Teaching and promoting conceptual thinking in engineering education is challenging. Two recently introduced design thinking models are compared in order to explore the reasons behind this challenge. The comparison results in key distinctions between divergent and convergent thinking, and between concept and knowledge domains. The differentiating principle is shown to be a common principle of the two models, truth-value, or logical status, of the propositions that engineers make. Building on this insight, divergent thinking by inquiry is identified as a mechanism for promoting conceptual thinking, and a specific implementation of engineering portfolios is proposed as a pedagogical tool.

In this paper, we have developed a model-based processor (MBP) for a microcantilever-array sensor to detect target species in solution. We perform a proof-of-concept experiment, fit model parameters to the measured data and use them to develop a Gauss-Markov simulation. We then investigate two cases of interest, averaged deflection data and multichannel data. For this evaluation we extract model parameters via a model-based estimation, perform a Gauss-Markov simulation, design the optimal MBP and apply it to measured experimental data. The performance of the MBP in the multichannel case is evaluated by comparison to a "smoother" (averager) typically used for microcantilever signal analysis. It is shown that the MBP not only provides a significant gain (~80 dB) in signal-to-noise ratio (SNR), but also consistently outperforms the smoother by 40-60 dB. Finally, we apply the processor to the smoothed experimental data and demonstrate its capability for chemical detection. The MBP performs quite well, apart from a correctable systematic bias error.

There are good reasons to be skeptical about any efforts to bring together two fields of inquiry that have historically had little to do with each other - that is, personality psychology and the study of human development. Personality psychologists are by training, and maybe even temperament, suspicious of the idea of development, for to them it means change (i.s. instability, inconsistency), and personality is nothing if it is not at least somewhat enduring. Developmentalists, on the other hand, specialize in a certain kind of change - meaningful and orderly change over time.

Severe eye injuries occur in 30 percent of demining accidents. Visors are known to be effective personal protective equipment when worn properly, but deminers often lift or remove their visors because scratches, glare or fog make them hard to see through, or because they are hot, heavy and uncomfortable to wear. Addressing each of these specific design problems could increase visor use and prevent a significant number of debilitating injuries. This paper presents methods for preventing and eliminating scratches on demining visors.

The relevance of the acyl homoserine lactone (acyl-HSL) quorum signals N-3-oxododecanoyl-homoserine lactone (3OC12HSL) and N-butanoyl-homoserine lactone to the biology and virulence of Pseudomonas aeruginosa is well investigated. Previously, P. aeruginosa was shown to degrade long-chain, but not short-chain, acyl-HSLs as sole carbon and energy sources (J. J. Huang, J.-I. Han, L.-H. Zhang, and J. R. Leadbetter, Appl. Environ. Microbiol. 69:5941-5949, 2003). A gene encoding an enzyme with acyl-HSL acylase activity, pvdQ (PA2385), was identified, but it was not required for acyl-HSL utilization. This indicated that P. aeruginosa encodes another acyl-HSL acylase, which we identify here. A comparison of total cell proteins of cultures grown with long-acyl acyl-HSLs versus other substrates implicated the involvement of a homolog of PvdQ, the product of gene PA1032, for which we propose the name QuiP. Transposon mutants of quiP were defective for growth when P. aeruginosa was cultured in medium containing decanoyl-HSL as a sole carbon and energy source. Complementation with a functional copy of quiP rescued this growth defect. WhenP. aeruginosa was grown in buffered lysogeny broth, constitutive expression of QuiP in P. aeruginosa led to decreased accumulations of the quorum signal 3OC12HSL, relative to the wild type. Heterologous expression of QuiP was sufficient to confer long-chain acyl-HSL acylase activity upon Escherichia coli. Examination of gene expression patterns during acyl-HSL-dependent growth of P. aeruginosa further supported the involvement of quiP in signal decay and revealed other genes also possibly involved. It is not yet known under which ÔÇ£naturalÔÇØ conditions quiP is expressed or how P. aeruginosa balances the expression of its quorum-sensing systems with the expression of its acyl-HSL acylase activities.

It has been widely documented that individuals who explain negative life events with a depressogenic attributional style (stable, global attributions) tend to have increased rates of depression and other poor outcomes (e.g., Sweeny, Anderson, & Bailey, 1986). The Content Analysis of Verbatim Explanations (CAVE) is a method of assessing attributional style in spontaneously-generated causal attributions appearing in accounts of real events (Peterson, Schulman, Castellon, & Seligman, 1992). Seventy life story interviews obtained from a diverse community sample of midlife adults were coded for attributional style with the CAVE technique and also for the theme of contamination (scenes in which good events turn to bad outcomes, McAdams, Reynolds, Lewis, Patten, & Bowman, 2001). While depressogenic attributional style and contamination sequences were unrelated to each other, both were shown to independently predict self-reported depression and low life satisfaction. In addition, while the observed relationships between depressogenic attributional style and these selfreport variables were no longer significant after controlling for neuroticism, a similar pattern was not observed for contamination sequences. This study forges possible connections between cognitive theories of depression and the narrative study of adult identity.

