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On the existence in human auditory pathways of channels selectively tuned to the modulation present in frequency-modulated tones.

1. The sensitivity of detecting modulation in a test tone sinusoidally frequency-modulated at a rate varphi(test) is diminished after exposure to a conditioning tone more deeply frequency-modulated at a rate varphi(cond) provided that varphi(cond) is not very different from varphi(test), the sound amplitude being kept constant for each tone at a comfortable hearing level 40-45 dB above threshold.2. When varphi(cond) = varphi(test) the frequency deviation in the modulated test tone must be increased to about three times the unconditioned threshold magnitude to be detectable immediately after exposure to the conditioning tone. Detection sensitivity returns to normal in about one minute.3. At low modulation frequencies the conditioning effects are tuned, being much diminished when varphi(cond) differs from varphi(test) by a few cycles per second.4. Comparing monaural with contra-aural conditioning demonstrates a considerable interaural transfer of about 60-80% of the effect, indicating that the conditioning and its selectivity are predominantly central phenomena.5. The magnitude of the deterioration in detection sensitivity after conditioning is about 3 x at modulation frequencies between about 3/sec and 30/sec. It diminishes at lower and higher modulation frequencies and is effectively absent at 100/sec modulation. The bandwidth of the effect increases from a few cycles per second at the lower end of this range, to some tens of cycles per second at the upper end.6. For the same modulation frequency, the conditioning is relatively insensitive to the mean ;carrier' audiofrequency, f(0). The band width in terms of carrier frequency is at least as wide as ;critical bands'. With a test signal f(0) = 250 Hz, varphi(test) = 8/sec, conditioning is still appreciable for a conditioning tone of varphi(cond) = 8/sec but centred upon f(0) = 150 Hz or = 350 Hz. Conditioning is thus not explicable in terms of coincidences between particular spectral components in the conditioning and test tones.7. Whereas the sensitivity of detecting 8/sec amplitude modulation in a tone is conditioned by prior exposure to either amplitude- or frequency-modulated tones, in contrast the detectability of 8/sec frequency-modulated signals is conditioned only by prior exposure to frequency-modulated tones and not by amplitude-modulated conditioning tones. This underlines the special place of frequency modulation in human audition and emphasizes that the operative stimulus cannot be some aspect common to amplitude modulation and frequency modulation, like identical periodicity or coincident positioning of bands in the integrated spectra of the tones, but points to the instantaneous frequency-modulated wave form as the adequate stimulus.8. These findings strongly suggest that the human auditory pathways contain ;channels' in their organization which determine a final response selectively tuned to particular frequency-modulations. Periodicity coding alone cannot adequately explain this effect which may well only be understood in terms of a ;place' theory of frequency selectivity.9. This organization is well suited to subserve the recognition of frequency-modulation patterns in acoustic signals rather independently of the mean audiofrequency that carries the frequency modulation.

Acoustic Stimulation↗

RAG-1 and RAG-2-dependent assembly of functional complexes with V(D)J recombination substrates in solution.

V(D)J recombination is initiated by RAG-1 and RAG-2, which introduce double-strand DNA breaks at recombination signal sequences (RSSs) of antigen receptor gene segments to produce signal ends, terminating in blunt, double-strand breaks, and coding ends, terminating in DNA hairpins. While the formation of RAG-RSS complexes has been documented, observations regarding the individual contributions of RAG-1 and RAG-2 to RSS recognition are in conflict. Here we describe an assay for formation and maintenance of functional RAG-RSS complexes in the course of the DNA cleavage reaction. Under conditions of in vitro cleavage, the RAG proteins sequester intact substrate DNA in a stable complex which is formed prior to strand scission. The cleavage reaction subsequently proceeds through nicking and hairpin formation without dissociation of substrate. Notably, the presence of both RAG-1 and RAG-2 is essential for formation of stable, functional complexes with substrate DNA under conditions of the sequestration assay. Two classes of substrate mutation are distinguished by their effects on RAG-mediated DNA cleavage in vitro. A mutation of the first class, residing within the RSS nonamer and associated with coordinate impairment of nicking and hairpin formation, greatly reduces the stability of RAG association with intact substrate DNA. In contrast, a mutation of the second class, lying within the RSS heptamer and associated with selective abolition of hairpin formation, has little or no effect on the half-life of the RAG-substrate complex.

