bluuebunny/crossref_metadata_2025 huggingface dataset:
WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase
Authors: Su Fei , Overholtzer Michael , Besser Daniel , Levine Arnold J.
Published: July 2002

WISP-1 (Wnt-1-inducedsecreted protein) was identified as an oncogene regulated by the Wnt-1–β-catenin pathway. WISP-1 belongs to the CCN family of growth factors, which are cysteine-rich, heparin-binding, secreted proteins associated with the extracellular matrix, and can interact with cellular integrins. Expression of WISP-1 in some cells results in transformation and tumorigenesis. Here it is shown that WISP-1 can activate the antiapoptotic Akt/PKB signaling pathway. It also is demonstrated that WISP-1 can prevent cells from undergoing apoptosis following DNA damage through inhibition of the mitochondrial release of cytochrome c and up-regulation of antiapoptotic Bcl-XL. Furthermore, the results show that WISP-1 protects cells from p53-dependent cell death, but not Fas-ligand activated cell death, suggesting that there may be cross talk between the tumor suppressor protein p53 and WISP-1 signaling pathways. WISP-1 acts to block cell death at a late stage in the p53-mediated apoptosis pathway.
Nef of HIV‐1 interacts directly with calcium‐bound calmodulin
Authors: Hayashi Nobuhiro , Matsubara Mamoru , Jinbo Yuji , Titani Koiti , Izumi Yoshinobu , Matsushima Norio
Published: July 2002

It was recently found that the myristoyl group of CAP‐23/NAP‐22, a neuron‐specific protein kinase C substrate, is essential for the interaction between the protein and Ca2+‐bound calmodulin (Ca2+/CaM). Based on the N‐terminal amino acid sequence alignment of CAP‐23/NAP‐22 and other myristoylated proteins, including the Nef protein from human immunodeficiency virus (HIV), we proposed a new hypothesis that the protein myristoylation plays important roles in protein–calmodulin interactions. To investigate the possibility of direct interaction between Nef and calmodulin, we performed structural studies of Ca2+/CaM in the presence of a myristoylated peptide corresponding to the N‐terminal region of Nef. The dissociation constant between Ca2+/CaM and the myristoylated Nef peptide was determined to be 13.7 nM by fluorescence spectroscopy analyses. The NMR experiments indicated that the chemical shifts of some residues on and around the hydrophobic clefts of Ca2+/CaM changed markedly in the Ca2+/CaM‐Nef peptide complex with the molar ratio of 1:2. Correspondingly, the radius of gyration determined by the small angle X‐ray scattering measurements is 2–3 Å smaller that of Ca2+/CaM alone. These results demonstrate clearly that Nef interacts directly with Ca2+/CaM.
Human observer detection experiments with mammograms and power‐law noise
Authors: Burgess Arthur E. , Jacobson Francine L. , Judy Philip F.
Published: July 2002

We determined contrast thresholds for lesion detection as a function of lesion size in both mammograms and filtered noise backgrounds with the same average power spectrum, Experiments were done using hybrid images with digital images of tumors added to digitized normal backgrounds, displayed on a monochrome monitor. Four tumors were extracted from digitized specimen radiographs. The lesion sizes were varied by digital rescaling to cover the range from 0.5 to 16 mm. Amplitudes were varied to determine the value required for 92% correct detection in two‐alternative forced‐choice (2AFC) and 90% for search experiments. Three observers participated, two physicists and a radiologist. The 2AFC mammographic results demonstrated a novel contrast‐detail (CD) diagram with threshold amplitudes that increased steadily (with slope of 0.3) with increasing size for lesions larger than 1 mm. The slopes for prewhitening model observers were about 0.4. Human efficiency relative to these models was as high as 90%. The CD diagram slopes for the 2AFC experiments with filtered noise were 0.44 for humans and 0.5 for models. Human efficiency relative to the ideal observer was about 40%. The difference in efficiencies for the two types of backgrounds indicates that breast structure cannot be considered to be pure random noise for 2AFC experiments. Instead, 2AFC human detection with mammographic backgrounds is limited by a combination of noise and deterministic masking effects. The search experiments also gave thresholds that increased with lesion size. However, there was no difference in human results for mammographic and filtered noise backgrounds, suggesting that breast structure can be considered to be pure random noise for this task. Our conclusion is that, in spite of the fact that mammographic backgrounds have nonstationary statistics, models based on statistical decision theory can still be applied successfully to estimate human performance.
Representations of electric and magnetic fields
Authors: Herrmann F. , Hauptmann H. , Suleder M.
Published: July 2002

We propose for the graphical representation of fields not to limit ourselves to field lines but also to draw the orthogonal surfaces. Just as the ends of the electric or magnetic field lines tell us where the sources of the flux of a field are located, the borders of the orthogonal surfaces indicate to us the sources of the field’s circulation.
Scattering of ultrasonic waves by void inclusions
Authors: Ruffino E. , Delsanto P. P.
Published: July 2002

The Local Interaction Simulation Approach (LISA) has been applied to study the propagation of ultrasonic pulses in materials containing void inclusions. First the case of a single scatterer has been considered, with the conclusion that a void must be represented by at least four cells of the discretization lattice. Then the case of ultrasound propagation in a material with both a regular and random distribution of inclusions has been studied. Interesting interference effects have been obtained and it can be concluded that in both cases LISA allows reliable and efficient simulations to be performed.
Aging and temporal discrimination in auditory sequences
Authors: Fitzgibbons Peter J. , Gordon-Salant Sandra
Published: July 2002

