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This supporting information includes: Figure S1. Sidewall views of some key models after 45 cm shortening. Figure S2. Velocity fields of Type A models at different shortening stages. Figure S3. Sequential sidewall views of Type A model ZC33. Figure S4. Sequential sidewall views of Type A model ZC25. Figure S5. Sequential sidewall views of Type A model ZC24.Animations of the eleven models, including: 1) Type A model ZC12: ��s/��d = 105.102) Type A model ZC13: ��s/��d = 1.383) Type A model ZC16: ��s/��d = 1.154) Type A model ZC17: ��s/��d = 0.175) Type A model ZC18: ��s/��d = 0.156) Type A model ZC19: ��s/��d = 0.147) Type A model ZC20: ��s/��d = 0.098) Type A model ZC22: ��s/��d = 0.059) Type B model ZC47: ��s1/��d1 = 37.36; ��s2/��d = 0.8110) Type B model ZC49: ��s1/��d1 = 15.86; ��s2/��d = 0.34 11) Type B model ZC52: ��s1/��d1 = 68.63; ��s2/��d2 = 5.00

In this paper, the H − /H ∞ detection for faults and attacks in a Cyber-physical system (CPS) is studied. The complex network environment with random delay, limited communication, actuator cyber attack and sensor cyber attack is considered. And the above system with fault and attack coexisting is discretized by delta operator in high-speed sampling. A set of H − /H ∞ observers is constructed, which enables the system to detect the possible fault signal and attack signal respectively and quickly. By using Lyapunov-Krasovskii functional and linear matrix inequalities approach, the sufficient conditions for the system to have asymptotic stability and H − /H ∞ performance are given. The feasibility and effectiveness of the proposed method are analyzed through several simulation examples.

In addition to external malicious attacks, there are also the faults caused by the network itself in Cyber-physical systems (CPSs). In this paper, the CPS fault detection with control time-delay is considered, and a discrete time system based on delta operator is designed to solve the various problems with high-speed sampling. To reduce the influence of random disturbance on the system, and increase the sensitivity of fault detection at the same time, a H − /H ∞ fault detection filter is constructed by the method of Lyapunov-Krasovskii functional and linear matrix inequalities (LMIs). Eventually, the results of the experiment are provided to verify the effectiveness of the proposed method.

In this paper, the fault detection problem for a multi-packet transmission network control system with limited communication and random delay is studied. The communication sequence method is introduced to deal with the limited communication problems in the system, and a multi-packet transmission is equivalent to a Markov jump process. A fault detection filter based on delta domain is established for the system model to generate the residual signal. The residual and fault signals are further used to generate the residual error so that the fault signal can be detected intuitively. Through linear matrix inequality (LMI) method and Lyapunov-Krasinskii stability theory, the designed H ∞ fault detection filter’s stability conditions are gained. Finally, a numerical simulation example is shown to demonstrate the availability of the proposed method.

Data from offshore oil and gas explorations have revealed that mud diapirs occur widely not only at continental margins but also in foreland basins and may have played an important role in the entrapment of oil and gas. Although the structural features and formation mechanism of salt diapirs have been extensively investigated, mud diapirs are still not fully understood, largely due to the difficulty of identifying them from seismic data. In this paper, the structural features and main controlling factors of mud diapirs in the Andaman Sea Basin are investigated based on seismic profiles combined with drilling data and regional tectonic settings. The results show that there are five types of mud diapir in the Andaman Sea Basin: turtleback mud diapir, mud dome, piercing mud diapir, mud volcano and gas chimney-like mud diapir. Turtleback mud diapirs mainly occur in the southern segment of the accretionary wedge of the Andaman Sea Basin, which is far from the Bengal Fan and characterized by low deposition rate and strong compression tectonic setting. Piercing mud diapirs exist mainly in the central segment of the accretionary wedge, which is close to provenances of sediments and characterized by rapid sedimentation rates, large mudstone thickness and transpressional tectonic setting. Mud domes and mud volcanoes mainly occur in the northern segment of the accretionary wedge, which is characterized by rapid sedimentation rates, large mudstone thickness and sedimentary wedge growth tectonic setting. The gas chimney-like mud diapirs only occur in the northern segment of the back-arc depression close to the Sagaing strike-slip fault belt, which is characterized by high deposition rate, large mudstone thickness and high geothermal gradient. These features suggest that thick mudstone deposit, rapid sedimentation rates, large geothermal gradient, strong tectonic stress and gravitational spreading and sliding may have prompted the formation of mud diapirs in the Andaman Sea Basin.

