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Biomedical subjects

T H Chang

Publications and source records attributed to T H Chang.

At least 19 recordsLinked to original sources

Rise and fall time behavior of the gyrotron backward-wave oscillator.

The rise and fall time behavior of a pulsed microwave oscillator is a problem of academic interest. It is also of importance to radar and other applications because it can lead to phase and frequency jitters or even lock the entire pulse into an undesired mode. Here we present a study of the rise and fall time behavior in the gyrotron backward-wave oscillator (gyro-BWO). Single-mode simulations reveal that, during the rise and fall portions of the electron beam pulse, oscillation frequencies of the axial modes vary in such a way that their transit angles remain at the respective optimum values. Thus, axial mode competition and mode switching can readily take place in these transient stages. Time-dependent simulations demonstrate that, under both the gradual and instant turn-on conditions, the axial modes compete in a pattern governed by the characteristic asymmetry of the mode profiles. Other aspects of physics interest include the analysis and explanation of a resultant hysteresis effect between the rise and fall portions of the beam pulse. These understandings are expected to provide the basis for achieving a stable gyro-BWO operating at a single mode throughout the entire beam pulse.

Journal Article↗

Transition of absolute instability from global to local modes in a gyrotron traveling-wave amplifier.

The gyrotron traveling-wave amplifier employing the distributed-loss scheme is capable of very high gain and effective in suppressing the global absolute instabilities. This study systematically characterizes the local absolute instabilities and their transitional behavior. The local absolute instabilities are analyzed using a model that incorporates the penetration of the field from the copper section into the lossy section. The axial modes were characterized from the perspective of beam-wave interaction and were found to share many characteristics with the global modes. The transition from global modes to local modes as the distributed loss increases was demonstrated. The electron transit angle in the copper section, which determines the feedback criterion, governs the survivability of an oscillation. In addition, the oscillation thresholds predicted using this model are more accurate than those obtained using a simplified model.

Journal Article↗

Dynamics of mode competition in the gyrotron backward-wave oscillator.

The axial modes of the gyrotron backward-wave oscillator (gyro-BWO) each exhibit a distinctive asymmetry in axial field profile. As a result, and in sharp contrast to the behavior of the familiar resonator-based gyrotron oscillator, particle simulations of the gyro-BWO reveal a radically different pattern of mode competition in which a fast-growing and well-established mode is subsequently suppressed by a later-starting mode with a more favorable field profile. This is verified in a Ka-band experiment and the interaction dynamics are elucidated with a time-frequency analysis.

Journal Article↗

Absolute instabilities in a high-order-mode gyrotron traveling-wave amplifier.

The absolute instability is a subject of considerable physics interest as well as a major source of self-oscillations in the gyrotron traveling-wave amplifier (gyro-TWT). We present a theoretical study of the absolute instabilities in a TE01 mode, fundamental cyclotron harmonic gyro-TWT with distributed wall losses. In this high-order-mode circuit, absolute instabilities arise in a variety of ways, including overdrive of the operating mode, fundamental cyclotron harmonic interactions with lower-order modes, and second cyclotron harmonic interaction with a higher-order mode. The distributed losses, on the other hand, provide an effective means for their stabilization. The combined configuration thus allows a rich display of absolute instability behavior together with the demonstration of its control. We begin with a study of the field profiles of absolute instabilities, which exhibit a range of characteristics depending in large measure upon the sign and magnitude of the synchronous value of the propagation constant. These profiles in turn explain the sensitivity of oscillation thresholds to the beam and circuit parameters. A general recipe for oscillation stabilization has resulted from these studies and its significance to the current TE01 -mode, 94-GHz gyro-TWT experiment at UC Davis is discussed.

Journal Article↗

J/psi polarization in 800-GeV p-Cu interactions.

We present measurements of the polarization of the J/psi produced in 800-GeV proton interactions with a copper target. Polarization of the J/psi is sensitive to the ccmacr; production and hadronization processes. A longitudinal polarization is observed at large x(F), while at small x(F) the state is produced essentially unpolarized or slightly transversely polarized. No significant variation of the polarization is observed versus p(T).

Journal Article↗

Linear and time-dependent behavior of the gyrotron backward-wave oscillator.