This study examined age-related changes in temporal sensitivity to increments in the inter-onset intervals (IOI) of successive components in tonal sequences. Temporal discrimination was examined using reference stimulus patterns consisting of five 50-ms, 4000-Hz components with equal tonal IOIs selected from the range 100–600 ms. Discrimination was examined in separate conditions by measuring the relative difference limen (DL) for increments of tonal IOI in comparison sequences. In some conditions, comparison sequences featured equal increments of all tonal IOIs to examined listener sensitivity to uniform changes of sequence rate, or tempo. Other conditions measured the DL for increments of a single target IOI within otherwise uniform-rate comparison sequences. For these measurements, the single target IOI was either fixed in sequence location, or randomized in location across listening trials. Listeners in the study included four groups of young and elderly adults with and without high-frequency hearing loss. The results for all listeners showed the relative DL for rate discrimination to decrease from a maximum at the 100-ms IOI to a smaller stable value across the range of longer sequence IOI. All listeners also exhibited larger relative DLs for discrimination of single target intervals compared to rate discrimination for equivalent reference IOI values. Older listeners showed poorer performance than younger listeners in all conditions, with the largest age differences observed for discrimination of brief single intervals that were varied randomly in sequence location. None of the results revealed significant effects of hearing loss on performance of younger and older listeners.
Directivity factors for linear arrays of velocity sensors
Authors: Cray Benjamin A. , Nuttall Albert H.
Published: July 2002

Some of the features unique to beamforming a linear array of acoustic velocity sensors, which are not present with scalar-sensing elements (such as conventional pressure sensors), are described in this paper. Four types of sensors are considered here: a uniaxial motion sensor, which measures acoustic particle velocity along a single axis; a biaxial motion sensor measuring velocity in two orthogonal directions; a triaxial motion sensor that measures all three orthogonal components of the velocity vector; and a sensor, denoted as an acoustic vector sensor, that measures acoustic pressure as well as the complete velocity vector. Comparisons are made of the directivity index for each type of sensor and for linear arrays of sensors. It is shown that uniaxial velocity sensors can have a maximum directivity factor three times greater than an omnidirectional pressure sensor, a gain in directivity index of 4.8 dB. Not surprisingly, this directivity gain is highly dependent on signal arrival direction. Indeed, a uniaxial velocity sensor’s directivity can be less than that of an omnidirectional pressure, indicative of a loss in signal level. These comparisons further indicate that a single vector sensor can provide 6 dB of directivity gain, four times the directivity of a pressure sensor. Line arrays of directional sensors can have a directivity index approximately 5 dB greater than that of an identical line array of pressure sensors for approximately all azimuthal array steerings.
Reconciling frequency selectivity and phase effects in masking
Authors: Oxenham Andrew J. , Dau Torsten
Published: July 2002

The effects of auditory frequency selectivity and phase response on masking were studied using harmonic tone complex maskers with a 100-Hz fundamental frequency. Positive and negative Schroeder-phase complexes (m+ and m−), were used as maskers and the signal was a long-duration sinusoid. In the first experiment, thresholds for signal frequencies of 1 and 4 kHz were measured as a function of masker bandwidth and number of components. A large difference in thresholds between the m+ and m− complexes was found only when masker components were presented ipsilateral to the signal over a frequency range wider than the traditional critical band, regardless of the absolute number of components. In the second experiment, frequency selectivity was measured in harmonic tone complexes with fixed or random phases as well as in noise, using a variant of the notched-noise method with a fixed masker level. The data showed that frequency selectivity is not affected by masker type, indicating that the wide listening bandwidth suggested by the first experiment cannot be ascribed to broader effective filters in complex-tone maskers than in noise maskers. The third experiment employed a novel method of measuring frequency selectivity, which has the advantage that the overall level at the input and the output of the auditory filter remains roughly constant across all conditions. The auditory filter bandwidth measured using this method was wider than that measured in the second experiment, but may still be an underestimate, due to the effects of off-frequency listening. The data were modeled using a single-channel model with various initial filters. The main findings from the simulations were: (1) the magnitude response of the Gammatone filter is too narrow to account for the phase effects observed in the data; (2) none of the other filters currently used in auditory models can account for both frequency selectivity and phase effects in masking; (3) the Gammachirp filter can be made to provide a good account of the data by altering its phase response. The final conclusion suggests that masker phase effects can be accounted for with a single-channel model, while still remaining consistent with measures of frequency selectivity: effects that appear to involve broadband processing do not necessarily require across-channel mechanisms.
An acoustic boundary element method based on energy and intensity variables for prediction of high-frequency broadband sound fields
Authors: Franzoni Linda P. , Bliss Donald B. , Rouse Jerry W.
Published: July 2002

