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Biomedical subjects

C T Miller

Publications and source records attributed to C T Miller.

At least 19 recordsLinked to original sources
PubMed2006

Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma.

Esophageal adenocarcinoma (EA) is characterized by a poor prognosis making the identification of clinically targetable proteins essential for improving patient outcome. We report the involvement of multiple alterations of the MET pathway in EA development and progression. Microarray analysis of Barrett's metaplasia, dysplasia, and EA revealed overexpression of the MET oncogene in EAs but only those with MET gene amplification. STS-amplification mapping revealed that the boundary of the MET amplicon in these EAs is defined by fragile site FRA7G. We also identified an amplicon at 11p13 that resulted in amplification and overexpression of CD44, a gene involved in MET autophosphorylation upon HGF stimulation. Tissue microarrays with phospho-MET-specific antibodies demonstrated a uniformly high abundance of MET activation in primary EA and cells metastatic to lymph nodes but to a lesser extent in a subset of metaplastic and dysplastic Barrett's samples. Increased expression of multiple genes in the MET pathway associated with invasive growth, for example, many MMPs and osteopontin, also was found in EAs. Treatment of EA-derived cell lines with geldanamycin, an inhibitor for tyrosine kinases including MET receptor kinase, reduced cell migration and induced EA cell apoptosis. The data indicate that upregulation of the MET pathway may contribute to the poor outcome of EA patients and that therapeutic agents targeting this pathway may help improve patient survival.

Adenocarcinoma↗
PubMed2004

Examination of Darcys law for flow in porous media with variable porosity.

Henry Darcy's experimental studies in 1856 of saturated water flowthrough a homogeneous porous medium contained in a vertical column have provided the basis for the quantitative description of fluid flow in a wide variety of both natural and engineered porous medium environmental systems. Extrapolation of Darcy's original observations and conclusions has led to several commonly applied equations used to model flow in porous media. This work examines this original experimental study, summarizes the appropriate mathematical expressions that ensue directly from the data, and indicates expressions in common use that are suggested, but not actually supported, by the data. The paradoxes that exist in the common approaches for the case of a porous medium with a spatiallyvariable porosity are illustrated. A modified form of Darcy's law, and also of the Hubbert potential, is derived based upon fundamental notions of averaging. The modified form of Darcy's law derived here reduces to the conventional form for a homogeneous porous medium.

Gravitation↗
PubMed2004

Efficient, near-complete removal of DNAPL from three-dimensional, heterogeneous porous media using a novel combination of treatment technologies.

Remediation of porous media containing an entrapped dense nonaqueous phase liquid (DNAPL) is extremely difficult due to the heterogeneity and three-dimensional spatial nature of typical natural systems. A novel treatment technology based on surfactant- and gravity-induced mobilization, dense brine containment and collection, and a vapor-phase extraction polishing step is proposed as a means to remediate such systems. Laboratory experiments are performed using the suggested methodology applied to three-dimensional, heterogeneous systems, which are packed based upon a realization from a correlated random field. Entrapped DNAPL is effectively removed as a result of each component of the technology. Following vapor extraction, less than 1% of the original DNAPL mass remained in the system. While these results are very promising, several open issues must be resolved before this technology can be considered mature; both the investigation of some of these issues and a summary of remaining needs are addressed.

Gravitation↗
PubMed2003

Multiple acoustic features underlie vocal signal recognition in tamarins: antiphonal calling experiments.

We examine which acoustic features are relevant for recognition of the cotton-top tamarin (Saguinus oedipus) combination long-call. This vocalization, emitted by both males and females, functions in maintaining group cohesion, territory defense and mate attraction. Using the tamarins' natural antiphonal vocal response to hearing a combination long-call as the primary measure of recognition, we presented subjects with synthetic exemplars of combination long-calls in which we manipulated across one of three acoustic dimensions: frequency, time and amplitude. Results indicated that although acoustic features in the frequency and time domains are important for combination long-call recognition, the changes in amplitude within and between syllables are not. Furthermore, while the fundamental frequency appears to be the used to encode information about the frequency contour, the temporal information is derived from the harmonics. Overall, these results suggest that tamarins use a specific suite of acoustic features for combination long-call recognition.

