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This study aimed to assess the efficacy of a guided online mindfulness-based intervention (iMBI) for community residents experiencing emotional distress during the COVID-19 pandemic in Hong Kong. In a randomized controlled trial, 64 participants were recruited from collaborating community-based mental health service units in Hong Kong and assigned to either the treatment (n = 32) or control (n = 32) groups. The treatment group received a guided iMBI consisting of 16 online modules, weekly telephone counseling, and two half-day online workshops on mindfulness practice. In contrast, the waitlist control group did not receive any intervention during the initial stage. Using a 2 (two groups) × time (pre versus post) repeated measures linear mixed model and one-way analysis of variance, authors demonstrated that the treatment group experienced a significantly larger reduction in anxiety and depressive symptoms with a large effect size compared with the control group. Additionally, the treatment group showed a significantly greater improvement in mindfulness with a moderate effect size. The findings support the effectiveness of guided iMBI for community residents experiencing emotional distress during the COVID-19 pandemic in Hong Kong., The authors would like to sincerely thank the collaborating community-based mental health service units and the participants for their cooperation and support toward this research study, funded by the Hong Kong Baptist University [REF: RC-FNRA-IG/19-20/SOSC/06].

Objective: This study investigated the effectiveness of a low-intensity online mindfulness-based Intervention (iMBI) for alleviating anxiety in university students during the COVID-19 pandemic. Methods: In a randomized controlled trial involving 134 participants from a local university in Hong Kong, subjects were randomly assigned to either the intervention group (n = 67) or the inactive control group (n = 67). The intervention group participated in a low-intensity iMBI comprising 16 online modules and two half-day online mindfulness workshops over an eight-week period. Outcomes were measured via an online platform using standardized assessment scales, including the Beck Anxiety Inventory and the Chinese Five Facets Mindfulness Questionnaire, at three different time points: pre-intervention, post-intervention and at a three-month follow-up. Results: Intent-to-treat analysis using 2 (group) × 3 (time) repeated measures of covariance (ANCOVA) showed that the intervention group, compared to the control group, showed a significant reduction in anxiety symptoms with a medium effect size (Cohen's d = 0.5) and a significant improvement in mindfulness skills with a medium effect size (Cohen's d = 0.5) at post-intervention. The effects of the intervention in reducing anxiety and improving mindfulness persisted at the three-month follow-up. Conclusion: The results of this study demonstrate the effectiveness of the low-intensity iMBI in alleviating anxiety among university students., This research study is funded by Hong Kong Baptist University (Reference no.: RC-FNRA-IG/19-20/SOSC/06).

BackgroundQuantitative ventricular volumetry and function are important in the management of congenital heart disease (CHD). Ferumoxytol-enhanced (FE) 4D multiphase, steady state imaging with contrast enhancement (MUSIC) enables high-resolution, 3D cardiac phase-resolved magnetic resonance imaging (MRI) of the beating heart and extracardiac vessels in a single acquisition and without concerns about renal impairment. We aim to evaluate the semi-automatic quantification of ventricular volumetry and function of 4D MUSIC MRI using 2D and 3D software platforms.MethodsThis HIPAA-compliant and IRB-approved study prospectively recruited 50 children with CHD (3 days to 18 years) who underwent 4D MUSIC MRI at 3.0T between 2013-2017 for clinical indications. Each patient was either intubated in the neonatal intensive care unit (NICU) or underwent general anesthesia at MRI suite. For 2D analysis, we reformatted MUSIC images in Digital Imaging and Communications in Medicine (DICOM) format into ventricular short-axis slices with zero interslice gap. For 3D analysis, we imported DICOMs into a commercially available 3D software platform. Using semi-automatic thresholding, we quantified biventricular volume and ejection fraction (EF). We assessed the bias between MUSIC-derived 2D vs. 3D measurements and correlation between MUSIC vs. conventional 2D balanced steady-state free precession (bSSFP) cine images. We evaluated intra- and inter-observer agreement.ResultsThere was a high degree of correlation between MUSIC-derived volumetric and functional measurements using 2D vs. 3D software (r=0.99, P<0.001). Volumes derived using 3D software platforms were larger than 2D by 0.2 to 2.0 mL/m2 whereas EF measurements were higher by 1.2-3.0%. MUSIC volumetric and functional measures derived from 2D and 3D software platforms corresponded highly with those derived from multi-slice SSFP cine images (r=0.99, P<0.001). The mean difference in volume for reformatted 4D MUSIC relative to bSSFP