DNA↗

Transcatheter arterial chemoembolization of hepatocellular carcinoma: usefulness of coded phase-inversion harmonic sonography.

OBJECTIVE: The purpose of our study was to assess the value of coded phase-inversion harmonic sonography performed approximately 1 week after the patients had undergone transcatheter arterial chemoembolization with iodized oil for hepatocellular carcinoma. SUBJECTS AND METHODS: We studied 40 patients with 44 nodules measuring 1.5-11.0 cm in diameter (mean +/- SD, 3.9 +/- 2.0 cm) who underwent transcatheter arterial chemoembolization. Coded phase-inversion harmonic sonography, a technique based on a combination of phase-inversion harmonics and coded technology, was performed with a contrast agent approximately 1 week after chemoembolization. The results were compared with those obtained using dynamic CT (n = 44 lesions) and dynamic MR imaging (n = 20 lesions). We also evaluated the recurrence of hepatocellular carcinoma during clinical follow-up in 17 patients who did not undergo additional local therapy. RESULTS: The detection rates of intratumoral vascularity of coded phase-inversion harmonic sonography, dynamic CT, and dynamic MR imaging were, respectively, 38 (86%) of 44 lesions, 19 (43%) of 44 lesions, and 10 (50%) of 20 lesions. Of 19 nodules of hepatocellular carcinoma treated only by transcatheter arterial chemoembolization, 17 nodules showed enhancement on coded phase-inversion harmonic sonography, suggesting incomplete responses. In all 17 nodules, apparent recurrence was noted on dynamic CT during clinical follow-up, even in nodules that had been observed to be completely filled with iodized oil 1 week after the chemoembolization. CONCLUSION: We found coded phase-inversion harmonic sonography to be highly sensitive and accurate for evaluating the treatment response in patients with hepatocellular carcinoma even shortly after treatment. Consequently, it allows early recognition of the need for additional local ablation therapy and estimation of the risk of hepatocellular carcinoma recurrence.

Aged↗

Modality effects in the coding and reproduction of rhythms.

The temporal coding assumption is that time of presentation is coded more accurately for auditory events than for visual events. This assumption has been used to explain the modality effect, in which recall of recent auditory events is superior to recall of recent visual events. We tested the temporal coding assumption by examining the coding and reproduction of quintessentially temporal stimuli-rhythms. The rhythms were produced by sequences of short and long auditory stimuli or short and long visual stimuli; in either case, the task was to reproduce the temporal sequence. The results from four experiments demonstrated reproduction of auditory rhythms superior to that of visual rhythms. We conclude that speech-based explanations of modality effects cannot accommodate these findings, whereas the findings are consistent with explanations based on the temporal coding assumption.

Adult↗

DNA technology.

Scientific developments in molecular biology enable clinical laboratory testing to directly examine genetic information coded in biologic specimens. These efforts, accomplished by the use of DNA probe technology in the in situ hybridization and other tests will allow for the specific identification of pathogens; recognition of genetic diseases; and the critical evaluation of the genetic basis of cancer. The authors discuss the concepts and uses of DNA testing.

Cloning, Molecular↗

[The automated diagnosis of different forms of ischemic heart disease in the practice of a telecardiology diagnostic center].

The data of the authors' work based on the experience gained with 36,500 telecardiological consultations provided within the framework of the counselling center point to the importance of taking into consideration, in addition to the ECG readings, of the clinical data on the patient to formulate the final diagnosis. In order to obtain formalized clinical information, a coding chart including 19 signs with regard to the gradation in the monotonously increasing extent of derangements has been elaborated. The mathematic maintenance of the work using algorithms of image recognition made it possible to derive a linear formula for computing the magnitude of the total diagnostic index. According to its magnitude the patient's pathology can be attributed to one of the three classes: 0--no coronary heart disease. I--steady angina pectoris, II--acute coronary heart disease. Judging from the examination sequence the percentage of errors does not exceed 8.3% with a tendency towards overdiagnosis of coronary heart disease.