Acoustic Stimulation↗
PubMed2001

Pore-scale modeling of saturated permeabilities in random sphere packings.

We use two pore-scale approaches, lattice-Boltzmann (LB) and pore-network modeling, to simulate single-phase flow in simulated sphere packings that vary in porosity and sphere-size distribution. For both modeling approaches, we determine the size of the representative elementary volume with respect to the permeability. Permeabilities obtained by LB modeling agree well with Rumpf and Gupte's experiments in sphere packings for small Reynolds numbers. The LB simulations agree well with the empirical Ergun equation for intermediate but not for small Reynolds numbers. We suggest a modified form of Ergun's equation to describe both low and intermediate Reynolds number flows. The pore-network simulations agree well with predictions from the effective-medium approximation but underestimate the permeability due to the simplified representation of the porous media. Based on LB simulations in packings with log-normal sphere-size distributions, we suggest a permeability relation with respect to the porosity, as well as the mean and standard deviation of the sphere diameter.

Models, Theoretical↗
PubMed2001

Remediation of DNAPL pools using dense brine barrier strategies.

Although dense nonaqueous phase liquid (DNAPL) pools are an important source of groundwater contamination, little experimental data have been generated to develop a mature level of understanding of the problem, and few strategies specifically aimed at remediation have been advanced. We discuss the dominant importance of these features in subsurface systems, present novel two- and three-dimensional heterogeneous experimental systems, and show results from two evolving strategies for remediating DNAPL pools. These strategies involve the joint use of a dense brine barrier and controlled mobilization of trapped DNAPL using small-volume surfactant flushes. These experiments demonstrate a controlled, substantial reduction of entrapped DNAPL in both two- and three-dimensional heterogeneous domains, using less than a single pore volume of flushing solution in some cases.

Porosity↗
PubMed2001

Specification and morphogenesis of the zebrafish larval head skeleton.

Forward genetic analyses can reveal important developmental regulatory genes and how they function to pattern morphology. This is because a mutated gene can produce a novel, sometimes beautiful, phenotype that, like the normal phenotype, immediately seems worth understanding. Generally the loss-of-function mutant phenotype is simplified from the wild-type one, and often the nature of the pattern simplification allows one to deduce how the wild-type gene contributes to patterning the normal, more complex, morphology. This truism seems no less valid for the vertebrate head skeleton than for other and simpler cases of patterning in multicellular plants and animals. To show this, we review selected zebrafish craniofacial mutants. "Midline group" mutations, in genes functioning in one of at least three signal transduction pathways, lead to neurocranial pattern truncations that are primarily along the mediolateral axis. Mutation of lazarus/pbx4, encoding a hox gene partner, and mutation of valentino/kreisler, a hox gene regulator, produce anterior-posterior axis disruptions of pharyngeal cartilages. Dorsoventral axis patterning of the same cartilages is disrupted in sucker/endothelin-1 mutants. We infer that different signal transduction pathways pattern cartilage development along these three separate axes. Patterning of at least the anterior-posterior and dorsoventral axes have been broadly conserved, e.g., reduced Endothelin-1 signaling similarly perturbs cartilage specification in chick, mouse, and zebrafish. We hypothesize that Endothelin-1 also is an upstream organizer of the patterns of cellular interactions during cartilage morphogenesis.

Animals↗
PubMed2001

Cotton-top tamarins (Saguinus oedipus) fail to show mirror-guided self-exploration.

To investigate the problem of inter- and intraspecific differences on the mirror test, we conducted two experiments on cotton-top tamarins. Experiment 1 employed a technique similar to one used recently on chimpanzees, and provided no evidence of mirror-mediated touching of the marked area. In a control condition, involving colored dye applied to one arm, two subjects also failed to show self-directed touching, even though they clearly looked at their newly dyed arm. Under these test conditions, cotton-top tamarins fail to show mirror-guided self-exploration. Experiment 2 examined whether this failure was due to insufficient mirror exposure, as well as other details of the testing conditions. In particular, we replicated the design of a previously successful experiment on mirror-mediated recognition in tamarins [Hauser et al., 1995], providing four new animals with a protracted period (three weeks) of mirror exposure prior to dying their hair. In parallel with results from Experiment 1, we observed no evidence of mirror-mediated behavior (recognition) in Experiment 2.