The aggressive brain tumor glioblastoma (GBM) is characterized by rapid cellular infiltration of brain tissue, raising the possibility that disease progression could potentially be slowed by disrupting the machinery of cell migration. The LIM kinase isoforms LIMK1 and LIMK2 (LIMK1/2) play important roles in cell polarization, migration, and invasion and are markedly upregulated in GBM and many other infiltrative cancers. Yet, it remains unclear whether LIMK suppression could serve as a viable basis for combating GBM infiltration. In this study, we investigated effects of LIMK1/2 suppression on GBM invasion by combining GBM culture models, engineered invasion paradigms, and mouse xenograft models. While knockdown of either LIMK1 or LIMK2 only minimally influenced invasion in culture, simultaneous knockdown of both isoforms strongly reduced the invasive motility of continuous culture models and human GBM tumor-initiating cells (TIC) in both Boyden chamber and 3D hyaluronic acid spheroid invasion assays. Furthermore, LIMK1/2 functionally regulated cell invasiveness, in part, by disrupting polarized cell motility under confinement and cell chemotaxis. In an orthotopic xenograft model, TICs stably transduced with LIMK1/2 shRNA were implanted intracranially in immunocompromised mice. Tumors derived from LIMK1/2 knockdown TICs were substantially smaller and showed delayed growth kinetics and more distinct margins than tumors derived from control TICs. Overall, LIMK1/2 suppression increased mean survival time by 30%. These findings indicate that LIMK1/2 strongly regulate GBM invasive motility and tumor progression and support further exploration of LIMK1/2 as druggable targets. SIGNIFICANCE: Targeting the actin-binding proteins LIMK1 and LIMK2 significantly diminishes glioblastoma invasion and spread, suggesting the potential value of these proteins as therapeutic targets.

When obtaining interior 3D voxel data from triangular meshes, most existing methods fail to handle low quality meshes which happens to take up a big portion on the internet. In this work we present a robust voxelization method that is based on tetrahedral mesh generation within a user defined error bound. Comparing to other tetrahedral mesh generation methods, our method produces much higher quality tetrahedral meshes as the intermediate outcome, which allows us to utilize a faster voxelization algorithm that is based on a stronger assumption. We show the results comparing to various methods including the state-of-the-art. Our contribution includes a framework which takes triangular mesh as an input and produces voxelized data, a proof to an unproved algorithm that performs better than the state-of-the-art, and various experiments including parallelization built on the GPU and CPU. We further tested our method on various dataset including Princeton ModelNet and Thingi10k to show the robustness of the framework, where near 100% availability is achieved, while others can only achieve around 50%., Comment: 11 pages, 7 figures

Objective This prospective longitudinal cohort study at six tertiary referral centers in Canada and Denmark describes the clinical efficiency and surgical safety of cochlear implantation with the Oticon Medical Neuro cochlear implant system, including the Neuro Zti implant, the EVO electrode array, and the Neuro One sound processor. Methods Patients were adult cochlear implant candidates with bilateral sensorineural hearing loss. Results The mean HINT scores in quiet pre-operatively and at 3, 6, and 12 months post-activation were 13%, 58%, 67%, and 72%, respectively, and in noise (+10 dB SNR) 13%, 46%, 53%, and 59%, respectively. The mean improvement from baseline to 6 months post-activation was 54% in quiet and 40% in noise. The surgical major complication incidence rate was 0% and the post-surgical major complication incidence rate (until 12 months post-activation) was 4%. There was no adverse event that was fatal, that required explantation, or that resulted in sound processor nonuse, and no implant failure. Conclusion Cochlear implantation with the Oticon Medical Neuro system enables speech identification both in quiet and in noise and audiologic outcomes continue to improve in the year following activation. No substantial adverse events occurred during the surgical implantation procedure and during the 12 months post-activation., Funding Agencies|Oticon Medical

The rhizosphere microbiome (rhizobiome) plays a critical role in plant health and development. However, the processes by which the constituent microbes interact to form and maintain a community are not well understood. To investigate these molecular processes, we examined pairwise interactions between 11 different microbial isolates under select nutrient-rich and nutrient-limited conditions. We observed that when grown with media supplemented with 56 mM glucose, two microbial isolates were able to inhibit the growth of six other microbes. The interaction between microbes persisted even after the antagonistic microbe was removed, upon exposure to spent media. To probe the genetic basis for these antagonistic interactions, we used a barcoded transposon library in a proxy bacterium, Pseudomonas putida, to identify genes which showed enhanced sensitivity to the antagonistic factor(s) secreted by Acinetobacter sp. 02. Iron metabolism-related gene clusters in P. putida were implicated by this systems-level analysis. The supplementation of iron prevented the antagonistic interaction in the original microbial pair, supporting the hypothesis that iron limitation drives antagonistic microbial interactions between rhizobionts. We conclude that rhizobiome community composition is influenced by competition for limiting nutrients, with implications for growth and development of the plant.