The ways institutions have structured their initial innovation with online learning vary greatly. Initial business model decisions present different challenges in terms of how institutions will integrate online learning. This paper looks at several common business models and the opportunities and challenges that each presents to institutions that want to fully integrate online learning.

Despite the rapid growth in the adoption of online learning, there is a dearth of detailed information on effective business models, business strategies and effective practices on which to build sustainable online education programs. A survey instrument was developed as an initial attempt to define business models and business strategies for online learning. The survey results yielded some interesting data about which online learning financial models seem to have more or less "control" of which business functions. The sample was a convenience one and as such will require further filtering of data. It is also clear that more needs to be done to define business strategies and models and thus provide guidance to this growing segment of higher education.

Cell migration on 2D surfaces is governed by a balance between counteracting tractile and adhesion forces. Although biochemical factors such as adhesion receptor and ligand concentration and binding, signaling through cell adhesion complexes, and cytoskeletal structure assembly/disassembly have been studied in detail in a 2D context, the critical biochemical and biophysical parameters that affect cell migration in 3D matrices have not been quantitatively investigated. We demonstrate that, in addition to adhesion and tractile forces, matrix stiffness is a key factor that influences cell movement in 3D. Cell migration assays in which Matrigel density, fibronectin concentration, and ╬▓1 integrin binding are systematically varied show that at a specific Matrigel density the migration speed of DU-145 human prostate carcinoma cells is a balance between tractile and adhesion forces. However, when biochemical parameters such as matrix ligand and cell integrin receptor levels are held constant, maximal cell movement shifts to matrices exhibiting lesser stiffness. This behavior contradicts current 2D models but is predicted by a recent force-based computational model of cell movement in a 3D matrix. As expected, this 3D motility through an extracellular environment of pore size much smaller than cellular dimensions does depend on proteolytic activity as broad-spectrum matrix metalloproteinase (MMP) inhibitors limit the migration of DU-145 cells and also HT-1080 fibrosarcoma cells. Our experimental findings here represent, to our knowledge, discovery of a previously undescribed set of balances of cell and matrix properties that govern the ability of tumor cells to migration in 3D environments.

The abstract in unavailable.

An integrated set of courses, or Integrated Course Block (ICB), developed for incoming first-year students at the Franklin W. Olin College of Engineering, is presented. Bound by a common theme of `Kinetic Sculptures', the individual courses in this ICB are mathematics (single variable calculus and ordinary differential equations), physics (kinetics and dynamics of linear and rotational motion, thermodynamics and fluids), and an open-ended engineering project. The project part of the ICB allows students to explore the motion through the design of kinetic (moving) sculptures while utilizing the mathematics and physics concepts learned in the accompanying courses. This paper considers the 'Kinetic Sculptures' ICB from the pedagogical and epistemological points of view by presenting its implementation and discussing the results and analysis of three student surveys taken during three semesters, and seven semesters after participating in the ICB.

When a bubble collapses mildly the interior pressure field is spatially uniform; this is an assumption often made to close the Rayleigh-Plesset equation of bubble dynamics. The present work is a study of the self-consistency of this assumption, particularly in the case of violent collapses. To begin, an approximation is developed for a spatially non-uniform pressure field, which in a violent collapse is inertially driven. Comparisons of this approximation show good agreement with direct numerical solutions of the compressible Navier-Stokes equations with heat and mass transfer. With knowledge of the departures from pressure uniformity in strongly forced bubbles, one is in a position to develop criteria to assess when pressure uniformity is a physically valid assumption, as well as the significance of wave motion in the gas. An examination of the Rayleigh-Plesset equation reveals that its solutions are quite accurate even in the case of significant inertially driven spatial inhomogeneity in the pressure field, and even when wave-like motions in the gas are present. This extends the range of utility of the Rayleigh-Plesset equation well into the regime where the Mach number is no longer small; at the same time the theory sheds light on the interior of a strongly forced bubble.

Direct measurements of individual bubble oscillations in lithotripsy fields have been performed using light-scattering techniques. Studies were performed with bubble clouds in gassy water as well as single levitated bubbles in degassed water. There is direct evidence that the bubble survives the inertial collapse, rebounding several times before breaking up. Bubble dynamics calculations agree well with the observations, provided that vapor trapping (a reduction in condensation during bubble collapse) is included. Furthermore, the afterbounces are dominated by vapor diffusion, not gas diffusion. Vapor trapping is important in limiting the collapse strength of bubbles, and in sonochemical activity.

Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between both is important for future clinical management. We report a family initially described as a familial MTC by pentagastrin stimulation test and clinical outcome, in which we found a 12 bp deletion within the catalytic domain of the protooncogene RET in the index case tumor alone. Linkage study suggests that it is a sporadic MTC. Therefore, in view of these results, in kindred with just one MTC case, borderline pentagastrin test values must be carefully assessed. In addition, this and other mutations can help us to understand some features about domains that play an important role in the normal function of this tyrosine kinase receptor and involved in MTC.