Formation of axial modes in the gyrotron backward-wave oscillator is examined in the perspective of optimum conditions for beam-wave interactions. Distinctive linear properties are revealed and interpreted physically. Nonlinear implications of these properties (specifically, the role of high-order axial modes) are investigated with time-dependent simulations. Nonstationary oscillations exhibit self-modulation behavior while displaying no evidence of axial mode competition. Reasons for the erratic frequency tuning are investigated and stable tuning regimes are identified as a remedy.

Journal Article↗

Visualization of new virus-like-particles in Trichomonas vaginalis.

In the present work, we demonstrate virus-like particles (VLPs) with various morphological variations in Trichomonas vaginalis. The VLPs were distinct based on size, shape and electron density, with VLPs being either electron-dense or electron-lucent. We used electron microscopy thin sections of several T. vaginalis strains virus-infected, and also negative staining of fractions obtained after purification by CsCl buoyant density gradient centrifugation. The particles observed in fractions are identical to those previously described, but by thin sections, we found new forms. The shapes found were icosahedral, spherical and oblong, and the sizes varied from 33 to 120nm in diameter with the most common VLP being spherical and having a size range from 83 to 104nm. The VLPs were found in the cytoplasm closely associated with the Golgi complex, with some VLPs budding from the Golgi, and other VLPs were detected adjacent to the plasma membrane. Unidentified cytoplasmic inclusions were observed in the region close to the VLPs and Golgi. Clusters of the already described icosahedral virus were also observed in the cytoplasm, although less frequently. These results indicate that T. vaginalis organisms may be infected with different dsRNA viruses simultaneously.

Animals↗

Characterization of stationary and nonstationary behavior in gyrotron oscillators.

The transition from the stationary state to a sequence of nonstationary states in the gyromonotron oscillator is experimentally characterized for the first time. We have also demonstrated the stationary operation of a gyrotron backward-wave oscillator at a beam current far in excess of the generally predicted nonstationary threshold. This difference in nonlinear behavior has been investigated and shown to be fundamental with a comparative analysis of the feedback mechanisms, energy deposition profiles, and field shaping processes involved in these two types of oscillations.

Journal Article↗

Observation of polarization in bottomonium production at square root of s = 38.8 GeV.

We present a measurement of the polarization observed for bottomonium states produced in p-Cu collisions at square root of s = 38.8 GeV. The angular distribution of the decay dimuons of the Upsilon(1S) state shows no polarization at small values of the fractional longitudinal momentum x(F) and transverse momentum p(T) but significant positive transverse production polarization for either p(T)>1.8 GeV/c or for x(F)>0.35. The Upsilon(2S+3S) (unresolved) states show a large transverse production polarization at all values of x(F) and p(T) measured. These observations challenge NRQCD calculations of the polarization expected in the hadronic production of bottomonium states.

Journal Article↗

Specific alterations of U1-C protein or U1 small nuclear RNA can eliminate the requirement of Prp28p, an essential DEAD box splicing factor.

While some members of the ubiquitous DExD/H box family of proteins have RNA helicase activity in vitro, their roles in vivo remain virtually unknown. Here, we show that the function of an otherwise essential DEAD box protein, Prp28p, can be bypassed by mutations that alter either the protein U1-C or the U1 small nuclear RNA. Further analysis suggests that the conserved L13 residue in the U1-C protein makes specific contact to stabilize the U1 snRNA/5' splice site duplex in the prespliceosome, and that Prp28p functions to counteract the stabilizing effect of the U1-C protein, thereby promoting the dissociation of the U1 small nuclear ribonucleoprotein particle from the 5' splice site. Thus, in addition to unwinding RNA, the DExD/H box proteins may affect RNA-RNA rearrangements by antagonizing specific RNA-stabilizing proteins.

DEAD-box RNA Helicases↗

Primary tumour volume delineation in nasopharyngeal carcinoma and correlation with 1997 AJCC tumour stage classification.