The Lower Silurian Longmaxi shale is the most important marine shale gas play in South China. Several hundred wells have been drilled to date, of which more than 150 wells have obtained high initial production (IP). Outside of the Sichuan Basin, however, wells drilled in the Lower Silurian Longmaxi shale do not reach flow rates that are commercial. Developing an understanding of the key factors controlling the IPs of Longmaxi shale is important in screening shale-resource plays. In this study, the TOC, thermal maturity, porosity, and gas saturation data obtained from Longmaxi shale of southeastern Chongqing area outside Sichuan Basin have been compared with that of Sichuan Basin. The results of this study show that the shales encountered display similar properties including TOC (>2%), thermal maturity (2.5–3.5% EqRo), and total porosity (3–6%). A good correlation between IPs and pressure coefficient suggest that the free gas content of gas shale controls on IPs. Porosity and gas saturation of gas shale are the main factors to control its free gas volume. The gas saturations in Longmaxi shale from high initial production wells in Sichuan Basin mainly range between 50 and 90%, however, that of shale in the southeastern Chongqing area are decreased to 10–30%. This is the directly reason for low IPs of wells. The contrasting gas saturation of Longmaxi shale between Sichuan Basin and the adjacent fold-thrust belts are interpreted to reflect, in part, differences in sealed condition of fluid system. Intensive tectonic movements caused the exhumation, faulting and fracturing, that reduced or destroyed the sealed ability of shale fluid system, which are the major factors for enhancing water saturation, decreasing fluid pressure and IPs. Finally, the study proposes several most favorable zones for Longmaxi shale gas exploration and development.

The Eastern Sichuan–Xuefeng fold-thrust belt (CXFTB) located in South China has received wide attention due to its distinctive deformation styles and close relationships with natural gas preservation, but its deformation evolution still remains controversial. In order to study further this issue, we designed three sets of analogue models. Based on the results of the models, we suggest that: 1) the deformation in the CXFTB may simultaneously initiate along two zones nearby the Dayong and Qiyueshan faults at ∼190 Ma, and then progressively propagate into the interiors of the Western Hunan-Hubei and Eastern Sichuan domains at ∼140–150 Ma, and finally reach the front of the Huayingshan fault at ∼120 Ma; 2) the difference in decollement depth is the main factor determining the patterns of folds in different domains of the CXFTB; and 3) the Eastern Sichuan domain may have a basement significantly different from those of the Western Sichuan and Western Hunan-Hubei domains.

This paper addresses the problem of fault detection for networked control systems with random packet dropout and delay via delta operator. The packet dropout and delay which in the networked control systems are both random, and described by Markov chain process. So the system model is converted to Markovian jump systems. A fault detection filter based on the observer is proposed to generate the residual signal, thus making the residual systems to be asymptotically stable and satisfy the H-infinity performance in delta domain. The parameters of the fault detection filter are obtained by linear matrix inequality(LMI). The numerical example is provided to show the effectiveness of the proposed method.

Various factors are inferred to influence the structural evolution of fold-and-thrust belts or thrust wedges, but the effects of lateral friction (such as that exerted by the opposite block of a strike-slip fault in nature or by sidewalls in analogue models) have rarely been given sufficient attention and hence are still far from being fully understood. Up to now, seaward-vergent and dually vergent thrust wedges have been satisfactorily explained by the classic Coulomb wedge theory and can be well reproduced in analogue and numerical models. In contrast, landward-vergent thrust wedges, which are uncommon in nature (e.g., those occurring in the Cascadia subduction zone), have not yet been adequately explained by the classic Coulomb wedge theory and can only be reproduced in a few analogue models under particular conditions. In order to look closer at the effects of lateral friction on the structural evolution of fold-and-thrust belts and to explore the origin of landward-vergent thrust wedges, we conducted a series of sandbox models under different conditions of lateral friction and various ratios of initial average lateral frictional stress to basal shear stress (τ s /τ d ). Results of our models revealed that in the presence of a weak or ductile basal decollement, the direction of lateral friction can dictate not only the deformation propagation direction and the surface slope direction, but also the structural vergence of fold-and-thrust belts. Fold-and-thrust belts normally show a structural vergence in the same direction as the direction of lateral friction but a deformation propagation direction and surface slope direction opposite to the direction of lateral friction. According to the results of models and the relationships between structural vergence and lateral friction direction occurring both in Cascadia and the analogue models, we propose that an extremely high τ s /τ d ratio due to an extremely weak basal decollement and landward-directed lateral friction exerted by the opposite blocks of basement-involved strike-slip faults are probably the two key factors responsible for the origin of landward-vergent thrust wedges in Cascadia. This work illustrates that effects of lateral friction should be properly taken into account both in the kinematic analysis and designs of models to simulate fold-and-thrust belts in the presence of weak or ductile basal decollements.

