Integrated high-quality factor optical resonators in diamond.

The realization of an integrated diamond photonic platform, based on a thin single crystal diamond film on top of a silicon dioxide/silicon substrate, is reported. Using this approach, we demonstrate high-quality factor single crystal diamond race-track resonators, operating at near-infrared wavelengths (1550 nm). The devices are integrated with low-loss diamond waveguides terminated with polymer pads (spot size converters) to facilitate in- (out-) coupling of light from (to) an optical fiber. Optical characterization of these resonators reveal quality factors as high as ~250,000 and overall insertion losses as low as 1 dB/facet. Scattering induced mode splitting as well as signatures of nonlinear effects such as optical bistability are observed at an input pump power of ~100 mW in the waveguides.

Radio imaging of the very-high-energy gamma-ray emission region in the central engine of a radio galaxy.

The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.

Spontaneous clearance of hepatitis C after liver and renal transplantation.

Spontaneous clearance of hepatitis C virus (HCV) is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

Controlled generation of squeezed states of microwave radiation in a superconducting resonant circuit.

Superconducting oscillators have been successfully used for quantum control and readout devices in conjunction with superconducting qubits. Also, squeezed states can improve the accuracy of measurements to subquantum, or at least subthermal, levels. Here, we show theoretically how to produce squeezed states of microwave radiation in a superconducting oscillator with tunable parameters. Its resonance frequency can be changed by controlling an rf SQUID inductively coupled to the oscillator. By repeatedly shifting the resonance frequency between any two values, it is possible to produce squeezed and subthermal states of the electromagnetic field in the (0.1-10) GHz range, even when the relative frequency change is small. We propose experimental protocols for the verification of squeezed state generation, and for their use to improve the readout fidelity when such oscillators serve as quantum transducers.

Speech perception in children with cochlear implants: effects of lexical difficulty, talker variability, and word length.

The present results demonstrated that all 3 factors --lexical difficulty, stimulus variability, and word length--significantly influenced spoken word recognition by children with multichannel cochlear implants. Lexically easy words were recognized significantly better than lexically hard words, regardless of talker condition or word length of the stimuli. These results support the earlier findings of Kirk et al(12) obtained with live-voice stimulus presentation and suggest that lexical effects are very robust. Despite the fact that listeners with cochlear implants receive a degraded speech signal, it appears that they organize and access words from memory relationally in the context of other words. The present results concerning talker variability contradict those previously reported in the literature for listeners with normal hearing(7,11) and for listeners with mild-to-moderate hearing loss who use hearing aids.(14) The previous investigators used talkers and word lists different from those used in the current study and found that word recognition declined as talker variability increased. In the current study, word recognition was better in the multiple-talker condition than in the single-talker condition. Kirk(15) reported similar results for postlingually deafened adults with cochlear implants who were tested on the recorded word lists used in the present study. Although the talkers were equally intelligible to listeners with normal hearing in the pilot study, they were not equally intelligible to children or adults with cochlear implants. It appears that either the man in the single-talker condition was particularly difficult to understand or that some of the talkers in the multiple-talker condition were particularly easy to understand. Despite the unexpected direction of the talker effects, the present results demonstrate that children with cochlear implants are sensitive to differences among talkers and that talker characteristics influence their spoken word recognition. We are conducting a study to assess the intelligibility of each of the 6 talkers to listeners with cochlear implants. Such studies should aid the development of equivalent testing conditions for listeners with cochlear implants. There are 2 possible reasons the children in the present study identified multisyllabic words better than monosyllabic words. First, they may use the linguistic redundancy cues in multisyllabic words to aid in spoken word recognition. Second, multisyllabic words come from relatively sparse lexical neighborhoods compared with monosyllabic tokens. That is, multisyllabic words have fewer phonetically similar words, or neighbors, competing for selection than do monosyllabic stimuli. These lexical characteristics most likely contribute to the differences in identification noted as a function of word length. The significant lexical and word length effects noted here may yield important diagnostic information about spoken word recognition by children with sensory aids. For example, children who can make relatively fine phonetic distinctions should demonstrate only small differences in the recognition of lexically easy versus hard words or of monosyllabic versus multisyllabic stimuli. In contrast, children who process speech using broad phonetic categories should show much larger differences. That is, they may not be able to accurately encode words in general or lexically hard words specifically. Further study is warranted to determine the interaction between spoken word recognition and individual word encoding strategies.

Intra- and extracellular water dynamics on rehydration in cholera and noncholera patients.