OBJECTIVE: To investigate the variability in primary tumour volume in nasopharyngeal carcinoma and compare it with the tumour staging of the 1997 American Joint Committee on Cancer. DESIGN: Prospective study. SETTING: Tertiary care centre. METHOD: A series of 33 newly diagnosed patients who were treated with high-dose radiotherapy participated in the study. MAIN OUTCOME MEASURES: Using computed tomographic scans, primary tumour volumes were measured using the summation-of-areas technique, and the variability in tumour volume was determined. The Mann-Whitney test was used for statistical analysis. RESULTS: A large variation in primary tumour volume was observed, especially in advanced-stage cases. CONCLUSIONS: Nasopharyngeal carcinoma shows considerable variability in primary tumour volume. Incorporation of primary tumour volume may lead to further refinement of the 1997 tumour staging system.

Adult↗

Does a reduction in family medicine clerkship time affect educational outcomes?

BACKGROUND AND OBJECTIVES: Little is known about the relationship between the length of a family medicine clerkship and its educational outcomes. After our family medicine clerkship time decreased from 6 weeks to 4 weeks in July 1997, we studied how this change in clerkship length affected educational outcomes. METHODS: Educational outcomes for the 2-year periods before and after the change were examined and compared whenever possible. Outcome measurements included student ratings of different aspects of the clerkship and student performance on clerkship examinations. RESULTS: Students' exposure to common clinical problems was unaffected by the change. For the 4-week clerkship, there was a slight increase in student ratings of the adequacy of number of patients seen, the opportunity to follow-up with patients, the ability to develop health promotion plans, and overall satisfaction. Because the combinations of examinations used differed each year, student performance on clerkship examinations could not be directly compared. CONCLUSIONS: Educational outcomes of the 4-week clerkship were similar to the 6-week clerkship. A few key outcomes improved. Various curricular and structural changes instituted for the 4-week clerkship contributed to the stability in outcomes. Reports from other medical schools may give additional insight into understanding this relationship.

Adult↗

Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor gamma in non-small cell lung cancer.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor belonging to the steroid receptor superfamily. It is a key regulator of adipogenic differentiation, the ligands of which have also been demonstrated to induce differentiation in human breast and colon cancer cell lines. This study examined PPARgamma, in non-small cell lung cancer (NSCLC). PPARgamma mRNA and protein were expressed in NSCLC cell lines, with highest levels in adenocarcinomas. PPARgamma protein was also expressed in 50% of primary lung cancers by immunohistochemistry. Treatment of multiple cell lines with two distinct PPARgamma ligands in the presence of serum resulted in growth arrest, irreversible loss of capacity for anchorage-independent growth, decreased activity and expression of matrix metalloproteinase 2, and modulation of multiple markers in a manner consistent with differentiation. Specifically, there was up-regulation of general markers of the differentiated state such as gelsolin, Mad, and p21. Down-regulation of specific markers of progenitor lineages for the peripheral lung, i.e., the type II pneumocyte lineage markers MUC1 and surfactant protein-A and the Clara cell lineage marker CC10, also occurred. In addition, HTI56, a marker of terminally differentiated type I pneumocytes, was also induced. Consistent with a more mature, less malignant phenotype, ligand treatment also inhibited the expression of cyclin D1 and led to hypophosphorylation of the retinoblastoma protein. In contrast, in the absence of serum, ligand treatment rapidly resulted in apoptosis and substantially earlier onset of differentiation. Taken together, these results show that depending on the growth milieu, ligands of PPARgamma induce differentiation and apoptosis in NSCLC, suggesting clinical utility for these agents.

Antineoplastic Agents↗

Wound healing: captopril, an angiogenesis inhibitor, and Staphylococcus aureus peptidoglycan.