A boundary element method is formulated in terms of time-averaged energy and intensity variables. The approach is applicable to high modal density fields but is not restricted to the usual low-absorption, diffuse, and quasiuniform assumptions. A broadband acoustic energy/intensity source is the basic building block for the method. A directivity pattern for the source is derived to account for local spatial correlation effects and to model specular reflections approximately. A distribution of infinitesimal, uncorrelated, directional sources is used to model the boundaries of an enclosure. These sources are discretized in terms of boundary elements. A system of equations results from applying boundary conditions in terms of incident, reflected, and absorbed intensity. The unknown source power for each element is determined from this system of equations. A two-dimensional model problem is used to demonstrate and verify the method. Exact numerical solutions were also obtained for this model problem. The results show that spatially varying mean-square pressure levels are accurately predicted at very low computational cost.
Analysis of one-dimensional wave scattering by the random walk method
Authors: Budaev B. V. , Bogy D. B.
Published: July 2002

The random walk method is applied to a one-dimensional Helmholtz equation with a variable wave number. The solution is represented as a mathematical expectation of a specified functional on paths in a complex space. This solution degenerates to the ray-method approximation in domains where the latter method may be used, but the probabilistic formulas presented describe also backscattered waves whose existence is not explained by the standard asymptotic techniques. The numerical results confirm the efficiency of the random walk approach to the analysis of wave propagation.
Correlation dimension of electroglottographic data from healthy and pathologic subjects
Authors: Behrman Alison , Baken R. J.
Published: July 2002

This paper considers the effects of nonstationarity, noise, and finite data sets on the estimation of the correlation dimension of time-series data characterizing the vibratory behavior of the vocal folds. The electroglottographic signal of sustained /a/ phonations from 10 healthy subjects and 20 subjects with vocal fold pathologies were used to reconstruct the state space in successively higher embeddings using the method of lags. The dimension values were calculated from the scaling region (the level area of the slope plots) which did not increase for higher embeddings. Reasonably defined scaling regions were found in all of the data from the healthy subjects and from five of the pathologic subjects, with values saturating between the first and second embeddings. The EGG data from those five pathologic subjects were nearly periodic. From the remaining 15 subjects, the scaling regions were highly constricted with nonconstant slopes, so that dimension values could not be confidently estimated. The results suggest that the correlation dimension is a highly subjective measure which is not usefully applied to abnormal EGG data. It is recommended that, if used, correlation dimension statistics need to be presented cautiously, and graphical presentation of the data should be included.
Nonlinear wide-angle paraxial acoustic propagation in shallow-water channels
Authors: Kulkarni Rahul S. , Siegmann William L. , Collins Michael D.
Published: July 2002

A time-domain model that describes wide-angle paraxial propagation of acoustic pulses in shallow water is developed. This model incorporates weak nonlinear effects and depth variability in both ambient density and sound speed. Derivations of paraxial approximations are based on an iterative approach, in which the wide-angle approximation is obtained by using a narrow-angle equation to approximate the second range derivative in the two-way equation. Scaling arguments are used to obtain a more tractable simplification of the equation. The wide-angle equation is solved numerically by splitting into components representing distinct physical processes and using a modified version of the time-domain parabolic equation (TDPE) code [M. D. Collins, J. Acoust. Soc. Am. 84, 2114–2125 (1988)]. A high-order upwind flux-correction method is modified to handle the nonlinear component. Numerical results are presented for adiabatic propagation in a shallow, isospeed channel. It is demonstrated that nonlinear effects are significant, even at small ranges, if the peak source pressure is high enough. Both nonlinear and wide-angle effects are illustrated, and their differences are discussed.
Rib resonances present in the scattering response of a ribbed cylindrical shell
Authors: Marcus Martin H. , Sarkissian Angie
Published: July 2002

The presence of ribs in an evacuated, finite cylindrical shell, placed in a fluid medium, produces highlights in its scattering response at certain resonant frequencies. These resonances are identified from the end-incident bistatic response of a ribbed cylindrical shell and are shown to be produced by the flexural vibrations of individual ribs satisfying the boundary conditions of an annular plate.
Moving frame technique for planar acoustic holography
Authors: Kwon Hyu-Sang , Kim Yang-Hann
Published: July 2002

Acoustic holography is one of the best methods to visualize sound fields. The quality of the visualized sound is primarily determined by the size of the hologram, its microphone spacing, and the number of microphones. This paper describes a way to virtually increase the hologram size and the spatial resolution of the holograph. For a stationary sound field, the method continuously sweeps the sound field by a line array of microphones. For moving sound sources, radiating sound is measured by using a line array of microphones fixed in space. In both cases, the measured signals have Doppler effects. The theoretical formulation has been systematically addressed by employing a moving coordinate which has relative motion between the measurement coordinate and the hologram coordinate. Simulations and experiments support the proposed theory. The drawback is that the method is only applicable to discrete frequencies.
Nonlinear aspects of outdoor propagation of acoustic pulses produced by weak explosions
Authors: Moreno Antonio , Colina Carlos de la , Simón Francisco
Published: July 2002

This paper deals with some nonlinear characteristics of acoustic pulses generated by weak explosions with regard to establishing a probe signal for the experimental study of ground characteristics and outdoor sound propagation. These explosions cover the intensity range of signals commonly used on experimental studies, e.g., studies of the impulse response of rooms and the transmission loss and absorption characteristics of noise barriers. After a brief introduction of time history and spectra of such signals, compared to linear pulses and nonlinear pulses of explosions of a higher nonlinear range particular attention is paid to air absorption up to 20 kHz. Evolution of the pulse signature as it propagates as well as global pick attenuation and attenuation in 1/3 octave frequency bands are discussed compared to linear processes and well established nonlinear theories, offering as a conclusion a simple and practical model that accounts well for the transformations undergone by the pulse when it propagates under reference atmospheric conditions. These characteristics are intended as a reference for comparison of experimental studies on the influence of the ground and obstacles of different acoustic nature involved in propagation processes. [Work supported by the Spanish National Research Program, DCICYT AMB 95-0101.]
The lowest-order small slope approximation for rough surface scattering
Authors: Thorsos Eric I. , Broschat Shira L.
Published: July 2002