In single-bubble sonoluminescence, repeated brief flashes of light are produced in a gas bubble strongly driven by a periodic acoustic field. A startling hypothesis has been made by Lohse and co-workers [Phys. Rev. Lett. 78, 1359 (1997)] that the non-noble gases in an air bubble undergo chemical reaction into soluble products, leaving only argon. In the present work, this dissociation hypothesis is supported by simulations, although the associated temperatures of about 7000 K seem too low for bremsstrahlung, which has been proposed as the dominant light emission mechanism. This suggests that emission from water vapor and its reaction products, heretofore not included, may play an important role.

The cyanobacterium Synechocystis sp. strain PCC 6308 has been shown to exhibit predictable physiological responses to acid stress. Originally isolated from a Wisconsin lake, this cyanobacterium grows optimally under alkaline conditions in the laboratory. After acid stress at a pH of between 4.4 and 7.7, cells return to exponential growth following a lag phase. The organism's response to this tolerable acid stress involves cell concentration-dependent neutralization of the external medium to pH 6 or above within 5 min, maintenance of a transmembrane pH gradient, and maintenance of photosystem II efficiency. Lethal acid stress, at a pH below 4.4, results in the formation of aggregates of denatured proteins observed as granules near the cell periphery, the disruption of the transmembrane pH gradient, cell color change to blue, and damage to photosystem II.

We present results of a systematic x-ray scattering study of the effects of Mg doping on the high-field incommensurate phase ofCuGeO3. Lorentzian-squared line shapes, the changing of the first-order transition to second order, and the destruction of long-range order with infinitesimal doping are observed, consistent with random-field effects in a three-dimensional XY system. Values for the soliton width in pure and lightly doped CuGeO3 are deduced. We find that even a very small doping has a drastic effect on the shape of the lattice modulation.

In a classical paper Plesset has determined conditions under which a bubble changing in volume maintains a spherical shape. The stability analysis was further developed by Prosperetti to include the effects of liquid viscosity on the evolving shape modes. In the present work the theory is further modified to include the changing density of the bubble contents. The latter is found to be important in violent collapses where the densities of the gas and vapor within a bubble may approach densities of the liquid outside. This exerts a stabilizing influence on the Rayleigh–Taylor mechanism of shape instability of spherical bubbles. A comparison with experimental data shows good agreement with the new theory; the Rayleigh–Taylor instability does provide an extinction threshold for violently collapsing bubbles. It is also explained why earlier works did not produce a slope in the Rayleigh–Taylor stability curve that conforms with that of the present work.

Light emission from gallium arsenide (GaAs) p–n junctions biased in avalanche breakdown have been modeled over the range of 1.4–3.4 eV. The model emphasizes direct and indirect recombination processes and bulk self-absorption. Comparisons between measured and simulated spectra for sample junctions from custom and commercially fabricated GaAs devices demonstrate that the model is simple, accurate, and consistent with fundamental physical device theory. The model also predicts the junction depth with accuracy.

Vascular adaptation—or structural changes of microvessels in response to physical and metabolic stresses—can influence physiological processes like angiogenesis and hypertension. To better understand the influence of these stresses on adaptation, Pries et al. (1998, 2001a,b, 2005) have developed a computational model for microvascular adaptation. Here, we reformulate this model in a way that is conducive to a dynamical systems analysis. Using th ese analytic methods, we determine the equilibrium geometries of a single vessel under different conditions and classify its type of stability. We demonstrate that our closed-form solution for vessel geometry exhibits the same regions of stability as the numerical predictions of Pries et al. (2005, Remodeling of blood vessels: responses of diameter and wall thickness to hemodynamic and metabolic stimuli. Hypertension, 46, 725–731). Our analytic approach allows us to predict the existence of limit-cycle oscillations and to extend the model to consider a fixed pressure across the vessel in addition to a fixed flow. Under these fixed pressure conditions, we show that the vessel stability is affected and that the multiple equilibria can exist.

The postfragmentation probability density of daughter flocs is one of the least well-understood aspects of modeling flocculation. We use three-dimensional positional data of Klebsiella pneumoniae bacterial flocs in suspension and the knowledge of hydrodynamic properties of a laminar flow field to construct a probability density function of floc volumes after a fragmentation event. We provide computational results which predict that the primary fragmentation mechanism for large flocs is erosion. The postfragmentation probability density function has a strong dependence on the size of the original floc and indicates that most fragmentation events result in clumps of one to three bacteria eroding from the original floc. We also provide numerical evidence that exhaustive fragmentation yields a limiting density inconsistent with the log-normal density predicted in the literature, most likely due to the heterogeneous nature of K. pneumoniae flocs. To support our conclusions, artificial flocs were generated and display similar postfragmentation density and exhaustive fragmentation.

