bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrieval and on-the-fly alignment of sequence fragments from

the HIV database
Authors: Gaschen Brian , Kuiken Carla , Korber Bette , Foley Brian
Published: July 2002

Motivation: The amount of HIV-1 sequence data generated (presently around 42000 sequences, of which more than 22000 are from the V3 region of the viral envelope) presents a challenge for anyone working on the analysis of these data. A major problem is obtaining the region of interest from the stored sequences, which often contain but are not limited to that region. In addition, multiple alignment programs generally cannot deal with the large numbers of sequences that are available for many HIV-1 regions. We set out to provide our users with a tool that will retrieve and create an initial alignment of the HIV sequences that are available for a given genomic region.

Results: The MPAlign (Multiple Pairwise Alignment) web interface is a collection of Perl scripts that retrieves sequences from the Los Alamos HIV sequence database based on a number of search parameters. All sequences were pairwise-aligned to a model sequence using the Hidden Markov Model-based program HMMER. The HMMER model is general enough to accommodate virtually all HIV-1 sequences stored in the database. To create a multiple sequence alignment, gaps were inserted into the sequences during retrieval, so that they are aligned to one another. Retrieving and aligning the almost 560 gp120 sequences (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({\sim}\) \end{document}1500 nt) stored in the database is at least 1500 times faster than a similar Clustal alignment.

Availability: At http://www.hiv.lanl.gov/

Contact: Brian Gaschen at bkg@lanl.gov

* To whom correspondence should be addressed.
Avoiding cross hybridization by choosing nonredundant targets
on cDNA arrays
Authors: Nielsen H. B. , Knudsen S.
Published: July 2002

Summary: PROBEWIZ designs PCR primers for amplifying probes for cDNA arrays. The probes are designed to have minimal homology to other expressed sequences from a given organism. The primer selection is based on user-defined penalties for homology, primer quality, and proximity to the 3′end.

Availability: PROBEWIZ is accessible from http://www.cbs.dtu.dk/services/DNAarray/probewiz.html

Contact: hbjorn@cbs.dtu.dk; steen@cbs.dtu.dk
DRAGON View: information visualization for annotated microarray
data
Authors: Bouton Christopher M. L. S. , Pevsner Jonathan
Published: July 2002

Summary: The DRAGON View information visualization tools aid in the comprehensive analysis of large-scale gene expression data that has been annotated with biologically relevant information through the generation of three types of complementary graphical outputs.

Availability: The DRAGON View tools are freely available on the DRAGON web site at http://pevsnerlab.kennedykrieger.org/dragonview.htm.

Contact: pevsner@kennedykrieger.org; cbouton@jhmi.edu

* To whom correspondence should be addressed.

3 Present address: LION Bioscience Research Inc.
Analysis of matched mRNA measurements from two different
microarray technologies
Authors: Kuo Winston Patrick , Jenssen Tor-Kristian , Butte Atul J. , Ohno-Machado Lucila , Kohane Isaac S.
Published: July 2002

Motivation: The existence of several technologies for measuring gene expression makes the question of cross-technology agreement of measurements an important issue. Cross-platform utilization of data from different technologies has the potential to reduce the need to duplicate experiments but requires corresponding measurements to be comparable.

Methods: A comparison of mRNA measurements of 2895 sequence-matched genes in 56 cell lines from the standard panel of 60 cancer cell lines from the National Cancer Institute (NCI 60) was carried out by calculating correlation between matched measurements and calculating concordance between cluster from two high-throughput DNA microarray technologies, Stanford type cDNA microarrays and Affymetrix oligonucleotide microarrays.

Results: In general, corresponding measurements from the two platforms showed poor correlation. Clusters of genes and cell lines were discordant between the two technologies, suggesting that relative intra-technology relationships were not preserved. GC-content, sequence length, average signal intensity, and an estimator of cross-hybridization were found to be associated with the degree of correlation. This suggests gene-specific, or more correctly probe-specific, factors influencing measurements differently in the two platforms, implying a poor prognosis for a broad utilization of gene expression measurements across platforms.

Contact: wpkuo@mit.edu

* To whom correspondence should be addressed.

1 These authors contributed equally to this work.
A comparative review of statistical methods for discovering
differentially expressed genes in replicated microarray experiments
Authors: Pan Wei
Published: July 2002

Motivation: A common task in analyzing microarray data is to determine which genes are differentially expressed across two kinds of tissue samples or samples obtained under two experimental conditions. Recently several statistical methods have been proposed to accomplish this goal when there are replicated samples under each condition. However, it may not be clear how these methods compare with each other. Our main goal here is to compare three methods, the t-test, a regression modeling approach (Thomas et al. , Genome Res. , 11, 1227–1236, 2001) and a mixture model approach (Pan et al. , http://www.biostat.umn.edu/cgi-bin/rrs?print+2001,2001a,b) with particular attention to their different modeling assumptions.