BACKGROUND: Captopril, an angiotensin-converting enzyme inhibitor, used for treating hypertension and heart failure, inhibits angiogenesis in the corneas of rats in response to basic fibroblast growth factor, slows the growth of experimental tumors in rats, and leads to the regression of Kaposi's sarcoma. Because angiogenesis is key to wound healing, we hypothesized that captopril would impair wound healing. We hypothesized also that because local application at operation of Staphylococcus aureus peptidoglycan (SaPG) increases angiogenesis and accelerates wound healing in rats, SaPG would prevent or ameliorate the postulated captopril-impaired wound healing. MATERIALS AND METHODS: In each experiment, rats were divided randomly into two groups: one drinking tap water, and the other, tap water containing 0.5 mg captopril/ml. All ate chow and drank ad libitum, pre-operatively (4-12 days) and postoperatively (7 days). In experiments 1 and 2, bilateral paravertebral 5.5-cm skin incisions were made aseptically (intraperitoneal sodium pentobarbital), and closed with interrupted No. 35 stainless-steel sutures. On one side, the wound was immediately inoculated with 157 microliter pyrogen-free isotonic saline and on the other side the wound was inoculated with 157 microliter saline containing 4.7 mg SaPG (860 microgram SaPG/cm incision). In the third experiment, polyvinyl alcohol (PVA) sponges (16-17 mg dry wt each) containing either 50 microliter saline or 0.5 mg SaPG in 50 microliter saline were implanted subcutaneously, two on each side, via 1-cm incisions closed with a single suture. In the fourth experiment, 5.5-cm bilateral skin incisions and subcutaneous implantation of PVA sponges were done as described but all sites were instilled with saline only. All rats were euthanized (CO(2) asphyxia) 7 days postoperatively. RESULTS: Wound breaking strength (WBS) of the saline-treated incisions was significantly higher (P < 0.001) in captopril-treated rats than in controls (172 +/- 13 g vs 105 +/- 6 g) in experiment 1 and higher, but not significantly in captopril-treated rats in experiment 2 (153 +/- 8 g vs 114 +/- 6 g) (PNS). SaPG inoculation of the incisions increased WBS significantly in both control and captopril-treated rats: 187 +/- 11 g vs 105 +/- 6 g (P < 0.001) and 283 +/- 16 g vs 172 +/- 13 g (P < 0.001), respectively, in experiment 1, and 217 +/- 13 g vs 114 +/- 6 g (P < 0.0001) (controls) and 266 +/- 17 g vs 153 +/- 8 g (captopril-treated rats) (P < 0.0001) in experiment 2. In experiment 3, subcutaneous PVA saline-inoculated sponge reparative tissue hydroxyproline (OHP) content was similar in control and captopril-treated rats, and SaPG inoculation increased reparative tissue OHP significantly in both groups: 2458 +/- 218 microgram/100 mg dry sponge vs 3869 +/- 230 microgram/100 mg (P < 0.001) (controls) and 2489 +/- 166 microgram/100 mg vs 4176 +/- 418 microgram/100 mg (P < 0.001) (captopril-treated rats). Histologically, angiogenesis and reparative tissue collagen were similar in control and captopril-treated rats, in both saline-inoculated and SaPG-inoculated sponges. In experiment 4 (all incisions and subcutaneous PVA sponges were saline-inoculated), there was no significant difference in WBS between control and captopril-treated rats (107 +/- 6 g vs 96 +/- 5 g, NS). PVA sponge reparative tissue OHP was significantly higher in captopril-treated rats: 3698 +/- 170 microgram/100 mg dry sponge vs 2534 +/- 100 microgram/100 mg (P < 0.0001). CONCLUSION: Unexpectedly, in four experiments, captopril did not inhibit WBS or PVA sponge reparative tissue angiogenesis or collagen accumulation; in fact, WBS was increased significantly in one of three experiments, and PVA sponge reparative tissue OHP was increased significantly in one of two experiments. Also, captopril did not interfere with the wound healing-accelerating effect of SaPG.

Angiotensin-Converting Enzyme Inhibitors↗

Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo.

The myogenic factor Myf5 plays a key role in muscle cell determination, in response to signalling cascades that lead to the specification of muscle progenitor cells. We have adopted a YAC transgenic approach to identify regulatory sequences that direct the complex spatiotemporal expression of this gene during myogenesis in the mouse embryo. Important regulatory regions with distinct properties are distributed over 96 kb upstream of the Myf5 gene. The proximal 23 kb region directs early expression in the branchial arches, epaxial dermomyotome and in a central part of the myotome, the epaxial intercalated domain. Robust expression at most sites in the embryo where skeletal muscle forms depends on an enhancer-like sequence located between -58 and -48 kb from the Myf5 gene. This element is active in the epaxial and hypaxial myotome, in limb muscles, in the hypoglossal chord and also at the sites of Myf5 transcription in prosomeres p1 and p4 of the brain. However later expression of Myf5 depends on a more distal region between -96 and -63 kb, which does not behave as an enhancer. This element is necessary for expression in head muscles but strikingly only plays a role in a subset of trunk muscles, notably the hypaxially derived ventral body muscles and also those of the diaphragm and tongue. Transgene expression in limb muscle masses is not affected by removal of the -96/-63 region. Epaxially derived muscles and some hypaxial muscles, such as the intercostals and those of the limb girdles, are also unaffected. This region therefore reveals unexpected heterogeneity between muscle masses, which may be related to different facets of myogenesis at these sites. Such regulatory heterogeneity may underlie the observed restriction of myopathies to particular muscle subgroups.