Linear dunes, which are widespread on Earth and on some other planets, are generally considered to have a depositional origin and to form by loose sand under a bidirectional wind regime or by stabilized sand under a unidirectional wind regime, while the wind-rift (erosional origin) model has commonly been rejected due largely to lack of sufficient evidence and difficulty in morphodynamic interpretations. The linear dunes in the Qaidam Basin have been proposed to form as self-extending lee dunes under a unidirectional wind regime owing to a high level of total silt, clay, and salt (TSCS) content or cohesiveness of sediments, and they have undergone southward lateral migration at rates of up to 3 m/yr. We present herein results from studies of the sediments, internal structures, and optically stimulated luminescence (OSL) ages to show that: (1) the linear dunes in the Qaidam Basin are most likely of erosional origin similar to yardangs with orientations controlled by strikes of joints; (2) TSCS content or related sediment cohesion is unlikely to be an important factor determining the formation of these linear dunes; and (3) the linear dunes consist of 0.81–3.21 ka cross-strata with small lateral migration rates of 0.02–0.04 m/yr. Our findings evidently suggest that linear dunes can be of erosional origin. We therefore propose that the possibility of erosional origin should not be ruled out for linear dunes in some other dune fields on Earth as well as on Titan. If the control of tectonic structures on the orientation of wind-eroded ridges is taken into account, morphodynamic interpretations for the wind-rift model may become much simpler.

Zhou J, Bates BE, Kurichi JE, Kwong PL, Xie D, Stineman MG. Factors influencing receipt of outpatient rehabilitation services among veterans following lower extremity amputation. Objective To determine patient-, treatment-, and facility-level characteristics associated with receiving outpatient rehabilitation services after lower extremity amputation within the Veterans Affairs (VA) system. Design Observational study. Setting All Veterans Affairs Medical Centers (VAMCs). Participants Veterans (N=4165) with lower extremity amputation discharged from VAMCs between October 1, 2002, and September 20, 2004. Interventions Not applicable. Main Outcome Measures Receipt of outpatient rehabilitation services up to 1 year postdischarge. A Cox proportional hazards model was used to determine the adjusted hazard ratio and 95% confidence interval of veterans to receive outpatient services. Results Sixty-five percent of veterans with lower extremity amputation received outpatient services. Older veterans, patients admitted for surgical amputation from extended care rather than transferred from another hospital, and those with transfemoral and/or bilateral rather than unilateral transtibial amputations were less likely to receive outpatient services. Those with serious comorbidities and those who had procedures for acute central nervous system disorders, active cardiac pathology, serious nutritional compromise, and severe renal disease during the surgical hospitalization less often initiated outpatient care. Patients who received inpatient consultative rehabilitation compared with inpatient specialized rehabilitation, and who were treated in the Northeast compared with the Southeast less often initiated outpatient care. Finally, those discharged to home or other locations rather than extended care had an initial increased likelihood of receiving outpatient service, but by 180 days postdischarge those discharged to extended care were more likely to initiate outpatient services. Conclusions Both clinical characteristics and types of rehabilitation services received appear to influence the receipt of outpatient rehabilitation services. Geographic location also affected the receipt of outpatient rehabilitation, suggesting that care patterns are not standardized across the nation.

The cochlear nucleus (CN) is the first auditory structure to receive binaural information via CN-commissural connections. In spite of an abundance of evidence that CN-commissural neurons are glycinergic and thus inhibitory, physiological, and anatomical evidence suggests that a small group of CN-commissural neurons are excitatory. In this study, we examined the excitatory portion of the CN-commissural pathway by combining anterograde tract tracing with immunohistochemistry of vesicular glutamate transporters (VGLUTs) and retrograde tract tracing with immunohistochemistry of glycine and GABA. VGLUTs accumulate glutamate in synaptic vesicles and are prime markers for glutamatergic neurons. The terminal endings of CN-commissural projections were typically en passant or small terminal boutons, but large, irregular swellings were also observed, confined to the granule cell domain (GCD). Both small and large terminal endings in the GCD colabeled with VGLUT2, but not VGLUT1. In addition, some CN-commissural cells themselves received VGLUT2-positive puncta on their somata. After large injections into the CN, 37% of the total number of retrogradely labeled commissural neurons was immunonegative to glycine or GABA. Retrograde labeling after a restricted GCD injection revealed a majority of putative excitatory CN-commissural neurons as multipolar, in the marginal regions of the ventral CN, medially as well as in the small cell cap region and deep dorsal CN. These results provide direct anatomical evidence that an excitatory commissural projection is present, and VGLUT2 is associated with this pathway both as its source and as a recipient.