The small slope approximation (SSA) [A. G. Voronovich, Sov. Phys. JETP 62, 65–70 (1985)] for scattering from rough surfaces leads to a systematic series and improved accuracy is obtained by using higher terms in the series. Numerical implementation of the lowest-order SSA for the scattering cross section has the same level of effort required as for the Kirchhoff approximation (a single integration for one-dimensional surfaces, a double integral for two-dimensional surfaces), while higher orders require higher-order integrations. Thus the accuracy of the lowest-order SSA is of considerable practical interest. In this paper, the accuracy of lowest-order SSA will be illustrated for surfaces with power-law roughness spectra through comparison with exact numerical results. Both Dirichlet and two-fluid boundary conditions will be considered. For typical power-law spectra, the accuracy of the lowest-order SSA is generally quite good. [Work supported by ONR.]
Source levels for shallow underwater sound charges
Authors: Hannay D. E. , Chapman N. R.
Published: July 2002

This paper presents a simple method for removing the surface-reflected component from the explosion waveform of signal underwater sound (SUS) charges detonated at shallow depths, in order to obtain accurate estimates of the source levels. The method is based on the repeated subtraction of time-shifted segments of portions of the source waveform that are uncontaminated by the surface reflection. The technique provides a method for an accurate estimation of the source levels for charges detonated at depths shallower than 90 m. The method is evaluated by comparing the source levels from the processed waveforms with results obtained by scaling source levels for deeper charges to depths of 58 and 18.3 m.
Modal characteristics of in-plane vibration of rectangular plates
Authors: Farag N. H. , Pan J.
Published: July 2002

The equations of in-plane vibration of thin plates are solved for rectangular panels with two parallel edges clamped, while the other two edges are either both clamped, both free, or one clamped and one free. The propagation characteristics of in-plane waves are investigated and the frequency bands of attenuation and propagation of the waves are identified. Simple expressions for the cutoff frequencies of different wave components are derived. The nature of the coupling between in-plane longitudinal and in-plane shear waves is mathematically and physically illustrated. Although all the modes in a plate panel are coupled through Poisson’s effect, it is shown that the coupling is very weak in plate panels with all edges clamped as compared to the cases where one or two parallel edges are free. As a first order approximation, the resonant modes of in-plane waves are classified into uncoupled and coupled mode pairs. By using the coupled mode pairs approximation, it is possible to predict the dynamic response of the plate panel with a reasonable accuracy. Simple expressions are given for approximate estimation of the resonance frequencies of coupled and uncoupled modes. Mode shapes are given, for each case of edge conditions, which satisfy both the displacement and force conditions at the plate edges. A simple procedure is given for the determination of resonance frequencies and mode shapes without excessive computations. The predicted resonance frequencies and mode shapes are compared to the finite element results and good agreement is found. The mode shapes of the in-plane vibration are depicted for the first eight resonant modes for each case of edge conditions.
Free localized vibrations of a semi-infinite cylindrical shell
Authors: Kaplunov Julius D. , Kossovich Leonid Yu. , Wilde Maria V.
Published: July 2002

Free vibrations of a semi-infinite cylindrical shell, localized near the edge of the shell are investigated. The dynamic equations in the Kirchhoff–Love theory of shells are subjected to asymptotic analysis. Three types of localized vibrations, associated with bending, extensional, and super-low-frequency semi-membrane motions, are determined. A link between localized vibrations and Rayleigh-type bending and extensional waves, propagating along the edge, is established. Different boundary conditions on the edge are considered. It is shown that for bending and super-low-frequency vibrations the natural frequencies are real while for extensional vibrations they have asymptotically small imaginary parts. The latter corresponds to the radiation to infinity caused by coupling between extensional and bending modes.
An Experimental Appraisal of Viscoelastic Models
Authors: Spriggs Thomas W. , Huppler John D. , Bird R. Byron
Published: July 2002

Eleven differential and nine integral rheological models for viscoelastic fluids are tabulated in a uniform notation. Included among these are several very recently published models and three previously unpublished models. Representative experimental data are presented and used in qualitative and quantitative evaluations of the models. Comparisons between the models and the experimental data are summarized in a table where a six-point rating scheme is used to assess the ability of several models to quantitatively describe seven material functions. The table indicates which models show promise for future work.
Dynamic rheological behavior of flocculated fumed silica suspensions
Authors: Khan Saad A. , Zoeller Nancy J.
Published: July 2002