To estimate the intra- and extracellular body water compartments during rehydration of patients with cholera and noncholera diarrhea by bioimpedance analyzer, we studied 30 patients with acute watery diarrhea. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW) of severely dehydrated adult patients were measured with a dual frequency bioimpedance analyzer at different phases of rehydration. Fluid compartments between cholera and noncholera patients were compared. Cholera patients gained more TBW than noncholera patients during recovery. Unlike patients with noncholera diarrhea, the gain in cholera patients was mainly contributed by the ICW (1.5 +/- 1.6 vs 3.0 +/- 1.2 liters, respectively, P < 0.01). It was also observed that the recovery of the ICW compartment in cholera patients occurred rapidly within the first 2 hr after infusion. Differential dynamics of body water compartments in cholera compared to noncholera patients as observed in this study may contribute further to understanding the mechanism of dehydration in diarrheal disease, which might help in improving case management.

A three-dimensional analysis of mandibular arch changes following curve of Spee leveling in nonextraction orthodontic treatment.

The present study was conducted to determine the effects of curve of Spee leveling on three-dimensional arch length and specific components of arch form. The mandibular pretreatment and posttreatment dental casts of 33 patients treated orthodontically without the extraction of teeth were digitized with a three-dimensional positioning transducer integrated with a graphics calculator. Statistical analysis was carried out with general linear models and the calculation of Pearson correlation coefficients of the relationships between the dependent variable of the curve of Spee leveling and the independent variables of arch length, arch depth, and three arch widths. The regression and correlation analyses essentially showed no relationship between the independent variables (arch length, arch depth, and the three arch widths) and the dependent variable (curve of Spee leveling). Although the three-dimensional arch length was increased after leveling of the curve of Spee in 24 of the 33 dental casts evaluated, the results from the statistical analyses indicated that this increased arch length was not necessarily the result of the curve of Spee leveling but may have been caused by other variables.

A sensitive ELISPOT assay to detect low-frequency human T lymphocytes.

We extended the sensitivity of the ELISPOT assay by including an antigen-driven proliferation step prior to a final restimulation with antigen and irradiated antigen presenting cells (APCs). This improved sensitivity made the modified ELISPOT assay better suited to the detection of rare or low frequency T lymphocytes than the standard ELISPOT assay or alternatives such as limiting dilution analysis or in situ hybridization. Use of ELISA-grade plastic or polyvinylidene difluoride (PVDF) plates for the detection of different cytokines improved the signal-to-noise ratio for counting cytokine spots, and use of video computer imaging software improved objective quantitation. Analysis of antigen-reactive peripheral blood mononuclear cells (PBMC) from multiple sclerosis (MS) patients using both the traditional and our modified ELISPOT assay demonstrate a > 10-fold increase in numbers of myelin basic protein (MBP)-responsive T cells detected (an average of less than 1 spot forming cell (SFC) per 2 x 10(5) PBMC with the standard assay compared to 19 SFC per 2 x 10(5) PBMC with the modified assay). In addition, the modified ELISPOT assay could be performed with frozen PBMC, which permitted greater flexibility in sample processing, multiple use of a single sample as an internal standard, and simultaneous analysis of samples collected at different time points. This modified ELISPOT assay has many applications, including analysis of cytokine profiles in rare T cell populations, identification of antigen-responsive individuals as PBMC donors for T lymphocyte cloning or for therapeutic intervention, and assessment of vaccine or therapeutic efficacy as a surrogate clinical marker.

Investigation of video techniques for dynamic measurements of relative vertebral-body motion in vitro.

The precision and accuracy of techniques for analysis of lumbar spinal-segment motions were evaluated using a specially designed orthogonal axis fixture and video image processing. Triplicate validation tests were performed by monitoring precisely controlled motions of the triaxial measurement device. The errors of the overall measurements were found to be less than 0.5 mm for axial and 1 degree for rotational displacements. The system accuracy was within 0.230 mm based on the calculation of the points on a calibration frame. The geometry of the calibration frame was designed with the capability to analyze the 3-D motion properties of a swine lumbar spine. Statistical analyses of the validation test data showed that the precision and accuracy of this motion-analysis system offer new opportunities for the measurement of total-length spinal-motion profiles. The system was then applied utilizing fresh thawed swine spines to test the limits of relative-motion measurements for the centers of adjacent vertebrae in a coupled unit. Lateral-medial and anterior-posterior video images of spines and the triaxial measurement devices were made simultaneously while applying cyclic axial and torsional loads. The distribution of data from six spines illustrated biological variability of relative displacements for adjacent coupled vertebrae.

Induction of tolerance in experimental autoimmune myasthenia gravis with solubilized MHC class II:acetylcholine receptor peptide complexes.