Results: It is pointed out that all the three methods are based on using the two-sample t-statistic or its minor variation, but they differ in how to associate a statistical significance level to the corresponding statistic, leading to possibly large difference in the resulting significance levels and the numbers of genes detected. In particular, we give an explicit formula for the test statistic used in the regression approach. Using the leukemia data of Golub et al. (Science , 285, 531–537, 1999), we illustrate these points. We also briefly compare the results with those of several other methods, including the empirical Bayesian method of Efron et al. (J. Am. Stat. Assoc. , to appear, 2001) and the Significance Analysis of Microarray (SAM) method of Tusher et al. (Proc. Natl Acad. Sci. USA , 98, 5116–5121, 2001).

Contact: weip@biostat.umn.edu
Xdigitise: visualization of hybridization experiments
Authors: Wruck Wasco , Griffiths Huw , Steinfath Matthias , Lehrach Hans , Radelof Uwe , O'Brien John
Published: July 2002

Xdigitise is a software system for visualization of hybridization experiments giving the user facilities to analyze the corresponding images manually or automatically. Images of the high-density DNA arrays are displayed as well as the results of an external image analysis bundled with Xdigitise, e.g. the spot locations are marked and the duplicate correlations are shown by a color scale.

Availability: Xdigitise can be downloaded from http://www.molgen.mpg.de/~xdigitise.

Contact: wruck_w@molgen.mpg.de

* To whom correspondence should be addressed.
Membrane raft microdomains mediate lateral assemblies required for HIV‐1 infection
Authors: Mañes Santos , del Real Gustavo , Lacalle Rosa Ana , Lucas Pilar , Gómez‐Moutón Concepción , Sánchez‐Palomino Sonsoles , Delgado Rafael , Alcamí José , Mira Emilia , Martínez‐A Carlos
Published: July 2002

HIV‐1 infection triggers lateral membrane diffusion following interaction of the viral envelope with cell surface receptors. We show that these membrane changes are necessary for infection, as initial gp120–CD4 engagement leads to redistribution and clustering of membrane microdomains, enabling subsequent interaction of this complex with HIV‐1 co‐receptors. Disruption of cell membrane rafts by cholesterol depletion before viral exposure inhibits entry by both X4 and R5 strains of HIV‐1, although viral replication in infected cells is unaffected by this treatment. This inhibitory effect is fully reversed by cholesterol replenishment of the cell membrane. These results indicate a general mechanism for HIV‐1 envelope glycoprotein‐mediated fusion by reorganization of membrane microdomains in the target cell, and offer new strategies for preventing HIV‐1 infection.
The atypical protein kinase Cs
Authors: Moscat Jorge , Diaz‐Meco María T
Published: July 2002

Since its discovery more than 10 years ago, the atypical PKC (aPKC) subfamily has attracted great interest. A number of reports have shown that the kinases of this subfamily play critical roles in signaling pathways that control cell growth, differentiation and survival. Recently, several investigators have identified a number of aPKC‐interacting proteins whose characterization is helping to unravel the mechanisms of action and functions of these kinases. These interactors include p62, Par‐6, MEK5 and Par‐4. The details of how these adapters serve to link the aPKCs to different receptor signaling pathways and substrates in response to specific stimuli are crucial not only for developing an understanding of the roles and functions of the aPKCs themselves, but also for more generally establishing a view of how specificity in signal transduction is achieved.
Expression of endothelin 1 and endothelin A receptor in HPV‐associated cervical carcinoma: new potential targets for anticancer therapy
Authors: Venuti Aldo , Salani Debora , Manni Vanessa , Poggiali Federica , Bagnato Anna
Published: July 2002

ABSTRACT Human papillomaviruses (HPV) are associated with cervical cancer and interact with growth factors that may enhance malignant transformation of cervical carcinoma cells. Endothelin‐1 (ET‐1) is released from HPV transfected keratinocytes and induces increased growth response in these cell lines in comparison with normal cells. In the present study several cervical carcinoma cell lines have been analyzed to investigate the expression of ET‐1 and its receptors as well as their involvement in tumor growth. All HPV‐positive cancer cells secreted ET‐1 and expressed mRNA for ET‐1 and its receptors, whereas a HPV‐negative carcinoma cell line expressed only the ETBR mRNA and didn't secrete ET‐1. Binding studies showed that HPV‐associated cells expressed an increased number of functional ETAR. ET‐1 stimulated a marked dose‐dependent increase in [3H]‐thymidine incorporation with respect to the normal cells whereas ET‐3 and ETBR agonists had no effect. In HPV‐positive cancer cells, a specific antagonist of ETAR inhibited the proliferation induced by ET‐1 and substantially reduced the basal growth rate of unstimulated cervical tumor cells, whereas the ETBR antagonist had no effect. These results demonstrate that ET‐1 participates in the progression of neoplastic growth in HPV‐associated carcinoma, in which ETAR are increased and could be targeted for antitumor therapy.—Venuti, A., Salani, D., Manni, V., Poggiali, F., Bagnato, A. Expression of endothelin 1 and endothelin A receptor in HPV‐associated cervical carcinoma: new potential targets for anticancer therapy. FASEB J. 14, 2277–2283 (2000)
Magnetoencephalography in the study of human somatosensory cortical processing
Authors: Hari R. , Forss N.
Published: July 2002