Fumed silica suspensions in low molecular weight solvents are used in many photonic and microelectronic applications. The rheology of these thixotropic systems plays a major role in the effectiveness of their usage. In this study, we use dynamic rheological measurements to examine the particle–particle and particle–solvent interactions of fumed silica with hydrophilic and hydrophobic surface groups dispersed in both polar and nonpolar solvents, polypropylene glycol and mineral oil, respectively. We find the mineral oil-based suspensions to have a frequency-independent elastic modulus (G′) for all solids concentration, whereas the polypropylene glycol-based systems exhibit a ‘‘sol–gel’’ transition to a frequency-independent G′ at high concentrations. The results are explained in terms of different solvent particle mechanisms present in the two systems. The behavior of the mineral oil suspensions are dominated by particle–particle interactions through hydrogen bonds, resulting in a gel structure. The polypropylene glycol systems, on the other hand, are dominated by the interactions of the polar solvent with the fumed silica thereby preventing the formation of a 3D gel network. Static light-scattering experiments are used to probe the microstructure of both suspensions. We find the presence of a gel-like network in mineral oil but not in polypropylene glycol, corroborating the rheological results. In addition, both rheology and light-scattering data for the mineral oil suspensions are consistent with the prediction of a diffusion-limited cluster–cluster aggregation model.
Reentrant corner flows of Newtonian and non-Newtonian fluids
Authors: Koplik Joel , Banavar Jayanth R.
Published: July 2002

Computations of the flow of non-Newtonian fluids in the presence of a reentrant corner have a long history of convergence problems, which are believed to originate from a nonsquare-integrable stress singularity. Local flow analyses near such a corner have been inconclusive, due to the nonlinearity and the model dependence of the governing equations. We have used molecular dynamics simulations to compute the flow of both a Newtonian liquid and a model polymer melt through a channel with a reentrant corner, providing an unbiased and convergent calculation. The fluids interact via Lennard–Jones potentials, and for the polymer case we employ FENE chains of length up to 30. For the Newtonian fluid, the shear stress near the corner is found to agree with the Stokes flow prediction of Moffatt. In the non-Newtonian case, the shear stress has a stronger apparent divergence, increasing with velocity but not with chain length, which appears to saturate at an integrable value of approximately 0.8. The molecular origin of the stress enhancement is the additional elongation and rotation of the molecules near the reentrant corner.
A novel processing aid for polymer extrusion: Rheology and processing of polyethylene and hyperbranched polymer blends
Authors: Hong Ye , Cooper-White J. J. , Mackay M. E. , Hawker C. J. , Malmström E. , Rehnberg N.
Published: July 2002

The use of hyperbranched polymers (HBPs) as a processing aid for linear low density polyethylene (LLDPE) was investigated. Various generation (or pseudo-generation) HBPs were used which had either 16 carbon atom alkanes or a mixture of 20/22 carbon atom alkanes on the end groups. In addition, the degree of end group substitution was studied. Blends of up to 10% HBP content were mixed via extrusion at 170 °C to produce 1 mm diameter fibers. Processability, surface appearance and the rheological properties of the blends were evaluated. It was found the power requirement for extrusion was significantly decreased as a result of reduced blend viscosity, and also, the mass flow rate for a given extruder speed was greater than virgin LLDPE for all HBP blends. Melt fracture and sharkskin of the blends was successfully eliminated, and minimal preprocessing time was required for the effect to take place. Surface analysis using x-ray photoelectron spectroscopy and transmission electron microscope techniques were performed with both showing that the HBP had a preference to accumulate at the fiber surface. Rheological experiments were similarly affected, therefore, the blend viscosity is really a composite of a HBP rich phase and a neat LLDPE phase. It is hypothesized that the HBP rich phase acted as a lubricating layer at the polymer/die wall interface. The HBP with a greater degree of end group substitution acted better as a processing/rheological property aid. Blends of LLDPE and paraffin wax were also studied. The surface appearance of HBPs/LLDPE blends was superior to those blends mixed with paraffin wax, as was the extruder performance. The results suggest that HBPs, at trace levels (≈500 ppm), may offer a number of advantages when used as a processing aid for LLDPE.
An X-ray diffraction study of poly(ethylene-2,6-naphthalate), PEN
Authors: Blanton T. N.
Published: July 2002

X-ray diffraction techniques have been applied to study the crystallization of poly(ethylene-2,6-naphthalate), PEN. Uniaxial and biaxial orientation of amorphous cast PEN films resulted in stress-induced crystallization of the triclinic α-PEN polymorph. Annealing of the amorphous PEN samples in the range of 160–240 °C produced thermally induced crystallization of α-PEN. Slow cooling of amorphous PEN from the melt state generated α-PEN as well as the triclinic β-PEN polymorph.
After the Genome—A Brief History of Proteomics
Authors: Suran Melissa
Published: August 2022

This Medical News feature explores the past and present of proteomics.
Association Between Low-Dose Methotrexate Exposure and Melanoma
Authors: Yan Mabel K. , Wang Charlie , Wolfe Rory , Mar Victoria J. , Wluka Anita E.
Published: August 2022

Importance

Methotrexate is widely used for the treatment of inflammatory disorders, including rheumatoid arthritis. Studies suggest that methotrexate may be associated with an increased risk of melanoma.

Objective

To determine whether methotrexate exposure is associated with an increased risk of cutaneous melanoma.

Data Sources

MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to May 12, 2022, for eligible studies.

Study Selection

Case-control studies, cohort studies, or randomized clinical trials (RCTs) were included if they examined the odds or risk of cutaneous melanoma in individuals exposed to low-dose methotrexate in comparison with individuals unexposed. No language limitations were applied.

