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PubMed1999

Comparison of two methods for selecting minimum stimulation levels used in programming the Nucleus 22 cochlear implant.

Minimum stimulation levels for active electrodes in a Nucleus 22 cochlear implant were set at threshold (clinical default value) and raised levels (M = +2.04 dB) to determine if raised levels would improve recipients' understanding of soft speech sounds with the SPEAK speech coding strategy. Eight postlinguistically deaf adults participated in a 4-phase A1B1A2B2 test design. Speech recognition was evaluated with consonant-vowel nucleus-consonant (CNC) words in quiet and sentences in noise, both presented at 50, 60, and 70 dB SPL during 2 weekly sessions at the end of each phase. Group mean scores were significantly higher with the raised level program for words and phonemes at 50 and 60 dB SPL and for sentences at 50 and 70 dB SPL. All participants chose to use the raised level program in everyday life at the end of the study. The results suggest that clinical use of a raised level program for Nucleus 22 recipients has the potential to make soft sounds louder and, therefore, more salient in everyday life. Further research is needed to determine if this approach is appropriate for other cochlear implant devices.

Acoustic Stimulation↗

PubMed2002

NotI subtraction and NotI-specific microarrays to detect copy number and methylation changes in whole genomes.

Methylation, deletions, and amplifications of cancer genes constitute important mechanisms in carcinogenesis. For genome-wide analysis of these changes, we propose the use of NotI clone microarrays and genomic subtraction, because NotI recognition sites are closely associated with CpG islands and genes. We show here that the CODE (Cloning Of DEleted sequences) genomic subtraction procedure can be adapted to NotI flanking sequences and to CpG islands. Because the sequence complexity of this procedure is greatly reduced, only two cycles of subtraction are required. A NotI-CODE procedure can be used to prepare NotI representations (NRs) containing 0.1-0.5% of the total DNA. The NRs contain, on average, 10-fold less repetitive sequences than the whole human genome and can be used as probes for hybridization to NotI microarrays. These microarrays, when probed with NRs, can simultaneously detect copy number changes and methylation. NotI microarrays offer a powerful tool with which to study carcinogenesis.

Animals↗

PubMed2005

cDNA cloning and functional expression of jerdostatin, a novel RTS-disintegrin from Trimeresurus jerdonii and a specific antagonist of the alpha1beta1 integrin.

Jerdostatin represents a novel RTS-containing short disintegrin cloned by reverse transcriptase-PCR from the venom gland mRNA of the Chinese Jerdons pit viper Trimeresurus jerdonii. The jerdostatins precursor cDNA contained a 333-bp open reading frame encoding a signal peptide, a pre-peptide, and a 43-amino acid disintegrin domain, whose amino acid sequence displayed 80% identity with that of the KTS-disintegrins obtustatin and viperistatin. The jerdostatin cDNA structure represents the first complete open reading frame of a short disintegrin and points to the emergence of jerdostatin from a short-coding gene. The different residues between jerdostatin and obtustatin/viperistatin are segregated within the integrin-recognition loop and the C-terminal tail. Native jerdostatin (r-jerdostatin-R21) and a R21K mutant (r-jerdostatin-K21) were produced in Escherichia coli. In each case, two conformers were isolated. One-dimensional (1)H NMR showed that conformers 1 and 2 of r-jerdostatin-R21 represent, respectively, well folded and unfolded proteins. The two conformers of the wild-type and the R21K mutant inhibited the adhesion of alpha(1)-K562 cells to collagen IV with IC(50) values of 180 and 703 nm, respectively. The IC(50) values of conformers 2 of r-jerdostatin-R21 and r-jerdostatin-K21 were, respectively, 5.95 and 12.5 microm. Neither r-jerdostatin-R21 nor r-jerdostatin-K21 showed inhibitory activity toward other integrins, including alpha(IIb)beta(3), alpha(v)beta(3), alpha(2)beta(1), alpha(5)beta(1), alpha(4)beta(1), alpha(6)beta(1), and alpha(9)beta(1) up to a concentration of 24 mum. Although the RTS motif appears to be more potent than KTS inhibiting the alpha(1)beta(1) integrin, r-jerdostatin-R21 is less active than the KTS-disintegrins, strongly suggesting that substitutions outside the integrin-binding motif and/or C-terminal proteolytic processing are responsible for the decreased inhibitory activity.

Amino Acid Sequence↗

PubMed2001

Hemispheric asymmetry in the induction of false memories.