Magnetoencephalography (MEG) is a totally non–invasive research method which provides information about cortical dynamics on a millisecond time–scale. Whole–scalp magnetic field patterns following stimulation of different peripheral nerves indicate activation of an extensive cortical network. At the SI cortex, the responses reflect mainly the activity of area 3b, with clearly somatotopical representations of different body parts. The SII cortex is activated bilaterally and it also receives, besides tactile input, nociceptive afference. Somatically evoked MEG signals may also be detected from the posterior parietal cortex, central mesial cortex and the frontal lobe. The serial versus parallel processing in the cortical somatosensory network is still under debate.
Critical roles of PPARβ/δ in keratinocyte response to inflammation
Authors: Tan Nguan Soon , Michalik Liliane , Noy Noa , Yasmin Rubina , Pacot Corinne , Heim Manuel , Flühmann Beat , Desvergne Beatrice , Wahli Walter
Published: July 2002

The immediate response to skin injury is the release of inflammatory signals. It is shown here, by use of cultures of primary keratinocytes from wild-type and PPARβ/δ−/− mice, that such signals including TNF-α and IFN-γ, induce keratinocyte differentiation. This cytokine-dependent cell differentiation pathway requires up-regulation of the PPARβ/δ gene via the stress-associated kinase cascade, which targets an AP-1 site in thePPARβ/δ promoter. In addition, the pro-inflammatory cytokines also initiate the production of endogenous PPARβ/δ ligands, which are essential for PPARβ/δ activation and action. Activated PPARβ/δ regulates the expression of genes associated with apoptosis resulting in an increased resistance of cultured keratinocytes to cell death. This effect is also observed in vivo during wound healing after an injury, as shown in dorsal skin of PPARβ/δ+/+ and PPARβ/δ+/− mice.
Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3
Authors: Qian Ying , Fritzsch Bernd , Shirasawa Senji , Chen Chih-Li , Choi Yoojin , Ma Qiufu
Published: July 2002

Brainstem visceral sensory and (nor)adrenergic neurons play crucial roles in modulating cardiovascular and respiratory functions. The origins and formation of these neurons are poorly understood. Here we show that these two classes of neurons are derived fromMash1-positive precursor cells, and can be prospectively identified by combinatorial expression of two homeobox genes,Rnx and Phox2 (Phox2a or Phox2b). It was previously shown that Rnx-deficient mice die from respiratory failure. Here we show that Rnx function is required for formation of first-order relay visceral sensory neurons in the brainstem. In addition, as in Phox2b-deficient mice, the development of most (nor)adrenergic centers is compromised inRnx mutants. We also provide genetic evidence to show that Rnx and Phox2 proteins may function independently to specify the (nor)adrenergic phenotype. Our studies reveal a surprising ontogenetic relationship between relay visceral sensory and (nor)adrenergic neurons, and suggest that it may be a common theme in the developing nervous system that the same set of transcriptional regulators is associated with formation of multiple components within a neuronal network.
Relating Whole-Genome Expression Data with Protein-Protein Interactions
Authors: Jansen Ronald , Greenbaum Dov , Gerstein Mark
Published: July 2002

We investigate the relationship of protein-protein interactions with mRNA expression levels, by integrating a variety of data sources for yeast. We focus on known protein complexes that have clearly defined interactions between their subunits. We find that subunits of the same protein complex show significant coexpression, both in terms of similarities of absolute mRNA levels and expression profiles, e.g., we can often see subunits of a complex having correlated patterns of expression over a time course. We classify the yeast protein complexes as either permanent or transient, with permanent ones being maintained through most cellular conditions. We find that, generally, permanent complexes, such as the ribosome and proteasome, have a particularly strong relationship with expression, while transient ones do not. However, we note that several transient complexes, such as the RNA polymerase II holoenzyme and the replication complex, can be subdivided into smaller permanent ones, which do have a strong relationship to gene expression. We also investigated the interactions in aggregated, genome-wide data sets, such as the comprehensive yeast two-hybrid experiments, and found them to have only a weak relationship with gene expression, similar to that of transient complexes. (Further details ongenecensus.org/expression/interactions andbioinfo.mbb.yale.edu/expression/interactions.)
Interrelating Different Types of Genomic Data, from Proteome to Secretome: 'Oming in on Function
Authors: Greenbaum Dov , Luscombe Nicholas M. , Jansen Ronald , Qian Jiang , Gerstein Mark
Published: July 2002

With the completion of genome sequences, the current challenge for biology is to determine the functions of all gene products and to understand how they contribute in making an organism viable. For the first time, biological systems can be viewed as being finite, with a limited set of molecular parts. However, the full range of biological processes controlled by these parts is extremely complex. Thus, a key approach in genomic research is to divide the cellular contents into distinct sub-populations, which are often given an “-omic” term. For example, the proteome is the full complement of proteins encoded by the genome, and the secretome is the part of it secreted from the cell. Carrying this further, we suggest the term “translatome” to describe the members of the proteome weighted by their abundance, and the “functome” to describe all the functions carried out by these. Once the individual sub-populations are defined and analyzed, we can then try to reconstruct the full organism by interrelating them, eventually allowing for a full and dynamic view of the cell. All this is, of course, made possible because of the increasing amount of large-scale data resulting from functional genomics experiments. However, there are still many difficulties resulting from the noisiness and complexity of the information. To some degree, these can be overcome through averaging with broad proteomic categories such as those implicit in functional and structural classifications. For illustration, we discuss one example in detail, interrelating transcript and cellular protein populations (transcriptome and translatome). Further information is available athttp://bioinfo.mbb.yale.edu/what-is-it.
A Green's function approach to local rf heating in interventional MRI
Authors: Yeung Christopher J. , Atalar Ergin
Published: July 2002