Data Extraction and Synthesis

Two independent reviewers extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed. To assess study quality, the Cochrane risk of bias tool was used for RCTs, and the Joanna Briggs Institute Checklist was used for cohort and case-control studies. Odds ratio from case-control studies and relative risk or hazard ratio from cohort studies or RCTs were pooled, and a random-effects model meta-analysis was conducted.

Main Outcomes and Measures

Prespecified outcome was the odds ratio, hazard ratio, or risk ratio of cutaneous melanoma comparing low-dose methotrexate exposure with nonexposure.

Results

Seventeen studies (8 RCTs, 5 cohort studies, 4 case-control studies) were eligible for inclusion, and of these, 12 studies with 16 642 cases of melanoma were pooled in the primary analysis. Indications for methotrexate included rheumatoid arthritis, psoriasis, psoriatic arthritis, and inflammatory bowel disease and were unknown in 5 studies. Compared with unexposed individuals, study participants with methotrexate exposure had a small increased risk of melanoma (pooled relative risk, 1.15; 95% CI, 1.08-1.22), but this did not persist in a sensitivity analysis excluding the largest study (pooled relative risk, 1.11; 95% CI, 1.00-1.24). Subgroup analyses according to comparator group (comparing methotrexate exposure with either immunomodulator alone vs immunomodulator and methotrexate) or the indication for methotrexate being rheumatoid arthritis provided similar risk estimates. Using geographical population melanoma incidence rates, a number needed to harm of 18 630 was calculated in Australia, and 41 425 in North America.

Conclusions and Relevance

In this systematic review and meta-analysis, low-dose methotrexate exposure was associated with an increased melanoma risk, but the absolute risk increase could be considered negligible.
Association of 24-Hour Activity Pattern Phenotypes With Depression Symptoms and Cognitive Performance in Aging
Authors: Smagula Stephen F. , Zhang Gehui , Gujral Swathi , Covassin Naima , Li Jingen , Taylor Warren D. , Reynolds Charles F. , Krafty Robert T.
Published: August 2022

Importance

Evidence regarding the nature and prevalence of 24-hour activity pattern phenotypes in older adults, especially those related to depression symptoms and cognition, is needed to guide the development of targeted mechanism research and behavioral interventions.

Objectives

To identify subgroups of older adults with similar 24-hour activity rhythm characteristics and characterize associated depression symptoms and cognitive performance.

Design, Setting, and Participants

From January to March 2022, a cross-sectional analysis of the 2011-2014 National Health and Nutrition Examination and Survey (NHANES) accelerometer study was conducted. The NHANES used a multistage probability sample that was designed to be representative of noninstitutionalized adults in the US. The main analysis included participants 65 years or older who had accelerometer and depression measures weighted to represent approximately 32 million older adults.

Exposures

Latent profile analysis identified subgroups with similar 24-hour activity pattern characteristics as measured using extended-cosine and nonparametric methods.

Main Outcomes and Measures

Covariate-adjusted sample-weighted regressions assessed associations of subgroup membership with (1) depression symptoms defined as 9-Item Patient Health Questionnaire (PHQ-9) scores of 10 or greater (PHQ-9) and (2) having at least psychometric mild cognitive impairment (p-MCI) defined as scoring less than 1 SD below the mean on a composite cognitive performance score.

Results

The actual clustering sample size was 1800 (weighted: mean [SD] age, 72.9 [7.3] years; 57% female participants). Clustering identified 4 subgroups: (1) 677 earlier rising/robust (37.6%), (2) 587 shorter active period/less modelable (32.6%), (3) 177 shorter active period/very weak (9.8%), and (4) 359 later settling/very weak (20.0%). The prevalence of a PHQ-9 score of 10 or greater differed significantly across groups (cluster 1, 3.5%; cluster 2, 4.7%; cluster 3, 7.5%; cluster 4, 9.0%; χ2﻿ P = .004). The prevalence of having at least p-MCI differed significantly across groups (cluster 1, 7.2%; cluster 2, 12.0%; cluster 3, 21.0%; cluster 4, 18.0%; χ2﻿ P < .001). Five of 9 depression symptoms differed significantly across subgroups.

Conclusions and Relevance

In this cross-sectional study, findings indicate that approximately 1 in 5 older adults in the US may be classified in a subgroup with weak activity patterns and later settling, and approximately 1 in 10 may be classified in a subgroup with weak patterns and shorter active duration. Future research is needed to investigate the biologic processes related to these behavioral phenotypes, including why earlier and robust activity patterns appear protective, and whether modifying disrupted patterns improves outcomes.
ATP levels influence cell movement during the mound phase in Dictyostelium discoideum as revealed by ATP visualization and simulation
Authors: Hiraoka Haruka , Wang Jiewen , Nakano Tadashi , Hirano Yasuhiro , Yamazaki Shinichi , Hiraoka Yasushi , Haraguchi Tokuko
Published: August 2022