The purpose of this study was to investigate hemispheric asymmetry in verbal memory by using a false recognition paradigm and a standard list learning paradigm, which can induce high false recognition for semantically related distractors. The experiment showed that the LH could discriminate the targets from the related distractors more accurately than the RH. This result was attributed to the hemispheric difference in the hit rate rather than in false recognition. The results of the present study suggest that the model of RH coarse semantic coding and LH fine semantic coding is applicable not only to language processing but also to verbal memory.

Journal Article↗

PubMed2001

Polymorphisms in candidate asthma genes.

The triad of reversible airway obstruction, bronchial hyperresponsiveness, and airway inflammation characterizes asthma. The etiology of asthma is complex and involves the interaction of multiple genetic foci and a variety of environmental factors, such as protein allergens, chemical sensitizers, and viral or bacterial proteins. Candidate asthma genes have been identified that may be linked or associated with the asthmatic phenotype. Potential candidate asthma genes include cytokine genes, receptor genes, transcription factors, immune recognition genes, and genes regulating lipid mediator generation. Although polymorphisms within either the promoter or coding region of individual asthma candidate genes have been identified, the association between these genetic polymorphisms and the asthmatic phenotype remains incompletely defined. Furthermore, genetic polymorphisms mediating the asthmatic phenotype are rarely identified in individual patients. This manuscript reviews several of the specific mutations and polymorphisms that have been identified in candidate asthma genes, such as the high affinity IgE receptor, the beta2-adrenergic receptor, the interleukin-4 promoter and receptor, the tumor necrosis factor gene, and the 5-lipoxygenase promoter.

Arachidonate 5-Lipoxygenase↗

PubMed1998

Use of bioptic amorphic lenses to expand the visual field in patients with peripheral loss.

PURPOSE: To test the effectiveness of a bioptic form of a peripheral vision-enhancement lens in patients with retinitis pigmentosa (RP), choroideremia, and Usher's syndrome Type II. METHODS: Fifteen patients with peripheral visual field loss were trained in the use of the amorphic lenses for driving and other everyday activities for a 3-month period. A cross-over study design was used, where one group of eight patients received training during the first 3 months of the 6-month study, and another group of seven patients received training during the second 3 months. All patients were administered a battery of clinical, psychophysical, functional, mobility, and driving assessment tests at the beginning of the study, at 3 months, and at 6 months. The assessment tests were coded according to the primary visual skill involved in the task. These visual skills included: recognition, peripheral detection, scanning, tracking, visual memory, and mobility. RESULTS: After training, the patients showed improvement in all visual skills categories on the assessment tests, with overall improvement of 37%. There was no significant difference in the levels of improvement between the two groups. Those with smaller visual field extents showed significantly greater improvement on peripheral detection and scanning tasks. Those patients trained during the first 3 months of the study maintained their skills when tested at the 6-month point. CONCLUSION: Patients with peripheral vision loss may benefit from a rehabilitation program which combines low vision training with amorphic lenses in a bioptic configuration.

Adult↗

PubMed2000

Human and mouse gene structure: comparative analysis and application to exon prediction.

We describe a novel analytical approach to gene recognition based on cross-species comparison. We first undertook a comparison of orthologous genomic loci from human and mouse, studying the extent of similarity in the number, size and sequence of exons and introns. We then developed an approach for recognizing genes within such orthologous regions by first aligning the regions using an iterative global alignment system and then identifying genes based on conservation of exonic features at aligned positions in both species. The alignment and gene recognition are performed by new programs called and, respectively. performed well at exact identification of coding exons in 117 orthologous pairs tested.

Amino Acids↗

PubMed1985

Lateralization effects in reading pointed and unpointed Hebrew.

Hebrew has two forms of spelling, pointed and unpointed. In the pointed spelling, diacritical signs (pointing) are added to consonantal letters to convey vowel information. These are omitted in the unpointed spelling. Since pointing conveys information that is critical for the prelexical derivation of phonology, it was hypothesized that its absence would prove detrimental for left hemisphere (LH) but not for right hemisphere (RH) reading and that, for the former, pointing effects would increase with increasing word length. Three experiments, one involving lexical decision and two involving word pronunciation, yielded little support for these hypotheses; rather, pointing had an overall adverse effect on performance, and this effect tended to be more pronounced for LH reading. In general, however, the results indicated an LH advantage. Since for central vision pointing has been found to aid performance under similar conditions, the results were seen to suggest a distinction between the visual and the phonological effects of pointing: pointing may impair early stages of visual analysis but may aid in the derivation of speech codes.

