shows megahertz frequency response, and it can also handle rather high current density (363 A/cm2 at 2.4 V). This opens the way for the formation of high-performance organic electronic devices.
Fabrication of vertically aligned carbon nanowalls using capacitively coupled plasma-enhanced chemical vapor deposition assisted by hydrogen radical injection
Authors: Hiramatsu M. , Shiji K. , Amano H. , Hori M.
Published: May 2004

Two-dimensional carbon nanostructures (carbon nanowalls) were fabricated using capacitively coupled radio-frequency plasma-enhanced chemical vapor deposition assisted by H radical injection. Carbon nanowalls were grown on Si, SiO2, and sapphire substrates without catalyst, and independent of substrate materials. Correlation between carbon nanowall growth and fabrication conditions, such as carbon source gases was investigated. In the case using C2F6/H2 system, aligned carbon nanowalls were grown vertically on the substrate, while carbon nanowalls grown using CH4/H2 system were waved and thin (<10 nm). In the case of the deposition without H radical injection, on the other hand, carbon nanowalls were not fabricated.
A Convenient Synthesis of 2-Substituted Thiazole-5-carboxylates
Authors: Fong Mei , Janowski Wit K. , Prager Rolf H. , Taylor Max R.
Published: May 2004

The photolysis of ethyl 5-oxo-2-phenyl-2,5-dihydroisoxazole-4-carboxylate in acetonitrile containing 0.5% tri- fluoroacetic acid in the presence of thioamides gives moderate (40–60%) yields of thiazole-5-carboxylate esters. In the absence of trifluoroacetic acid, the intermediate vinyl thioesters can be isolated. That addition of the thioamide to the first formed carbene was, through sulfur, confirmed by X-ray crystal structures of 2-methylthiazole-5-carboxylic acid and a byproduct.
Molten Salt as a Green Reaction Medium: Efficient and Chemoselective Dithioacetalization and Oxathioacetalization of Aldehydes Mediated by Molten Tetrabutylammonium Bromide
Authors: Ranu Brindaban C. , Das Arijit
Published: May 2004

Tetrabutylammonium bromide in the molten state has been demonstrated to be a very efficient catalyst and reaction medium for the highly chemoselective dithioacetalization and oxathioacetalization of aldehydes. The tetrabutylammonium bromide is recycled for subsequent reactions.
Metal-Catalyzed Oxidative Damage and Oligomerization of the Amyloid-β Peptide of Alzheimer’s Disease
Authors: Ali Feda E. A. , Barnham Kevin J. , Barrow Colin J. , Separovic Frances
Published: May 2004

The most common form of dementia in old age is Alzheimer’s disease (AD). The presence in the brain of senile plaque is the major pathological marker of AD. The plaques are primarily composed of aggregated amyloid-β peptide (Aβ). Aβ is a 40–42 amino acid peptide that is a proteolytic product derived from the β-amyloid precursor protein. The function of Aβ and the exact mechanism of Aβ aggregation and neurotoxicity are unclear. However, metal coordination by Aβ plays an important role in inducing aggregation and the generation of reactive oxygen species, which appears to be at least partially responsible for Aβ neurotoxicity. In this review we examine the role of copper and zinc ions in Aβ neurotoxicity, especially with regards to the generation of free radicals. We discuss the role of copper or zinc ions in oxidative damage and Aβ conformational changes and the relationship of these metals to AD.
Structure of membrane-bound α-synuclein studied by site-directed spin labeling
Authors: Jao Christine C. , Der-Sarkissian Ani , Chen Jeannie , Langen Ralf
Published: May 2004

Many of the proposed physiological functions of α-synuclein, a protein involved in the pathogenesis of Parkinson's disease, are related to its ability to interact with phospholipids. To better understand the conformational changes that occur upon membrane binding of monomeric α-synuclein, we performed EPR analysis of 47 singly labeled α-synuclein derivatives. We show that membrane interaction is mediated by major conformational changes within seven N-terminal 11-aa repeats, which reorganize from a highly dynamic structure into an elongated helical structure devoid of significant tertiary packing. Furthermore, we find that analogous positions from different repeats are in equivalent locations with respect to membrane proximity. These and other findings suggest a curved membrane-dependent α-helical structure, wherein each 11-aa repeat takes up three helical turns. Similar helical structures could also apply to apolipoproteins and other lipid-interacting proteins with related 11-aa repeats.
Molecular sorting by stochastic resonance
Authors: Alcor Damien , Croquette Vincent , Jullien Ludovic , Lemarchand Annie
Published: May 2004

