Hydrothermal 15N15N abundances constrain the origins of mantle nitrogen.

Nitrogen is the main constituent of the Earth's atmosphere, but its provenance in the Earth's mantle remains uncertain. The relative contribution of primordial nitrogen inherited during the Earth's accretion versus that subducted from the Earth's surface is unclear1-6. Here we show that the mantle may have retained remnants of such primordial nitrogen. We use the rare 15N15N isotopologue of N2 as a new tracer of air contamination in volcanic gas effusions. By constraining air contamination in gases from Iceland, Eifel (Germany) and Yellowstone (USA), we derive estimates of mantle δ15N (the fractional difference in 15N/14N from air), N2/36Ar and N2/3He. Our results show that negative δ15N values observed in gases, previously regarded as indicating a mantle origin for nitrogen7-10, in fact represent dominantly air-derived N2 that experienced 15N/14N fractionation in hydrothermal systems. Using two-component mixing models to correct for this effect, the 15N15N data allow extrapolations that characterize mantle endmember δ15N, N2/36Ar and N2/3He values. We show that the Eifel region has slightly increased δ15N and N2/36Ar values relative to estimates for the convective mantle provided by mid-ocean-ridge basalts11, consistent with subducted nitrogen being added to the mantle source. In contrast, we find that whereas the Yellowstone plume has δ15N values substantially greater than that of the convective mantle, resembling surface components12-15, its N2/36Ar and N2/3He ratios are indistinguishable from those of the convective mantle. This observation raises the possibility that the plume hosts a primordial component. We provide a test of the subduction hypothesis with a two-box model, describing the evolution of mantle and surface nitrogen through geological time. We show that the effect of subduction on the deep nitrogen cycle may be less important than has been suggested by previous investigations. We propose instead that high mid-ocean-ridge basalt and plume δ15N values may both be dominantly primordial features.

Near-equilibrium isotope fractionation during planetesimal evaporation.

Silicon and Mg in differentiated rocky bodies exhibit heavy isotope enrichments that have been attributed to evaporation of partially or entirely molten planetesimals. We evaluate the mechanisms of planetesimal evaporation in the early solar system and the conditions that controled attendant isotope fractionations. Energy balance at the surface of a body accreted within ~1 Myr of CAI formation and heated from within by 26Al decay results in internal temperatures exceeding the silicate solidus, producing a transient magma ocean with a thin surface boundary layer of order < 1 meter that would be subject to foundering. Bodies that are massive enough to form magma oceans by radioisotope decay (≥ 0.1% M ⊕) can retain hot rock vapor even in the absence of ambient nebular gas. We find that a steady-state rock vapor forms within minutes to hours and results from a balance between rates of magma evaporation and atmospheric escape. Vapor pressure buildup adjacent to the surfaces of the evaporating magmas would have inevitably led to an approach to equilibrium isotope partitioning between the vapor phase and the silicate melt. Numerical simulations of this near-equilibrium evaporation process for a body with a radius of ~ 700 km yield a steady-state far-field vapor pressure of 10-8 bar and a vapor pressure at the surface of 10-4 bar, corresponding to 95% saturation. Approaches to equilibrium isotope fractionation between vapor and melt should have been the norm during planet formation due to the formation of steady-state rock vapor atmospheres and/or the presence of protostellar gas. We model the Si and Mg isotopic composition of bulk Earth as a consequence of accretion of planetesimals that evaporated subject to the conditions described above. The results show that the best fit to bulk Earth is for a carbonaceous chondrite-like source material with about 12% loss of Mg and 15% loss of Si resulting from near-equilibrium evaporation into the solar protostellar disk of H2 on timescales of 104 to 105 years.

Multiple receptor tyrosine kinases promote the in vitro phenotype of metastatic human osteosarcoma cell lines.

The survival rate for osteosarcoma patients with localized disease is 70% and only 25% for patients with metastases. Therefore, novel therapeutic and prognostic tools are needed. In this study, extensive screening and validation strategies identified Axl, EphB2, FGFR2, IGF-1R and Ret as specific receptor tyrosine kinases (RTKs) that are activated and promote the in vitro phenotype of two genetically different metastatic osteosarcoma cell lines. Initial phosphoproteomic screening identified twelve RTKs that were phosphorylated in 143B and/or LM7 metastatic human osteosarcoma cells. A small interfering RNA (siRNA) screen demonstrated that siRNA pools targeting ten of the twelve RTKS inhibited the in vitro phenotype of one or both cell lines. To validate the results, we individually tested the four siRNA duplexes that comprised each of the effective siRNA pools from the initial screen. The pattern of phenotype inhibition replicated the pattern of mRNA knockdown by the individual duplexes for seven of the ten RTKs, indicating the effects are consistent with on-target silencing. Five of those seven RTKs were further validated using independent approaches including neutralizing antibodies (IGF-1R), antisense-mediated knockdown (EphB2, FGFR2, and Ret) or small molecule inhibitors (Axl), indicating that those specific RTKs promote the in vitro behavior of metastatic osteosarcoma cell lines and are potential therapeutic targets for osteosarcoma. Immunohistochemistry demonstrated that Axl is frequently activated in osteosarcoma patient biopsy samples, further supporting our screening and validation methods to identify RTKs that may be valuable targets for novel therapies for osteosarcoma patients.