Adult↗

Ménière's disease: trauma, distress and adaptation studied through focus interview analyses.

In order to investigate, in depth, the role of psychological factors in Ménière's disease, i.e. how the patients experience and interpret their symptoms during the process of this illness, a qualitative method "focus group interviews" was used as a study design. The focus group included four subjects; one woman and three men. In addition, semi-structured interviews were performed with each of four more subjects having the disease, three women and one man, in order to guarantee representativity in terms of gender and age. Through the focus interview analyses eight final codes and a number of sub-codes were developed. Results clearly pointed out the significance of the first traumatic attack of the disease as well as early signs; different "psychosomatic" symptoms prior to the attacks. The recognition of fear and phobic reactions in the manifestation of the vertigo attack was considered as an important observation, as attacks often were triggered by distressing thoughts as well as by sensory sensations. Other areas, touched upon for future investigation, were crisis adaptation and illness function.

Adaptation, Psychological↗

Signal recognition particle 14 binds to importin α in Plasmodium falciparum.

BACKGROUND: The eukaryotic signal recognition particle (SRP) consists of six proteins and one SRP RNA. This ribonucleoprotein complex assembles inside the nucleus. Nucleocytoplasmic transport is an essential process for the biogenesis of signal recognition particles (SRPs) as well as for the survival of a cell. There are studies on cells that indicate the import receptor is responsible for import of SRP proteins into nucleus, but there is a lack of evidence that SRP proteins directly bind with import receptors. METHODS AND RESULTS: Coding sequences of SRP 14 and importin α were amplified from synthesized cDNA and genomic DNA, respectively, of Plasmodium falciparum cultivated in vitro culture. The amplified products were cloned and expressed in E. coli, followed by purification. A binding study was conducted on glutathione-agarose as well as in a 96-well plate format at different concentrations of SRP 14 with immobilized importin α. CONCLUSION: This is the first report of direct binding between importin α and a eukaryotic signal recognition particle 14 (SRP 14). A cost-effective 96-well plate-based assay has also been developed to study the binding of cargoes of importin α.

Plasmodium falciparum↗

High fidelity medical simulation in the difficult environment of a helicopter: feasibility, self-efficacy and cost.

BACKGROUND: This study assessed the feasibility, self-efficacy and cost of providing a high fidelity medical simulation experience in the difficult environment of an air ambulance helicopter. METHODS: Seven of 12 EM residents in their first postgraduate year participated in an EMS flight simulation as the flight physician. The simulation used the Laerdal SimMantrade mark to present a cardiac and a trauma case in an EMS helicopter while running at flight idle. Before and after the simulation, subjects completed visual analog scales and a semi-structured interview to measure their self-efficacy, i.e. comfort with their ability to treat patients in the helicopter, and recognition of obstacles to care in the helicopter environment. After all 12 residents had completed their first non-simulated flight as the flight physician; they were surveyed about self-assessed comfort and perceived value of the simulation. Continuous data were compared between pre- and post-simulation using a paired samples t-test, and between residents participating in the simulation and those who did not using an independent samples t-test. Categorical data were compared using Fisher's exact test. Cost data for the simulation experience were estimated by the investigators. RESULTS: The simulations functioned correctly 5 out of 7 times; suggesting some refinement is necessary. Cost data indicated a monetary cost of 440 dollars and a time cost of 22 hours of skilled instructor time. The simulation and non-simulation groups were similar in their demographics and pre-hospital experiences. The simulation did not improve residents' self-assessed comfort prior to their first flight (p > 0.234), but did improve understanding of the obstacles to patient care in the helicopter (p = 0.029). Every resident undertaking the simulation agreed it was educational and it should be included in their training. Qualitative data suggested residents would benefit from high fidelity simulation in other environments, including ground transport and for running codes in hospital. CONCLUSION: It is feasible to provide a high fidelity medical simulation experience in the difficult environment of the air ambulance helicopter, although further experience is necessary to eliminate practical problems. Simulation improves recognition of the challenges present and provides an important opportunity for training in challenging environments. However, use of simulation technology is expensive both in terms of monetary outlay and of personnel involvement. The benefits of this technology must be weighed against the cost for each institution.