Current safety regulations for local radiofrequency (rf) heating, developed for externally positioned rf coils, may not be suitable for internal rf coils that are being increasingly used in interventional MRI. This work presents a two‐step model for rf heating in an interventional MRI setting: (1) the spatial distribution of power in the sample from the rf pulse (Maxwell's equations); and (2) the transformation of that power to temperature change according to thermal conduction and tissue perfusion (tissue bioheat equation). The tissue bioheat equation is approximated as a linear, shift‐invariant system in the case of local rf heating and is fully characterized by its Green's function. Expected temperature distributions are calculated by convolving (averaging) transmit coil specific absorption rate (SAR) distributions with the Green's function. When the input SAR distribution is relatively slowly varying in space, as is the case with excitation by external rf coils, the choice of averaging methods makes virtually no difference on the expected heating as measured by temperature change However, for highly localized SAR distributions, such as those encountered with internal coils in interventional MRI, the Green's function method predicts heating that is significantly different from the averaging method in current regulations. In our opinion, the Green's function method is a better predictor since it is based on a physiological model. The Green's function also elicits a time constant and scaling factor between SAR and that are both functions of the tissue perfusion rate. This emphasizes the critical importance of perfusion in the heating model. The assumptions made in this model are only valid for local rf heating and should not be applied to whole body heating.
Detection of tumorigenesis in rat bladders with optical coherence tomography
Authors: Pan Yingtian , Lavelle John P. , Bastacky Sheldon I. , Meyers Susan , Pirtskhalaishvili Georgi , Zeidel Mark L. , Farkas Daniel L.
Published: July 2002

Optical coherence tomography (OCT) is a novel technique that enables noninvasive cross‐sectional imaging of biological tissues. Because of its high resolution (∼10 μm), superior dynamic range (140 dB in our case) and up to 2–3 mm penetration depth, OCT is potentially useful for noninvasive screening of superficial lesions. Bladder cancer arises within the transitional epithelium. Despite the ability to visualize the epithelium via cystoscopy, it is often difficult to detect early epithelial cancers and to determine their penetration to the underlying layers. To investigate the potential of OCT to enhance imaging of bladder cancers and other epithelial lesions, we applied OCT to normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of porcine bladder (a close homolog of human bladder) confirm the ability of this method to image human tissues. To determine whether OCT can track the course of bladder cancer, a standard rat model of bladder cancer in which Fisher rats are exposed to methyl‐nitroso‐urea (MNU), was followed both with OCT and histological studies. Our results show that the micro morphology of porcine bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlated with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion as well as the abnormal growth of urothelium (e.g., papillary hyperplasia and carcinomas). By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. This is the first OCT study of any tumor documented in a systematic fashion, and the results suggest the potential of OCT for the noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering. However, because of the depth limitation, OCT may have limited applications in staging the invasion of higher‐state urothelial cancers, especially for papillary carcinomas.
Neutrino physics
Authors: Haxton Wick C. , Holstein Barry R.
Published: July 2002

The basic concepts of neutrino physics are presented at a level appropriate for integration into elementary courses on quantum mechanics and/or modern physics.
Acoustic remote sensing of internal solitary waves and internal tides in the Strait of Gibraltar
Authors: Tiemann Christopher O. , Worcester Peter F. , Cornuelle Bruce D.
Published: July 2002

High-frequency underwater acoustic transmissions across the Strait of Gibraltar are used to examine the feasibility of acoustically measuring several physical processes in the Strait, a difficult area to sample with conventional instruments. Internal undular bores propagate along the interface between an upper layer of Atlantic water and a lower layer of Mediterranean water. As they cross the acoustic path they are recognized by their scattering effects in the acoustic record. The time between internal bore crossings is influenced more by the tidal phase of the bore release at the Camarinal Sill than by variability in the bore’s propagation time to the acoustic path. When internal bores were present, the acoustic arrival patterns could be classified as one of three types with different internal bore and internal tide amplitudes. The arrival types alternate during spring to neap tide transitions, suggesting that internal bore amplitude is not linearly related to tidal height. The sensitivity of acoustic observables to several physical parameters is investigated using a forward model, and a demonstration of inverse techniques provides estimates of several physical parameters from spring tidal cycles.
Measuring parameters that control acoustic propagation in granular sediments near the seafloor
Authors: Stoll Robert D.
Published: July 2002

Propagation of acoustic waves in granular sediments near the water-sediment interface is controlled by a number of parameters such as fluid and grain compressibility, permeability, and the compressibility and shear stiffness of the skeletal frame in a water environment. A new experimental technique for evaluating several of these properties is described wherein a cylindrical, water-saturated sample is subjected to vertical, steady-state fluid flow. By controlling the hydraulic gradient, any desired vertical, effective stress may be generated and acoustic measurements then made across the diameter. When the effective stress is reduced to zero, acoustic measurements yield the compressibility of the grains, whereas at nonzero effective stress levels, it is possible to assess the effects of depth of embedment which causes changes in the compressibility and stiffness of the frame. Finally, by measuring the flow rate at each gradient, a direct evaluation of permeability is made. Preliminary measurements agree with most historical evaluations of these parameters suggesting that some recent work which challenges the traditional values is in error. [Work supported by ONR, code 321OA.]
Modeling and measurement of nonlinear dynamic behavior in piezoelectric ceramics with application to 1-3 composites
Authors: Royston T. J. , Houston B. H.
Published: July 2002