Animals↗

Gastroesophageal variceal bleeding caused by hepatoportal arteriovenous fistula.

Hepatoportal arteriovenous fistulas are usually traumatic in origin and may result in portal hypertension and serious complications. We report a 34-year-old female with a history of abdominal trauma, who developed symptoms of tarry stools and hematemesis 5 years later. Esophageal and gastric varices with bleeding were diagnosed by upper gastrointestinal endoscopy. Abdominal ultrasonography and computerized tomography favored noncirrhotic portal hypertension. An extrahepatic hepatoportal arteriovenous fistula was demonstrated by angiography. The patient underwent surgery to correct the condition. The liver had a smooth surface and both the common hepatic and gastroduodenal arteries were ligated during surgery. The postoperative course was uneventful. The varices later disappeared.

Adult↗

Prediction of the rates of fertilization, cleavage, and pregnancy success by cumulus-coronal morphology in an in vitro fertilization program.

OBJECTIVE: To examine the relation between the grading of cumulus-coronal morphology at oocyte retrieval and the rates of fertilization, cleavage, and pregnancy success in IVF-ET cycles. DESIGN: Retrospective study. SETTING: University-affiliated medical center. PATIENT(S): Infertile women who underwent IVF-ET treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization and cleavage of the oocytes and the pregnancy outcome. RESULT(S): Mature grade 3 cumulus-oocyte complexes (COCs) constituted the highest percentage among all grades and had a higher fertilization rate than COCs of other grades (77% versus 65%, 43%, and 28% for grades 2, 1, and 4, respectively). The cleavage and polyspermy rates did not correlate with cumulus-coronal morphology grading. The pregnancy rate was higher in cycles with >50% grade 3 COCs than in cycles with < or =50% grade 3 COCs (32% versus 16%). In cycles with >80% grade 3 COCs, the pregnancy rate was 57%. The correlation between the percentage of grade 3 COCs and the pregnancy rate was independent of patient age and the number of COCs retrieved. CONCLUSION(S): The cumulus-coronal morphology grade correlates with the fertilization rate but not with the cleavage or polyspermy rate. In vitro fertilization cycles that have a greater percentage of grade 3 COCs have an increased chance of resulting in pregnancy. The cumulus-coronal morphology grade predicts pregnancy success in IVF-ET cycles.

Adult↗

Induction of differentiation accompanies inhibition of Cdk2 in a non-small cell lung cancer cell line.

Induction of differentiation in a variety of model systems is accompanied by cell cycle exit and inhibition of Cdk2 kinase activity. We asked whether inhibition of Cdk2 activity is sufficient to allow differentiation to occur in a non-small cell lung cancer cell line. Treatment of NCI-H358 with flavopiridol, an inhibitor of multiple Cdk's, resulted in growth arrest and induction of mucinous differentiation. The onset of differentiation coincided temporally with loss of Cdk2 kinase activity. Western analysis revealed that flavopiridol treatment resulted in depletion of both cyclin E and D1, suggesting that loss of the regulatory subunits is at least partially responsible for the loss of Cdk kinase activity. Similarly, roscovitine, an inhibitor of Cdk's 1, 2, and 5, but not Cdk4, also induced differentiation in NCI-H358, although the resulting pattern of expression of cell cycle regulatory genes differed from the pattern obtained with flavopiridol. Furthermore, stable expression of an antisense Cdk2 construct in NCI-H358 also resulted in the appearance of a marker of mucinous differentiation. These results show that the inhibition of activity of cyclin dependent kinases, particularly Cdk2, by multiple different mechanisms is accompanied by differentiation. Thus, induction of differentiation is one potential mechanism of action for agents that down-regulate Cdk activity.

CDC2-CDC28 Kinases↗