Comment on "Experimental test of self-shielding in vacuum ultraviolet photodissociation of CO".

Chakraborty et al. (Reports, 5 September 2008, p. 1328) suggested that experimental results provide support for CO photodissociation having caused the oxygen isotope ratio associated with the early solar nebula. We point out that further analysis is required before other mechanisms, such as self-shielding, are shown to be of little importance.

Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation.

The strength of synapses between auditory nerve (AN) fibers and ventral cochlear nucleus (VCN) neurons is an important factor in determining the nature of neural integration in VCN neurons of different response types. Synaptic strength was analyzed using cross-correlation of spike trains recorded simultaneously from an AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as chopper, primarylike, and onset using previously defined criteria, although onset neurons usually were not analyzed because of their low discharge rates. The correlograms showed an excitatory peak (EP), consistent with monosynaptic excitation, in AN-VCN pairs with similar best frequencies (49% 24/49 of pairs with best frequencies within +/-5%). Chopper and primarylike neurons showed similar EPs, except that the primarylike neurons had shorter latencies and shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical bushy cells were not observed, probably because of the low probability of recording from one. The small EPs observed in primarylike neurons, presumably spherical bushy cells, could be derived from small terminals that accompany end bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were consistent with the smaller synaptic terminals on multipolar and globular bushy cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of threshold, showing that VCN responses to steady tones shift from a 1:1 relationship between AN and VCN spikes at low sound levels to a more autonomous mode of firing at high levels. In the high level mode, the pattern of output spikes seems to be determined by the properties of the postsynaptic spike generator rather than the input spike patterns. The EP amplitudes did not change significantly when the presynaptic spike was preceded by either a short or long interspike interval, suggesting that synaptic depression and facilitation have little effect under the conditions studied here.

CO self-shielding as the origin of oxygen isotope anomalies in the early solar nebula.

The abundances of oxygen isotopes in the most refractory mineral phases (calcium-aluminium-rich inclusions, CAIs) in meteorites have hitherto defied explanation. Most processes fractionate isotopes by nuclear mass; that is, 18O is twice as fractionated as 17O, relative to 16O. In CAIs 17O and 18O are nearly equally fractionated, implying a fundamentally different mechanism. The CAI data were originally interpreted as evidence for supernova input of pure 16O into the solar nebula, but the lack of a similar isotope trend in other elements argues against this explanation. A symmetry-dependent fractionation mechanism may have occurred in the inner solar nebula, but experimental evidence is lacking. Isotope-selective photodissociation of CO in the innermost solar nebula might explain the CAI data, but the high temperatures in this region would have rapidly erased the signature. Here we report time-dependent calculations of CO photodissociation in the cooler surface region of a turbulent nebula. If the surface were irradiated by a far-ultraviolet flux approximately 10(3) times that of the local interstellar medium (for example, owing to an O or B star within approximately 1 pc of the protosun), then substantial fractionation of the oxygen isotopes was possible on a timescale of approximately 10(5) years. We predict that similarly irradiated protoplanetary disks will have H2O enriched in 17O and 18O by several tens of per cent relative to CO.

Proprioceptive information from the pinna provides somatosensory input to cat dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) is a second-order auditory structure that also receives nonauditory information, including somatosensory inputs from the dorsal column and spinal trigeminal nuclei. Here we investigate the peripheral sources of the somatosensory inputs to DCN. Electrical stimulation was applied to cervical nerves C1-C8, branches of C2, branches of the trigeminal nerve, and hindlimb nerves. The largest evoked potentials in the DCN were produced by C2 stimulation and by stimulation of its branches that innervate the pinna. Electrical stimulation of C2 produced a pattern of inhibition and excitation of DCN principal cells comparable with that seen in previous studies with stimulation of the primary somatosensory nuclei, suggesting that the same pathway was activated. Because C2 contains both proprioceptive and cutaneous fibers, we applied peripheral somatosensory stimulation to identify the effective somatosensory modalities. Only stimuli that activate pinna muscle receptors, such as stretch or vibration of the muscles connected to the pinna, were effective in driving DCN units, whereas cutaneous stimuli such as light touch, brushing of hairs, and stretching of skin were ineffective. These results suggest that the largest somatosensory inputs to the DCN originate from muscle receptors associated with the pinna. They support the hypothesis that a role of the DCN in hearing is to coordinate pinna orientation to sounds or to support correction for the effects of pinna orientation on sound-localization cues.

