Showing papers by "University of California, Irvine published in 2002"

Direct evidence for neutrino flavor transformation from neutral current interactions in the Sudbury Neutrino Observatory

Abstract: Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.

Spatializing States: Toward an Ethnography of Neoliberal Governmentality

Abstract: In this exploratory article, we ask how states come to be understood as entities with particular spatial characteristics, and how changing relations between practices of government and national territories may be challenging long-established modes of state spatiality. In the first part of this article, we seek to identify two principles that are key to state spatialization: vertically (thestate is "above"society) andencompassm ent (thestate "encompasses" its localities). We use ethnographic evidence from a maternal health project in India to illustrate our argument that perceptions of verticality and encompassment are produced through routine bureaucratic practices. In the second part, we develop a concept of transnational governmentality as a way of grasping how new practices of government and new forms of "grassroots" politics may call into question the principles of vertical ity and encompassment that have long helped to legitimate and naturalize states' authority over "the local." [states, space, governmentality, globalization, neoliberalism, India, Africa] Recent years have seen a new level of anthropological concern with the modern

Principled design of the modern Web architecture

Abstract: The World Wide Web has succeeded in large part because its software architecture has been designed to meet the needs of an Internet-scale distributed hypermedia application. The modern Web architecture emphasizes scalability of component interactions, generality of interfaces, independent deployment of components, and intermediary components to reduce interaction latency, enforce security, and encapsulate legacy systems. In this article we introduce the Representational State Transfer (REST) architectural style, developed as an abstract model of the Web architecture and used to guide our redesign and definition of the Hypertext Transfer Protocol and Uniform Resource Identifiers. We describe the software engineering principles guiding REST and the interaction constraints chosen to retain those principles, contrasting them to the constraints of other architectural styles. We then compare the abstract model to the currently deployed Web architecture in order to elicit mismatches between the existing protocols and the applications they are intended to support.

Executing SQL over encrypted data in the database-service-provider model

Abstract: Rapid advances in networking and Internet technologies have fueled the emergence of the "software as a service" model for enterprise computing. Successful examples of commercially viable software services include rent-a-spreadsheet, electronic mail services, general storage services, disaster protection services. "Database as a Service" model provides users power to create, store, modify, and retrieve data from anywhere in the world, as long as they have access to the Internet. It introduces several challenges, an important issue being data privacy. It is in this context that we specifically address the issue of data privacy.There are two main privacy issues. First, the owner of the data needs to be assured that the data stored on the service-provider site is protected against data thefts from outsiders. Second, data needs to be protected even from the service providers, if the providers themselves cannot be trusted. In this paper, we focus on the second challenge. Specifically, we explore techniques to execute SQL queries over encrypted data. Our strategy is to process as much of the query as possible at the service providers' site, without having to decrypt the data. Decryption and the remainder of the query processing are performed at the client site. The paper explores an algebraic framework to split the query to minimize the computation at the client site. Results of experiments validating our approach are also presented.

Brain monoglyceride lipase participating in endocannabinoid inactivation

Abstract: The endogenous cannabinoids (endocannabinoids) are lipid molecules that may mediate retrograde signaling at central synapses and other forms of short-range neuronal communication. The monoglyceride 2-arachidonoylglycerol (2-AG) meets several criteria of an endocannabinoid substance: (i) it activates cannabinoid receptors; (ii) it is produced by neurons in an activity-dependent manner; and (iii) it is rapidly eliminated. 2-AG inactivation is only partially understood, but it may occur by transport into cells and enzymatic hydrolysis. Here we tested the hypothesis that monoglyceride lipase (MGL), a serine hydrolase that converts monoglycerides to fatty acid and glycerol, participates in 2-AG inactivation. We cloned MGL by homology from a rat brain cDNA library. Its cDNA sequence encoded for a 303-aa protein with a calculated molecular weight of 33,367 daltons. Northern blot and in situ hybridization analyses revealed that MGL mRNA is heterogeneously expressed in the rat brain, with highest levels in regions where CB1 cannabinoid receptors are also present (hippocampus, cortex, anterior thalamus, and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL distribution has striking laminar specificity, suggesting a presynaptic localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat cortical neurons increased MGL expression and attenuated N-methyl-D-aspartate/carbachol-induced 2-AG accumulation in these cells. No such effect was observed on the accumulation of anandamide, another endocannabinoid lipid. The results suggest that hydrolysis by means of MGL is a primary mechanism for 2-AG inactivation in intact neurons.