Female↗

PubMed1985

Cloning and sequencing of a Moraxella bovis pilin gene.

Moraxella bovis pili have been shown to play a major role in both infectivity and protective immunity of bovine infectious keratoconjunctivitis. Sonicated M. bovis DNA from the piliated strain EPP63 was inserted into the vector lambda gt11 with EcoRI linkers. Recombinant phage were screened with an oligonucleotide probe based on the amino-terminal portion of the DNA sequence of a Neisseria gonorrhoeae pilin gene. Two candidate phages produced a protein that comigrated with EPP63 beta pilin in sodium dodecyl sulfate-polyacrylamide gels and bound anti-pilus antisera. The 1.9-kilobase insert from one of these, lambda gt11M182, was subcloned in both orientations into pBR322, forming the plasmids pMxB7 and pMxB9, both of which produced beta pilin, as did pMxB12, a HindIII deletion derivative of pMxB7. In HB101(pMxB12), the M. bovis pilin protein was shown to be primarily localized in the inner membrane. The entire 939-base-pair insert of pMxB12 was sequenced, revealing a ribosome binding site just upstream of the coding region and an AT-rich region further upstream containing some potential RNA polymerase recognition sites. The translation of the sequence predicts a six-amino-acid leader sequence preceding the phenylalanine that begins the mature protein. Codon usage analysis of the M. bovis beta pilin gene revealed greater use of the CUA codon for leucine than usual for a well-expressed Escherichia coli gene. Comparisons of the M. bovis EPP63 beta pilin protein sequence with other pilin gene sequences are presented.

Amino Acid Sequence↗

PubMed1987

Nucleotide sequence of the coding and flanking regions of the human parainfluenza virus 3 hemagglutinin-neuraminidase gene: comparison with other paramyxoviruses.

The nucleotide sequence of the human parainfluenza virus 3 (HPIV3) hemagglutinin-neuraminidase (HN) gene has been determined using cDNA clones derived from both HPIV3 genomic RNA and mRNA. The HN mRNA contains 1,882 nucleotides, not including the poly(A) tail. Primer extension experiments were carried out to locate the 5' terminal nucleotide of the HN mRNA. The 3' end of the mRNA was located at a putative polyadenylation signal. The HPIV3 HN mRNA has one large open reading frame that codes for 572 amino acids with a deduced molecular weight of 64,178. Potential polymerase recognition signals for the HN and L genes were located in the flanking regions. The HN protein of HPIV3 shares some common features with the previously sequenced HN proteins of Sendai virus and Simian virus 5. The features include: an N-terminal membrane anchor, two regions of highly conserved amino acid sequence and strong conservation in the positions of the cysteine residues. The relationship is closest between Sendai virus and HPIV3.

Amino Acid Sequence↗

PubMed2005

Neural correlates of memory for items and for associations: an event-related functional magnetic resonance imaging study.

Although results from cognitive psychology, neuropsychology, and behavioral neuroscience clearly suggest that item and associative information in memory rely on partly different brain regions, little is known concerning the differences and similarities that exist between these two types of information as a function of memory stage (i.e., encoding and retrieval). We used event-related functional magnetic resonance imaging to assess neural correlates of item and associative encoding and retrieval of simple images in 18 healthy subjects. During encoding, subjects memorized items and pairs. During retrieval, subjects made item recognition judgments (old vs. new) and associative recognition judgments (intact vs. rearranged). Relative to baseline, item and associative trials activated bilateral medial temporal and prefrontal regions during both encoding and retrieval. Direct contrasts were then performed between item and associative trials for each memory stage. During en- coding, greater prefrontal, hippocampal, and parietal activation was observed for associations, but no significant activation was observed for items at the selected threshold. During recognition, greater activation was observed for associative trials in the left dorsolateral prefrontal cortex and superior parietal lobules bilaterally, whereas item recognition trials showed greater activation of bilateral frontal regions, bilateral anterior medial temporal areas, and the right temporo-parietal junction. Post hoc analyses suggested that the anterior medial temporal activation observed during item recognition was driven mainly by new items, confirming a role for this structure in novelty detection. These results suggest that although some structures such as the medial temporal and prefrontal cortex play a general role in memory, the pattern of activation in these regions can be modulated by the type of information (items or associations) interacting with memory stages.