Stimulation of T lymphocytes through the T cell receptor in the absence of costimulatory signal(s) induces a state of unresponsiveness to subsequent antigen presentation. We have employed solubilized complexes consisting of rat class II MHC molecules containing an immunodominant peptide of the acetylcholine receptor (AChR alpha 100-116) to induce unresponsiveness in the autoreactive T lymphocytes mediating an animal model of myasthenia gravis. In vitro incubation of rat T cell lines specific for peptide AChR alpha 100-116 with solubilized complexes of MHC II and AChR alpha 100-116 (MHC II:AChR alpha 100-116) rendered the T cells unresponsive to subsequent stimulation by antigen presenting cells and the peptide. T cell lines with a broader specificity to the entire AChR protein pentamer had an 81% reduction in proliferation to AChR following a preincubation with solubilized MHC II:AChR alpha 100-116. Treatment with the solubilized MHC II:AChR alpha 100-116 induced phosphatidylinositol 4,5-bisphosphate hydrolysis, an early signalling event associated with binding to the TCR. Rats primed with AChR and injected intravenously with MHC II:AChR alpha 100-116 had reduced in vitro T cell proliferation to the AChR alpha 100-116 peptide and to whole AChR. Solubilized MHC II:AChR alpha 100-116 injected i.v. into rats exhibiting serological clinical symptoms of experimental autoimmune myasthenia gravis (EAMG) prevented death in 67% of the treated animals, compared to a 0-20% survival rate in all other control groups. These results demonstrate that solubilized MHC II complexed with an immunodominant autoantigenic peptide is tolerogenic and improves the survival rate of rats with EAMG, suggesting the basis for an antigen-specific therapy in autoimmune diseases such as MG.

Spontaneous swallowing rate and emotional state. Possible mechanism for stress-related gastrointestinal disorders.

Excessive spontaneous swallowing has been associated with a variety of common gastrointestinal symptoms including abdominal pain, heartburn, and bloating and may contribute to disorders such as hiatus hernia, duodenal ulcer, and irritable bowel syndrome. The present study investigated the hypothesis that changes in emotional state alter spontaneous swallowing rate. Subjects were 38 generally healthy undergraduates assigned to either a pleasant low arousal, neutral, or aversive high arousal condition. Each experimental session was divided into 30-min baseline and arousal manipulation periods. Spontaneous swallowing rate increased significantly with emotional arousal: for low, neutral, and high arousal groups, means were 7.9 +/- 1.9 (SE), 15.8 +/- 2.4, and 23.7 +/- 3.6 swallows/30 min, respectively. Other physiological and self-report measures, used to check the effectiveness of the arousal manipulation, varied appropriately with experimental procedures. These results indicate that changes in emotional state alter spontaneous swallowing rate in generally healthy individuals. Further research with patients is needed to establish whether stress-induced increases in swallowing rate produce or exacerbate clinically significant gastrointestinal symptomatology.

Comparing abilities of children with profound hearing impairments to learn consonants using electropalatography or traditional aural-oral techniques.

Two groups of nine children with profound hearing impairments and low intelligibility were taught to produce the consonants /t,d,k,g,s,z,S/ using either electropalatographic (palatometry) or traditional aural-oral techniques. Testing was completed pre-, immediately post-, and 6 months post-treatment by examining productions of CV syllables (V = /i,a/) using electropalatography-determined linguapalatal contacts and listener identifications. Intelligibility was also measured using the CID Picture Speech Intelligibility Evaluation (SPINE) test. Both groups improved their consonant productions as a result of 26 50-minute sessions. Sessions were given twice daily over 3- to 4-week training periods. Immediately post-treatment, the electropalatography-trained subjects produced better consonants as measured by linguapalatal contact patterns and listener identifications. The linguapalatal-contact patterns learned by the electropalatography-trained group better matched normal speaker productions than did those of the traditionally trained group. Both groups showed equal improvement for both post-treatment conditions when tested with the CID SPINE test. Although further research is needed, the results of this study suggest that electropalatographic techniques are, at least, equal alternatives to traditional aural-oral speech training techniques for speakers with profound hearing impairments.

Application of the ILISPOT-IDIP system for the enumeration of different sizes of IgA spot forming cells in the murine small and large intestine.