Two-photon imaging of lymphocyte motility and antigen response in intact lymph node.

Abstract: Lymphocyte motility is vital for trafficking within lymphoid organs and for initiating contact with antigen-presenting cells. Visualization of these processes has previously been limited to in vitro systems. We describe the use of two-photon laser microscopy to image the dynamic behavior of individual living lymphocytes deep within intact lymph nodes. In their native environment, T cells achieved peak velocities of more than 25 micrometers per minute, displaying a motility coefficient that is five to six times that of B cells. Antigenic challenge changed T cell trajectories from random walks to “swarms” and stable clusters. Real-time two-photon imaging reveals lymphocyte behaviors that are fundamental to the initiation of the immune response.

Nationwide longitudinal study of psychological responses to September 11

Abstract: ContextThe September 11, 2001, attacks against the United States provide a unique opportunity to examine longitudinally the process of adjustment to a traumatic event on a national scale.ObjectiveTo examine the degree to which demographic factors, mental and physical health history, lifetime exposure to stressful events, September 11–related experiences, and coping strategies used shortly after the attacks predict psychological outcomes over time.Design, Setting, and ParticipantsA national probability sample of 3496 adults received a Web-based survey; 2729 individuals (78% participation rate) completed it between 9 and 23 days (75% within 9 to 14 days) after the terrorist attacks. A random sample of 1069 panelists residing outside New York, NY, were drawn from the wave 1 sample (n = 2729) and received a second survey; 933 (87% participation rate) completed it approximately 2 months following the attacks. A third survey (n = 787) was completed approximately 6 months after the attacks.Main Outcome MeasuresSeptember 11–related symptoms of acute stress, posttraumatic stress, and global distress.ResultsSeventeen percent of the US population outside of New York City reported symptoms of September 11–related posttraumatic stress 2 months after the attacks; 5.8% did so at 6 months. High levels of posttraumatic stress symptoms were associated with female sex (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.17-2.31), marital separation (OR, 2.55; 95% CI, 1.06-6.14), pre–September 11 physician-diagnosed depression or anxiety disorder (OR, 1.84; 95% CI, 1.33-2.56) or physical illness (OR, 0.93; 95% CI, 0.88-0.99), severity of exposure to the attacks (OR, 1.31; 95% CI, 1.11–1.55), and early disengagement from coping efforts (eg, giving up: OR, 1.68; 95% CI, 1.27-2.20; denial: OR, 1.33; 95% CI, 1.07-1.64; and self-distraction: OR, 1.31; 95% CI, 1.07-1.59). In addition to demographic and pre–September 11 health variables, global distress was associated with severity of loss due to the attacks (β = .07; P = .008) and early coping strategies (eg, increased with denial: β = .08; P = .005; and giving up: β = .05; P = .04; and decreased with active coping: β = −.08; P = .002).ConclusionsThe psychological effects of a major national trauma are not limited to those who experience it directly, and the degree of response is not predicted simply by objective measures of exposure to or loss from the trauma. Instead, use of specific coping strategies shortly after an event is associated with symptoms over time. In particular, disengaging from coping efforts can signal the likelihood of psychological difficulties up to 6 months after a trauma.

Towards robust regional estimates of CO2 sources and sinks using atmospheric transport models.