Adult↗

Genetic evidence for substrate and periplasmic-binding-protein recognition by the MalF and MalG proteins, cytoplasmic membrane components of the Escherichia coli maltose transport system.

We isolated mutants of Escherichia coli in which the maltose-binding protein (MBP) is no longer required for growth on maltose as the sole source of carbon and energy. These mutants were selected as Mal+ revertants of a strain which carries a deletion of the MBP structural gene, malE. In one class of these mutants, maltose is transported into the cell independently of MBP by the remaining components of the maltose system. The mutations in these strains map in either malF or malG. These genes code for two of the cytoplasmic membrane components of the maltose transport system. In some of the mutants, MBP actually inhibits maltose transport. We demonstrate that these mutants still transport maltose actively and in a stereospecific manner. These results suggest that the malF and malG mutations result in exposure of a substrate recognition site that is usually available only to substrates bound to MBP.

ATP-Binding Cassette Transporters↗

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

UNLABELLED: Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with Systemic Lupus Erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within the IRF7 gene. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in IFN-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of a homologous risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent genetic IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits. HIGHLIGHTS: Genetic analysis using modern and evolutionary datasets identifies a persistent and highly prevalent lupus-associated coding haplotype in IRF7 at 11p15 The IRF7 lupus risk haplotype increases IFN-α production by monocytes and airway epithelial cells The IRF7 lupus risk haplotype increases IRF7 DNA binding strength and alters DNA sequence specificity A homologous lupus risk variant in mouse Irf7 enhances control of vesicular stomatitis virus and exacerbates autoantibody production.

Journal Article↗

Recognition of individual heart rate patterns with cepstral vectors.

Heart rate patterns may contain diagnostic as well as forensic information. To test these possibilities, individual heart rate patterns were represented as heart-rate cepstral vectors (HRCVs) computed in 12 dimensions via linear predictive coding (LPC) of brief segments of heart rate. A library of codebook vectors was computed for 12 cardiac patients from a standard ECG database. Statistical classification of subjects was based on the minimal weighted distances between test and codebook vectors. Weights were based on the ratio of inter- to intrasubject variances of their cepstral coefficients. Results showed that: (1) HRCV coefficients adequately reproduced the HRV spectrum, and (2) HRCV distances could be used to identify individuals within the group with a reliability of 93%. Thus, heart rate variations are an individual characteristic that can be represented as a single 12-dimensional vector.

Heart Diseases↗

Components and recognition of facial expression in the communication of emotion by actors.

This article addresses the issue of the communication of emotion by actors. In Study 1, the facial behavior of 6 actors portraying emotions as felt or unfelt were analyzed with the Facial Action Coding System. Results indicated that the portrayals of felt emotions were closer to the expression of genuine emotion than the portrayals of unfelt emotions for 3 of the 6 emotions under investigation. Study 2 examined the decoding of actors' portrayals from facial behavior. Decoders were found to be very accurate in recognizing the emotional category but not in judging the encoding condition.

Adolescent↗

Impaired recognition of anger following damage to the ventral striatum.

