These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion.

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis

A carefully spoken vowel can generally be identified from the pattern of peaks and valleys in the envelope of its short-term power spectrum, and such patterning is usually necessary for the identification of the vowel. The present experiments demonstrate that segments of sound with uniform spectra, devoid of peaks and valleys, can be identified reliably as vowels under certain circumstances. In Experiment 1, 1,000 msec of a segment whose spectrum contained peaks in place of valleys and vice versa (i.e., the complement of a vowel) preceded a 25-msec spectral amplitude transition, during which the valleys became filled, leading into a 250-msec segment with a uniform spectrum. The segment with the uniform spectrum was identified as the vowel whose complement had preceded it. Experiment 2 showed that this effect was eliminated if the duration of the complement was less than 150 msec, if more than 500 msec of silence separated the uniform spectrum from the complement, or if the uniform spectrum and the complement were presented to different ears. This third result and comparisons with parameters of auditory aftereffects obtained by others with nonspeech stimuli suggest that the effect is rooted in peripheral adaptation processes and that central processes responsible for selective attention and perceptual grouping play only a minor role at most. Experiment 3 demonstrated that valleys in the spectral structure of a complement need be only 2 dB deep to generate the effect. The effect should therefore serve to enhance changes in spectral structure in natural speech and to alleviate the consequences of uneven frequency responses in communication channels.In a pilot experiment, we established that waveforms with uniform spectra, devoid of peaks and valleys, can be identified reliably as different vowels under certain circumstances. We synthesized waveforms whose spectra were complementary to those of rectangular approximations to the vowels Iii and /e/, These complementary spectra had peaks in place of valleysand vice versa. We created stimuli in which a 4OO-msec segment of waveform with a uniform flat spectrum was surrounded by two SOO-msec segments of one of the two vowelcomplements. Fifty-millisecond spectral amplitude transitions linked the two types of waveform. The segments with uniform spectra sounded like the vowels whose complements surrounded them. Taking a more realistic vowel spectrum as a starting point, Figure I displays a progression of power spectra computed at SO-msec intervals during a sequence in which the complement of the vowel lal surrounds a segment with a uniform spec-

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The linguistic properties of the FAAF test material are expounded in relation to its objectives. It is shown from reference data that there are lexical effects inherent in the use of real-word minimal pairs rather than nonsense syllables. These are word-frequency effects upon phonemes in initial position and effects of imageability upon phonemes in final position. However, those effects are not large enough to undermine the use of the FAAF as an acoustical phonetically structured material reflecting the analysis of auditory information. Normative data on a range of signal-to-noise ratios are presented. These data have helped to delimit the subsets of items that best reflect variations in performance under easy and under difficult conditions. This offers a mapping of the percentage correct from scores at one or two fixed S/N ratios required for a given level of performance and hence permits comparison with SRT(N) measures.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives.Ethylene glycol monomethyl ether (EGME) and ethylene glycol monoethyl ether (EGEE) were administered orally to young male rats at doses varying from 50 to 500 mg/kg/day and 250 to 1000 mg/kg/day for EGME and EGEE, respectively, for 11 days. At sequential times animals were killed and testicular histology examined. The initial and major site of damage following EGME treatment was restricted to the primary spermatocytes undergoing postzygotene meiotic maturation and division. EGEE produced damage of an identical nature, but a larger dose was required to elicit equivalent severity (500 mg EGEE/kg being approximately equivalent to 100 mg EGME/kg). Additionally, within the spermatocyte population, differential sensitivity was observed depending on the precise stage of meiotic maturation: dividing (stage XIV) and early pachytene (stages I?II) > late pachytene (stages VIII-XIII) > mid-pachytene (stages III?VII). Equivalent doses of methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) gave injury similar to the corresponding glycol ether.When animals were pretreated with inhibitors of alcohol metabolism followed by a testicular toxic dose of EGME (500 mg/kg), an inhibitor of alcohol dehydrogenase (pyrazole) offered complete protection. Pretreatment with the aldehyde dehydrogenase inhibitors disulfiram or pargyline did not ameliorate the testicular toxicity of EGME. In mixed cultures of Sertoli-germ cells, MAA and not EGME produced effects on spermatocytes analogous to that seen in vivo, at concentrations approximately equivalent to steady-state plasma levels after a single oral dose of EGME (500 mg/kg). It would seem likely that a metabolite (MAA or possibly methoxyacetaldehyde) and not EGME is responsible for the production of testicular damage.