Cell migration plays an important role in multicellular organism development. The cellular slime mold Dictyostelium discoideum is a useful model organism for the study of cell migration during development. Although cellular ATP levels are known to determine cell fate during development, the underlying mechanism remains unclear. Here, we report that ATP‐rich cells efficiently move to the central tip region of the mound against rotational movement during the mound phase. A simulation analysis based on an agent‐based model reproduces the movement of ATP‐rich cells observed in the experiments. These findings indicate that ATP‐rich cells have the ability to move against the bulk flow of cells, suggesting a mechanism by which high ATP levels determine the cell fate of differentiation.
Effect of Microstructural Evolution on Mechanical Properties and Fracture Modes of AlSi10Mg Blocks Fabricated by Selective Laser Melting after Stress Relief Annealing
Authors: Li Jianzhu , Li Yujie , Wang Zhe , Li Changguang , Yuan Hai , Hao Yun
Published: August 2022

AlSi10Mg parts fabricated by selective laser melting (SLM) are frequently reported to have heterogeneous microstructures. How this affects the mechanical properties of SLM parts still requires further study. Herein, AlSi10Mg blocks with simple cuboid shape are printed and annealed at 300 °C. Their microstructure changes significantly from edge to center and from top to bottom. Low‐temperature annealing is not sufficient to eliminate structural heterogeneity. Before annealing, the Si‐rich phase is fine and mainly exists in the form of a eutectic network. The as‐printed blocks have high tensile strength, and the fracture surface exhibits a mix of transcellular pits and pores. After annealing, the network structure is completely broken or disappeared in most locations in the blocks. The Si‐rich phase is significantly coarsened and even segregated locally along the melt pool boundaries. Yield strength is reduced by 25%–47%, but elongation values are doubled. Tensile samples are fractured by an along‐the‐pool boundary fracture mode along the boundary. Micropores formed during the printing process are aggregated in the about 200 μm thick outer surface layer of the block. They also have a significant effect on the local elongation both before and after annealing.
Lattice‐Mismatch‐Driven Small‐Angle Moiré Twists in Epitaxially Grown 2D Vertical Layered Heterostructures
Authors: Lu Yang , Chen Jun , Coupin Matthew J. , Sinha Sapna , Warner Jamie H.
Published: August 2022

Artificially introduced small twist angles at the interfaces of vertical layered heterostructures (VLHs) have allowed deterministic tuning of electronic and optical properties such as strongly correlated electronic phases and Moiré excitons. But creating a Moiré twist in van der Waals (vdWs) systems by manual stacking is challenging in reproducibility, uniformity, and accuracy of the twist angle, which hinders future studies. Here, it is demonstrated that contrary to the commonly believed 0°‐orientation in vdWs epitaxy, these VLHs show small twist angles controlled by the low‐order commensurate phase with low energy and local atomic relaxation. A commensurate multilevel map is proposed to predict possible orientations. Remarkably, high‐mismatch VLHs show discrete and sometimes non‐zero twist angles dependent on their natural mismatch value. Such framework is experimentally confirmed in five epitaxially grown VLHs under high‐angle annular dark field scanning transmission electron microscopy (HAADF‐STEM), and can provide significant insights for large‐scale engineering of twist angle in VLHs.
Black Phosphorous Mediates Surface Charge Redistribution of CoSe2 for Electrochemical H2O2 Production in Acidic Electrolytes
Authors: Zheng Ya‐Rong , Hu ShaoJin , Zhang Xiao‐Long , Ju Huanxin , Wang Zhenbin , Tan Peng‐Ju , Wu Rui , Gao Fei‐Yue , Zhuang Taotao , Zheng Xiao , Zhu Junfa , Gao Min‐Rui , Yu Shu‐Hong
Published: August 2022

Electrochemical generation of hydrogen peroxide (H2O2) by two‐electron oxygen reduction offers a green method to mitigate the current dependence on the energy‐intensive anthraquinone process, promising its on‐site applications. Unfortunately, in alkaline environments, H2O2 is not stable and undergoes rapid decomposition. Making H2O2 in acidic electrolytes can prevent its decomposition, but choices of active, stable, and selective electrocatalysts are significantly limited. Here, the selective and efficient two‐electron reduction of oxygen toward H2O2 in acid by a composite catalyst that is composed of black phosphorus (BP) nailed chemically on the metallic cobalt diselenide (CoSe2) surface is reported. It is found that this catalyst exhibits a 91% Faradic efficiency for H2O2 product at an overpotential of 300 mV. Moreover, it can mediate oxygen to H2O2 with a high production rate of ≈1530 mg L−1 h−1 cm−2 in a flow‐cell reactor. Spectroscopic and computational studies together uncover a BP‐induced surface charge redistribution in CoSe2, which leads to a favorable surface electronic structure that weakens the HOO* adsorption, thus enhancing the kinetics toward H2O2 formation.
Observation of Coexisting Dirac Bands and Moiré Flat Bands in Magic‐Angle Twisted Trilayer Graphene
Authors: Li Yiwei , Zhang Shihao , Chen Fanqiang , Wei Liyang , Zhang Zonglin , Xiao Hanbo , Gao Han , Chen Moyu , Liang Shijun , Pei Ding , Xu Lixuan , Watanabe Kenji , Taniguchi Takashi , Yang Lexian , Miao Feng , Liu Jianpeng , Cheng Bin , Wang Meixiao , Chen Yulin , Liu Zhongkai
Published: August 2022