To sort a targeted species from a mixture, we introduce a procedure that relies on the enhancement of its effective diffusion coefficient. We use the formation of a host–guest complex between α-cyclodextrin and a dye to evidence the dye dispersion when the medium is submitted to an oscillating field. In particular, we demonstrate that the effective diffusion coefficient of the dye may be increased far beyond its intrinsic value by tuning the driving field frequency in the stochastic resonance regime. We use this effect to selectively sort from a mixture a dye that is addressed by its rate constants for association with α-cyclodextrin.
Augmented Delayed Infarct Expansion and Reactive Astrocytosis after Permanent Focal Ischemia in Apolipoprotein E4 Knock-In Mice
Authors: Mori Takashi , Town Terrence , Kobayashi Mariko , Tan Jun , Fujita Shinobu C. , Asano Takao
Published: May 2004

Using homozygous human apolipoprotein E2 (apoE2) (2/2)-, apoE3 (3/3)-, or apoE4 (4/4)-knock-in (KI) mice, we aimed to examine whether an apoE isoform-specific exacerbation of delayed infarct expansion occurs after permanent middle cerebral artery occlusion (pMCAO). Compared with 2/2- or 3/3-KI mice, 4/4-KI mice exhibited significantly larger infarct volumes and worse neurologic deficits after pMCAO, with no significant differences between the latter two groups. Infarct volume in 4/4-KI mice was significantly increased from 1 to 5 days after pMCAO, whereas that in 2/2- or 3/3-KI mice was not significantly altered. DNA fragmentation in the peri-infarct area as detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatenick end-labeling was increased to a similar degree in all of the KI mice by 5 days after pMCAO, with no significant differences among the mouse groups. At every time-point examined, human apoE was most markedly expressed in the peri-infarct area, with similar immunoreactivity among the three lines of KI mice. The glial fibrillary acidic protein immunoreactive burden in the peri-infarct area was progressively increased through 7 days in 4/4-KI mice, but not in 2/2- or 3/3-KI mice. Taken together, these data show that the apoE4 isoform acts to aggravate delayed infarct expansion and peri-infarct reactive astrocytosis during the subacute phase of pMCAO in genetically engineered apoE-KI mice.
Bcl-2 Transfection via Herpes Simplex Virus Blocks Apoptosis-Inducing Factor Translocation after Focal Ischemia in the Rat
Authors: Zhao Heng , Yenari Midori A. , Cheng Danye , Barreto-Chang Odmara L. , Sapolsky Robert M. , Steinberg Gary K.
Published: May 2004

Apoptosis plays a critical role in many neurologic diseases, including stroke. Cytochrome c release and activation of various caspases are known to occur after focal and global ischemia. However, recent reports indicate that caspase-independent pathways may also be involved in ischemic damage. Apoptosis-inducing factor (AIF) is a novel flavoprotein that helps mediate caspase-independent apoptotic cell death. AIF translocates from mitochondria to nuclei where it induces caspase-independent DNA fragmentation. Bcl-2, a mitochondrial membrane protein, protects against apoptotic and necrotic death induced by different insults, including cerebral ischemia. In the present study, Western blots confirmed that AIF was normally confined to mitochondria but translocated to nuclei or cytosol 8, 24, and 48 hours after onset of ischemia. Overall, AIF protein levels also increased after stroke. Confocal microscopy further demonstrated that nuclear AIF translocation occurred in the peri-infarct region but not in the ischemic core where only some cytosolic AIF release was observed. Our data also suggest that AIF translocated into nuclei after cytochrome c was released into the cytosol. Bcl-2 transfection in the peri-infarct region blocked nuclear AIF translocation and improved cortical neuron survival.
Using Weighted Kaplan‐Meier Statistics in Nonparametric Comparisons of Paired Censored Survival Outcomes
Authors: Murray Susan
Published: May 2004