Complex orthogonal designs (CODs) of rate 1/2 have been considered recently for use in analog transmissions and as an alternative to maximum rate CODs due to the savings in decoding delay as the number of antennas increases. While algorithms have been developed to show that an upper bound on the minimum decoding delay for rate 1/2 CODs with n=2m-1 or n=2m columns is ν(n) = 2m-1 or ν(n) = 2m, depending on the parity of n modulo 8, it remains open to determine the exact minimum delay. This paper shows that this bound ν(n) is also a lower bound on minimum decoding delay for a major class of rate 1/2 CODs, named balanced complex orthogonal designs (BCODs), and that this is the exact minimum decoding delay for most BCODs. These rate 1/2 codes are conjugation-separated and thus permit a linearized description of the transceiver signal. BCODs also display other combinatorial properties that are expected to be useful in implementation, such as having no linear processing. An elegant construction is provided for a class of rate 1/2 CODs that have no zero entries, effectively no irrational coefficients, no linear processing, and have each variable appearing exactly twice per column. The resulting codes meet the aforementioned bound on decoding delay in most cases. This class of CODs will be useful in practice due to their low peak-to-average power ratio (PAPR) and other desirable properties.

Dual emission laser induced fluorescence (DELIF) is a technique for measuring the instantaneous thin fluid film thickness in dynamic systems. Two fluorophores within the system produce laser induced emissions that are filtered and captured by two cameras. The ratio of the images from these cameras is used to cancel the effect of the laser beam profile on the image intensity. The resultant intensity ratio can be calibrated to a fluid film thickness. The utilization of a 2-dye system when applied to Chemical Mechanical Polishing (CMP) is complicated by the fluorescence of the polymeric polishing pad and the light scattering particles in the polishing slurry. We have developed a model of DELIF for CMP with 1-dye employing the polishing pad as the second fluorophore. While scattering particles in the slurry decrease the overall intensity of the individual images, the contrast in the image ratio increases. Using the 1-dye DELIF system to measure thin slurry films, our model results indicate that a cubic calibration may be needed. However, experimental results suggest a linear calibration is achieved for slurry films between 0 and 133 mu m thick with scattering coefficients as high as 8.66 mm(-1) at a wavelength equal to 410 nm.

Complex orthogonal designs (CODs) have been successfully implemented in wireless systems as complex orthogonal space-time block codes (COSTBCs). Certain properties of the underlying CODs affect the performance of the codes. In addition to the main properties of a COD's rate and decoding delay, a third consideration is whether the COD can achieve transceiver signal linearization, a property that facilitates practical implementation by, for example, significantly simplifying the receiver structure for iterative decoding. It has been shown that a COD can achieve this transceiver signal linearization if the nonzero entries in any given row of the matrix are either all conjugated or all nonconjugated. This paper determines the conditions under which maximum rate CODs can achieve this desirable property. For an odd number of transmit antennas, it is shown that maximum rate CODs that achieve the lower bound on decoding delay can also achieve transceiver signal linearization. In contrast, for an even number of transmit antennas, maximum rate CODs that achieve the lower bound on delay cannot achieve this linearization. In this latter case, linearization is possible only if the COD achieves at least twice the lower bound on delay. This work highlights the tradeoffs among these three important properties.

Specific phobias are highly prevalent among college students and can be quite debilitating. However, students often do not present for treatment for phobias and, when they do, often do not receive effective treatment. This article will present a case study of the effective treatment of specific phobia using cognitive-behavioral therapy with an emphasis on in vivo exposure. It will provide a template for how to conduct this efficient and effective therapy and suggest several benefits of incorporating this treatment into the repertoire offered by a college counseling center.

An asymptotic technique is developed to find the Signal-to-Interference-plus-Noise-Ratio (SINR) and spectral efficiency of a link with N receiver antennas in wireless networks with non-homogeneous distributions of nodes. It is found that with appropriate normalization, the SINR and spectral efficiency converge with probability 1 to asymptotic limits as N increases. This technique is applied to networks with power-law node intensities, which includes homogeneous networks as a special case, to find a simple approximation for the spectral efficiency. It is found that for receivers in dense clusters, the SINR grows with N at rates higher than that of homogeneous networks and that constant spectral efficiencies can be maintained if the ratio of N to node density is constant. This result also enables the analysis of a new scaling regime where the distribution of nodes in the network flattens rather than increases uniformly. It is found that in many cases in this regime, N needs to grow approximately exponentially to maintain a constant spectral efficiency. In addition to strengthening previously known results for homogeneous networks, these results provide insight into the benefit of using antenna arrays in non-homogeneous wireless networks, for which few results are available in the literature.