The immunofluorescence-linked immunospot (ILISPOT) assay associated with the immunofluorescence digital image processing (IDIP) system was originally developed in our laboratory to allow enumeration of immunoglobulin (Ig) producing, spot forming cells (SFC) in a more objective and quantitative manner. In this study, the ILISPOT-IDIP system was further advanced in order to analyze different sizes of SFC (e.g., IgA producing cells) including large (L), medium (M), and small (S) cells which correspond to high (> 2.4 pg), medium (1.2-2.4 pg) and low (< 1.2 pg) IgA secreting cells by the adaptation of real time image processor and intensified video camera system. When the ILISPOT-IDIP system was used to characterize the frequency of IgA secreting cells among mononuclear cells isolated from different parts of the murine gastrointestinal (GI) tract including the small (upper, middle and lower sections) and large (colon and rectum) intestine, the small intestine contained higher numbers of IgA SFC (approximately 8.4 x 10(5) SFC/10(6) cells) when compared with large intestine (approximately 1.3 x 10(5) SFC/10(6) cells). Among the 3 areas of small intestine, the upper (approximately 3.7 x 10(5) SFC/10(6) cells) and middle (approximately 2.4 x 10(5) SFC/10(6) cells) parts had higher numbers of IgA SFC when compared to the lower small (approximately 2.3 x 10(5) SFC/10(6) cells) intestine. When these IgA producing cells in different parts of the intestine were classified into three groups according to the size of individual spots, the upper and middle intestine contained higher frequencies of large (approximately 20%) and medium (approximately 20%) SFC which corresponded to high and medium IgA secretors in comparison to the lower small (approximately 9%) and large (approximately 6%) intestine. In contrast, the lower small and large intestine were dominated by small SFC since approximately 85% of IgA producing cells were categorized as low secretors. Using the advanced ILISPOT-IDIP system, a unique distribution of different sizes (or secretion rates) of IgA producing SFC was elucidated in the different regions of the mouse small and large intestine.

Esophageal speaker articulation of /s,z/: a dynamic palatometric assessment.

Esophageal talker linguapalatal contact patterns and durations during /s/ and /z/ productions were examined using dynamic palatometry instrumentation. It was found that sibilant groove narrowing is a physiologic compensation for a reduced air supply in esophageal speech. The place of esophageal /s, z/ articulation was on the anterior portion of the alveolar ridge as seen in normal speakers. Average medial groove width for esophageal /s/ was narrower than the 5-7-mm groove characteristic of normal speakers. Groove widths averaged 3 mm for /s/ and 4 mm for /z/. Systematic changes in groove widths across speech sounds, syllable position, and vowel context were also observed. Use of a narrower lingual groove was interpreted as a significant articulatory maneuver to meter out a limited intraoral air supply and effect more normal fricative durations.

Temporomandibular joint sounds and condyle/disk relations on magnetic resonance images.

This study compared the condyle/disk relationships on magnetic resonance images (MRIs) in a group of subjects with completely silent temporomandibular joints (TMJ) when tested clinically with those in subjects with readily discernible TMJ sounds. The sounds were recorded with an accelerometer as the transducer. Selected degrees of jaw separation were electronically determined and recorded with interocclusal wafers for use with the imaging process. Of the "silent joints" 89% were found to have sounds when tested with the accelerometer. These "subclinical" sounds tended to be of shorter duration and occurred at a greater degree of vertical opening than the clinically discernable sounds. The MRIs of the group with clinically discernable sounds tended to show a change in the relationship between the head of the condyle and the intermediate zone of the disk, at the degree of jaw separation of the sound occurrence, whereas no condyle/disk change occurred in the group with "clinically silent joints." It is likely that all joints create sound during function. The different characteristics of the subclinical sounds versus the clinical sounds may indicate differing sound origins.

Immunofluorescence-digital image processing system for the quantitation of secreted immunoglobulin by single cells.

To quantitate the amount of secreted immunoglobulin (Ig) by a single cell, the immunofluorescence digital image processing (IDIP) system was adapted to the modified enzyme-linked immunospot (ELI-SPOT) assay. In this assay, an immunofluorescence (tetramethylrhodamine isothiocyanate) conjugated antibody was used for the detection of spots instead of the usual method of enzyme coupling. We have named this the immunofluorescence-linked immunospot (ILISPOT) assay. In addition to the quantitation of secreted Ig by single cells, this method allowed us to objectively determine the exact number of Ig producing spot forming cells (SFC). 96 well culture plates were pre-coated with goat anti-mouse Ig. The mouse IgM producing hybridoma (E-3-4) was incubated in the plates for 4 h at 37 degrees C. Cells were removed prior to the addition of biotinylated goat anti-mouse mu antibody. After overnight incubation, immunofluorescence conjugated avidin was added for the visualization of spots by the IDIP system. The IDIP system consists of a fluorescent microscope equipped with a video camera and computer. The gray scale of secreted IgM was initially established as a standard by the known amount of purified IgM. By using digital image processing, the number of spots and the gray scale of individual spots were computed. The shape and pattern of gray scale data were used to distinguish between the real spots and pseudo spots. This IDIP system could detect as little as 0.19 pg of secreted IgM (1.2 x 10(5) molecules) and an average of approximately 1.33 pg (8.3 x 10(5) molecules) produced by a single cell. Adaptation of the digital image processing system to the ILISPOT assay allowed the measurement of both the amount of Ig produced at the single cell level and also the exact numbers of SFC present in a totally objective fashion.