Adult↗

PubMed2002

Scalable hybrid computation with spikes.

We outline a hybrid analog-digital scheme for computing with three important features that enable it to scale to systems of large complexity: First, like digital computation, which uses several one-bit precise logical units to collectively compute a precise answer to a computation, the hybrid scheme uses several moderate-precision analog units to collectively compute a precise answer to a computation. Second, frequent discrete signal restoration of the analog information prevents analog noise and offset from degrading the computation. And, third, a state machine enables complex computations to be created using a sequence of elementary computations. A natural choice for implementing this hybrid scheme is one based on spikes because spike-count codes are digital, while spike-time codes are analog. We illustrate how spikes afford easy ways to implement all three components of scalable hybrid computation. First, as an important example of distributed analog computation, we show how spikes can create a distributed modular representation of an analog number by implementing digital carry interactions between spiking analog neurons. Second, we show how signal restoration may be performed by recursive spike-count quantization of spike-time codes. And, third, we use spikes from an analog dynamical system to trigger state transitions in a digital dynamical system, which reconfigures the analog dynamical system using a binary control vector; such feedback interactions between analog and digital dynamical systems create a hybrid state machine (HSM). The HSM extends and expands the concept of a digital finite-state-machine to the hybrid domain. We present experimental data from a two-neuron HSM on a chip that implements error-correcting analog-to-digital conversion with the concurrent use of spike-time and spike-count codes. We also present experimental data from silicon circuits that implement HSM-based pattern recognition using spike-time synchrony. We outline how HSMs may be used to perform learning, vector quantization, spike pattern recognition and generation, and how they may be reconfigured.

Action Potentials↗

PubMed2003

Biological activity of recombinant bovine interferon tau using an Autographa californica nuclear polyhedrosis virus expression system.

Bovine interferon (bIFN) tau, which plays a key role in maternal-fetal recognition of pregnancy, was expressed by an Autographa californica nuclear polyhedrosis virus expression system. cDNA coding bIFNtau was derived from cultured trophoblast cells. The recombinant (r) bIFNtau had high antiviral activity (1 x 10 (8) IU/mg) and the molecular weight of rbIFNtau was estimated to be 23 kDa by Western blotting analysis. We investigated the biological effect of rbIFNtau on prostaglandin (PG) F(2alpha) synthesis in cultured bovine endometrial epithelial cells in the presence or absence of oxytocin (OT, 100 nM). rbIFNtau suppressed basal and OT-induced PGF(2alpha) production in a dose-dependent manner (1-1,000 ng/ml). These results showed that biologically active rbIFNtau was produced in the baculovirus expression system, and that rbIFNtau had the ability to suppress the synthesis of PGF(2alpha) from bovine endometrial epithelial cells.

Animals↗

PubMed2006

Orientation-specific computation in stereoscopic vision.

The left and right eyes receive subtly different images from a visual scene. Binocular disparities of retinal image locations are correlated with variation in the depth of objects in the scene and make stereoscopic depth perception possible. Disparity stereoscopically specifies a stimulus; changing the stimulus in a way that conserves its disparity leaves the stimulus stereoscopically unchanged. Therefore, a person's ability to use stereo to see the depth separating any two objects should depend only on the disparities of the objects, which in turn depend on where the objects are, not what they are. However, I find that the disparity difference between two stimuli by itself predicts neither stereoacuity nor perceived depth. Human stereo vision is shown here to be most sensitive at detecting the relative depth of two gratings when they are parallel. Rotating one grating by as little as 10 degrees lowers sensitivity. The rotation can make a perceptible depth separation invisible, although it changes neither the relative nor absolute disparities of the gratings, only their relative orientations. The effect of relative orientation is not confined to stimuli that, like gratings, vary along one dimension or to stimuli perceived to have a dominant orientation. Rather, it is the relative orientation of the one-dimensional components of stimuli, even broadband stimuli, that matters. This limit on stereoscopic depth perception appears to be intrinsic to the visual system's computation of disparity; by taking place within orientation bands, the computation renders the coding of disparity inseparable from the coding of orientation.

Depth Perception↗

PubMed2004

Vaccination: foot-and-mouth disease experience in South America.