In a majority conversion process, the vertices of a graph can be in one of the two states, colored or uncolored, and these states are dynamically updated so that a vertex becomes colored at a certain time period if at least half of its neighbors were in the colored state in the previous time period. A dynamic monopoly is a set of vertices in a graph that when initially colored will eventually cause all vertices in the graph to become colored. This paper establishes a connection between dynamic monopolies and the well-known feedback vertex sets which are sets of vertices whose removal results in an acyclic graph. More specifically, we show that dynamic monopolies and feedback vertex sets are equivalent in graphs wherein all vertices have degree 2 or 3. We use this equivalence to provide exact values for the minimum size of dynamic monopolies of planar hexagonal grids, as well as upper and lower bounds on the minimum size of dynamic monopolies of cylindrical and toroidal hexagonal grids. For these last two topologies, the respective upper and lower bounds differ by at most one.

The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three-dimensional (3D) hydrogel systems have been used to explore the effects of the mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, self-assembling peptide (SAP) gels that are able to recapitulate normal epithelial acini morphogenesis and gene expression in a 3D context. By exploiting the range of viscoelasticity attainable with these SAP gels, and their ability to recreate native-like ECM fibril topology with minimal variability in ligand density and pore size, we were able to reconstitute normal and tumor-like phenotypes and gene expression patterns in nonmalignant mammary epithelial cells. Accordingly, this SAP hydrogel system presents the first tunable system capable of independently assessing the interplay between ECM stiffness and multi-cellular epithelial phenotype in a 3D context.

We prove the existence and uniqueness, for wave speeds sufficiently large, of monotone traveling wave solutions connecting stable to unstable spatial equilibria for a class of -dimensional lattice differential equations with unidirectional coupling. This class of lattice equations includes some cellular neural networks, monotone systems, and semi-discretizations for hyperbolic conservation laws with a source term. We obtain a variational characterization of the critical wave speed above which monotone traveling wave solutions are guaranteed to exist. We also discuss non-monotone waves, and the coexistence of monotone and non-monotone waves.

An L(2,1)-labeling of a graph G is a function f:V(G)→{0,1,…,k} such that |f(x)−f(y)|≥2 if x and y are adjacent vertices, and |f(x)−f(y)|≥1 if x and y are at distance 2. Such labelings were introduced as a way of modeling the assignment of frequencies to transmitters operating in close proximity within a communications network. The lambda number of G is the minimum k over all L(2,1)-labelings of G. This paper considers the lambda number of the matched sum of two same-order disjoint graphs, wherein the graphs have been connected by a perfect matching between the two vertex sets. Matched sums have been studied in this context to model possible connections between two different networks with the same number of transmitters. We completely determine the lambda number of matched sums where one of the graphs is a complete graph or a complete graph minus an edge. We conclude by discussing some difficulties that are encountered when trying to generalize this problem by removing more edges from a complete graph.

Polydimethylsiloxane (PDMS) posts with a diameter of 80 mu m were used to measure the shearing forces at the wafer-pad interface during chemical mechanical planarization (CMP). Measurements are made at 10 kHz with measurable forces between 40 and 400 mu N. The structures were polished using a stiff, ungrooved pad and 3 wt % fumed silica slurry at velocities of 0.3 and 0.6 m/s and average wafer-pad normal load of 5.0 and 9.1 kPa. Due to the small fraction of the pad that contacts the wafer, the local microscale forces can be much larger than the global average force might suggest. Observed lateral forces on the structures averaged, in time, between 230 and 310 mu N with RMS deviations of the force about the mean between 47 and 64 mu N. The faster polishing case shows a 30% higher mean force, and a 20% reduction in the RMS variation of force. Little change is seen in the force characteristics when increasing from 5.0 to 9.1 kPa downforce. A mathematical model is developed to interpret these forces, allowing estimation of the local pad properties. The model suggests that 5000 asperity contacts are present per square millimeter, asperity lateral stiffness is 0.3 N/m, and asperity slip-off force is 19 mu N. (C)

Polyester bees are all over the Northeast. The interesting thing about them is that they dig underground tunnels, about the width of your pinky finger, where they lay their eggs. To protect their larvae from heat, cold, fungus, bacteria and other dangers, the bees line these chambers with a clear, cellophanelike substance. The larvae then live underground for most of their lives in these reinforced cells.

Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are dominantly inherited conditions which predispose to the development of endocrine neoplasia. Evidence is presented that sequence changes within the coding region of the RET proto-oncogene, a putative transmembrane tyrosine kinase, may be responsible for the development of neoplasia in these inherited disorders. Single strand conformational variants (SSCVs) in exons 7 and 8 of the RET proto-oncogene were identified in eight MEN 2A and four FMTC families. The variants were observed only in the DNA of individuals who were either affected or who had inherited the MEN2A or FMTC allele as determined by haplotyping experiments. The seven variants identified were sequenced directly. All involved point mutations within codons specifying cysteine residues, resulting in nonconservative amino acid changes. Six of the seven mutations are located in exon 7. A single mutation was found in exon 8. Variants were not detected in four MEN 2B families studied for all exon assays available, nor were they detectable in 16 cases of well documented sporadic medullary thyroid carcinoma or pheochromocytoma that were tested for exon 7 variants. Coinheritance of the mutations with disease and the physical and genetic proximity of the RET proto-oncogene provide evidence that RET is responsible for at least two of the three inherited forms of MEN 2. Neither the normal function, nor the ligand of RET are yet known. However, its apparent involvement in the development of these inherited forms of neoplasia as well as in papillary thyroid carcinoma suggest an important developmental or cell regulatory role for the protein.