Summary. This research introduces methods for nonparametric testing of weighted integrated survival differences in the context of paired censored survival designs. The current work extends work done by Pepe and Fleming (1989, Biometrics45, 497–507), which considered similar test statistics directed toward independent treatment group comparisons. An asymptotic closed‐form distribution of the proposed family of tests is presented, along with variance estimates constructed under null and alternative hypotheses using nonparametric maximum likelihood estimates of the closed‐form quantities. The described method allows for additional information from individuals with no corresponding matched pair member to be incorporated into the test statistic in sampling scenarios where singletons are not prone to selection bias. Simulations presented over a range of potential dependence in the paired censored survival data demonstrate substantial power gains associated with taking into account the dependence structure. Consequences of ignoring the paired nature of the data include overly conservative tests in terms of power and size. In fact, simulation results using tests for independent samples in the presence of positive correlation consistently undershot both size and power targets that would have been attained in the absence of correlation. This additional worrisome effect on operating characteristics highlights the need for accounting for dependence in this popular family of tests.
Nonparametric Tests for the Gap Time Distributions of Serial Events Based on Censored Data
Authors: Lin D. Y. , Ying Zhiliang
Published: May 2004

Summary. This article deals with the problem of comparing two populations with respect to the distribution of the gap time between two successive events when each subject can experience a series of events and when the event times are potentially right censored. Several families of nonparametric tests are developed, all of which allow arbitrary distributions and dependence structures for the serial events. The asymptotic and small‐sample properties of the proposed tests are investigated. An illustration with data taken from a colon cancer study is provided. The related problem of testing the independence of two successive gap times is also studied.
Bayesian Semiparametric Models for Survival Data with a Cure Fraction
Authors: Ibrahim Joseph G. , Chen Ming‐Hui , Sinha Debajyoti
Published: May 2004

Summary. We propose methods for Bayesian inference for a new class of semiparametric survival models with a cure fraction. Specifically, we propose a semiparametric cure rate model with a smoothing parameter that controls the degree of parametricity in the right tail of the survival distribution. We show that such a parameter is crucial for these kinds of models and can have an impact on the posterior estimates. Several novel properties of the proposed model are derived. In addition, we propose a class of improper noninformative priors based on this model and examine the properties of the implied posterior. Also, a class of informative priors based on historical data is proposed and its theoretical properties are investigated. A case study involving a melanoma clinical trial is discussed in detail to demonstrate the proposed methodology.
Estimation and Prediction for Cancer Screening Models Using Deconvolution and Smoothing
Authors: Pinsky Paul F.
Published: May 2004

Summary. The model that specifies that cancer incidence, I, is the convolution of the preclinical incidence, g and the density of time in the preclinical phase, f, has frequently been utilized to model data from cancer screening trials and to estimate such quantities as sojourn time, lead time, and sensitivity. When this model is fit to the above data, the parameters of f as well as the parameter(s) governing screening sensitivity must be estimated. Previously, g was either assumed to be equal to clinical incidence or assumed to be a constant or exponential function that also had to be estimated. Here we assume that the underlying incidence, I, in the study population (in the absence of screening) is known. With I known, g then becomes a function of f, which can be solved for using (numerical) deconvolution, thus eliminating the need to estimate g or make assumptions about it. Since numerical deconvolution procedures may be highly unstable, however, we incorporate a smoothing procedure that produces a realistic g function while still closely reproducing the original incidence function I upon convolution with f. We have also added the concept of competing mortality to the convolution model. This, along with the realistic preclinical incidence function described above, results in more accurate estimates of sojourn time and lead time and allows for estimation of quantities related to overdiagnosis, which we define here.
A Flexible Parametric Model for Combining Current Status and Age at First Diagnosis Data
Authors: Dunson David B. , Baird Donna D.
Published: May 2004