The nonlinear vibratory behavior of a 1-3 piezoceramic composite is characterized theoretically and experimentally. The developed theoretical model for the electroelastic behavior of the 1-3 composite follows conventional assumptions made by prior investigators but includes nonlinear terms to account for hysteresis in the embedded PZT phase. Experimental measurements of the quasistatic and dynamic mechanical response of the 1-3 with embedded PZT-4 or PZT-5H phases to harmonic electrical excitation over a range of excitation frequencies and two different mechanical loading conditions quantify the nature and level of nonlinearity and illustrate its dependence on the type of PZT material and the mechanical coupling conditions of the 1-3 to its surroundings. Good agreement exists between theoretical predictions and experimental measurements.
A multiple-frequency method for potentially improving the accuracy and precision of in situ target strength measurements
Authors: Demer David A. , Soule Michael A. , Hewitt Roger P.
Published: July 2002

The effectiveness of a split-beam echosounder system to reject echoes from unresolvable scatterers, thereby improving the measurements of in situ target strengths (TS) of individuals, is dramatically enhanced by combining synchronized signals from two or more adjacent split-beam transducers of different frequencies. The accuracy and precision of the method was determined through simulations and controlled test tank experiments using multiple standard spheres and 38- and 120-kHz split-beam echosounders. By utilizing the angular positional information from one of the split-beam transducers, additional corresponding TS measurements were shown to be obtainable from a juxtaposed single-beam transducer. Both methods were utilized to extract in situ TS measurements of Antarctic scatterers simultaneously at 38, 120, and 200 kHz. The ultimate efficiency of the multiple-frequency technique is shown to be limited by phase measurement precision, which in turn is limited by the scattering complexity of targets and the receiver bandwidth. Imprecise phase measurements also result in significant beam-compensation uncertainty in split-beam measurements. Differences in multi-frequency TS measurements provided information about the identity of constituents in a mixed species assemblage. The taxa delineation method has potential, but is limited by compounding measurement uncertainties at the individual frequencies and sparse spectral sampling.
On the apparent source width (ASW) for bandpass noises related to the IACC and the width of the interaural cross-correlation function (WIACC)
Authors: Sato Shin-ichi , Ando Yoichi
Published: July 2002

It has been shown that the ASW for 1/3 octave band noises and music signal can be described as functions of the IACC and the WIACC, which is defined as the time interval of the interaural cross-correlation function within 10% of the maximum [Sato and Ando, J. Acoust. Soc. Am. 100, 2592(A) (1996); 102, 3188(A) (1997)]. In this study, it is examined whether or not the ASW for bandpass noises with different bandwidth Δf also can be calculated with the IACC and the WIACC. In order to control the WIACC, the bandwidth of the bandpass noises of 500 Hz center frequency was changed in the range of 1/3–3 octave. Results of the scale values of ASW obtained by the paired comparison method are compared with calculated ASW. [Work supported by the Grant-in-Aid for Scientific Research JSPS.]
Speech intelligibility and acoustic characteristics of Mandarin speakers with cerebral palsy
Authors: Jeng Jing-Yi , Weismer Gary , Kent Ray
Published: July 2002

Reduced speech intelligibility is often associated with individuals having cerebral palsy. The purpose of the present study was to investigate the speech intelligibility and acoustic characteristics of three subtypes of cerebral palsy (athetoid, spastic, mixed) among adult speakers of Mandarin. A Mandarin word intelligibility test was constructed using phonetic contrasts known from previous studies to be especially sensitive to the dysarthria associated with cerebral palsy. These included tonal contrasts, whose relationship to speech intelligibility deficits in persons with cerebral palsy is not well understood. Acoustic measures consisted of formant frequencies, segment durations, and measures of tone. Preliminary results show that speech intelligibility of athetoid speakers is often worse than that of spastic speakers, and that there are also reliable acoustic differences between the groups. A multidimensional scaling analysis of the perceptual results and regression models of the relationship of the acoustic to the perceptual variables will also be reported. [Work supported by NIH DC00319.]
Wave propagation in micro-heterogeneous porous media: A model based on an integro-differential wave equation
Authors: Hanyga Andrzej , Rok Vladimir E.
Published: July 2002

A model hyperbolic partial differential equation with singular convolution operators and infinitely smooth solutions is studied. It is shown that short pulses, including finite-bandwidth pulses, propagate with a delay with respect to the wavefront. For a two-parameter family of such equations Green’s functions are obtained in a simple self-similar form. As an application, it is demonstrated that the Gurevich–Lopatnikov dispersion law for a thin-layered porous medium can be approximated by a hyperbolic equation with singular memory.
Effects of reverberation on spatial, prosodic, and vocal-tract size cues to selective attention
Authors: Darwin C. J. , Hukin R. W.
Published: July 2002