Williams syndrome (WS) (Williams et al. 1961; Beurenet al. 1962) is a multisystem disorder characterized by mental retardation, a specific neurobehavioral profile,characteristic facies, infantile hypercalcemia, cardiovascular abnormalities, progressive joint limitation, hernias, and soft skin. Recent studies have shown that hemizygosity at the elastin (ELN) gene locus on chromosome7q is associated with WS (Ewart et al. 1993). Furthermore, two FISH studies using cosmid recombinants containing the 5' or the 3' end of the ELN gene revealed deletion of the entire ELN gene in 90%-96% of classical WS cases (Lowery et al. 1995; Nickerson et al. 1995). However, the size of the 7ql 1.23 deletions and the mechanism by which these deletions arise are not known.

The near-resonant response of suspended, elastic cables driven by planar excitation is investigated using a two degree-of-fredom model. The model captures the interaction of a symmetric in-plane mode and an out-of-plane mode with near commensurable natural frequencies in a 2:1 ratio. The modes are coupled through quadratic and cubic nonlinearities arising from nonlinear cable stretching. The existence and stability of periodic solutions are investigated using a second order perturbation analysis. The first order analysis shows that suspended cables may exhibit saturation and jump phenomena. The second order analysis, however, reveals that the cubic nonlinearities and higher order corrections disrupt saturation. The stable, steady state solutions for the second order analysis compare favorably with results obtained by numerically integrating the equations of motion.

A new microelectronic gas sensor utilizing polycrystallinediamondfilm in conjunction with a catalytic metal has been developed for hydrogen detection. The sensor is fabricated in a layered Pd/i-diamond/p-diamond metal-insulator-semiconductor (MIS) Schottky-diode configuration on a tungsten substrate. The performance of the sensor for H2 detection has been examined in the temperature range 27-300°C. The analysis of the steady-state reaction kinetics has confirmed that the hydrogen adsorption process is responsible for the barrier-height change in the diamond-based MIS Schottky diode. The use ofdiamond-film technology opens the door to the development of a microelectronic gas sensor that can operate at a wider and higher temperature range than the ones based on present silicon technology.

Studies are presented of single-particle ion effects in body-tied CMOS/silicon-on-insulator (SOI) devices. It is shown that two mechanisms can contribute to SOI soft-error rates: a direct ion-induced photocurrent and a local lateral bipolar current. The total amount of charge collected is sensitive to the relative locations of the ion strike and the body-to-source tie.

Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty-seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity at 15 loci on chromosome 17p. Eighty % (39 of 49) of informative tumors had allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region, including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic carcinomas. The smallest region of overlapping deletion extends from D17S28 to D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential tumor suppressor function include HIC-1, DPH2L (N. J. Philips et al. Isolation of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies 1 kb centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat. Med., 1: 570–577, 1995) but remains a candidate because 5′-regulatory elements may lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an interval including D17S28, D17S30, and D17S654, whereas CRK is excluded from this interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1region deletions because the latter changes are seen only in high-stage carcinomas. Microsatellite instability plays only a minor role in sporadic ovarian carcinogenesis because only 1 of 57 tumors showed this finding.

Introductory computer science education is entrenched in an outdated computational model. Although it corresponds neither to our computing environments nor our work, we teach our students a single-thread-of-control static problem-solving view of the role of the computer program: computation as calculation. In this model, the job of a computer program is to start with a problem, calculate its answer, return that answer, and stop. This program-as-an-island bears little resemblance to most of today's software. We can dramatically improve this situation--and, as a corollary, all of undergraduate computer science--by teaching our students from the very beginning to conceptualize computation with a model of computer programs as simultaneous ongoing entities embedded in and interacting with a dynamic environment: computation as interaction; computation as it occurs in spreadsheets and video games, web applications and robots.

Holoprosencephaly (HPE) is a genetically and phenotypically heterogenous disorder involving the development of forebrain and midface, with an incidence of 1:16,000 live born and 1:250 induced abortions. This disorder is associated with several distinct facies and phenotypic variability: in the most extreme cases, anophthalmia or cyclopia is evident along with a congenital absence of the mature nose. The less severe form features facial dysmorphia characterized by ocular hypertelorism, defects of the upper lip and/or nose, and absence of the olfactory nerves or corpus callosum. Several intermediate phenotypes involving both the brain and face have been described. One of the gene loci, HPE3, maps to the terminal band of chromosome 7. We have performed extensive physical mapping studies and established a critical interval for HPE3, and subsequently identified the sonic hedgehog (SHH) gene as the prime candidate for the disorder. SHH lies within 15-250 kilobases (kb) of chromosomal rearrangements associated with HPE, suggesting that a 'position effect' has an important role in the aetiology of HPE. As detailed in the accompanying report, this role for SHH is confirmed by the detection of point mutations in hereditary HPE patients.