Abstract: Information about regional carbon sources and sinks can be derived from variations in observed atmospheric CO2 concentrations via inverse modelling with atmospheric tracer transport models. A consensus has not yet been reached regarding the size and distribution of regional carbon fluxes obtained using this approach, partly owing to the use of several different atmospheric transport models. Here we report estimates of surface-atmosphere CO2 fluxes from an intercomparison of atmospheric CO2 inversion models (the TransCom 3 project), which includes 16 transport models and model variants. We find an uptake of CO2 in the southern extratropical ocean less than that estimated from ocean measurements, a result that is not sensitive to transport models or methodological approaches. We also find a northern land carbon sink that is distributed relatively evenly among the continents of the Northern Hemisphere, but these results show some sensitivity to transport differences among models, especially in how they respond to seasonal terrestrial exchange of CO2. Overall, carbon fluxes integrated over latitudinal zones are strongly constrained by observations in the middle to high latitudes. Further significant constraints to our understanding of regional carbon fluxes will therefore require improvements in transport models and expansion of the CO2 observation network within the tropics.

IFN-γ-Inducible Protein 10 (IP-10; CXCL10)-Deficient Mice Reveal a Role for IP-10 in Effector T Cell Generation and Trafficking

Abstract: IFN-γ-inducible protein 10 (IP-10, CXCL10), a chemokine secreted from cells stimulated with type I and II IFNs and LPS, is a chemoattractant for activated T cells. Expression of IP-10 is seen in many Th1-type inflammatory diseases, where it is thought to play an important role in recruiting activated T cells into sites of tissue inflammation. To determine the in vivo function of IP-10, we constructed an IP-10-deficient mouse (IP-10−/−) by targeted gene disruption. Immunological analysis revealed that IP-10−/− mice had impaired T cell responses. T cell proliferation to allogeneic and antigenic stimulation and IFN-γ secretion in response to antigenic challenge were impaired in IP-10−/− mice. In addition, IP-10−/− mice exhibited an impaired contact hypersensitivity response, characterized by decreased ear swelling and reduced inflammatory cell infiltrates. T cells recovered from draining lymph nodes also had a decreased proliferative response to Ag restimulation. Furthermore, IP-10−/− mice infected with a neurotropic mouse hepatitis virus had an impaired ability to control viral replication in the brain. This was associated with decreased recruitment of CD4+ and CD8+ lymphocytes into the brain, reduced levels of IFN-γ and the IFN-γ-induced chemokines monokine induced by IFN-γ (Mig, CXCL9) and IFN-inducible T cell α chemoattractant (I-TAC, CXCL11) in the brain, decreased numbers of virus-specific IFN-γ-secreting CD8+ cells in the spleen, and reduced levels of demyelination in the CNS. Taken together, our data suggest a role for IP-10 in both effector T cell generation and trafficking in vivo.

Calcium dyshomeostasis and intracellular signalling in alzheimer's disease

Abstract: Calcium modulates many neural processes, including synaptic plasticity and apoptosis. Dysregulation of intracellular calcium signalling has been implicated in the pathogenesis of Alzheimer's disease. Increased intracellular calcium elicits the characteristic lesions of this disorder, including the accumulation of amyloid-β, the hyperphosphorylation of TAU and neuronal death. Conversely, neurodegeneration that is induced by amyloid-β or TAU is probably mediated by changes in calcium homeostasis. Disruption of calcium regulation in the endoplasmic reticulum mediates the most significant signal-transduction cascades that are associated with Alzheimer's disease. Moreover, mutations that cause familial Alzheimer's disease have been linked to intracellular calcium signalling pathways. Destabilization of calcium signalling seems to be central to the pathogenesis of Alzheimer's disease, and targeting this process might be therapeutically beneficial.

Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence

Abstract: Multiphoton microscopy relies on nonlinear light-matter interactions to provide contrast and optical sectioning capability for high-resolution imaging. Most multiphoton microscopy studies in biological systems have relied on two-photon excited fluorescence (TPEF) to produce images. With increasing applications of multiphoton microscopy to thick-tissue "intravital" imaging, second-harmonic generation (SHG) from structural proteins has emerged as a potentially important new contrast mechanism. However, SHG is typically detected in transmission mode, thus limiting TPEF/SHG coregistration and its practical utility for in vivo thick-tissue applications. In this study, we use a broad range of excitation wavelengths (730-880 nm) to demonstrate that TPEF/SHG coregistration can easily be achieved in unstained tissues by using a simple backscattering geometry. The combined TPEF/SHG technique was applied to imaging a three-dimensional organotypic tissue model (RAFT). The structural and molecular origin of the image-forming signal from the various tissue constituents was determined by simultaneous spectroscopic measurements and confirming immunofluorescence staining. Our results show that at shorter excitation wavelengths (<800 nm), the signal emitted from the extracellular matrix (ECM) is a combination of SHG and TPEF from collagen, whereas at longer excitation wavelengths the ECM signal is exclusively due to SHG. Endogenous cellular signals are consistent with TPEF spectra of cofactors NAD(P)H and FAD at all excitation wavelengths. The reflected SHG intensity follows a quadratic dependence on the excitation power, decays exponentially with depth, and exhibits a spectral dependence in accordance with previous theoretical studies. The use of SHG and TPEF in combination provides complementary information that allows noninvasive, spatially localized in vivo characterization of cell-ECM interactions in unstained thick tissues.

Measurement of Day and Night Neutrino Energy Spectra at SNO and Constraints on Neutrino Mixing Parameters

Abstract: The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is 14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.

Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy.

Abstract: Prostaglandins (PGs), bioactive lipid molecules produced by cyclooxygenase enzymes (COX-1 and COX-2), have diverse biological activities, including growth-promoting actions on gastrointestinal mucosa. They are also implicated in the growth of colonic polyps and cancers. However, the precise mechanisms of these trophic actions of PGs remain unclear. As activation of the epidermal growth factor receptor (EGFR) triggers mitogenic signaling in gastrointestinal mucosa, and its expression is also upregulated in colonic cancers and most neoplasms, we investigated whether PGs transactivate EGFR. Here we provide evidence that prostaglandin E2 (PGE2) rapidly phosphorylates EGFR and triggers the extracellular signal-regulated kinase 2 (ERK2)--mitogenic signaling pathway in normal gastric epithelial (RGM1) and colon cancer (Caco-2, LoVo and HT-29) cell lines. Inactivation of EGFR kinase with selective inhibitors significantly reduces PGE2-induced ERK2 activation, c-fos mRNA expression and cell proliferation. Inhibition of matrix metalloproteinases (MMPs), transforming growth factor-alpha (TGF-alpha) or c-Src blocked PGE2-mediated EGFR transactivation and downstream signaling indicating that PGE2-induced EGFR transactivation involves signaling transduced via TGF-alpha, an EGFR ligand, likely released by c-Src-activated MMP(s). Our findings that PGE2 transactivates EGFR reveal a previously unknown mechanism by which PGE2 mediates trophic actions resulting in gastric and intestinal hypertrophy as well as growth of colonic polyps and cancers.

Network Learning: The Effects of Partners' Heterogeneity of Experience on Corporate Acquisitions

Abstract: To examine the effects of interorganizational network structures on acquisition decisions, we propose a model whereby firms learn by sampling the diverse experiences of their network partners. We t...

e-Commerce Metrics for Net-Enhanced Organizations: Assessing the Value of e-Commerce to Firm Performance in the Manufacturing Sector

Abstract: In this study, we developed a set of constructs to measure e-commerce capability in Internet-enhanced organizations. The e-commerce capability metrics consist of four dimensions: information, transaction, customization, and supplier connection. These measures were empirically validated for reliability, content, and construct validity. Then we examined the nomological validity of these e-commerce metrics in terms of their relationships to firm performance, with data from 260 manufacturing companies divided into high IT-intensity and low IT-intensity sectors. Grounded in the dynamic capabilities perspective and the resource-based theory of the firm, a series of hypotheses were developed. After controlling for variations of industry effects and firm size, our empirical analysis found a significant relationship between e-commerce capability and some measures of firm performance (e.g., inventory turnover), indicating that the proposed metrics have demonstrated value for capturing e-commerce effects. However, our analysis showed that e-commerce tends to be associated with the increased cost of goods sold for traditional manufacturing companies, but there is an opposite relationship for technology companies. This result seems to highlight the role of resource complementarity for the business value of e-commerce--traditional companies need enhanced alignment between e-commerce capability and their existing IT infrastructure to reap the benefits of e-commerce.