The basic helix–loop–helix (bHLH) transcription factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) and optic nerve development. Using Math5-lacZ knockout mice, we have identified an additional expression domain for Math5 outside the eye, in functionally connected structures of the central auditory system. In the adult hindbrain, the cytoplasmic Math5-lacZ reporter is expressed within the ventral cochlear nucleus (VCN), in a subpopulation of neurons that project to medial nucleus of the trapezoid body (MNTB), lateral superior olive (LSO), and lateral lemniscus (LL). These cells were identified as globular and small spherical bushy cells based on their morphology, abundance, distribution within the cochlear nucleus (CN), co-expression of Kv1.1, Kv3.1b and Kcnq4 potassium channels, and projection patterns within the auditory brainstem. Math5-lacZ is also expressed by cochlear root neurons in the auditory nerve. During embryonic development, Math5-lacZ was detected in precursor cells emerging from the caudal rhombic lip from embryonic day (E)12 onwards, consistent with the time course of CN neurogenesis. These cells co-express MafB and are post-mitotic. Math5 expression in the CN was verified by mRNA in situ hybridization, and the identity of positive neurons was confirmed morphologically using a Math5-Cre BAC transgene with an alkaline phosphatase reporter. The hindbrains of Math5 mutants appear grossly normal, with the exception of the CN. Although overall CN dimensions are unchanged, the lacZ-positive cells are significantly smaller in Math5 −/− mice compared to Math5 +/− mice, suggesting these neurons may function abnormally. The auditory brainstem response (ABR) of Math5 mutants was evaluated in a BALB/cJ congenic background. ABR thresholds of Math5 −/− mice were similar to those of wild-type and heterozygous mice, but the interpeak latencies for Peaks II–IV were significantly altered. These temporal changes are consistent with a higher-level auditory processing disorder involving the CN, potentially affecting the integration of binaural sensory information.

Recent findings show that the vanilloid receptor subtype 1 (TRPV1) is expressed by cochlear outer hair cells and spiral ganglion cells, and that its expression is up-regulated in ganglion cells after aminoglycoside treatment. This study tested the hypothesis that agents that act on TRPV1 receptors affect the spectrum of ensemble background activity (EBA). Consecutive intracochlear perfusions of the TRPV1 agonist, capsaicin (CAP 0.1, 1, and 10 parts per million), as well as its antagonist capsazepine (CZP), were used to test effects of TRPV1 activation on EBA recorded from the cochlear base. Perfusion with CAP alone produced a dose-dependent increase of the 900-Hz peak ratio (power normalized re the overall spectrum) of the EBA. The CAP effect was attenuated during concurrent perfusion with CZP. These findings are consistent with the hypothesis that TRPV1 activation increases background activity of spiral ganglion cells and support a role of TRPV1 in gating spontaneous and evoked auditory nerve excitability.

Interactions between somatosensory and auditory systems occur at peripheral levels in the central nervous system. The cochlear nucleus (CN) receives innervation from trigeminal sensory structures: the ophthalmic division of the trigeminal ganglion and the caudal and interpolar regions of the spinal trigeminal nucleus (Sp5I and Sp5C). These projections terminate primarily in the granule cell domain, but also in magnocellular regions of the ventral and dorsal CN. Additionally, new evidence is presented demonstrating that cells in the lateral paragiganticular regions of the reticular formation (RF) also project to the CN. Not unlike the responses obtained from electrically stimulating the trigeminal system, stimulating RF regions can also result in excitation/inhibition of dorsal CN neurons. The origins and central connections of these projection neurons are associated with systems controlling vocalization and respiration. Electrical stimulation of trigeminal and RF projection neurons can suppress acoustically driven activity of not only CN neurons, but also neurons in the inferior colliculus. Together with the anatomical observations, these physiological observations suggest that one function of somatosensory input to the auditory system is to suppress responses to "expected" body-generated sounds such as vocalization or respiration. This would serve to enhance responses to "unexpected" externally-generated sounds, such as the vocalizations of other animals.

The deformation and uplifting history of the Qinghai–Tibet Plateau is a controversial issue, and so far there has been insufficient evidence for interpretation. Investigations of the Cenozoic deformation in the northeastern edge of this plateau may provide some relevant information. In this paper, the Cenozoic deformation history of the Qaidam Basin has been studied based on results from the balanced cross-section restoration of six geological sections. They indicate that: (1) the Qaidam Basin has been undergoing continuous shortening since the beginning of Cenozoic with two relatively fast shortening phases, the first during 42.8–40.5 Ma and the second during 2.8 Ma–present; (2) the shortening rate of the Qaidam Basin reached its maximum value since 2.8 Ma, and approximately 32% of the average total Cenozoic shortening took place in this period; and (3) the shortening of all sections reached approximately 50% of their respective total shortening by Miocene. The Cenozoic deformation history of the Qaidam Basin shows good synchroneity with uplifting history of the Qinghai–Tibet Plateau. It is therefore proposed that the deformation and uplifting in the south and north edges of the Qinghai–Tibet Plateau was almost synchronous, with the Altyn Tagh Fault formed at the beginning of India–Asia collision. Accordingly, it is postulated that since the India–Asia collision at the beginning of Cenozoic, the Indian Plate moved northward continuously with two relatively fast phases, the first during 42.8–40.5 Ma and the second during 2.8 Ma–present. Approximately 50% of the total Cenozoic northward displacement of the Indian Plate, of the total amount of crustal shortening and uplifting of the Qinghai–Tibet Plateau, and of the total Cenozoic strike slip displacement of the Altyn Tagh Fault were probably reached by the early Miocene. Moreover, another 30–40% might have taken place during 2.8 Ma–present. The periods during 42.8–40.5 Ma and during 2.8 Ma–present may also be the two fast phases for crustal shortening and uplifting of the Qinghai–Tibet Plateau and strike slip displacement of the Altyn Tagh Fault.