Comparative neuropsychology has identified a role for the ventral striatum (VS) in certain forms of aggression. To address whether the homologous region in humans also contributes to the emotion anger, we studied a case series of four human subjects with focal lesions affecting the VS. All four demonstrated a disproportionate impairment in recognizing human signals of aggression. By contrast, a control group of individuals with damage to more dorsal basal ganglia (BG) regions showed no evidence of an anger impairment. Our findings demonstrate that the VS makes a significant contribution to coding signals of aggression in humans, and emphasize the importance of an approach to human affective neuroscience based on cross-species homologies. The results are discussed in relation to the ventral striatal dopamine system's role in the pursuit of biological resources in general. We propose that the role of the VS in the recognition of human signals of anger may reflect a more general role in the coordination of behaviour relevant to the acquisition and protection of valued resources, including detection of signals of conspecific challenge (anger).

Adult↗

[Tubular localization and drug recognition of kidney-specific organic anion transporters, OAT-K1 and OAT-K2].

The renal proximal tubular cells play a principal role in limiting or preventing toxicity by actively secreting organic anions from the circulation into the urine. We isolated a cDNA coding a novel rat kidney specific organic anion transporter, OAT-K1, mediating transport of methotrexate (MTX). Moreover, we have isolated a new cDNA coding a rat OAT-K2, showing the 91% amino acid identity with OAT-K1. In this study, the mRNA distribution along the nephron segments and the transport characteristics of OAT-K1 and OAT-K2 have been analyzed. By the use of a reverse transcription-coupled PCR, OAT-K1 and OAT-K2 mRNAs were detected predominantly in the proximal straight tubules. When expressed in Xenopus oocytes, OAT-K1 mediated the uptake of MTX and folate, but not of taurocholate (TCA) and prostaglandin E2 (PGE2), although OAT-K2 stimulated the uptake of MTX, folate, TCA and PGE2. In stable transfectants (MDCK OAT-K1 and MDCK-OAT-K2), each transporter was localized functionally to the apical membrane and showed transport activity similar to those in the oocytes. The efflux of preloaded MTX was enhanced in both MDCK-OAT-K1 and MDCK-OAT-K2 cells. These results suggest that both OAT-K1 and OAT-K2 are apical membrane bidirectional organic anion transporters, and participate in epithelial transport of lipophilic organic anions in the kidney.

Animals↗

Communication effectiveness of symbolic safety signs with different user groups.

Contrary to popular belief, little systematic evaluation has been undertaken of how well public information signs convey their intended message. The application of a proposed evaluation procedure, involving an initial Recognition Test and a subsequent Recall Test, to a set of occupational safety signs is reported. Respondents comprised migrants and native-born Australian attending adult literacy classes, including a group of recently-arrived Vietnamese. Despite inter-group differences in the total number of signs correctly identified on both Recognition and Recall Tests, the same signs gave rise to difficulty for all groups. The sources of difficulty are discussed in terms of distinctiveness of referents, comprehension of shape and colour code, and translation from symbol to referent. The implications of the test results for user education programmes is also considered.

Journal Article↗

Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors.

Previous pharmacological experiments provide conflicting findings that describe both facilitatory and inhibitory effects of neuronal histamine on learning and memory. Here, we examined learning and memory and synaptic plasticity in mice with a null mutation of gene coding histamine H1 or H2 receptor in order to clarify the role of these receptors in learning and memory processes. Learning and memory were evaluated by several behavioral tasks including object recognition, Barnes maze and fear conditioning. These behavioral tasks are highly dependent on the function of prefrontal cortex, hippocampus or amygdala. Object recognition and Barnes maze performance were significantly impaired in both H1 receptor gene knockout (H1KO) and H2 receptor gene knockout (H2KO) mice when compared to the respective wild-type (WT) mice. Conversely, both H1KO and H2KO mice showed better auditory and contextual freezing acquisition than their respective WT mice. Furthermore, we also examined long-term potentiation (LTP) in the CA1 area of hippocampus in H1KO and H2KO mice and their respective WT mice. LTP in the CA1 area of hippocampus was significantly reduced in both H1KO and H2KO mice when compared with their respective WT mice. In conclusion, our results demonstrate that both H1 and H2 receptors are involved in learning and memory processes for which the frontal cortex, amygdala and hippocampus interact.

Analysis of Variance↗