Summary.In some cross‐sectional studies of chronic disease, data consist of the age at examination, whether the disease was present at the exam, and recall of the age at first diagnosis. This article describes a flexible parametric approach for combining current status and age at first diagnosis data. We assume that the log odds of onset by a given age and of detection by a given age conditional on onset by that age are nondecreasing functions of time plus linear combinations of covariates. Piecewise linear models are used to characterize changes across time in the baseline odds. Methods are described for accommodating informatively missing current status data and inferences based on the age‐specific incidence of disease prior to a landmark event (e.g., puberty, menopause). Our formulation enables straightforward maximum likelihood estimation without requiring restrictive parametric or Markov assumptions. The methods are applied to data from a study of uterine fibroids.
A Regression Modeling Approach for Describing Patterns of HIV Genetic Variation
Authors: Mayer‐Hamblett Nicole , Self Steve
Published: May 2004

Summary.We introduce a novel approach for describing patterns of HIV genetic variation using regression modeling techniques. Parameters are defined for describing genetic variation within and between viral populations by generalizing Simpson's index of diversity. Regression models are specified for these variation parameters and the generalized estimating equation framework is used for estimating both the regression parameters and their corresponding variances. Conditions are described under which the usual asymptotic approximations to the distribution of the estimators are met. This approach provides a formal statistical framework for testing hypotheses regarding the changing patterns of HIV genetic variation over time within an infected patient. The application of these methods for testing biologically relevant hypotheses concerning HIV genetic variation is demonstrated in an example using sequence data from a subset of patients from the Multicenter AIDS Cohort Study.
Catch Estimation with Restricted Randomization in the Effort Survey
Authors: Dauk Philip C. , Schwarz Carl J.
Published: May 2004

Summary. One common method for estimating total catch is to multiply an estimate for CPUE, the catch per unit effort, by an estimate of total effort obtained from an independent second survey. In general, estimating total effort requires that sample times are chosen at random over the full fishing period; however, in practice, this may not always be possible and the usual estimator may be severely biased. Such a restriction in randomization is likely when aircraft are used to make instantaneous counts of fishing activity. This article proposes alternate estimators for use with both access and roving designs in conjunction with effort surveys for which sample times are not random. Ratio type estimators based on activity counts are developed under various scenarios and their performance examined under simulation. In addition, optimizing strategies for use with multiple activity counts are explored. Finally, data from an in‐river gill net fishery on the Eraser River is used to illustrate these results.
Abalone I: Analyzing Mark‐Recapture‐Recovery Data Incorporating Growth and Delayed Recovery
Authors: Catchpole E. A. , Freeman S. N. , Morgan B. J. T. , Nash W. J.
Published: May 2004

Summary. Abalone are semimobile marine gastropods that form the basis of Australia's second most valuable fishery. A site off the coast of Port Arthur, Tasmania, was visited on six occasions. On each occasion, any unmarked live abalone found were marked with a unique identification number and were recorded. Any previously marked abalone found had its identification number and whether or not it was still alive recorded. This results in integrated mark‐recapture‐recovery data, as in Catchpole et al. (1998, Biometrics54, 33–46). During the study period, abalone grew in size, and we model the survival of individuals as a function of their size, estimated from a fitted growth curve. The shells of dead animals are long lasting, and we extend existing methodology to allow for the possibility that an animal found dead may have been dead but overlooked for several visits.
Exploring Extra‐Binomial Variation in Teratology Data Using Continuous Mixtures
Authors: Moore Dirk F. , Park Choon Keun , Smith Woollcott
Published: May 2004

Summary.Discrete data from animal teratology experiments are known to exhibit extra‐binomial variation. For example, we discuss a dominant lethal assay experiment in which male mice are exposed to various levels of radiation and are then mated to females. The response of interest is the number of resorptions out of the number of implantations. Most statistical work on analyzing such data has focused on modeling response rates as a function of dose of a suspected teratogen (radiation in this case) while accounting for the extra‐binomial variability when calculating standard errors of the regression coefficients. Sometimes, however, when an unobserved genetic or exposure variable is suspected, the shape of the mixing distribution is of interest. We propose a mixture of beta‐binomials (MBB) family of distributions that includes the non‐parametric mixture of binomials model of Laird (1978) as a special case. The MBB family can accommodate a mixing distribution with one or more modes, and we develop a bootstrap test for multimodality. We apply the method to data from a dominant lethal teratology experiment.
Model Selection in Estimating Equations
Authors: Pan Wei
Published: May 2004

