bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency modulation detection in cochlear implant subjects
Authors: Chen Hongbin , Zeng Fan-Gang
Published: October 2004

Frequency modulation (FM) detection was investigated in acoustic and electric hearing to characterize cochlear-implant subjects’ ability to detect dynamic frequency changes and to assess the relative contributions of temporal and spectral cues to frequency processing. Difference limens were measured for frequency upward sweeps, downward sweeps, and sinusoidal FM as a function of standard frequency and modulation rate. In electric hearing, factors including electrode position and stimulation level were also studied. Electric hearing data showed that the difference limen increased monotonically as a function of standard frequency regardless of the modulation type, the modulation rate, the electrode position, and the stimulation level. In contrast, acoustic hearing data showed that the difference limen was nearly a constant as a function of standard frequency. This difference was interpreted to mean that temporal cues are used only at low standard frequencies and at low modulation rates. At higher standard frequencies and modulation rates, the reliance on the place cue is increased, accounting for the better performance in acoustic hearing than for electric hearing with single-electrode stimulation. The present data suggest a speech processing strategy that encodes slow frequency changes using lower stimulation rates than those typically employed by contemporary cochlear-implant speech processors.
Effects of pulse rate and electrode array design on intensity discrimination in cochlear implant users
Authors: Kreft Heather A. , Donaldson Gail S. , Nelson David A.
Published: October 2004

The effects of pulse rate on intensity discrimination were evaluated in 14 subjects with Clarion C-I cochlear implants. Subjects had a standard [Clarion spiral electrode array (SPRL group)] or perimodiolar electrode array [Clarion HiFocus electrode array with electrode positioning system (HF+EPS group)]. Weber fractions for intensity discrimination [WfdB=10 log ΔI/I] were evaluated at five levels over dynamic range at each of three pulse rates (200, 1625 and 6500 pps) using monopolar stimulation. Weber fractions were smaller for 200 pps stimuli than for 1625 or 6500 pps stimuli in both groups. Weber fractions were significantly smaller for SPRL subjects (mean WfdB=−9.1 dB) than for HF+EPS subjects (mean WfdB=−6.7 dB). Intensity difference limens (DLs) expressed as a percentage of dynamic range (DR) (ΔI%DR=ΔI/DRdB*100) did not vary systematically with pulse rate in either group. Larger intensity DLs combined with smaller dynamic ranges led to fewer intensity steps over the dynamic range for HF+EPS subjects (average 9 steps) compared to SPRL subjects (average 23 steps). The observed effects of pulse rate and electrode array design may stem primarily from an inverse relationship between absolute current amplitude and the size of intensity DLs. The combination of smaller dynamic ranges and larger Weber fractions in HF+EPS subjects could be the result of increased variability of neural outputs in these subjects.
Experimental validation of a tractable numerical model for focused ultrasound heating in flow-through tissue phantoms
Authors: Huang Jinlan , Holt R. Glynn , Cleveland Robin O. , Roy Ronald A.
Published: October 2004

Heating from high intensity focused ultrasound (HIFU) can be used to control bleeding, both from individual blood vessels as well as from gross damage to the capillary bed. The presence of vascularity can limit one’s ability to elevate the temperature owing to convective heat transport. In an effort to better understand the heating process in tissues with vascular structure we have developed a numerical simulation that couples models for ultrasound propagation, acoustic streaming, ultrasound heating and blood cooling in a Newtonian viscous medium. The 3-D simulation allows for the study of complicated biological structures and insonation geometries. We have also undertaken a series of in vitro experiments employing non-uniform flow-through tissue phantoms and designed to provide verification of the model predictions. We show that blood flow of 2 cm/s (6.4 ml/min through a 2.6 mm ‘vessel’) can reduce peak temperature in a vessel wall by 25%. We also show that HIFU intensities of 6.5×105 W/m2 can induce acoustic streaming with peak velocities up to 5 cm/s and this can reduce heating near a vessel wall by more than 10%. These results demonstrate that convective cooling is important in HIFU and can be accounted for within simulation models.
The distinctness of speakers’ productions of vowel contrasts is related to their discrimination of the contrasts
Authors: Perkell Joseph S. , Guenther Frank H. , Lane Harlan , Matthies Melanie L. , Stockmann Ellen , Tiede Mark , Zandipour Majid
Published: October 2004

This study addresses the hypothesis that the more accurately a speaker discriminates a vowel contrast, the more distinctly the speaker produces that contrast. Measures of speech production and perception were collected from 19 young adult speakers of American English. In the production experiment, speakers repeated the words cod, cud, who’d, and hood in a carrier phrase at normal, clear, and fast rates. Articulatory movements and the associated acoustic signal were recorded, yielding measures of contrast distance between /ɑ/ and /ʌ/ and between /u/ and /ʊ/. In the discrimination experiment, sets of seven natural-sounding stimuli ranging from cod to cud and who’d to hood were synthesized, based on productions by one male and one female speaker. The continua were then presented to each of the 19 speakers in labeling and discrimination tasks. Consistent with the hypothesis, speakers with discrimination scores above the median produced greater acoustic contrasts than speakers with discrimination scores at or below the median. Such a relation between speech production and perception is compatible with a model of speech production in which articulatory movements for vowels are planned primarily in auditory space.
Asymptotic accuracy of geoacoustic inversions
Authors: Zanolin Michele , Ingram Ian , Thode Aaron , Makris Nicholas C.
Published: October 2004