Three experiments explored the resistance to simulated reverberation of various cues for selective attention. Listeners decided which of two simultaneous target words belonged to an attended rather than to a simultaneous unattended sentence. Attended and unattended sentences were spatially separated using interaural time differences (ITDs) of 0, ±45, ±91 or ±181 μs. Experiment 1 used sentences resynthesized on a monotone, with sentence pairs having F0 differences of 0, 1, 2, or 4 semitones. Listeners’ weak preference for the target word with the same monotonous F0 as the attended sentence was eliminated by reverberation. Experiment 1 also showed that listeners’ ability to use ITD differences was seriously impaired by reverberation although some ability remained for the longest ITD tested. In experiment 2 the sentences were spoken with natural prosody, with sentence stress in different places in the attended and unattended sentences. The overall F0 of each sentence was shifted by a constant amount on a log scale to bring the F0 trajectories of the target words either closer together or further apart. These prosodic manipulations were generally more resistant to reverberation than were the ITD differences. In experiment 3, adding a large difference in vocal-tract size (±15%) to the prosodic cues produced a high level of performance which was very resistant to reverberation. The experiments show that the natural prosody and vocal-tract size differences between talkers that were used retain their efficacy in helping selective attention under conditions of reverberation better than do interaural time differences.
Infrared Spectroscopic Study of Decomposition of Ti (  N  (  CH 3 ) 2 ) 4
Authors: Driessen Joost P. A. M. , Schoonman Joop , Jensen Klavs F.
Published: July 2002

The decomposition of

Ti
(
N
(

CH

3

)

2

)

4

(TDMAT) has been studied in

N

2

and

H

2

environments and surface temperatures between 473 and 623 K by using Fourier transform infrared spectroscopy. The pressure in the system was 5 Torr, with a TDMAT partial pressure of 0.3 Torr. The evolution of gas-phase species was monitored by characteristic infrared absorption. For temperatures less than 478 K, an average number of more than three ligands per TDMAT molecule is observed. Approximately one ligand per two TDMAT molecules decomposes into methane- and carbon-containing species in the coating. This slow decomposition pathway implies intermolecular hydrogen transfer between multiple TDMAT molecules. A decomposition mechanism consistent with the experimental observations is proposed. For temperatures greater than 478 K, the conversion rate of TDMAT into products increases drastically. Less gaseous species are observed, Auger electron spectroscopy measurements show more carbon contamination in the coating, and additional absorption peaks appear in the IR spectra. Nuclear magnetic resonance spectroscopy indicates that these peaks can be assigned to a mixture of oligomers of TDMAT reaction fragments that desorb from the hot surface. The increased carbon content at elevated temperatures is attributed to incomplete desorption of ligands or metallacycle formation. © 2001 The Electrochemical Society. All rights reserved.
Proper Annealing for Enhanced Quality of Silicon Dioxide Thin Film on Gallium Arsenide
Authors: Huang C. J.
Published: July 2002

Previous work of this research group produced high quality and stable silicon dioxide(SiO2)films on gallium arsenide (GaAs) substrates by liquid phase deposition (LPD) at room temperature. This study presents a method to improve theseSiO2layers via aN2Oprocess utilizing fluorine, which controls the physical and chemical properties of the oxides. A maximum growth rate of 1303 Å/h and a refractive index of 1.44 were obtained. Previous LPD deposition had better charge density than did conventional vacuum deposition. The method proposed herein produces a practical and reliableSiO2film with a charge density of∼8.6×1010 cm−2,improved over previous LPDSiO2,allowing increased ultralarge-scale integration potential. © 2001 The Electrochemical Society. All rights reserved.
Evolution of Copper-Oxide Damascene Structures in Chemical Mechanical Polishing : I. Contact Mechanics Modeling
Authors: Lai Jiun-Yu , Saka Nannaji , Chun Jung-Hoon
Published: July 2002

Nonplanarity arising from the chemical mechanical polishing of Cu-oxide damascene structures results in the exposure field (die-size) being partially out of focus in the subsequent lithography process. Thus the corresponding mechanisms of within-die polishing must be determined and the within-die nonplanarity due to polishing needs to be minimized to increase the process yield. In this paper, contact mechanics models were developed to explain the role of pattern geometry on the variation of material removal rate. The effects of Cu linewidth, area fraction, and the elastic properties of the polishing pad on pad displacement into low features were examined to focus on the mechanical aspects of the process. The pressure distribution on the high features was determined and the rate of pattern planarization was quantified. Experiments on patterned Cu wafers were conducted to verify the model. Based on these results, the planarization and polishing behavior and the within-die nonplanarity due to the variation of pattern geometry were discussed. © 2001 The Electrochemical Society. All rights reserved.
Aspirin for the Primary Prevention of Atherosclerotic Cardiovascular Disease in Women
Authors: Shufelt Chrisandra L. , Mora Samia , Manson JoAnn E.
Published: July 2022