In addition to ascending auditory inputs, the external cortex of the inferior colliculus (ICX) receives prominent somatosensory inputs. To elucidate the extent of interaction between auditory and somatosensory representations at the level of IC, we explored the dual projections from the cochlear nucleus (CN) and the spinal trigeminal nucleus (Sp5) to the inferior colliculus (IC) in the guinea pig, using both retrograde and anterograde tracing techniques. Injections of retrograde tracers into ICX resulted in cell-labeling primarily in the contralateral DCN and pars interpolaris and caudalis of Sp5. Labeled cells in DCN were either fusiform or multipolar cells, whereas those in Sp5 varied in size and shape. Injections of anterograde tracers into either CN or Sp5 resulted in terminal labeling in ICX primarily on the contralateral side. Most projection fibers from Sp5 terminated in a laminar pattern from ventromedial to dorsolateral within the ventrolateral ICX, the ventral border of IC, and the ventromedial edge of IC (collectively termed "the ventrolateral border region of IC," ICXV). Less dense anterograde labeling was observed in lateral and rostral ICX. Injecting different tracers into both Sp5 and CN confirmed the overlapping areas of convergent projections from Sp5 and CN in IC: The most intense dual labeling was seen in the ICXV, and less intense dual labeling was also observed in the rostral part of ICX. This convergence of projection fibers from CN and Sp5 provides an anatomical substrate for multimodal integration in the IC.

In addition to input from auditory centers, the cochlear nucleus (CN) receives inputs from nonauditory centers, including the trigeminal sensory complex. The detailed anatomy, however, and the functional implications of the nonauditory innervation of the auditory system are not fully understood. We demonstrated previously that the trigeminal ganglion projects to CN, with terminal labeling most dense in the marginal cell area and secondarily in the magnocellular area of the ventral cochlear nucleus (VCN). We continue this line of study by investigating the projection from the spinal trigeminal nucleus to CN in guinea pig. After injections of the retrograde tracers FluoroGold or biotinylated dextran amine (BDA) in VCN, labeled cells were found in the spinal trigeminal nuclei, most densely in the pars interpolaris and pars caudalis with ipsilateral dominance. The anterograde tracers Fluoro-Ruby or BDA were stereotaxically injected into the spinal trigeminal nucleus. Most labeled puncta were found in the marginal area of VCN and the fusiform cell layer of dorsal cochlear nucleus (DCN). A smaller number of labeled puncta was located in the molecular and deep layers of DCN and the magnocellular area of VCN. The trigeminal projection to CN may provide somatosensory information necessary for pursuing a sound source or for vocal production. These projections may have a role in the generation and modulation of tinnitus.

The binaural interaction component (BIC=sum of monaural-true binaural) of the auditory brainstem response appears to reflect central binaural fusion/lateralization processes. Auditory middle-latency responses (AMLRs) are more robust and may reflect more completely such binaural processing. The AMLR also demonstrates such binaural interaction. The fusion of dichotically presented tones with an interaural frequency difference (IFD) offers another test of the extent to which electrophysiological and psychoacoustical measures agree. The effect of IFDs on both the BIC of the AMLR and a psychoacoustical measure of binaural fusion thus were examined. The perception of 20-ms tone bursts at/near 500 Hz with increasing IFDs showed, first, a deviated sound image from the center of the head, followed by clearly separate pitch percepts in each ear. Thresholds of detection of sound deviation and separation (i.e., nonfusion) were found to be 57 and 209 Hz, respectively. However, magnitudes of BICs of the AMLR were found to remain nearly. constant for IFDs up to the 400-Hz (limit of range tested), suggesting that the AMLR-BIC does not provide an objective index of this aspect of binaural processing, at least not under the conditions examined. The nature of lateralization due to IFDs and the concept of critical bands for binaural fusion are also discussed. Further research appears warranted to investigate the significance of the lack of effect of IFDs on the AMLR-BIC. Finally, the IFD paradigm itself would seem useful in that it permits determination of the limit for nonfusion of sounds presented binaurally, a limit not accessible via more conventional paradigms involving interaural time, phase, or intensity differences.

A separation-based biosensor that couples microdialysis directly to capillary electrophoresis with electrochemical detection (CEEC) is described. The system employs a 60 nl injection valve and a gap junction interface. For successful electrochemical detection, it is necessary to apply the separation voltage at the gap interface. This is in contrast to previously reported optically based systems in which it was possible to place the high voltage at the detection end. To protect the experimental animal from the high voltage employed for the separation, a cellulose acetate-based decoupler was placed between the injection valve and the injection interface. The effects of interface gap distance, transfer buffer flow rate and capillary i.d. on separation efficiency and peak height were investigated. In particular, it was found that electrokinetic injection of positively charged analytes into the CE was affected by the magnitude of the second field set up in the transfer capillary. The use of a 25 μm diameter capillary for the transfer line and a 75 μm capillary for the CE separation gave the best detector response and highest separation efficiency. The potential of this system for bioanalytical studies was demonstrated by monitoring transdermal delivery of nicotine following administration of a nicotine patch. Cutaneous concentrations of nicotine were monitored over a 24 h period with a resolution of 10 min.