Criteria necessary to accurately estimate a set of unknown geoacoustic parameters from remote acoustic measurements are developed in order to aid the design of geoacoustic experiments. The approach is to have estimation error fall within a specified design threshold by adjusting controllable quantities such as experimental sample size or signal-to-noise ratio (SNR). This is done by computing conditions on sample size and SNR necessary for any estimate to have a variance that (1) asymptotically attains the Cramer–Rao lower bound (CRLB) and (2) has a CRLB that falls within the specified design error threshold. Applications to narrow band deterministic signals received with additive noise by vertical and horizontal arrays in typical continental shelf waveguides are explored. For typical low-frequency scenarios, necessary SNRs and samples sizes can often approach prohibitively large values when a few or more important geoacoustic parameters are unknown, making it difficult to attain practical design thresholds for allowable estimation error.
Clear speech perception in acoustic and electric hearing
Authors: Liu Sheng , Del Rio Elsa , Bradlow Ann R. , Zeng Fan-Gang
Published: October 2004

When instructed to speak clearly for people with hearing loss, a talker can effectively enhance the intelligibility of his/her speech by producing “clear” speech. We analyzed global acoustic properties of clear and conversational speech from two talkers and measured their speech intelligibility over a wide range of signal-to-noise ratios in acoustic and electric hearing. Consistent with previous studies, we found that clear speech had a slower overall rate, higher temporal amplitude modulations, and also produced higher intelligibility than conversational speech. To delineate the role of temporal amplitude modulations in clear speech, we extracted the temporal envelope from a number of frequency bands and replaced speech fine-structure with noise fine-structure to simulate cochlear implants. Although both simulated and actual cochlear-implant listeners required higher signal-to-noise ratios to achieve normal performance, a 3–4 dB difference in speech reception threshold was preserved between clear and conversational speech for all experimental conditions. These results suggest that while temporal fine structure is important for speech recognition in noise in general, the temporal envelope carries acoustic cues that contribute to the clear speech intelligibility advantage.
Source parameter estimates of echolocation clicks from wild pygmy killer whales (Feresa attenuata) (L)
Authors: Madsen P. T. , Kerr I. , Payne R.
Published: October 2004

Pods of the little known pygmy killer whale (Feresa attenuata) in the northern Indian Ocean were recorded with a vertical hydrophone array connected to a digital recorder sampling at 320 kHz. Recorded clicks were directional, short (25 μs) transients with estimated source levels between 197 and 223 dB re. 1 μPa (pp). Spectra of clicks recorded close to or on the acoustic axis were bimodal with peak frequencies between 45 and 117 kHz, and with centroid frequencies between 70 and 85 kHz. The clicks share characteristics of echolocation clicks from similar sized, whistling delphinids, and have properties suited for the detection and classification of prey targeted by this odontocete.
A broadband model of sandy ocean sediments: Biot–Stoll with contact squirt flow and shear drag
Authors: Chotiros Nicholas P. , Isakson Marcia J.
Published: October 2004

Unlike the application of the Biot model for fused glass beads, which was conclusively demonstrated by Berryman [Appl. Phys. Lett. 37(4), 382–384 (1980)] using the experimental measurements by Plona [Appl. Phys. Lett. 36, 259–261 (1980)], the model for unconsolidated water-saturated sand has been more elusive. The difficulty is in the grain to grain contact physics. Unlike the fused glass beads, the connection between the unconsolidated sand grains is not easily modeled. Measurements over a broad range of frequencies show that the sound speed dispersion is significantly greater than that predicted by the Biot–Stoll model with constant coefficients, and the observed sound attenuation does not seem to follow a consistent power law. The sound speed dispersion may be explainable in terms of the Biot plus squirt flow (BISQ) model of Dvorkin and Nur [Geophysics 58(4), 524–533 (1993)]. By using a similar approach that includes grain contact squirt flow and viscous drag (BICSQS), the observed diverse behavior of the attenuation was successfully modeled.
Vocal tract resonances in singing: The soprano voice
Authors: Joliveau Elodie , Smith John , Wolfe Joe
Published: October 2004

The vocal tract resonances of trained soprano singers were measured while they sang a range of vowels softly at different pitches. The measurements were made by broad band acoustic excitation at the mouth, which allowed the resonances of the tract to be measured simultaneously with and independently from the harmonics of the voice. At low pitch, when the lowest resonance frequency R1 exceeded f0, the values of the first two resonances R1 and R2 varied little with frequency and had values consistent with normal speech. At higher pitches, however, when f0 exceeded the value of R1 observed at low pitch, R1 increased with f0 so that R1 was approximately equal to f0. R2 also increased over this high pitch range, probably as an incidental consequence of the tuning of R1. R3 increased slightly but systematically, across the whole pitch range measured. There was no evidence that any resonances are tuned close to harmonics of the pitch frequency except for R1 at high pitch. The variations in R1 and R2 at high pitch mean that vowels move, converge, and overlap their positions on the vocal plane (R2,R1) to an extent that implies loss of intelligibility.
Distortion product otoacoustic emission (DPOAE) input/output functions and the influence of the second DPOAE source
Authors: Mauermann Manfred , Kollmeier Birger
Published: October 2004