It is a concern for auditory fMRI studies that acoustic noise generated by the scanner produces an auditory response that can confound stimulus-induced activation. To establish how to minimize this problem, the present study mapped the time-course of the auditory response to a burst of acoustic scanner noise by employing a single-event method. Recorded bursts of scanner noise were interspersed with clustered-volume acquisitions at a range of stimulus-to-imaging delays to map the response with a temporal resolution of 1 sec. There were strong responses (1.5% signal change) to scanner noise in primary and secondary auditory cortex. In both cortical areas, the mean response rose to a peak by 4-5 sec after stimulus onset and decayed after a further 5-8 sec. The time course indicates that noise contamination in auditory fMRI can be substantially reduced by using a 9-12-sec repetition time, thus maximizing the dynamic range available for displaying the response to acoustical stimuli of interest. Magn Reson Med 43:601-606, 2000. The intense sound generated during echo-planar imaging is a concern for fMRI studies of auditory function. This acoustic scanner noise arises from interactions between the gradient coils and the magnet that generate coil vibrations. The acoustic properties of the scanner noise (e.g., bandwidth, fundamental frequency, spectral envelope) depend on the mechanical resonances of the coil assembles (1), on the type of imaging sequence used, and on its switching frequency. However, the noise is always intense and has been reported to exceed 97 dB (A) (2). Ear defenders and/or ear plugs attenuate background noise but, at best, reduce energy transmitted to the inner ear by only about 40 dB (3). Thus, scanner noise is still audible and its contaminating effects remain a concern. This contamination can take a number of forms. First, the scanner noise may mask the auditory stimulus so that subjects cannot adequately hear what is presented. Moreover , if different stimuli in an experiment are masked to different degrees, then stimulus effects may be confounded with effects of task difficulty. Second, scanner noise may reduce the dynamic range available for observing the stimulus-induced, blood-oxygen-level-dependent (BOLD) response, because the auditory response is elevated in baseline conditions that include scanner noise. The magnitude of the response to scanner noise alone has been quantified (4,5) and its effect on the dynamic range available for stimulus-induced activation has been investigated (6-9). Bandettini et al. (4) measured the effect of repeated bursts of scanner noise on the hemodynamic response in auditory cortex by subtracting one series of images obtained after 20 sec of silence from a second series obtained after a 20-sec period of EPI gradient noise. Difference images over the first 5 sec of the image series revealed that the preceding scanner noise induced activation in both primary and secondary auditory areas. Tala-vage et al. (5) presented different durations of scanner noise prior t...

The IHR-McCormick Automated Toy Discrimination Test (ATT) measures the minimum sound level at which a child can identify words presented in quiet in the sound field. This 'word-discrimination threshold' provides a direct measure of the ease with which a child can identify speech and a surrogate measure of auditory sensitivity. This paper describes steps taken to maximize the test-retest reliability of the ATT and to enable it to measure word-discrimination thresholds in noise as well as in quiet. It then describes the results of a clinical evaluation of the ATT in which paediatric audiologists measured word-discrimination thresholds in quiet from 215 successive attendees (in the age range 2 to 13 years) at a paediatric audiology clinic presenting over a 2-month period. When children with atypical cognition or delayed development of language were excluded, 72% of the children provided two word-discrimination thresholds and 83% provided at least one word-discrimination threshold. Children who failed to provide word-discrimination thresholds were generally younger than four years of age. Although a few children who could not perform pure-tone or warble-tone audiometry managed to provide word-discrimination thresholds, most children who could perform the ATT could also perform pure-tone audiometry. The average pure-tone threshold in the better-hearing ear could be predicted from the word-discrimination threshold with a 95% confidence interval of +/- 13 dB. The test-retest reliability of the ATT was measured in two ways. First, to enable comparison with published results, the within-subjects standard deviation of word-discrimination thresholds was calculated. It varied as a function of age and degree of impairment, but was never worse than 3.3 dB. Children of four years of age and older displayed the adult reliability of 2.3 dB. Second, the variability of absolute differences between word-discrimination thresholds was calculated. It was such that a change of 7 dB between two runs of the test (e.g. aided and unaided) would be expected to occur by change less than one time in 20. These results extend previous evaluations of the ATT to a clinically representative population and confirm that word-discrimination thresholds provide a useful complement to warble-tone and pure-tone audiometry.