Isotopic homogeneity of iron in the early solar nebula.

The chemical and isotopic homogeneity of the early solar nebula, and the processes producing fractionation during its evolution, are central issues of cosmochemistry. Studies of the relative abundance variations of three or more isotopes of an element can in principle determine if the initial reservoir of material was a homogeneous mixture or if it contained several distinct sources of precursor material. For example, widespread anomalies observed in the oxygen isotopes of meteorites have been interpreted as resulting from the mixing of a solid phase that was enriched in 16O with a gas phase in which 16O was depleted, or as an isotopic 'memory' of Galactic evolution. In either case, these anomalies are regarded as strong evidence that the early solar nebula was not initially homogeneous. Here we present measurements of the relative abundances of three iron isotopes in meteoritic and terrestrial samples. We show that significant variations of iron isotopes exist in both terrestrial and extraterrestrial materials. But when plotted in a three-isotope diagram, all of the data for these Solar System materials fall on a single mass-fractionation line, showing that homogenization of iron isotopes occurred in the solar nebula before both planetesimal accretion and chondrule formation.

Linear and nonlinear pathways of spectral information transmission in the cochlear nucleus.

At the level of the cochlear nucleus (CN), the auditory pathway divides into several parallel circuits, each of which provides a different representation of the acoustic signal. Here, the representation of the power spectrum of an acoustic signal is analyzed for two CN principal cells-chopper neurons of the ventral CN and type IV neurons of the dorsal CN. The analysis is based on a weighting function model that relates the discharge rate of a neuron to first- and second-order transformations of the power spectrum. In chopper neurons, the transformation of spectral level into rate is a linear (i.e., first-order) or nearly linear function. This transformation is a predominantly excitatory process involving multiple frequency components, centered in a narrow frequency range about best frequency, that usually are processed independently of each other. In contrast, type IV neurons encode spectral information linearly only near threshold. At higher stimulus levels, these neurons are strongly inhibited by spectral notches, a behavior that cannot be explained by level transformations of first- or second-order. Type IV weighting functions reveal complex excitatory and inhibitory interactions that involve frequency components spanning a wider range than that seen in choppers. These findings suggest that chopper and type IV neurons form parallel pathways of spectral information transmission that are governed by two different mechanisms. Although choppers use a predominantly linear mechanism to transmit tonotopic representations of spectra, type IV neurons use highly nonlinear processes to signal the presence of wide-band spectral features.

Pharmacological evidence of inhibitory and disinhibitory neuronal circuits in dorsal cochlear nucleus.

The dorsal cochlear nucleus (DCN) is rich in both glycine and GABA inhibitory neurotransmitter systems, and the response properties of its principal cells (pyramidal and giant cells) are strongly shaped by inhibitory inputs. For example, DCN principal cells often display highly nonmonotonic (so-called type IV) input-output functions in response to best-frequency (BF) tones. In this study, the inhibitory inputs onto the principal cell types and onto response types of known inhibitory interneurons were compared before and during iontophoretic application of the glycine- and GABA(A)-receptor antagonists, strychnine and bicuculline. Strychnine eliminates the central (on-BF) inhibitory area in type IV units, resulting in monotonic BF rate-level curves. Unexpectedly, bicuculline primarily enhances inhibition in principal-cell types; for example, type IV units are inhibited at lower sound levels in the presence of bicuculline. Principal cell types with weaker inhibitory inputs (type IV-T and type III units) are more strongly inhibited in the presence of bicuculline and usually are converted into type IV units. This enhancement of on-BF inhibition by bicuculline suggests a disinhibitory process involving GABA(A) action on a non-GABA(A)ergic inhibitory pathway. This latter pathway is probably glycinergic and involves type II units (deep-layer vertical cells) and/or complex-spiking units (superficial cartwheel cells) because both of these unit types are disinhibited by bicuculline. One intrinsic GABA(A) source could be the superficial stellate cells in DCN because bicuculline partly blocks the inhibition evoked by somatosensory-stimulated activation of the superficial granule-cell circuitry in DCN. Taken together, the results suggest that glycinergic circuits mediate directly the inhibition of DCN principal cells, but that GABA(A)ergic circuits modulate the strength of the inhibition.