Distortion product otoacoustic emissions (DPOAEs) at 2f1−f2 (f2/f1=1.2) have two components from different cochlear sources, i.e., a distortion component generated near f2 and a reflection component from the characteristic site of fDP. The interaction of the two sources may negatively affect the DPOAE input/output (I/O) functions that are used to predict either auditory thresholds or the compression characteristics of the basilar membrane. This study investigates the influence of the reflection component on DPOAE I/O functions in a frequency range for f2 from 1500 to 4500 Hz in steps of 18 Hz. A time windowing procedure is used to separate the components from the two DPOAE sources. With decreasing stimulus level, the relative contribution of the reflection component increases. I/O functions from the separated distortion component (DCOAE I/O functions) only show smooth changes in shape and slope with frequency, while “standard” DPOAE I/O functions show rapid changes between adjacent frequencies, indicating a strong influence from the interference with the second DPOAE source. A reduced variability for adjacent frequencies can be seen as well for prediction of hearing thresholds, when using DCOAE instead of DPOAE I/O functions.
Extracting coherent wave fronts from acoustic ambient noise in the ocean
Authors: Roux Philippe , Kuperman W. A. ,   the NPAL Group
Published: October 2004

A method to obtain coherent acoustic wave fronts by measuring the space–time correlation function of ocean noise between two hydrophones is experimentally demonstrated. Though the sources of ocean noise are uncorrelated, the time-averaged noise correlation function exhibits deterministic waveguide arrival structure embedded in the time-domain Green’s function. A theoretical approach is derived for both volume and surface noise sources. Shipping noise is also investigated and simulated results are presented in deep or shallow water configurations. The data of opportunity used to demonstrate the extraction of wave fronts from ocean noise were taken from the synchronized vertical receive arrays used in the frame of the North Pacific Laboratory (NPAL) during time intervals when no source was transmitting.
Schizosaccharomyces pombe
Pmr1p Is Essential for Cell Wall Integrity and Is Required for Polarized Cell Growth and Cytokinesis
Authors: Cortés Juan Carlos G. , Katoh-Fukui Reiko , Moto Kanako , Ribas Juan Carlos , Ishiguro Junpei
Published: October 2004

The
cps5
-
138
fission yeast mutant shows an abnormal lemon-like morphology at 28°C in minimal medium and a lethal thermosensitive phenotype at 37°C. Cell growth is completely inhibited at 28°C in a Ca
2+
-free medium, in which the wild type is capable of growing normally. Under these conditions, actin patches become randomly distributed throughout the cell, and defects in septum formation and subsequent cytokinesis appear. The mutant cell is hypersensitive to the cell wall-digesting enzymatic complex Novozym234 even under permissive conditions. The gene SPBC31E1.02c, which complements all the mutant phenotypes described above, was cloned and codes for the Ca
2+
-ATPase homologue Pmr1p. The gene is not essential under optimal growth conditions but is required under conditions of low Ca
2+
(<0.1 mM) or high temperature (>35°C). The green fluorescent protein-tagged Cps5 proteins, which are expressed under physiological conditions (an integrated single copy with its own promoter in the
cps5
Δ strain), display a localization pattern typical of endoplasmic reticulum proteins. Biochemical analyses show that 1,3-β-
d
-glucan synthase activity in the mutant is decreased to nearly half that of the wild type and that the mutant cell wall contains no detectable galactomannan when the cells are exposed to a Ca
2+
-free medium. The mutant acid phosphatase has an increased electrophoretic mobility, suggesting that incomplete protein glycosylation takes place in the mutant cells. These results indicate that
S. pombe
Pmr1p is essential for the maintenance of cell wall integrity and cytokinesis, possibly by allowing protein glycosylation and the polarized actin distribution to take place normally. Disruption and complementation analyses suggest that Pmr1p shares its function with a vacuolar Ca
2+
-ATPase homologue, Pmc1p (SPAPB2B4.04c), to prevent lethal activation of calcineurin for cell growth.
Epigenetic Control of Chromosome Breakage at the 5′ End of
Paramecium tetraurelia
Gene
A
Authors: Amar Laurence , Dubrana Karine
Published: October 2004

Macronuclei and micronuclei of ciliates have related genomes, with macronuclei developing from zygotic micronuclei through programmed DNA rearrangements. While
Paramecium tetraurelia
wild-type strain 51 and mutant strain d48 have the same micronuclear genome, qualitative differences between their macronuclear genomes have been described, demonstrating that programmed DNA rearrangements could be epigenetically controlled in ciliates. Macronuclear chromosomes end downstream of gene
A
(A51 Mac ends) and at the 5′ end of gene
A
(Ad48 Mac ends) in strains 51 and d48, respectively. To gain further insight into the process of chromosome end formation, we performed an extensive analysis of locus
A
rearrangement in strains d48 and 51, in strain d12, which harbors a gene
A
deletion, and in interstrain cross progeny. We show that (i) allele

A
d12

harbors a deletion of >16 kb, (ii) A51 Mac ends distribute over four rather than three DNA regions, (iii) strains d48 and 51 display only quantitative differences (rare Ad48 and A51 Mac ends do form in strains 51 and d48, respectively), (iv) the level of A51 Mac ends is severalfold enhanced in d12- and d48-derived progeny, and (v) this level inversely correlates with the level of Ad48 Mac ends in the d48 parent. Together, these data lead to a model in which the formation of Ad48 Mac ends is epigenetically controlled by a d48 factor(s). We propose that the d48 factor(s) may be derived from RNA molecules transcribed from the Ad48 Mac ends and encompassing the truncated
A
gene and telomeric repeats.
Pmt-Mediated O Mannosylation Stabilizes an Essential Component of the Secretory Apparatus, Sec20p, in
Candida albicans
Authors: Weber Yvonne , Prill Stephan K.-H. , Ernst Joachim F.
Published: October 2004