The BABAR detector

Abstract: BABAR, the detector for the SLAC PEP-II asymmetric e+e- B Factory operating at the upsilon 4S resonance, was designed to allow comprehensive studies of CP-violation in B-meson decays. Charged particle tracks are measured in a multi-layer silicon vertex tracker surrounded by a cylindrical wire drift chamber. Electromagentic showers from electrons and photons are detected in an array of CsI crystals located just inside the solenoidal coil of a superconducting magnet. Muons and neutral hadrons are identified by arrays of resistive plate chambers inserted into gaps in the steel flux return of the magnet. Charged hadrons are identified by dE/dx measurements in the tracking detectors and in a ring-imaging Cherenkov detector surrounding the drift chamber. The trigger, data acquisition and data-monitoring systems, VME- and network-based, are controlled by custom-designed online software. Details of the layout and performance of the detector components and their associated electronics and software are presented.

Structure‐Activity Analyses of β‐Amyloid Peptides: Contributions of the β25–35 Region to Aggregation and Neurotoxicity

Abstract: The neurodegeneration of Alzheimer's disease has been theorized to be mediated, at least in part, by insoluble aggregates of beta-amyloid protein that are widely distributed in the form of plaques throughout brain regions affected by the disease. Previous studies by our laboratory and others have demonstrated that the neurotoxicity of beta-amyloid in vitro is dependent upon its spontaneous adoption of an aggregated structure. In this study, we report extensive structure-activity analyses of a series of peptides derived from both the proposed active fragment of beta-amyloid, beta 25-35, and the full-length protein, beta 1-42. We examine the effects of amino acid residue deletions and substitutions on the ability of beta-amyloid peptides to both form sedimentable aggregates and induce toxicity in cultured hippocampal neurons. We observe that significant levels of peptide aggregation are always associated with significant beta-amyloid-induced neurotoxicity. Further, both N- and C-terminal regions of beta 25-35 appear to contribute to these processes. In particular, significant disruption of peptide aggregation and toxicity result from alterations in the beta 33-35 region. In beta 1-42 peptides, aggregation disruption is evidenced by changes in both electrophoresis profiles and fibril morphology visualized at the light and electron microscope levels. Using circular dichroism analysis in a subset of peptides, we observed classic features of beta-sheet secondary structure in aggregating, toxic beta-amyloid peptides but not in nonaggregating, nontoxic beta-amyloid peptides. Together, these data further define the primary and secondary structures of beta-amyloid that are involved in its in vitro assembly into neurotoxic peptide aggregates and may underlie both its pathological deposition and subsequent degenerative effects in Alzheimer's disease.

Providing database as a service

Abstract: We explore a novel paradigm for data management in which a third party service provider hosts "database as a service", providing its customers with seamless mechanisms to create, store, and access their databases at the host site. Such a model alleviates the need for organizations to purchase expensive hardware and software, deal with software upgrades, and hire professionals for administrative and maintenance tasks which are taken over by the service provider. We have developed and deployed a database service on the Internet, called NetDB2, which is in constant use. In a sense, a data management model supported by NetDB2 provides an effective mechanism for organizations to purchase data management as a service, thereby freeing them to concentrate on their core businesses. Among the primary challenges introduced by "database as a service" are the additional overhead of remote access to data, an infrastructure to guarantee data privacy, and user interface design for such a service. These issues are investigated. We identify data privacy as a particularly vital problem and propose alternative solutions based on data encryption. The paper is meant as a challenge for the database community to explore a rich set of research issues that arise in developing such a service.