Anovel microelectronic device utilizing the gas sensing properties of tinoxide SnOx and electrical properties of plasma enhanced chemical vapor deposited (PECVD) diamondfilm for oxygengas sensing at higher and wide temperature range is presented in this paper. The sensor is fabricated as a layer of catalyst/SnOx(adsorptive oxide)/i(intrinsic)-diamond/p+-diamond CAIS structure. The performance of the new microelectronic gassensor has demonstrated a large sensitivity to oxygengas. The response is reproducible and repeatable. Activation energy of oxygen adsorption by the new microelectronic gassensoris low. The sensor has also indicated CO detection in air ambient.

Three sets of linkage maps (index, comprehensive microsatellite, and unified) have been constructed for human chromosome 14 based on genotypes from the CEPH reference pedigrees. The index maps consist of 18 microsatellite markers, with heterozygosities of at least 68% and intermarker spacing no greater than 11 cM. The sex-average comprehensive microsatellite map is 125 cM in length and includes 115 markers with 54 loci uniquely placed with odds for marker order of at least 1000:1. The sex-average index map length is 121 cM, and the female- and male-specificmaps are 143 and 101 cM, respectively. A unified map was also constructed from 147 loci (162marker systems), which includes 32 RFLP markers in addition to the 115 microsatellites. The sex-average length of the unified map is 128 cM with 69 loci uniquely placed. Our maps are anchored by a microsatellite telomere marker sCAW1 (D14S826), developed from a telomere YAC clone TYAC196, which extends the linkage map to the physical terminus of the long arm of chromosome14. Furthermore, we have also physically mapped seven of the loci by fluorescence in situ hybridization of cosmid clones or Alu-PCR products amplified from YACs containing the markersequences. Together with previously established cytogenetic map designations for other loci, ourmaps display links between genetic markers for 10 of 13 cytogenetic bands of chromosome 14 at the 550 genome band resolution.

A chaotic mapping provides a technique for generating musical variations of an original work. This technique, based on the sensitivity of chaotic trajectories to initial conditions, produces changes in the pitch sequence of a piece. A sequence of musical pitches {pi}, i.e., any piece ranging from Bach (or earlier) to contemporary music, is paired with the x‐components {xi} of a Lorenz chaotic trajectory. Each pi is marked on the x axis at the point designated by its xi. In this way, the x axis becomes a pitch axis configured according to the notes of the original composition. Then, a second chaotic trajectory, whose initial condition differs from the first, is launched. Its x‐components trigger pitches on the pitch axis (via the mapping) that vary in sequence from the original work, thus creating a variation. There are virtually an unlimited number of variations possible, many appealing to expert and nonexpert alike.

We report the construction of an ∼1.7-Mb sequence-ready YAC/BAC clone contig of 8p22–p23. This chromosomal region has been associated with frequent loss of heterozygosity (LOH) in breast, ovarian, prostate, head and neck, and liver cancer. We first constructed a meiotic linkage map for 8p to resolve previously reported conflicting map orders from the literature. The target region containing a putative tumor suppressor gene was defined by allelotyping 65 cases of sporadic ductal carcinoma in situ with 18 polymorphic markers from 8p. The minimal region of loss encompassed the interval between D8S520 and D8S261, and one tumor had loss of D8S550 only. We chose to begin physical mapping of this minimal LOH region by concentrating on the distal end, which includes D8S550. A fine-structure radiation hybrid map for the region that extends from D8S520 (distal) to D8S1759 (proximal) was prepared, followed by construction of a single, integrated YAC/BAC contig for the interval. The ∼1730-kb contig consists of 13 YACs and 27 BACs. Fifty-four sequence-tagged sites (STSs) developed from BAC insert end-sequences and 11 expressed sequence tags were localized within the contig by STS content mapping. In addition, four unique cDNA clones from the region were isolated and fully sequenced. This integrated YAC/BAC resource provides the starting point for transcription mapping, genomic sequencing, and positional cloning of this region.

This paper concerns a relaxation of the assumption of uniform mixture composition in the interior of sonoluminescence bubbles. Intense temperature and pressure gradients within the bubble drive relative mass diffusion which overwhelms diffusion driven by concentration gradients. This thermal and pressure diffusion results in a robust compositional inhomogeneity in the bubble which lasts several orders of magnitude longer than the temperature peak or light pulse at the main collapse of the bubble. This effect has important consequences for control of sonoluminescence, gas dynamics, sonochemistry, and the physics of light production.