Sec20p is an essential endoplasmic reticulum (ER) membrane protein in yeasts, functioning as a tSNARE component in retrograde vesicle traffic. We show that Sec20p in the human fungal pathogen
Candida albicans
is extensively O mannosylated by protein mannosyltransferases (Pmt proteins). Surprisingly, Sec20p occurs at wild-type levels in a
pmt6
mutant but at very low levels in
pmt1
and
pmt4
mutants and also after replacement of specific Ser/Thr residues in the lumenal domain of Sec20p. Pulse-chase experiments revealed rapid degradation of unmodified Sec20p (38.6 kDa) following its biosynthesis, while the stable O
-
glycosylated form (50 kDa) was not formed in a
pmt1
mutant. These results suggest a novel function of O mannosylation in eukaryotes, in that modification by specific Pmt proteins will prevent degradation of ER-resident membrane proteins via ER-associated degradation or a proteasome-independent pathway.
Presence of a Poly(A) Binding Protein and Two Proteins with Cell Cycle-Dependent Phosphorylation in
Crithidia fasciculata
mRNA Cycling Sequence Binding Protein II
Authors: Mittra Bidyottam , Ray Dan S.
Published: October 2004

Crithidia fasciculata
cycling sequence binding proteins (CSBP) have been shown to bind with high specificity to sequence elements present in several mRNAs that accumulate periodically during the cell cycle. The first described CSBP has subunits of 35.6 (CSBPA) and 42 kDa (CSBPB). A second distinct binding protein termed CSBP II has been purified from
CSBPA
null mutant cells, lacking both CSBPA and CSBPB proteins, and contains three major polypeptides with predicted molecular masses of 63, 44.5, and 33 kDa. Polypeptides of identical size were radiolabeled in UV cross-linking assays performed with purified CSBP II and
32
P-labeled RNA probes containing six copies of the cycling sequence. The CSBP II binding activity was found to cycle in parallel with target mRNA levels during progression through the cell cycle. We have cloned genes encoding these three CSBP II proteins, termed RBP63, RBP45, and RBP33, and characterized their binding properties. The RBP63 protein is a member of the poly(A) binding protein family. Homologs of RBP45 and RBP33 proteins were found only among the kinetoplastids. Both RBP45 and RBP33 proteins and their homologs have a conserved carboxy-terminal half that contains a PSP1-like domain. All three CSBP II proteins show specificity for binding the wild-type cycling sequence in vitro. RBP45 and RBP33 are phosphoproteins, and RBP45 has been found to bind in vivo specifically to target mRNA containing cycling sequences. The levels of phosphorylation of both RBP45 and RBP33 were found to cycle during the cell cycle.
A β-Tubulin Mutation Selectively Uncouples Nuclear Division and Cytokinesis in
Tetrahymena thermophila
Authors: Smith Joshua J. , Yakisich J. Sebastian , Kapler Geoffrey M. , Cole Eric S. , Romero Daniel P.
Published: October 2004

The ciliated protozoan
Tetrahymena thermophila
contains two distinct nuclei within a single cell—the mitotic micronucleus and the amitotic macronucleus. Although microtubules are required for proper division of both nuclei, macronuclear chromosomes lack centromeres and the role of microtubules in macronuclear division has not been established. Here we describe nuclear division defects in cells expressing a mutant β-tubulin allele that confers hypersensitivity to the microtubule-stabilizing drug paclitaxel. Macronuclear division is profoundly affected by the
btu1
-
1
(K350M) mutation, producing cells with widely variable DNA contents, including cells that lack macronuclei entirely. Protein expressed by the
btu1
-
1
allele is dominant over wild-type protein expressed by the
BTU2
locus. Normal macronuclear division is restored when the
btu1
-
1
allele is inactivated by targeted disruption or expressed as a truncated protein. Immunofluorescence studies reveal elongated microtubular structures that surround macronuclei that fail to migrate to the cleavage furrows. In contrast, other cytoplasmic microtubule-dependent processes, such as cytokinesis, cortical patterning, and oral apparatus assembly, appear to be unaffected in the mutant. Micronuclear division is also perturbed in the K350M mutant, producing nuclei with elongated early-anaphase spindle configurations that persist well after the initiation of cytokinesis. The K350M mutation affects tubulin dynamics, as the macronuclear division defect is exacerbated by three treatments that promote microtubule polymerization: (i) elevated temperatures, (ii) sublethal concentrations of paclitaxel, and (iii) high concentrations of dimethyl sulfoxide. Inhibition of phosphatidylinositol 3-kinase (PI 3-kinase) with 3-methyladenine or wortmannin also induces amacronucleate cell formation in a
btu1
-
1
-dependent manner. Conversely, the myosin light chain kinase inhibitor ML-7 has no effect on nuclear division in the
btu1
-
1
mutant strain. These findings provide new insights into microtubule dynamics and link the evolutionarily conserved PI 3-kinase signaling pathway to nuclear migration and/or division in
Tetrahymena
.
Linkage between Mitochondrial Hypovirulence and Viral Hypovirulence in the Chestnut Blight Fungus Revealed by cDNA Microarray Analysis
Authors: Allen Todd D. , Nuss Donald L.
Published: October 2004