Summary.Model selection is a necessary step in many practical regression analyses. But for methods based on estimating equations, such as the quasi‐likelihood and generalized estimating equation (GEE) approaches, there seem to be few well‐studied model selection techniques. In this article, we propose a new model selection criterion that minimizes the expected predictive bias (EPB) of estimating equations. A bootstrap smoothed cross‐validation (BCV) estimate of EPB is presented and its performance is assessed via simulation for overdispersed generalized linear models. For illustration, the method is applied to a real data set taken from a study of the development of ewe embryos.
UMPU and Alternative Tests for Association in 2 × 2 Tables
Authors: Fuchs Camil
Published: May 2004

Summary.The use of the uniformly most powerful among the unbiased (UMPU) test was recently suggested for the study of gametic association between two polymorphic loci as an alternative to the Fisher's exact test (Zapata and Alvarez, 1997,Annals of Human Genetics61, 71–77). However, the proposed test is not UMPU for two‐sided alternatives. In this study, we present the UMPU test, discuss criticisms against the use of randomized tests, and compare the power of several tests. We show that, in many practical cases, the use of the UMPU test is less than desirable and propose the alternative adjusted‐more extreme tables (A‐MET) and the equal‐tails (ET) tests. We suggest that some of the general arguments against the use of randomized tests can be alleviated by a newly proposed extendedp‐value definition.
Statistical Inference in a Two‐Compartment Model for Hematopoiesis
Authors: Catlin Sandra N. , Abkowitz Janis L. , Guttorp Peter
Published: May 2004

Summary. We present a method for parameter estimation in a two‐compartment hidden Markov model of the first two stages of hematopoiesis. Hematopoiesis is the specialization of stem cells into mature blood cells. As stem cells are not distinguishable in bone marrow, little is known about their behavior, although it is known that they have the ability to self‐renew or to differentiate to more specialized (progenitor) cells. We observe progenitor cells in samples of bone marrow taken from hybrid cats whose cells contain a natural binary marker. With data consisting of the changing proportions of this binary marker over time from several cats, estimates for stem cell self‐renewal and differentiation parameters are obtained using an estimating equations approach.
Efficiency Gain from Auxiliary Data Requiring Additional Nuisance Parameters
Authors: Barker Richard J. , Kavalieris Laimonis
Published: May 2004

Summary. In a mark‐recapture study of an animal population, live‐recapture information may be supplemented by resightings from marked animals obtained throughout the period of the study and the two types of data analyzed simultaneously. The resighting data can only contribute to estimates of survival probability if they are jointly modeled with the live‐recapture data and require the inclusion of additional nuisance parameters. We show that, under quite general conditions, estimates of the original parameters are estimated with the same, or improved, precision despite the inclusion of the nuisance parameters. Banding data from female goldeneye ducks (Bucephala clangula) are used as an illustration.
Multiple Temporal Cluster Detection
Authors: Molinari Nicolas , Bonaldi Chistophe , Daurés Jean‐Pierre
Published: May 2004

Summary.This article proposes a simple method to determine single or multiple temporal clustering on a variable size population. By a transformation of the data set, the method based on a regression model allows consideration of a variable population size during the time of study. A model selection procedure and a resampling method are used to select the number of clusters. The results have applications in epidemiological studies of rare diseases.
Estimation of a Secondary Parameter in a Group Sequential Clinical Trial
Authors: Gorfine Malka
Published: May 2004