Animals↗
PubMed2001

The units of perception in the antiphonal calling behavior of cotton-top tamarins (Saguinus oedipus): playback experiments with long calls.

We investigated how the acoustic structure of the cotton-top tamarin monkey's (Saguinus oedipus) combination long call relates to the antiphonal calling behavior of conspecifics. Combination long calls can function as contact calls and are produced by socially isolated individuals. Often conspecifics respond to these calls with their own long calls. Structurally, these calls are always composed of one or more 'chirps' followed by two or more 'whistles'. We compared the antiphonal calling responses to playbacks of complete, naturally produced long calls versus single whistles or single chirps. Subjects responded significantly more to whole calls than to either syllable-type alone. Thus, our data suggest that, in terms of the antiphonal calling behavior of socially isolated conspecifics, the whole long call is the unit of perception.

Animals↗
PubMed2001

The synthesis and screening of 1,4,5,8-naphthalenetetracarboxylic diimide-peptide conjugates with antibacterial activity.

We have employed an initial combinatorial approach followed by systematic lead optimization to investigate a series of novel molecules that exhibit antimicrobial activity against Gram-negative and Gram-positive bacteria. The new molecules contain various sequences of amino acids, generally L-lysine and glycine, attached to the 1,4,5,8-naphthalenetetracarboxylic diimide aromatic unit. Systematic structure-activity studies found that increasing positive charge enhanced activity and molecules containing one naphthalenetetracarboxylic diimide unit as well as at least seven lysine residues were optimum for antimicrobial activity. The naphthalenetetracarboxylic diimide derivatives were found to be inactive against mammalian cell lines, making them excellent antimicrobial candidates. Our results indicate that combining positive charge with aromatic and/or hydrophobic elements may be an interesting new approach to antimicrobial agents and adds an important new dimension to the field of cationic peptides.

Anti-Bacterial Agents↗
PubMed2001

Amodal completion of acoustic signals by a nonhuman primate.

Evidence of amodal completion exists for both visual and auditory stimuli in humans. The importance of this mechanism in forming stable representations of sensory information suggests that it may be common among multiple modalities and species. Here we show that a species of nonhuman primate amodally completes biologically meaningful acoustic stimuli, which provides evidence that the neural mechanism mediating this aspect of auditory perception is shared among primates, and perhaps other taxonomic groups as well.

Acoustic Stimulation↗
PubMed2000

sucker encodes a zebrafish Endothelin-1 required for ventral pharyngeal arch development.

Mutation of sucker (suc) disrupts development of the lower jaw and other ventral cartilages in pharyngeal segments of the zebrafish head. Our sequencing, cosegregation and rescue results indicate that suc encodes an Endothelin-1 (Et-1). Like mouse and chick Et-1, suc/et-1 is expressed in a central core of arch paraxial mesoderm and in arch epithelia, both surface ectoderm and pharyngeal endoderm, but not in skeletogenic neural crest. Long before chondrogenesis, suc/et-1 mutant embryos have severe defects in ventral arch neural crest expression of dHAND, dlx2, msxE, gsc, dlx3 and EphA3 in the anterior arches. Dorsal expression patterns are unaffected. Later in development, suc/et-1 mutant embryos display defects in mesodermal and endodermal tissues of the pharynx. Ventral premyogenic condensations fail to express myoD, which correlates with a ventral muscle defect. Further, expression of shh in endoderm of the first pharyngeal pouch fails to extend as far laterally as in wild types. We use mosaic analyses to show that suc/et-1 functions nonautonomously in neural crest cells, and is thus required in the environment of postmigratory neural crest cells to specify ventral arch fates. Our mosaic analyses further show that suc/et-1 nonautonomously functions in mesendoderm for ventral arch muscle formation. Collectively our results support a model for dorsoventral patterning of the gnathostome pharyngeal arches in which Et-1 in the environment of the postmigratory cranial neural crest specifies the lower jaw and other ventral arch fates.