The phenomenon of transmissible hypovirulence (virulence attenuation) associated with biological control of natural populations of the chestnut blight fungus
Cryphonectria parasitica
can be experimentally reproduced by infection with hypovirus cDNA clones (viral hypovirulence) or by mutation of mitochondrial DNA (mtDNA) in the absence of virus infection (mitochondrial hypovirulence). We now report the use of an established
C. parasitica
cDNA microarray to monitor nuclear transcriptional responses to an mtDNA mutation of
C. parasitica
strain EP155, designated EP155/
mit2
, which was previously shown to induce elevated alternative oxidase activity and hypovirulence (C. B. Monterio-Vitorello, J. A. Bell, D. W. Fulbright, and H. A. Bertrand, Proc. Natl. Acad. Sci. USA
92:
5935-5939, 1995). Approximately 10% of the 2,200 genes represented on the microarray exhibited altered transcript accumulation as a result of the
mit2
mtDNA mutation. While genes involved in mitochondrial function were clearly represented in the EP155/
mit2
-responsive gene list, direct parallels to the well-characterized
Saccharomyces cerevisiae
retrograde response to mitochondrial dysfunction were not observed. Remarkably, 47% of the genes that were differentially expressed following the infection of strain EP155 by the prototypic hypovirus CHV1-EP713 had similarly changed transcript accumulation in the virus-free EP155/
mit2
mutant. These results establish a linkage between viral and mitochondrial hypovirulence and raise questions regarding the relationship between hypovirus infection and mitochondrial dysfunction. The combined set of transcriptional profile data provides a foundation for future studies on mitochondrion-to-nucleus communications in the context of hypovirus infection and senescence associated with mitochondrial dysfunction in filamentous fungi.
Control of Cell Type Proportioning in
Dictyostelium discoideum
by Differentiation-Inducing Factor as Determined by In Situ Hybridization
Authors: Maruo Toshinari , Sakamoto Haruyo , Iranfar Negin , Fuller Danny , Morio Takahiro , Urushihara Hideko , Tanaka Yoshimasa , Maeda Mineko , Loomis William F.
Published: October 2004

We have determined the proportions of the prespore and prestalk regions in
Dictyostelium discoideum
slugs by in situ hybridization with a large number of prespore- and prestalk-specific genes. Microarrays were used to discover genes expressed in a cell type-specific manner. Fifty-four prespore-specific genes were verified by in situ hybridization, including 18 that had been previously shown to be cell type specific. The 36 new genes more than doubles the number of available prespore markers. At the slug stage, the prespore genes hybridized to cells uniformly in the posterior 80% of wild-type slugs but hybridized to the posterior 90% of slugs lacking the secreted alkylphenone differentiation-inducing factor 1 (DIF-1). There was a compensatory twofold decrease in prestalk cells in DIF-less slugs. Removal of prespore cells resulted in cell type conversion in both wild-type and DIF-less anterior fragments. Thus, DIF-1 appears to act in concert with other processes to establish cell type proportions.
Identification of
Cryptococcus neoformans
Temperature-Regulated Genes with a Genomic-DNA Microarray
Authors: Kraus Peter R. , Boily Marie-Josée , Giles Steven S. , Stajich Jason E. , Allen Andria , Cox Gary M. , Dietrich Fred S. , Perfect John R. , Heitman Joseph
Published: October 2004

The
ability to survive and proliferate at 37°C is an essential
virulence attribute of pathogenic microorganisms. A partial-genome
microarray was used to profile gene expression in the human-pathogenic
fungus
Cryptococcus neoformans
during growth at
37°C. Genes with orthologs involved in stress responses were
induced during growth at 37°C, suggesting that a conserved
transcriptional program is used by
C. neoformans
to
alter gene expression during stressful conditions. A gene encoding the
transcription factor homolog Mga2 was induced at 37°C and found
to be important for high-temperature growth. Genes encoding fatty acid
biosynthetic enzymes were identified as potential targets of Mga2,
suggesting that membrane remodeling is an important component of
adaptation to high growth temperatures.
mga2Δ
mutants
were extremely sensitive to the ergosterol synthesis inhibitor
fluconazole, indicating a coordination of the synthesis of membrane
component precursors. Unexpectedly, genes involved in amino acid and
pyrimidine biosynthesis were repressed at 37°C, but components
of these pathways were found to be required for high-temperature
growth. Our findings demonstrate the utility of even partial-genome
microarrays for delineating regulatory cascades that contribute to
microbial
pathogenesis.
PP2A Phosphatase Activity Is Required for Stress and Tor Kinase Regulation of Yeast Stress Response Factor Msn2p
Authors: Santhanam Arti , Hartley Alan , Düvel Katrin , Broach James R. , Garrett Stephen
Published: October 2004