The extremely low sample volumes required for capillary electrophoresis and the high sensitivity and selectivity of electrochemical detection make capillary electrophoresis/electrochemistry (CEEC) a very useful method for bioanalysis. In this paper, two types of dual-electrode detectors for CEEC are described. The first employs a ring-disk microelectrode placed in a wall-jet configuration and is used for the selective detection of substances undergoing chemically reversible oxidations. Collection efficiencies obtained for catecholamines with this configuration were between 25 and 35%. The second electrode design consists of two adjacent carbon fibers embedded in an epoxy matrix and is analogous to the parallel dual-electrode configuration used in liquid chromatography/electrochemistry. This configuration can be used to confirm peak identity and purity by operating the electrodes at two different potentials. Alternatively, it is possible to perform simultaneous oxidative and reductive electrochemical detection.

One of the drawbacks of chemically modified electrodes for electrochemical detection in conjunction with capillary electrophoresis (CE) is that the optimal run buffer for the CE separation is often not compatible with the electrolyte conditions necessary for maximum detector response. This paper reports the development of a membrane-based on-column mixer for CE which makes it possible to perform the separation and detection using different buffer conditions. The mixer consists of a cellulose acetate tube ca. 2-mm length and 50-mm i.d. The pH and/or ionic strength of the CE run buffer can be altered at the detector end by placing the mixer in a cathodic buffer reservoir containing a modifying solution of either HCl or NaOH

Thiols and disulfides are separated and detected by capillary electrophoresis-electrochemical detection using a mixed-valence ruthenium cyanide-modified microelectrode. A carbon fiber array microelectrode was employed to maximize the signal-to-noise ratio. Detection limits for glutathione disulfide, cystine and homocystine were 2.5, 1.3 and 1.1 fmol, respectively. The response for cystine was linear over two orders of magnitude with a correlation coefficient of 0.992. The long-term stability and overall reproducibility of the electrode were investigated and found to be highly dependent on the cation concentration in the electrophoretic buffer. The selectivity of this technique for disulfides was demonstrated by the detection of cystine in the urine of a patient with kidney stones.

Electrocatalytic oxidation of sulfhydryl compounds was effective on a copper hexacyanoferrate (CuHCF) film glassy carbon electrode, at a significantly reduced overpotential (0.55 to 0.65 V) and for a broader pH range (2.0 to 7.0). The electrocatalysis was

Chemically modified electrodes (CMEs) prepared by the dispersion of metal oxide particles on a glassy carbon (GC) substrate greatly enhance the voltammetric response and amperometric detection of local anesthetics following liquid chromatography (LC). The enhancement is more pronounced with the GC electrodes dispersed by the metal oxides of higher oxidation states (+3, +4) and for the species exhibiting relatively slow electrode kinetics under given conditions. With an applied potential of 1.2 V (vs. SCE), LC amperometric detection of the analytes at the alpha-alumina modified GC surface gives detection limits 2-5 times lower than those obtained at the bare electrode. The metal oxide-dispersed electrodes display significant improvement in sensitivity, and selectivity and indicate excellent preparation reproducibility and performance stability.

A vitamin B-12 chemically modified electrode (CME) was constructed by adsorption of vitamin B-12 onto a glassy carbon surface. The electrode catalyzes the electrooxidation of hydrazine compounds over a wide pH range. The electrocatalytic behavior of hydrazines is elucidated with respect to the CME preparation conditions, solution pH, operating potential, mobile phase flow rate, and other variables. When applied to liquid chromatographic detection of the analytes, the vitamin B-12 CME yielded a linear response range over 2 orders of magnitude, and detection limits at the picomole level. The vitamin B-12 CME offers acceptable catalytic stability in both batch and flow systems.

A copper-based chemically modified electrode (CME) has been constructed and characterized for flow-through amperometric detection of catechol, resorcinol, and hydroquinone. Novel potential dependence of the detector response was first obtained for these analytes at the Cu CME, where negative peaks together with positive ones were observed in one definite chromatogram using amperometric detection. Its advantages in chromatographic applications were demonstrated. From these observations it is proposed that the detector response was governed by formation of copper complexes with the solutes. A dynamic linear range over two orders of magnitude was obtained, when operating the detector at +0.10 V vs. SCE, from which ng detection limits were achieved.