Amino Acid Sequence↗
PubMed1998

The shaping of pharyngeal cartilages during early development of the zebrafish.

In zebrafish the cartilages of the pharynx develop during late embryogenesis and grow extensively in the larva before eventually being replaced by bone. Here we examine chondrocyte arrangements, shapes, numbers, and divisions in the young hyoid cartilages. We observe two distinct developmental phases, morphogenesis and growth. The first phase generates stereotypically oriented chondrocyte stacks that might form by intercalations among cells within the precartilage condensations. In mutants that have deformed cartilages the orientation of the stacks is changed, and we propose that their correct formation underlies the correct initial shaping of the organ. The following period of rapid, nearly isometric cartilage growth occurs by divisions of chondrocytes that are largely located near the joints, and appears to be under quite separate regulation.

Animals↗
PubMed1996

Student doctors and women in labor: attitudes and expectations.

OBJECTIVE: To compare the attitudes and expectations that obstetric patients and medical students bring to the student-patient relationship in intrapartum care. METHODS: Written questionnaires were distributed to obstetric patients who had students assist in their labor and delivery care and to medical students who had completed their clinical clerkship year. Responses of 222 patients and 67 students were analyzed for differences in expectations of student participation and assessment of skills. RESULTS: Responses of medical students and patients were significantly different in all attitudes and expectations studied. One hundred thirty-six (61%) patients compared with 27 (40%) students identified the patients' wish to contribute to the education of students as the most important reason for agreeing to student participation. All patients felt that student participation should be requested rather than assigned, with 194 (87%) patients but only 30 (45%) students wishing to have the student absent from the room at the time of the request. Mean ratings of different student skills tended to be higher from patients (1.3-1.8 on a seven-point Likert scale) than from the students themselves (range 1.6-2.4). Although students' expectations of participation in patient care were high, patients indicated expectations of fairly low levels of student involvement in communication, examination, labor support, and procedures. CONCLUSION: Students have high expectations for their active involvement in intrapartum care and tend to under-estimate the sense of altruism that motivates patients to allow student participation. Patients have low expectations of levels of student participation in their care, but are overall quite satisfied with the skills of the students. These differences highlight the need for the development of educational objectives that clarify student roles in clinical clerkships and the process of informed consent for student participation.

Adolescent↗
PubMed1995

Three-dimensional finite-element simulation of a turbulent push-pull ventilation system.

A finite-element formulation with penalty approach to enforce continuity is employed here to simulate the three-dimensional velocity field resulting from a simple push-pull ventilation configuration. An analytic expression for the length scale and a transport equation for turbulent kinetic energy are coupled with the momentum equations. A coaxial square hood and jet are arranged with cross-draught perpendicular to the common centreline. Numerical predictions of the velocity and turbulence kinetic energy fields are evaluated in the plane of symmetry with hot film anemometry, and smoke-wire flow visualizations. The agreement of the simulated jet trajectories with flow visualizations is reasonable, as are velocities. Predictions of turbulence kinetic energy are not as good, particularly near the hood face. Despite the limitations the numerical approach is useful in assessing the impact of cross-draughts on the push-pull arrangement.

Air↗
PubMed1995

Do obese women have poorer social relationships than nonobese women? Reports by self, friends, and coworkers.

Both theory and research suggest that obese women may have relatively poor social relationships even if their self-reports about their relationships do not differ from the reports of nonobese women. Seventy-seven obese and 78 nonobese women completed self-report measures of social anxiety, social self-esteem, social competence, social network size, and perceived social support from friends and family. Friends and coworkers also rated these women on the same measures. The self-reports of obese and nonobese women did not differ significantly on any of these social measures, and ratings from friends and coworkers of obese women were not different from ratings of nonobese women by friends and coworkers. These results suggest that obese women may be able to overcome prejudice against obese people in their relationships with others.

Adult↗