In response to stress and nutrient starvation, the
Saccharomyces cerevisiae
transcription factor Msn2p accumulates in the nucleus and activates expression of a broad array of genes. Here, we analyze the role of the Tor (target of rapamycin) signaling pathway in mediating these responses. Inactivation of the Tor pathway component Tap42p using
tap42
(Ts) alleles causes a sustained nuclear localization similar to that after the addition of the Tor kinase inhibitor rapamycin. Effects of Tap42p inactivation and rapamycin addition could be suppressed by deletion of
TIP41
, which encodes a Tap42p-interacting protein. These results support the notion that rapamycin affects Msn2p by inactivating Tap42p function. Tap42p interacts with the catalytic subunit of PP2A (protein phosphatase 2A) and PP2A-like phosphatases. Deletion of either the catalytic or regulatory subunit that forms the PP2A phosphatase complex prevents nuclear accumulation of Msn2p in the
tap42
(Ts) strain and in wild-type strains treated with rapamycin. These results suggest that Tap42p is an inhibitor of PP2A phosphatase, which in turn inhibits nuclear export of Msn2p. Interestingly, PP2A function is also required for nuclear accumulation of Msn2p in response to stresses, such as heat and osmotic shock, as well as nitrogen (but not glucose) starvation. Thus, PP2A and the Tor kinase pathway transduce stress and nitrogen starvation signals to Msn2p. Finally, Msn2p localization is unaffected by conditional loss of 14-3-3 protein function, ruling out the possibility that 14-3-3 proteins act as a scaffold to sequester Msn2p in the cytoplasm.
Regulation of Flagellar Assembly by Glycogen Synthase Kinase 3 in
Chlamydomonas reinhardtii
Authors: Wilson Nedra F. , Lefebvre Paul A.
Published: October 2004

Chlamydomonas reinhardtii
controls flagellar assembly such that flagella are of an equal and predetermined length. Previous studies demonstrated that lithium, an inhibitor of glycogen synthase kinase 3 (GSK3), induced flagellar elongation, suggesting that a lithium-sensitive signal transduction pathway regulated flagellar length (S. Nakamura, H. Takino, and M. K. Kojima, Cell Struct. Funct.
12:
369-374, 1987). Here, we demonstrate that lithium treatment depletes the pool of flagellar proteins from the cell body and that the heterotrimeric kinesin Fla10p accumulates in flagella. We identify GSK3 in
Chlamydomonas
and demonstrate that its kinase activity is inhibited by lithium in vitro. The tyrosine-phosphorylated, active form of GSK3 was enriched in flagella and GSK3 associated with the axoneme in a phosphorylation-dependent manner. The level of active GSK3 correlated with flagellar length; early during flagellar regeneration, active GSK3 increased over basal levels. This increase in active GSK3 was rapidly lost within 30 min of regeneration as the level of active GSK3 decreased relative to the predeflagellation level. Taken together, these results suggest a possible role for GSK3 in regulating the assembly and length of flagella.
TheToxoplasma gondiiRhoptry Protein ROP4 Is Secreted into the Parasitophorous Vacuole and Becomes Phosphorylated in Infected Cells
Authors: Carey Kimberly L. , Jongco Artemio M. , Kim Kami , Ward Gary E.
Published: October 2004

Many intracellular pathogens are separated from the cytosol of their host cells by a vacuole membrane. This membrane serves as a critical interface between the pathogen and the host cell, across which nutrients are imported, wastes are excreted, and communication between the two cells takes place. Very little is known about the vacuole membrane proteins mediating these processes in any host-pathogen interaction. During a screen for monoclonal antibodies against novel surface or secreted proteins ofToxoplasma gondii, we identified ROP4, a previously uncharacterized member of the ROP2 family of proteins. We report here on the sequence, posttranslational processing, and subcellular localization of ROP4, a type I transmembrane protein. Mature, processed ROP4 is localized to the rhoptries, secretory organelles at the apical end of the parasite, and is secreted from the parasite during host cell invasion. Released ROP4 associates with the vacuole membrane and becomes phosphorylated in the infected cell. Similar results are seen with ROP2. Further analysis of ROP4 showed it to be phosphorylated on multiple sites, a subset of which result from the action of either host cell protein kinase(s) or parasite kinase(s) activated by host cell factors. The localization and posttranslational modification of ROP4 and other members of the ROP2 family of proteins within the infected cell make them well situated to play important roles in vacuole membrane function.
CbfA, the C-Module DNA-Binding Factor, Plays an Essential Role in the Initiation of
Dictyostelium discoideum
Development
Authors: Winckler Thomas , Iranfar Negin , Beck Peter , Jennes Ingo , Siol Oliver , Baik Unha , Loomis William F. , Dingermann Theodor
Published: October 2004

We recently isolated from
Dictyostelium discoideum
cells a DNA-binding protein, CbfA, that interacts in vitro with a regulatory element in retrotransposon TRE5-A. We have generated a mutant strain that expresses CbfA at <5% of the wild-type level to characterize the consequences for
D. discoideum
cell physiology. We found that the multicellular development program leading to fruiting body formation is highly compromised in the mutant. The cells cannot aggregate and stay as a monolayer almost indefinitely. The cells respond properly to prestarvation conditions by expressing discoidin in a cell density-dependent manner. A genomewide microarray-assisted expression analysis combined with Northern blot analyses revealed a failure of CbfA-depleted cells to induce the gene encoding aggregation-specific adenylyl cyclase ACA and other genes required for cyclic AMP (cAMP) signal relay, which is necessary for aggregation and subsequent multicellular development. However, the
cbfA
mutant aggregated efficiently when mixed with as few as 5% wild-type cells. Moreover, pulsing
cbfA
mutant cells developing in suspension with nanomolar levels of cAMP resulted in induction of
acaA
and other early developmental genes. Although the response was less efficient and slower than in wild-type cells, it showed that cells depleted of CbfA are able to initiate development if given exogenous cAMP signals. Ectopic expression of the gene encoding the catalytic subunit of protein kinase A restored multicellular development of the mutant. We conclude that sensing of cell density and starvation are independent of CbfA, whereas CbfA is essential for the pattern of gene expression which establishes the genetic network leading to aggregation and multicellular development of
D. discoideum
.
Firearm related deaths: the impact of regulatory reform
Authors: Ozanne-Smith J , Ashby K , Newstead S , Stathakis V Z , Clapperton A
Published: October 2004

Objectives:To examine trends in rates of firearm related deaths in Victoria, Australia, over 22 years in the context of legislative reform and describe and investigate impact measures to explain trends.