Thionine-containing chemically modified electrode ( cme ) was constructed with glassy carbon substrate by potential sweep oxidation, electrodeposition and adsorption procedures, and electrocatalytic reduction of hemoglobin was carried out and characterized at the cme under batch and flow conditions. Comparison of the catalytic response toward hemoglobin obtained at the cme was made mainly in terms of the potential dependence, the detectability and long-term stability. When used in flow injection analysis (FIA) experiments with the detector monitored at a constant potential applied at −0.35 vs sce , detection limit of 0.15–1.5 pmol level of hemoglobin injected was achieved at the cme , with linear response range over 2 orders of magnitude. All the cme s retained more than 70% of their initial hemoglobin response level over 8 h of continuous service in the flow-through system.

A new liquid chromatography electrochemical (LCEC) scheme for glucose sensing has been developed on the basis of a Prussian Blue chemically modified electrode (CME) of novel construction and characterized in terms of various experimental parameters by the flow injection analysis (FIA) technique. Unique hydrodynamic voltammograms were obtained for the first time at the CME in the flow-through amperometric detection of glucose, and subsequently both anodic and cathodic peaks could be expected on monitoring the operating potential in the modest positive or negative region. The unique pH dependence on the CME response towards glucose makes it perfectly compatible with conventional reversed phase liquid chromatography systems. On the basis of these features, practical application in glucose LCEC detection has been effectively performed; a linear response range over three orders of magnitude and a detection limit of subpicomole level were readily obtained. The capability of the established LCEC mode in the direct sensing of urinary glucose has been demonstrated.

In the normal guinea pig, contralateral sound inhibits more than a third of ventral cochlear nucleus (VCN) neurons but excites

Integration of multimodal information is essential for understanding complex environments. In the auditory system, multisensory integration first occurs in the cochlear nucleus (CN), where auditory nerve and somatosensory pathways converge (Shore, 2005). A unique feature of multisensory neurons is their propensity to receive cross-modal compensation after deafening. Based on our findings that the vesicular glutamate transporters, VGLUT1 and VGLUT2, are differentially associated with auditory nerve and somatosensory inputs to the CN, respectively (Zhou et al., 2007), we examined their relative distributions after unilateral deafening. After unilateral intracochlear injections of kanamycin (1 and 2 weeks), VGLUT1 immunoreactivity (ir) in the magnocellular CN ipsilateral to the cochlear damage was significantly decreased, whereas VGLUT2-ir in regions that receive nonauditory input was significantly increased 2 weeks after deafening. The pathway-specific amplification of VGLUT2 expression in the CN suggests that, in compensatory response to deafening, the nonauditory influence on CN is significantly enhanced. One undesirable consequence of enhanced glutamatergic inputs could be the increased spontaneous rates in CN neurons that occur after hearing loss and that have been proposed as correlates of the phantom auditory sensations commonly called tinnitus.

A copper-based chemically-modified electrode has been constructed and characterized by various experimental parameters in flow-through amperometric detection of carboxylic acids and phenolic acids. Novel hydrodynamic voltamperograms were first obtained in flow-through amperometric detection with the Cu-based CME and subsequently negative and positive peaks were observed in a single chromatogram. This unique and flexible potential dependence could be of great benefit in chromatographic speciation and quantification. These observations suggest that the detector response was governed by the complexation reaction of copper ions with the solutes.

Electrodeposition of the phenothiazine mediator titrant toluidine blue onto a glassy carbon substrate at an appropriate potential was used to construct a toluidine blue chemically modified electrode (CME) exhibiting electrocatalytic reduction for myoglobin and hemoglobin. The CME catalyzed the hemoprotein electroreduction at the reduction potential of the mediator molecule. When the CME as used as a detector for flow injection analysis at a constant applied potential of -0.30 V vs. a saturated calomel electrode, it gave detection limits of 20 and 50 ng (1.2 and 0.78 pmol) injected myoglobin and hemoglobin, respectively, with a dynamic linear concentration range over 2 orders of magnitude. After a brief equilibration period, the CME retained nearly 90% of its initial myoglobin response over 8 hours of continuous exposure to the flow-through system.

Steady-state voltammetric and flow-through thin-layer amperometric experiments were done to investigate the influence of various preliminary experimental conditions on the selectivity of a Nafion-coated electrode in the flow-through determination of cationic drugs (promethiazine was selected as a model compound). From the results guidelines were formulated to obtain optimum selectivity for cationic drugs with a Nafion-coated electrode in flow-through analysis.

Somatic tinnitus is clinically observed modulation of the pitch and loudness of tinnitus by somatic stimulation. This phenomenon and the association of tinnitus with somatic neural disorders indicate that neural connections between the somatosensory and auditory systems may play a role in tinnitus. Anatomical and physiological evidence supports these observations. The trigeminal and dorsal root ganglia relay afferent somatosensory information from the periphery to secondary sensory neurons in the brainstem, specifically, the spinal trigeminal nucleus and dorsal column nuclei, respectively. Each of these structures has been shown to send excitatory projections to the cochlear nucleus. Mossy fibers from the spinal trigeminal and dorsal column nuclei terminate in the granule cell domain while en passant boutons from the ganglia terminate in the granule cell domain and core region of the cochlear nucleus. Sources of these somatosensory-auditory projections are associated with proprioceptive and cutaneous, but not nociceptive, sensation. Single unit and evoked potential recordings in the dorsal cochlear nucleus indicate that these pathways are physiologically active. Stimulation of the dorsal column and the cervical dorsal root ganglia elicits short- and long-latency inhibition separated by a transient excitatory peak in DCN single units. Similarly, activation of the trigeminal ganglion elicits excitation in some DCN units and inhibition in others. Bimodal integration in the DCN is demonstrated by comparing responses to somatosensory and auditory stimulation alone with responses to paired somatosensory and auditory stimulation. The modulation of firing rate and synchrony in DCN neurons by somatatosensory input is physiological correlate of somatic tinnitus.