Given some changes in the world, the frame problem is the problem of determining that most things in the world haven't changed. Since change is generally taken to mean "change over time", the frame problem is generally assumed to be a problem of temporal reasoning, and most examples of the frame problem are couched in terms of the effects of actions. In this paper, I point out the fallacy underlying this approach, and demonstrate something very much like the frame problem that is completely independent of time: the counterfactual validity problem. I show that this "atemporal frame problem" proves damning for certain approaches to solving the frame problem. However, exploration of the differences between these two problems may help to identify more promising research directions.

Colored chromosome staining patterns, termed chromosomal ‘bar codes’ (CBCs), were obtained on human chromosomes by fluorescence in situhybridization (FISH) with pools of Alu-PCR products from YAC dones containing human DNA inserts ranging from 100 kbp to 1 Mbp. In contrast to conventional G- or R-bands, the chromosomal position, extent, Individual color and relative signal intensity of each ‘bar’ could be modified depending on probe selection and labeling procedures. Alu-PCR amplification products were generated from 31 YAC clones which mapped to 37 different chromosome bands. For multiple color FISH, Alu-PCR amplification products from various clones were either biotinylated or labeled with digoxigenin. Probes from up to twenty YAC clones were used simultaneously to produce CBCs on selected human chromosomes. Evaluation using a cooled CCD camera and digital image analysis confirmed the high reproducibility of the bars from one metaphase spread to another. Combinatorial FISH with mixtures of whole chromosome paint probes was applied to paint seven chromosomes simultaneously in different colors along with a set of YAC clones which map to these chromosomes. We discuss the potential to construct analytical chromosomal bar codes adapted to particular needs of cytogenetic investigations and automated image analysis.

The RET (combined in ransfection) gene encodes a receptor tyrosine kinase homolog involved in innervation of the gut and renal development. A chimeric epidermal growth factor receptor (EGFR)/RET receptor was constructed which contained the extracellular and transmembrane domains of the EGF receptor fused to the intracellular domain of RET. This construct was expressed in NIH 3T3 cells, and the functional properties of the receptor were characterized and compared with those of the wild type EGF receptor. Whereas the EGF receptor exhibited both high and low affinity binding sites for 125I-EGF, the EGFR/RET chimera exhibited only low affinity binding of 125I-EGF. The chimera was able to internalize EGF more rapidly than the wild type EGF receptor and recycled to the cell surface at twice the rate of the EGF receptor. Pulse-chase experiments indicated that EGF stimulated the degradation of the wild type EGF receptor but had no effect on the rate of degradation of the EGFR/RET receptor. The combination of increased recycling and decreased degradation resulted in the relatively inefficient down-regulation of the EGFR/RET chimera. Incubation of cells expressing the wild type EGF receptor with phorbol 12-myristate 13-acetate led to a reduction in 125I-EGF binding and a loss in EGF-stimulated tyrosine phosphorylation. However, phorbol 12-myristate 13-acetate treatment had only a limited effect on EGF binding and EGF-stimulated tyrosine kinase activity in cells expressing EGFR/RET chimeras. These findings suggest that the ret tyrosine kinase is not regulated by many of the common mechanisms used to terminate signaling via growth factor receptors. Such persistent activation of the Ret tyrosine kinase may be relevant to the physiological function of Ret in cells that normally express this growth factor receptor.

Pattern formation is analyzed and simulated in a nonlinear optical system involving all three space dimensions as well as time in an essential way. This system, counterpropagation in a Kerr medium, is shown to lose stability, for sufficient pump intensity, to a nonuniform spatial pattern. We observe hexagonal patterns in a self-focusing medium, and squares in a self-defocusing one, in good agreement with analysis based on symmetry and asymptotic expansions.

Black American men have a higher incidence of cancer of the prostate (CAP), multiple myeloma, and lung cancer than do white American men (discussed by Lyn et al.1993a). The basis for these differences no doubt includes environmental influences, because American blacks have also been found to have a higher incidence of CAP than do African blacks. However, genetic factors may play a role as well. For example, Lyn et al. (1993a) reported an increase in the frequency of an allele of the poly(ADPribose)polymerase (PADPRP) pseudogene locus onchromosome 13 in black Americans with CAP, suggesting the presence of a disease-susceptibility locus. Since only nine CAP patients were studied, proof of the significance of the finding for the general population of black Americans will rely on independent replication of the result and studies with larger sample sizes. We have doubled the number of black American CAP patients studied at the PADPRP pseudogene locus on chromosome13 and compared them with white Americans with CAP, along with reference samples. In addition, we have determined allele frequencies by using a larger number of white individuals, from the CEPH reference pedigree resource, and a larger number of black Americans than previously reported, which may reflect more accurately the allele frequencies in these populations. We also find a statistically significant association between an allele at the PADPRP pseudogene locus and CAP in black Americans; however, it is not the same allele reported by Lyn et al. (1993a). Furthermore, we tested CAP tumorDNA for chromosome 13 PADPRP pseudogene region deletions. In contrast to the report of Bhatia et al.(1990), we found no evidence for deletions that would suggest the presence of a tumor-suppressor gene in this region of chromosome 13.