Design:Mortality data were extracted from vital statistics for 1979–2000. Data on firearm related deaths that were unintentional deaths, assaults, suicides, and of undetermined intent were analyzed. Rates were calculated with population data derived from estimates by the Australian Bureau of Statistics. A quasi-experimental design that used a Poisson regression model was adopted to compare relative rates of firearm related deaths for Victoria and the rest of Australia over three critical periods of legislative reform. The Wilcoxon signed ranks test was used to assess changes in the types of firearm related deaths before and after 1998.

Results:In Victoria, two periods of legislative reform related to firearms followed mass shooting events in 1988 and 1996. A national firearm amnesty and buyback scheme followed the latter. Victorian and Australian rates of firearm related deaths before reforms (1979–86) were steady. After initial Victorian reforms, a significant downward trend was seen for numbers of all firearm related deaths between 1988 and 1995 (17.3% in Victoria compared with the rest of Australia, p<0.0001). A further significant decline between 1997 and 2000 followed the later reforms. After the later all state legislation, similar strong declines occurred in the rest of Australia from 1997 (14.0% reduction compared with Victoria, p = 0.0372). Victorian reductions were observed in frequencies of firearm related suicides, assaults, and unintentional deaths before and after the 1988 reforms, but statistical significance was reached only for suicide.

Conclusion:Dramatic reductions in overall firearm related deaths and particularly suicides by firearms were achieved in the context of the implementation of strong regulatory reform.
What makes community based injury prevention work? In search of evidence of effectiveness
Authors: Nilsen P
Published: October 2004

Community based injury prevention work has become a widely accepted strategy among safety promotion specialists. Hundreds of community based injury prevention programs have been implemented since the mid-1970s, but relatively few have been evaluated rigorously, resulting in a lack of consensus regarding the effectiveness of this approach. This study sought to identify key components that contribute to the effectiveness of these programs. The objective was to gain a better understanding of the community based model for injury prevention. The study was performed as a structured review of existing evaluations of injury prevention programs that employed multiple strategies to target different age groups, environments, and situations.

The results of this study suggested that there are complex relationships between the outcome and the context, structure, and process of community-wide injury prevention programs. The interconnectedness of these variables made it difficult to provide solid evidence to prioritise in terms of program effectiveness. The evaluations of multifaceted community oriented injury prevention programs were found to have many shortcomings. Meagre descriptions of community characteristics and conditions, insufficient assessment of structural program components, and failure to establish process-outcome relationships contributed to the difficulty of identifying key success factors of the programs.
Helping medical students to find their moral compasses: ethics teaching for second and third year undergraduates
Authors: Roff S , Preece P
Published: October 2004

The paper describes a two week course that has been offered as a special study module to intermediate level (second and third year) undergraduate medical students at Dundee University Medical School for the past five years. The course requires students to research the various aspects of ethical dilemmas that they have identified themselves, and to “teach” these issues to their colleagues in a short PowerPoint presentation as well as to prepare an extended 3000 word essay discussion. The course specifically asks students not to disclose their own ethical positions, as these are probably still in formation and the objective is to promote critical thinking capacity in ethical and moral issues as a prelude to the development of practical skills in dealing with clinical problems. The course is easy to resource for the school and has received universally high evaluations from the students since its inception.
Internists’ attitudes towards terminal sedation in end of life care
Authors: Kaldjian L C , Jekel J F , Bernene J L , Rosenthal G E , Vaughan-Sarrazin M , Duffy T P
Published: October 2004

Objective:To describe the frequency of support for terminal sedation among internists, determine whether support for terminal sedation is accompanied by support for physician assisted suicide (PAS), and explore characteristics of internists who support terminal sedation but not assisted suicide.

Design:A statewide, anonymous postal survey.

Setting:Connecticut, USA.

Participants:677 Connecticut members of the American College of Physicians.

Measurements:Attitudes toward terminal sedation and assisted suicide; experience providing primary care to terminally ill patients; demographic and religious characteristics.

Results:78% of respondents believed that if a terminally ill patient has intractable pain despite aggressive analgesia, it is ethically appropriate to provide terminal sedation (diminish consciousness to halt the experience of pain). Of those who favoured terminal sedation, 38% also agreed that PAS is ethically appropriate in some circumstances. Along a three point spectrum of aggressiveness in end of life care, the plurality of respondents (47%) were in the middle, agreeing with terminal sedation but not with PAS. Compared with respondents who werelessaggressive ormoreaggressive, physicians in this middle group were more likely to report having more experience providing primary care to terminally ill patients (p = 0.02) and attending religious services more frequently (p<0.001).