Vaccination against foot-and-mouth disease (FMD) constitutes an important component of the policy for its control and eradication in South America. Considering that immunization may not impair subclinical infection, it became advisable to ally to vaccination campaigns a surveillance instrument to monitor silent viral circulation. Novel approaches for the evaluation of antibodies to FMD non-capsid proteins (NCPs), developed and validated at PANAFTOSA proved valuable for assessing viral circulation in immunized populations. The extensive and coordinated application in South America of vaccination together with this serosurvey tool indicated the effectiveness of systematic vaccination to prevent FMD spread and to restrain silent viral circulation intra- and inter- herds, and gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America. The fitness of NCP tests to assess viral circulation in a population supported the incorporation into the OIE code of the "free of FMD with vaccination" category as a step prior to the recognition of the "free of FMD without vaccination" category. Likewise it released the path to allow animals, vaccinated for protective purposes during emergencies, to live for the term of their productive lives.

Animals↗

PubMed1986

Nucleus 22-channel cochlear implant: preliminary observations.

A carefully designed study was undertaken in 1982 to evaluate the performance of individuals who received the Nucleus 22-channel cochlear implant. All patients were profound-totally deaf, adults with a postlingual onset of impairment. The preoperative evaluation, prosthesis fitting, training, and postoperative testing were consistent across clinics. Single-subject studies, where each patient acted as his/her own control, revealed that of the 37 subjects, 16-24 obtained significant improvement (P less than or equal to 0.001) on unpracticed, unfamiliar recorded speech tests from the Minimal Auditory Capabilities (MAC) Battery, when using hearing alone (no lipreading). In addition, virtually all patients showed improvement in recognition of speech material with lipreading. The data support the efficacy of a feature extraction coding system where specific formant and amplitude information are transmitted via direct electrical stimulation to the cochlea.

Adult↗

PubMed1984

Memory demands and the development of young children's memory.

The primary purposes of this study were to determine the nature of and changes in early memory demands and to assess the relationship between memory demands and memory performance. 10 children at each of 2 ages--30 and 42 months--were observed in their homes for 4 2-hour sessions. Conversations between mothers and children were recorded and mother's memory-demand questions were coded for form and content from these conversations. Question form referred to whether recall or recognition was required and question content to the type of information requested--event or knowledge. Children also participated in 2 long-term memory tasks--production and verification. They were shown a dollhouse and asked to produce the names of objects that would belong in 2 rooms of the house and to verify whether particular miniature replicas of household objects belonged in the rooms. Although memory demands were frequently made, there were few changes between age 2 and 3 in the incidence or types of questions children were asked. At age 3, positive correlations were found between children's production and verification performance and content rather than form of mothers' memory-demand questions. At age 2 no overall relationships were found. Children were retested a year later on memory tasks, and for both age groups memory demands and performance were positively correlated even when initial memory-performance level was controlled. These results, along with other patterns in the data, suggested that mothers' memory demands have an impact on children's memory performance that provides at least partial support for Vygotsky's sociohistorical model of memory development.

Child Development↗

PubMed1992

A directed search for mutations in hemophilia A using restriction enzyme analysis and denaturing gradient gel electrophoresis. A study of seven exons in the factor VIII gene of 170 cases.

Genomic DNA from 170 unrelated hemophilia A patients was examined for gene defects in the coding region of the Factor VIII gene. Exons 18, 22-24 and 26 contain a CGA codon for arginine within the recognition sequence for the restriction enzyme Taq I. These five sites were amplified by the polymerase chain reaction and tested for abnormal Taq I restriction patterns. In five cases, the enzyme Taq I failed to digest the amplified fragments. Direct sequencing of the amplified products demonstrated a C to T transition in the coding strand of exons 18, 22 and 24 in three severe hemophilia A patients resulting in TGA termination codons. Two patients showed G to A transition in exons 24 and 26 reflecting a C to T transition in the non-coding strand substituting a glutamine for an arginine. Three deletions involving exon 26 and one exons 23-26 were found in severe hemophiliac patients. In contrast, exons 23 and 24 failed to amplify in one patient with a moderate form of the disease suggesting an in-frame splicing of exons 22 and 25. Exon 8 and the 3' end of exon 14 were analyzed by denaturing gradient gel electrophoresis (DGGE). Two patients with a moderate form of the disease demonstrated an abnormal electrophoretic pattern in exon 8 and sequencing demonstrated missense mutations at codon 372 for arginine within a thrombin activation site. One missense mutation was a C to T transition substituting cysteine for arginine and the other was an infrequent G to C transversion at an adjacent nucleotide changing the same arginine to proline.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