The formation of chondrules at high gas pressures in the solar nebula.

High-precision magnesium isotope measurements of whole chondrules from the Allende carbonaceous chondrite meteorite show that some aluminum-rich Allende chondrules formed at or near the time of formation of calcium-aluminum-rich inclusions and that some others formed later and incorporated precursors previously enriched in magnesium-26. Chondrule magnesium-25/magnesium-24 correlates with [magnesium]/[aluminum] and size, the aluminum-rich, smaller chondrules being the most enriched in the heavy isotopes of magnesium. These relations imply that high gas pressures prevailed during chondrule formation in the solar nebula.

Contrast enhancement improves the representation of /epsilon/-like vowels in the hearing-impaired auditory nerve.

This study examines the neural representation of the vowel /epsilon/ in the auditory nerve of acoustically traumatized cats and asks whether spectral modifications of the vowel can restore a normal neural representation. Four variants of /epsilon/, which differed primarily in the frequency of the second formant (F2), were used as stimuli. Normally, the rate-place code provides a robust representation of F2 for these vowels, in the sense that rate changes encode changes in F2 frequency [Conley and Keilson, J. Acoust. Soc. Am. 98, 3223 (1995)]. This representation is lost after acoustic trauma [Miller et al., J. Acoust. Soc. Am. 105, 311 (1999)]. Here it is shown that an improved representation of the F2 frequency can be gained by a form of high-frequency emphasis that is determined by both the hearing-loss profile and the spectral envelope of the vowel. Essentially, the vowel was high-pass filtered so that the F2 and F3 peaks were amplified without amplifying frequencies in the trough between F1 and F2. This modification improved the quality of the rate and temporal tonotopic representations of the vowel and restored sensitivity to the F2 frequency. Although a completely normal representation was not restored, this method shows promise as an approach to hearing-aid signal processing.

Spectral integration by type II interneurons in dorsal cochlear nucleus.

The type II unit is a prominent inhibitory interneuron in the dorsal cochlear nucleus (DCN), most likely recorded from vertical cells. Type II units are characterized by low rates of spontaneous activity, weak responses to broadband noise, and vigorous, narrowly tuned responses to tones. The weak responses of type II units to broadband stimuli are unusual for neurons in the lower auditory system and suggest that these units receive strong inhibitory inputs, most likely from onset-C neurons of the ventral cochlear nucleus. The question of the definition of type II units is considered here; the characteristics listed in the preceding text define a homogeneous type II group, but the boundary between this group and other low spontaneous rate neurons in DCN (type I/III units) is not yet clear. Type II units in decerebrate cats were studied using a two-tone paradigm to map inhibitory responses to tones and using noisebands of varying width to study the inhibitory processes evoked by broadband stimuli. Iontophoresis of bicuculline and strychnine and comparisons of two-tone responses between type II units and auditory nerve fibers were used to differentiate inhibitory processes occurring near the cell from two-tone suppression in the cochlea. For type II units, a significant inhibitory region is always seen with two-tone stimuli; the bandwidth of this region corresponds roughly to the previously reported excitatory bandwidth of onset-C neurons. Bandwidth widening experiments with noisebands show a monotonic decline in response as the bandwidth increases; these data are interpreted as revealing strong inhibitory inputs with properties more like onset-C neurons than any other response type in the lower auditory system. Consistent with these properties, iontophoresis of inhibitory antagonists produces a large increase in discharge rate to broadband noise, making tone and noise responses nearly equal.

Discriminability of vowel representations in cat auditory-nerve fibers after acoustic trauma.

This paper attempts to connect deficits seen in the neural representation of speech with perceptual deficits. Responses of auditory-nerve fibers were studied in cats exposed to acoustic trauma. Four synthetic steady-state vowels were used as test signals; these stimuli are identical, except that the second format (F2) resonator in the synthesizer was set to 1.4, 1.5, 1.7, or 2 kHz, producing four spectra that differ mainly in the vicinity of the F2 frequency. These stimuli were presented to a large population (523) of auditory-nerve fibers in four cats with sloping high-frequency threshold shifts that reached 50-70 dB at 2-4 kHz. In normal animals, May et al. [Auditory Neurosci 3, 135-162 (1996)] showed previously that the discharge rates of fibers with best frequencies near the F2 frequencies provide enough information to allow discrimination of these stimuli at the performance levels shown by cats in behavioral experiments. Here it is shown that, after acoustic trauma, there is essentially no rate information which would allow the vowels with different F2 frequencies to be discriminated. However, information that could allow discrimination remains in the temporal (phase-locked) aspects of the responses.