Summary. In this article, we investigate estimation of a secondary parameter in group sequential tests. We study the model in which the secondary parameter is the mean of the normal distribution in a subgroup of the subjects. The bias of the naive secondary parameter estimator is studied. It is shown that the sampling proportions of the subgroup have a crucial effect on the bias: As the sampling proportion of the subgroup at or just before the stopping time increases, the bias of the naive subgroup parameter estimator increases as well. An unbiased estimator for the subgroup parameter and an unbiased estimator for its variance are derived. Using simulations, we compare the mean squared error of the unbiased estimator to that of the naive estimator, and we show that the differences are negligible. As an example, the methods of estimation are applied to an actual group sequential clinical trial, The Beta‐Blocker Heart Attack Trial.
Case–Control Analysis with Partial Knowledge of Exposure Misclassification Probabilities
Authors: Gustafson Paul , Le Nhu D. , Saskin Refik
Published: May 2004

Summary.Consider case‐control analysis with a dichotomous exposure variable that is subject to misclassification. If the classification probabilities are known, then methods are available to adjust odds‐ratio estimates in light of the misclassification. We study the realistic scenario where reasonable guesses, but not exact values, are available for the classification probabilities. If the analysis proceeds by simply treating the guesses as exact, then even small discrepancies between the guesses and the actual probabilities can seriously degrade odds‐ratio estimates. We show that this problem is mitigated by a Bayes analysis that incorporates uncertainty about the classification probabilities as prior information.
Likelihood‐Based Modeling and Analysis of Data Underdispersed Relative to the Poisson Distribution
Authors: Faddy M. J. , Bosch R. J.
Published: May 2004

Summary. By using a generalization of the Poisson process, distributions can be constructed that show appropriate amounts of underdispersion relative to the Poisson distribution that may be apparent from observed data. These are then used to examine the differences between the distributions of numbers of fetal implants in mice corresponding to different doses of the herbicide 2,4,5‐T.
Principal Stratification in Causal Inference
Authors: Frangakis Constantine E. , Rubin Donald B.
Published: May 2004

Summary. Many scientific problems require that treatment comparisons be adjusted for posttreatment variables, but the estimands underlying standard methods are not causal effects. To address this deficiency, we propose a general framework for comparing treatments adjusting for posttreatment variables that yields principal effects based on principal stratification. Principal stratification with respect to a posttreatment variable is a cross‐classification of subjects defined by the joint potential values of that posttreatment variable under each of the treatments being compared. Principal effects are causal effects within a principal stratum. The key property of principal strata is that they are not affected by treatment assignment and therefore can be used just as any pretreatment covariate, such as age category. As a result, the central property of our principal effects is that they are always causal effects and do not suffer from the complications of standard posttreatment‐adjusted estimands. We discuss briefly that such principal causal effects are the link between three recent applications with adjustment for posttreatment variables: (i) treatment noncompliance, (ii) missing outcomes (dropout) following treatment noncompliance, and (iii) censoring by death. We then attack the problem of surrogate or biomarker endpoints, where we show, using principal causal effects, that all current definitions of surrogacy, even when perfectly true, do not generally have the desired interpretation as causal effects of treatment on outcome. We go on to formulate estimands based on principal stratification and principal causal effects and show their superiority.
Estimation in the Cox Proportional Hazards Model with Left‐Truncated and Interval‐Censored Data
Authors: Pan Wei , Chappell Rick
Published: May 2004

Summary.We show that the nonparametric maximum likelihood estimate (NPMLE) of the regression coefficient from the joint likelihood (of the regression coefficient and the baseline survival) works well for the Cox proportional hazards model with left‐truncated and interval‐censored data, but the NPMLE may underestimate the baseline survival. Two alternatives are also considered: first, the marginal likelihood approach by extending Satten (1996,Biometrika83, 355–370) to truncated data, where the baseline distribution is eliminated as a nuisance parameter; and second, the monotone maximum likelihood estimate that maximizes the joint likelihood by assuming that the baseline distribution has a nondecreasing hazard function, which was originally proposed to overcome the underestimation of the survival from the NPMLE for left‐truncated data without covariates (Tsai, 1988,Biometrika75, 319–324). The bootstrap is proposed to draw inference. Simulations were conducted to assess their performance. The methods are applied to the Massachusetts Health Care Panel Study data set to compare the probabilities of losing functional independence for male and female seniors.