This JAMA Insights Clinical Update discusses updated recommendations on the use of aspirin for primary prevention of atherosclerotic cardiovascular disease in women and stresses the importance of shared clinical decision-making.
Multi‐omic analysis in carcinoma of unknown primary (CUP): therapeutic impact of knowing the unknown
Authors: Kato Shumei , Gumas Sophia , Adashek Jacob J. , Okamura Ryosuke , Lee Suzanna , Sicklick Jason K. , Kurzrock Razelle
Published: July 2022

Carcinoma of unknown primary (CUP) is a difficult‐to‐manage malignancy. Multi‐omic profiles and treatment outcome vs. degree of precision matching were assessed. Tumours underwent next‐generation sequencing (NGS) [tissue and/or blood‐derived cell‐free DNA (cfDNA)]. Selected patients had transcriptome‐based immune profiling and/or programmed cell death 1 ligand 1 (PD‐L1) immunohistochemistry analysis. Patients could be reviewed by a Molecular Tumor Board, but physicians chose the therapy. Of 6497 patients in the precision database, 97 had CUP. The median number of pathogenic tissue genomic alterations was 4 (range, 0–25), and for cfDNA, was 2 (range, 0–9). Each patient had a distinct molecular landscape. Food and Drug Administration (FDA)‐approved biomarkers included the following: PD‐L1+ ≥ 1%, 30.9% of CUPs tested; microsatellite instability, 3.6%; tumour mutational burden ≥ 10 mutations·Mb−1, 23%; and neurotrophic receptor tyrosine kinase (NTRK) fusions, 0%. RNA‐based immunograms showed theoretically druggable targets: lymphocyte activation gene 3 protein (LAG‐3), macrophage colony‐stimulating factor 1 receptor (CSF1R), adenosine receptor A2 (ADORA2) and indoleamine 2,3‐dioxygenase 1 (IDO1). Overall, 56% of patients had ≥ 1 actionable biomarker (OncoKB database). To quantify the degree of matching (tumours to drugs), a Matching Score (MS; roughly equivalent to number of alterations targeted/total number of deleterious alterations) was calculated post hoc. Comparing evaluable treated patients [MS high, > 50% (N = 15) vs. low ≤ 50% (N = 47)], median progression‐free survival was 10.4 vs. 2.8 months (95% CI 0.11–0.64; HR 0.27; P = 0.002); survival, 15.8 vs. 6.9 months (95% CI 0.17–1.16; HR 0.45; P = 0.09); and clinical benefit rate (stable disease ≥ 6 months/partial/complete response), 71% vs. 24% (P = 0.003). Higher MS was the only factor that predicted improvement in outcome variables after multivariate analysis. In conclusion, CUPs are molecularly complex. Treatments with high degrees of matching to molecular alterations (generally achieved by individualized combinations) correlated with improved outcomes.
Cognitive reserve protects ALS‐typical cognitive domains: A longitudinal study.
Authors: Temp Anna G. M. , Kasper Elisabeth , Machts Judith , Vielhaber Stefan , Teipel Stefan , Hermann Andreas , Prudlo Johannes
Published: July 2022

Background and Objectives

To determine whether cognitive reserve (CR) as measured by verbal intelligence quotient, educational length, and achievement protects amyotrophic lateral sclerosis (ALS) patients' verbal fluency, executive functioning, and memory against brain volume loss over a period of 12 months.

Methods

This cohort study was completed between 2013 and 2016 with a follow‐up duration of 12 months. ALS patients were recruited from two specialist out‐patient clinics in Rostock and Magdeburg in Germany. Participants underwent cognitive testing and magnetic resonance imaging both at baseline and again after 12 months. The cognitive domains assessed included verbal memory in addition to executive functions such as verbal fluency, working memory, shifting and selective attention.

Results

Thirty‐eight ALS patients took part; 25 patients had no cognitive impairment (ALSni), and 13 were cognitively impaired (ALSci). On average, patients lost 294 mm3 in their superior frontal gyri, 225 mm3 in their orbitofrontal gyri, and 15.97 mm3 in their hippocampi over 12 months. There was strong evidence that CR protected letter fluency from further decline (Bayes factor [BF] >10) and moderate evidence that it supported learning effects in letter flexibility (BF >3). However, there is a lack of evidence supporting the notion that working memory, shifting, selective attention or verbal memory (BF = 1) are protected.

Discussion

As CR is easily determined and protects ALS‐specific cognitive domains over time, it should be regarded as a valuable predictive marker.
How Do Nonsurgical Interventions Improve Pain and Physical Function in People With Osteoarthritis? A Scoping Review of Mediation Analysis Studies
Authors: Lima Yuri Lopes , Lee Hopin , Klyne David M. , Dobson Fiona L. , Hinman Rana S. , Bennell Kim L. , Hall Michelle
Published: July 2022

Objective

Nonsurgical interventions are recommended for osteoarthritis (OA). However, how interventions change pain and physical function is unclear. Therefore, the objectives of this scoping review were to 1) identify what potential mediators of nonsurgical interventions on pain and physical function have been evaluated and 2) summarize the findings according to intervention, joint, and outcome.

Methods

We searched Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Scopus databases. Studies were included if they conducted a mediation analysis on a randomized controlled trial evaluating a nonsurgical intervention on OA of any joint. Outcomes were pain and physical function.