Oxygen reservoirs in the early solar nebula inferred from an Allende CAI.

Ultraviolet laser microprobe analyses of a calcium-aluminum-rich inclusion (CAI) from the Allende meteorite suggest that a line with a slope of exactly 1.00 on a plot of delta (17)O against delta (18)O represents the primitive oxygen isotope reservoir of the early solar nebula. Most meteorites are enriched in (17)O and (18)O relative to this line, and their oxygen isotope ratios can be explained by mass fractionation or isotope exchange initiating from the primitive reservoir. These data establish a link between the oxygen isotopic composition of the abundant ordinary chondrites and the primitive (16)O-rich component of CAIs.

Effects of high sound levels on responses to the vowel "eh" in cat auditory nerve.

The vowel "eh" was used to study auditory-nerve responses at high sound levels (60-110 dB). By changing the playback sampling rate of the stimulus, the second formant (F2) frequency was set at best frequency (BF) for fibers with BFs between 1 and 3 kHz. For vowel stimuli, auditory-nerve fibers tend to phase-lock to the formant component nearest the fiber's BF. The responses of fibers with BFs near F2 are captured by the F2 component, meaning that fibers respond as if the stimulus consisted only of the F2 component. These narrowband responses are seen up to levels of 80-100 dB, above which a response to F1 emerges. The F1 response grows, at the expense of the F2 response, and is dominant at the highest levels. The level at which the F1 response appears is BF dependent and is higher at lower BFs. This effect appears to be suppression of the F2 response by F1. At levels near 100 dB, a component 1/component 2 transition is observed. All components of the vowel undergo the transition simultaneously, as judged by the 180 degrees phase inversion that occurs at the C2 transition. Above the C2 threshold, a broadband response to many components of the vowel is observed. These results demonstrate that the neural representation of speech in normal ears is degraded at high sound levels, such as those used in hearing aids.

Outcome comparison of in vitro fertilization treatment with highly purified subcutaneous follicle-stimulating hormone (Fertinex, a urofollitropin) versus intramuscular menotropins.

OBJECTIVE: The aim of this study was to investigate various outcome measures of stimulation with highly purified subcutaneous follicle-stimulating hormone (Fertinex, a urofollitropin) compared with first- and second-generation urinary human menopausal gonadotropin standards (Pergonal, Metrodin). STUDY DESIGN: Retrospective analysis was restricted to our most efficient in vitro fertilization age group (23-34 years). Data from Institute for Assisted Reproduction in vitro fertilization cycles 1 through 11 with Pergonal, Metrodin, or both were tabulated for hormonal values, oocyte quality, and embryo outcome as baseline data. Patients in cycles 12 through 13 were treated with Fertinex and Pergonal or Fertinex alone and then reviewed for the same parameters. RESULTS: Two hundred thirty-eight in vitro fertilization records with embryo transfer were analyzed. Clinical pregnancy rates per embryo transfer in an optimal age group were similar despite use of first- through third-generation urinary gonadotropin preparations: Pergonal and Metrodin, 67%; Metrodin, 64%; Fertinex and Pergonal, 62%; and Fertinex, 54%. There were no discernible differences in hormonal response, oocyte recovery, or embryonic growth. CONCLUSION: Administered subcutaneously, the third-generation urinary gonadotropin preparation Fertinex is effective in in vitro fertilization treatment in young women.

Frequency-shaped amplification changes the neural representation of speech with noise-induced hearing loss.

Temporal response patterns of single auditory nerve fibers were used to characterize the effects of a common hearing-aid processing scheme, frequency-shaped amplification, on the encoding of the vowel /epsilon/ in cats with a permanent noise-induced hearing loss. These responses were contrasted with responses to unmodified stimuli in control and impaired cats. Noise-induced hearing loss leads to a degraded representation of the formant frequencies, in which strong phase locking to the formants is not observed in fibers with best frequencies (BFs) near the formants and there is a wide spread of formant phase locking to fibers with higher BFs (Miller et al., 1997a,b). Frequency shaping effectively limits the upward spread of locking to F1, which improves the representation of higher frequency components of the vowel. However, it also increases phase locking to harmonics in the trough between the formants, which decreases the contrast between F1 and the trough in the neural representation. Moreover, it does not prevent the spread to higher BFs of responses to the second and third formants. The results show a beneficial effect of frequency shaping, but also show that interactions between particular gain functions and particular spectral shapes can result in unwanted distortions of the neural representation of the signal.