Conclusions:Support for terminal sedation was widespread in this population of physicians, and most who agreed with terminal sedation did not support PAS. Most internists who support aggressive palliation appear likely to draw an ethical line between terminal sedation and assisted suicide.
Non-attendance at clinic: cycles of audit of a consultant based gastroenterology outpatient department
Authors: Bateson M C
Published: October 2004

Attempts were made to reduce defaulting rates for new appointments to see a consultant in a general medical and gastroenterology clinic. Despite optimising the operation of the clinic, the non-attendance rate remained unsatisfactory, and comparable to the average for the NHS. There were short term improvements in defaulting rates, which appeared to result from extraneous factors such as a general election and moving to new buildings. Though efforts to improve attendance rates seem appropriate to conserve resources, no definite recommendations can be made on the results of this study.
Paediatric liver transplantation: the surgical view
Authors: Vilca-Melendez H , Heaton N D
Published: October 2004

Liver transplantation is the accepted treatment for a wide variety of liver diseases in children. Over the past 10 years a number of innovative surgical techniques have been developed to overcome the shortage of size matched donors particularly in children less than 5 years of age. Graft and patient survival at one year after liver transplantation has continued to improve, and is now over 85% and higher for good risk cases. Complications are relatively common, but provided graft function is satisfactory, long term survival for these children is to be expected. The need for retransplantation has fallen significantly. Causes of early mortality include graft dysfunction and sepsis. Late mortality is due to sepsis, post-transplant lymphoproliferative disease, and non-compliance. Long term survival with good graft function and excellent quality of life is possible for the majority of children undergoing liver transplantation.
New drugs for the treatment of epilepsy: a practical approach
Authors: Beyenburg S , Bauer J , Reuber M
Published: October 2004

The availability of new antiepileptic drugs has broadened the spectrum of medical treatment options in epilepsy. The new agents, together with established drugs, offer substantial choice for doctors treating patients with focal or generalised epilepsy. The newer antiepileptic drugs are not necessarily more effective but usually better tolerated than the traditional agents, mainly because of favourable pharmacokinetic profiles and fewer interactions. Because treatment options have increased, drug therapy can now be tailored to the requirements of individual patients. Nevertheless, significant safety and efficacy issues continue to exist and there is a need for the development of even better agents. This review describes the clinical use of the new antiepileptic drugs, but focuses in particular on monotherapy, the treatment of generalised seizures, teratogenicity, and the cognitive side effect profile of the newer compounds.
HOMOGENEOUS SPACES OF NONPOSITIVE CURVATURE AND THEIR GEODESIC FLOW
Authors: HEBER JENS
Published: October 2004

Consider the geodesic flow on the unit tangent bundle SH of a 1-connected, irreducible homogeneous space H of nonpositive curvature. We prove that any flow invariant, isometry invariant C0-function on SH is necessarily constant, unless H is symmetric of higher rank. As the main applications, we obtain rigidity and partial classification results for spaces H whose geodesic symmetries are (asymptotically) volume-preserving.
PERCEPTION OF MUSIC AND DIMENSIONAL COMPLEXITY OF BRAIN ACTIVITY
Authors: BIRBAUMER N. , LUTZENBERGER W. , RAU H. , BRAUN C. , MAYER-KRESS G.
Published: October 2004

The nonlinear resonance hypothesis of music perception was tested in an experiment comparing a group of musically sophisticated and a group of less sophisticated subjects. The prediction that weakly chaotic music entrains less complex brain wave (EEG) oscillations at the prefrontal cortex was confirmed by using a correlational dimension algorithm. Strongly chaotic (stochastic) and periodic music both stimulated higher brain wave complexity. More sophisticated subjects who prefer classical music showed higher EEG dimensions while less sophisticated subjects responded with a drop in brain wave complexity to rhythmical weakly chaotic music. Subjects ratings of perceived complexity of the musical pieces followed mathematical (objective) structure of the music and did not reflect the changes in brain wave complexity. The results are interpreted in the context of an associated (Hebbian) network theory of nonlinear brain dynamics.
LOCALLY-INTERMINGLED BASINS OF ATTRACTION IN COUPLED CHUA’S CIRCUITS
Authors: KAPITANIAK TOMASZ , CHUA LEON O.
Published: October 2004

We show that two coupled chaotic systems initially operating on two different simultaneously co-existing attractors can be synchronized. Synchronization is achieved as one of the systems switches its evolution to the attractor of the other one. The final attractor of the synchronized state strongly depends on the precise position of trajectories on their attractors at the moment when coupling is introduced. Our system is the first reported example of locally-intermingled basins of attraction which occur in physical systems.
UNMASKING A MODULATED CHAOTIC COMMUNICATIONS SCHEME
Authors: SHORT KEVIN M.
Published: October 2004

This paper will address the problem of unmasking a new chaotic communication scheme using synchronizing circuits, where the Lorenz system is modulated by the message and the x-coordinate of the modulated system is added to the message and transmitted to the receiver. The receiver is driven into perfect synchrony with the transmitter even in the presence of the message, and since the message becomes part of the dynamics it provides very little distortion to the phase space of the dynamical system. However, this paper will demonstrate that it is still possible to extract a sinusoidal message from the transmitted signal. It will also be shown that it is possible to extract the sinusoidal signal solely from the x-coordinate, without secondarily adding back the message sinusoid before transmission. The message extraction is also shown to work for simple frequency-modulated and phase-modulated message signals. The modulated communication scheme does effectively nullify a multi-step unmasking technique which had been somewhat successful when applied to chaotic communication schemes which employed additive message signals.