Projections of glutamatergic somatosensory and auditory fibers to the cochlear nucleus (CN) are mostly nonoverlapping: projections from the spinal trigeminal nucleus (Sp5) terminate primarily in the granule cell domains (GCD) of CN, whereas type I auditory nerve fibers (ANFs) project to the magnocellular areas of the VCN (VCNm) and deep layers of Dorsal CN (DCN). Vesicular glutamate transporters (VGLUTs), which selectively package glutamate into synaptic vesicles, have different isoforms associated with distinct subtypes of excitatory glutamatergic neurons. Here we examined the distributions of VGLUT1 and VGLU2 expression in the CN and their colocalization with Sp5 and ANF terminals following injections of anterograde tracers into Sp5 and the cochlea in the guinea pig. The CN regions that showed the most intense expression of VGLUT1 and VGLUT2 were largely nonoverlapping and were consistent with ANF and Sp5 projections, respectively: VGLUT1 was highly expressed in VCNm and the molecular layer of the DCN, whereas VGLUT2 was expressed predominantly in the GCD. Half (47% +/- 3%) of the Sp5 mossy fiber endings colabeled with VGLUT2, but few (2.5% +/- 1%) colabeled with VGLUT1. In contrast, ANFs colabeled predominantly with VGLUT1. The pathway-specific expression of VGLUT isoforms in the CN may be associated with the intrinsic synaptic properties that are unique to each sensory pathway.

The determination of estrogens is important for the diagnosis of reproductive diseases and for monitoring the normal process of pregnancy. Previous separations of estrogens by capillary electrophoresis have employed a combination of cyclodextrins and surfactants. This paper describes the complete separation of five estrogens, 2-hydroxyestrone, 2-methoxyestradiol, estrone, estriol, and 17α-estradiol, using sulfobutyl ether β-cyclodextrin as the buffer additive. In this case, the separation can be accomplished with good efficiency without the addition of a surfactant or organic modifier to the run buffer.

The ensemble background activity (EBA) recorded from the round window has a spectral peak near 900 Hz that is generally attributed to spontaneous eighth-nerve activity, but other frequency regions are less well understood, including the issue of contribution of hair cell (HC) potentials. To further investigate the EBA, an intracochlear electrode pair was employed to record from the basal turn in guinea pig, applying the principles of differential recording. Results confirmed 900 Hz to be the dominant feature of the EBA power spectrum in/near quiet, wherein this peak was more robust in the average derivation and readily suppressed by kainic acid, consistent with its presumptive neural origin. Another broad spectral prominence, centered around 3000 Hz, was more prominent in the difference derivation, dominated the spectrum with increasing external (white) noise, and was much less sensitive to kainic acid, implying a predominantly HC origin. The findings demonstrate efficacy of intracochlear EBA recording, potentially extend EBA utility via the differential recording method, and further validate the EBA for monitoring spontaneous activity of the eighth nerve.

The type 1 vanilloid receptor (VR1) is a non-specific cation channel activated by capsaicin, lipoxygenase (LOX) products, heat and acid. This study demonstrates VR1 and 5-LOX expression by inner ear ganglion cells. A PCR product (210 bp) was amplified from both oligo(dT)- and random primer-generated cDNAs of rat spiral ganglion cells using VR1 gene-specific primers constructed from the 3' non-homologous region. This PCR product shared 100% sequence homology to a rat VR1 cDNA (GenBank accession no. AF029310) and a rat vanilloid receptor splice variant mRNA (GenBank accession no. AF158248). Frozen sections of PLP-fixed, decalcified Long-Evans rat temporal bones were stained immunohistochemically for VR1. Neurons and satellite cells in both the vestibular and spiral ganglia were VR1-immunopositive. Neurons and supporting cells in adjacent sections of these ganglia were immunopositive for 5-LOX. These findings raise the hypothesis that activation of VR1 by endogenous ligands may contribute to hypersensitivity of the eighth nerve to hair cell inputs in a variety of pathologic conditions, such as tinnitus, Meniere's disease and migraine. In particular, these data suggest that LOX activation during inflammatory processes or during cyclo-oxygenase inhibition (e.g. by aspirin) is a potential intrinsic source of VR1 activation in inner ear ganglia.