Improving the prediction of protein secondary structure in three and eight classes using recurrent neural networks and profiles.

Abstract: Secondary structure predictions are increasingly becoming the workhorse for several methods aiming at predicting protein structure and function. Here we use ensembles of bidirectional recurrent neural network architectures, PSI-BLAST-derived profiles, and a large nonredundant training set to derive two new predictors: (a) the second version of the SSpro program for secondary structure classification into three categories and (b) the first version of the SSpro8 program for secondary structure classification into the eight classes produced by the DSSP program. We describe the results of three different test sets on which SSpro achieved a sustained performance of about 78% correct prediction. We report confusion matrices, compare PSI-BLAST to BLAST-derived profiles, and assess the corresponding performance improvements. SSpro and SSpro8 are implemented as web servers, available together with other structural feature predictors at: http://promoter.ics.uci.edu/BRNN-PRED/. Proteins 2002;47:228–235. © 2002 Wiley-Liss, Inc.

Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus

Abstract: The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. Here we show that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock (clock-controlled). Receptor for PK2 (PKR2) is abundantly expressed in major target nuclei of the SCN output pathway. Inhibition of nocturnal locomotor activity in rats by intracerebroventricular delivery of recombinant PK2 during subjective night, when the endogenous PK2 mRNA level is low, further supports the hypothesis that PK2 is an output molecule that transmits behavioural circadian rhythm. The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output.

Segmenting Time Series: A Survey and Novel Approach

Abstract: In recent years, there has been an explosion of interest in mining time series databases. As with most computer science problems, representation of the data is the key to efficient and effective solutions. One of the most commonly used representations is piecewise linear approximation. This representation has been used by various researchers to support clustering, classification, indexing and association rule mining of time series data. A variety of algorithms have been proposed to obtain this representation, with several algorithms having been independently rediscovered several times. In this paper, we undertake the first extensive review and empirical comparison of all proposed techniques. We show that all these algorithms have fatal flaws from a data mining perspective. We introduce a novel algorithm that we empirically show to be superior to all others in the literature.

Locally adaptive dimensionality reduction for indexing large time series databases

Abstract: Similarity search in large time series databases has attracted much research interest recently. It is a difficult problem because of the typically high dimensionality of the data. The most promising solutions involve performing dimensionality reduction on the data, then indexing the reduced data with a multidimensional index structure. Many dimensionality reduction techniques have been proposed, including Singular Value Decomposition (SVD), the Discrete Fourier transform (DFT), and the Discrete Wavelet Transform (DWT). In this article, we introduce a new dimensionality reduction technique, which we call Adaptive Piecewise Constant Approximation (APCA). While previous techniques (e.g., SVD, DFT and DWT) choose a common representation for all the items in the database that minimizes the global reconstruction error, APCA approximates each time series by a set of constant value segments of varying lengths such that their individual reconstruction errors are minimal. We show how APCA can be indexed using a multidimensional index structure. We propose two distance measures in the indexed space that exploit the high fidelity of APCA for fast searching: a lower bounding Euclidean distance approximation, and a non-lower-bounding, but very tight, Euclidean distance approximation, and show how they can support fast exact searching and even faster approximate searching on the same index structure. We theoretically and empirically compare APCA to all the other techniques and demonstrate its superiority.

Hybrid choice models : Progress and challenges

Abstract: We discuss the development of predictive choice models that go beyond the random utility model in its narrowest formulation. Such approaches incorporate several elements of cognitive process that have been identified as important to the choice process, including strong dependence on history and context, perception formation, and latent constraints. A flexible and practical hybrid choice model is presented that integrates many types of discrete choice modeling methods, draws on different types of data, and allows for flexible disturbances and explicit modeling of latent psychological explanatory variables, heterogeneity, and latent segmentation. Both progress and challenges related to the development of the hybrid choice model are presented.