Results

Nine knee OA studies, evaluating diet plus exercise, exercise, unloading shoes, high‐expectation communication during acupuncture, and telephone‐based weight loss plus exercise were identified. Except for weight loss and self‐efficacy, putative mediators (knee muscle perfusion/extensor strength/adduction moment, systemic inflammatory biomarkers, physical activity, dietary intake, and pain beliefs) were evaluated by single studies. Ten mediators partially mediated intervention (diet plus exercise, exercise, high‐expectation communication) effects on pain and physical function. Eight mediators were common to pain and function (reduced weight, increased knee extensor strength, and increased self‐efficacy). Constant knee flexor muscle perfusion partially mediated exercise effects on pain, and knee pain relief partially mediated exercise effects on function.

Conclusion

In knee OA, some evidence suggests that the benefits of 1) diet and exercise are mediated through changes in body weight, systemic inflammation, and self‐efficacy; 2) exercise is mediated through changes in knee muscle strength and self‐efficacy; and 3) high‐expectation communication style is mediated through changes in self‐efficacy.
Biomineralization of Symbiotic Cultures of Bacteria and Yeast (SCOBY) Cellulose Aerogels
Authors: Jones Rollin J. , Srubar Wil V.
Published: July 2022

Microbial biomineralization is explored as a strategy for improving the thermal stability of symbiotic cultures of bacteria and yeast (SCOBY) cellulose aerogels. Cellulose pellicles were grown in kombucha tea and subsequently biomineralized with Sporosarcina pasteurii (S. pasteurii). The samples were exposed to one, two, or three cycles of ureolytic biomineralization. The microstructure and material properties of biomineralized samples were compared to experimental controls, which included a non‐biomineralized cellulose aerogel sample and an abiotic cellulose aerogel sample that was exposed to the biomineralization treatment without the addition of S. pasteurii. Results indicate that significant biomineralization (up to 38% CaCO3 by mass) occurred in the biomineralized SCOBY cellulose aerogels. Multiple biomineralization cycles enhance biomineralization of the sample surface and interior. Thermal conductivities of resultant aerogels measured ≈0.043–0.057 Wm−1 K−1 for all samples, indicating that biomineralization did not negatively affect the thermal conductivity of the SCOBY cellulose aerogels. Results further illustrate that biomineralization improved the thermal stability and flame resistance of SCOBY cellulose aerogels compared to experimental controls. Low thermal conductivity, improved thermal stability, and higher flame resistance of biomineralized SCOBY cellulose aerogels together indicate that thermally stable insulation materials can be produced exclusively from biological organisms.
A Highly Stable All‐Solid‐State Na–O2/H2O Battery with Low Overpotential Based on Sodium Hydroxide
Authors: Jiang Chenggong , Zhang Hui , Li Peng , Zhan Xiaoyi , Liu Zhenjie , Wang Liang , Mao Baohua , Li Qingtian , Wen Zhaoyin , Peng Zhangquan , Chen Shengli , Liu Zhi
Published: July 2022

The rechargeable all‐solid‐state Na–O2 battery is one of the most promising candidates for next‐generation energy storage devices owing to its high theoretical specific energy, safety, electrochemical stability, and abundant Na resources. However, the practical implementation of current all‐solid‐state Na–O2 batteries is still limited by low‐resistance interfaces, low energy efficiency, and poor cycle life. Herein, an all‐solid‐state Na–O2/H2O battery that can sustain highly reversible cycling with a low overpotential is reported. Using a customized silver–polymer composite cathode, this battery can be operated under ≈7% relative humidity (RH) at 80 °C and cycled for more than 100 times with a low overpotential (≈75 mV at 100th cycle) and high round trip efficiency >97% at 100th cycle) at an energy density of 20 mA g−1. Furthermore, mechanistic insight that the RH intimately controls the type and hydration state of the discharge product is also provided, and thereby the charge kinetics and battery performance are modulated. It is also revealed that silver catalyst can efficiently reduce the reaction barrier of NaOH decomposition. With the further optimization, this battery potentially can be implemented in real‐world applications and confer practical applicability that can extend to other energy‐storage systems, such as other metal–air batteries.
Recent Advances in the Development and Antimicrobial Applications of Metal–Phenolic Networks
Authors: Li Yue , Miao Yong , Yang Lunan , Zhao Yitao , Wu Keke , Lu Zhihui , Hu Zhiqi , Guo Jinshan
Published: July 2022

Due to the abuse of antibiotics and the emergence of multidrug resistant microorganisms, medical devices, and related biomaterials are at high risk of microbial infection during use, placing a heavy burden on patients and healthcare systems. Metal–phenolic networks (MPNs), an emerging organic–inorganic hybrid network system developed gradually in recent years, have exhibited excellent multifunctional properties such as anti‐inflammatory, antioxidant, and antibacterial properties by making use of the coordination between phenolic ligands and metal ions. Further, MPNs have received widespread attention in antimicrobial infections due to their facile synthesis process, excellent biocompatibility, and excellent antimicrobial properties brought about by polyphenols and metal ions. In this review, different categories of biomaterials based on MPNs (nanoparticles, coatings, capsules, hydrogels) and their fabrication strategies are summarized, and recent research advances in their antimicrobial applications in biomedical fields (e.g., skin repair, bone regeneration, medical devices, etc.) are highlighted.