Moiré superlattices that consist of two or more layers of 2D materials stacked together with a small twist angle have emerged as a tunable platform to realize various correlated and topological phases, such as Mott insulators, unconventional superconductivity, and quantum anomalous Hall effect. Recently, magic‐angle twisted trilayer graphene (MATTG) has shown both robust superconductivity similar to magic‐angle twisted bilayer graphene and other unique properties, including the Pauli‐limit violating and re‐entrant superconductivity. These rich properties are deeply rooted in its electronic structure under the influence of distinct moiré potential and mirror symmetry. Here, combining nanometer‐scale spatially resolved angle‐resolved photoemission spectroscopy and scanning tunneling microscopy/spectroscopy, the as‐yet unexplored band structure of MATTG near charge neutrality is systematically measured. These measurements reveal the coexistence of the distinct dispersive Dirac band with the emergent moiré flat band, showing nice agreement with the theoretical calculations. These results serve as a stepstone for further understanding of the unconventional superconductivity in MATTG.
Iron‐Catalyzed Oxidative Hydroxyamination of Alkenes of Unsaturated Keto Oximes with TBHP as the Hydroxy Source
Authors: Tao Li‐Ming , Yu Li‐Mei , Xu Jia‐Li , Kuang Jie , Wang Lu‐Bao , Li Chuan‐Hua
Published: August 2022

A new iron‐catalyzed hydroxyamination of alkenyl ketoximes using TBHP as the hydroxy source to selectively assemble cyclic nitrones is described. Using inexpensive FeCl3 as the catalyst and TBHP as both the oxidant and hydroxy source, this reaction enables the formation of two new bonds, one C−N bond and one C−O bond, in a single reaction initiating from the oxime side through the nitrogen‐center radical geneation, radical addition across the C=C bond and radical hydroxylation cascades. This reaction has advantages of exquisite selectvity and excellent functional group tolerance, thus providing an economical and efficient strategy for the construction of complex heterocyclic compounds.
Single Atom Ru Monolithic Electrode for Efficient Chlorine Evolution and Nitrate Reduction
Authors: Yao Yancai , Zhao Long , Dai Jie , Wang Jiaxian , Fang Chuyang , Zhan Guangming , Zheng Qian , Hou Wei , Zhang Lizhi
Published: August 2022

Fabricating single‐atom electrodes via atomic dispersion of active metal atoms into monolithic metal supports is of great significance to advancing the lab‐to‐fab translation of the electrochemical technologies. Here, we report an inherent oxide anchoring strategy to fasten ligand‐free isolated Ru atoms on the amorphous layer of monolithic Ti support by regulating the electronic metal‐support interactions. The prepared Ru single atom electrode exhibited exceptional electrochemical chlorine evolution activity, three orders of magnitude higher mass activity than that of commercial dimensionally stable anode, and also selectively reduced nitrate to ammonia with an unprecedented ammonia yield rate of 22.2 mol g−1 h−1 at −0.3 V. Furthermore, the Ru single atom monolithic electrode can be scaled up from 2×2 cm to 25×15 cm at least, thus demonstrating great potential for industrial electrocatalytic applications.
3,3‐Difluoroallyl Sulfonium Salts: Practical and Bench‐Stable Reagents for Highly Regioselective gem‐Difluoroallylations
Authors: Feng Xiao‐Tian , Ren Jin‐Xiu , Gao Xing , Min Qiao‐Qiao , Zhang Xingang
Published: August 2022

The site‐selective introduction of the difluoromethylene group into organic molecules has important applications in producing pharmaceuticals and agrochemicals. However, the general and efficient methods that can construct both C(sp2)−CF2R and C(sp3)−CF2R bonds remain challenging. Here, we disclose a new type of practical and bench‐stable difluoroalkylating reagent 3,3‐difluoroallyl sulfonium salt (DFAS) that can be practically prepared from inexpensive and bulk chemical feedstock 3,3,3‐trifluoropropene. This reagent allows highly regioselective gem‐difluoroallylation of various organozinc reagents, including aryl, primary, secondary, and tertiary alkyl zinc reagents, via copper catalysis under mild reaction conditions with high efficiency. The reaction can also be extended to a series of substituted DFASs. Application of the approach leads to the short synthesis of complex analogs, showing the prospect of DFASs in medicinal chemistry.
Periodically Interrupting Bonding Behavior to Reformat Delocalized Electronic States of Graphdiyne for Improved Electrocatalytic Hydrogen Evolution
Authors: Ma Kaikai , Wu Jing , Wang Xin , Sun Yu , Xiong Zhaozhao , Dai Fulong , Bai Haokun , Xie Yong , Kang Zhuo , Zhang Yue
Published: August 2022

π electron configuration plays a pivotal role in metal‐free carbon catalysts, and its delocalization degree overwhelmingly dominates catalytic activity. However, precise and targeted regulation of inherent π electrons still remain challenging. Here, one chemical‐bond‐targeted physical clipping strategy is proposed and effectively adopted in the cutting‐edge carbon material system of graphdiyne (GDY) as a concept‐of‐proof. The delocalized electrons are expected to be periodically reformatted for substantially enhancing π electron delocalization. Via theoretical screening and well‐designed experiments, periodical interruption of Csp−Csp2bonds in GDY can render sp−C sites with decent activity, ultimately yielding top‐ranking electrocatalytic performance without intentionally introducing external decoration. The as‐proposed concept endows a universal prescription to push the limit of delocalization degree, thus shedding novel light on the rational design of decent metal‐free catalysts.