Progestins are widely used for the treatment of gynecologic disorders and alone, or combined with an estrogen, are used as contraceptives. While their potencies, efficacies and side effects vary due to differences in structures, doses and routes of administration, little is known about their effects on the endometrial transcriptome in the presence or absence of estrogen. Herein, we assessed the transcriptome and pathways induced by progesterone (P4) and the three most commonly used synthetic progestins, medroxyprogesterone acetate (MPA), levonorgestrel (LNG), and norethindrone acetate (NETA), on human endometrial stromal fibroblasts (eSF), key players in endometrial physiology and reproductive success. While there were similar transcriptional responses, each progestin induced unique genes and biofunctions, consistent with their structural similarities to progesterone (P4 and MPA) or testosterone (LNG and NETA), involving cellular proliferation, migration and invasion. Addition of estradiol (E2) to each progestin influenced the number of differentially expressed genes and biofunctions in P4 and MPA, while LNG and NETA signatures were more independent of E2. Together, these data suggest different mechanisms of action for different progestins, with progestin-specific altered signatures when combined with E2. Further investigation is warranted for a personalized approach in different gynecologic disorders, for contraception, and minimizing side effects associated with their use.

The fusion of simultaneously recorded EEG and fMRI data is of great value to neuroscience research due to the complementary properties of the individual modalities. Traditionally, techniques such as PCA and ICA, which rely on strong non-physiological assumptions such as orthogonality and statistical independence, have been used for this purpose. Recently, tensor decomposition techniques such as parallel factor analysis have gained more popularity in neuroimaging applications as they are able to inherently contain the multidimensionality of neuroimaging data and achieve uniqueness in decomposition without making strong assumptions. Previously, the coupled matrix–tensor decomposition (CMTD) has been applied for the fusion of the EEG and fMRI. Only recently the coupled tensor–tensor decomposition (CTTD) has been proposed. Here for the first time, we propose the use of CTTD of a 4th order EEG tensor (space, time, frequency, and participant) and 3rd order fMRI tensor (space, time, participant), coupled partially in time and participant domains, for the extraction of the task related features in both modalities. We used both the sensor-level and source-level EEG for the coupling. The phase shifted paradigm signals were incorporated as the temporal initializers of the CTTD to extract the task related features. The validation of the approach is demonstrated on simultaneous EEG-fMRI recordings from six participants performing an N-Back memory task. The EEG and fMRI tensors were coupled in 9 components out of which seven components had a high correlation (more than 0.85) with the task. The result of the fusion recapitulates the well-known attention network as being positively, and the default mode network working negatively time-locked to the memory task.

The poor prognosis of glioblastoma (GBM) is associated with a highly invasive stem-like subpopulation of tumor-initiating cells (TICs), which drive recurrence and contribute to intra-tumoral heterogeneity through differentiation. These TICs are better able to escape extracellular matrix-imposed mechanical restrictions on invasion than their more differentiated progeny, and sensitization of TICs to extracellular matrix mechanics extends survival in preclinical models of GBM. However, little is known about the molecular basis of the relationship between TIC differentiation and mechanotransduction. Here we explore this relationship through a combination of transcriptomic analysis and studies with defined-stiffness matrices. We show that TIC differentiation induced by bone morphogenetic protein 4 (BMP4) suppresses expression of proteins relevant to extracellular matrix signaling and sensitizes TIC spreading to matrix stiffness. Moreover, our findings point towards a previously unappreciated connection between BMP4-induced differentiation, mechanotransduction, and metabolism. Notably, stiffness and differentiation modulate oxygen consumption, and inhibition of oxidative phosphorylation influences cell spreading in a stiffness- and differentiation-dependent manner. Our work integrates bioinformatic analysis with targeted molecular measurements and perturbations to yield new insight into how morphogen-induced differentiation influences how GBM TICs process mechanical inputs.

Study questionDo seminal plasma (SP) and its constituents affect the decidualization capacity and transcriptome of human primary endometrial stromal fibroblasts (eSFs)?Summary answerSP promotes decidualization of eSFs from women with and without inflammatory disorders (polycystic ovary syndrome (PCOS), endometriosis) in a manner that is not mediated through semen amyloids and that is associated with a potent transcriptional response, including the induction of interleukin (IL)-11, a cytokine important for SP-induced decidualization.What is known alreadyClinical studies have suggested that SP can promote implantation, and studies in vitro have demonstrated that SP can promote decidualization, a steroid hormone-driven program of eSF differentiation that is essential for embryo implantation and that is compromised in women with the inflammatory disorders PCOS and endometriosis.Study design, size, durationThis is a cross-sectional study involving samples treated with vehicle alone versus treatment with SP or SP constituents. SP was tested for the ability to promote decidualization in vitro in eSFs from women with or without PCOS or endometriosis (n = 9). The role of semen amyloids and fractionated SP in mediating this effect and in eliciting transcriptional changes in eSFs was then studied. Finally, the role of IL-11, a cytokine with a key role in implantation and decidualization, was assessed as a mediator of the SP-facilitated decidualization.Participants/materials, setting, methodseSFs and endometrial epithelial cells (eECs) were isolated from endometrial biopsies from women of reproductive age undergoing benign gynecologic procedures and maintained in vitro. Assays were conducted to assess whether the treatment of eSFs with SP or SP constituents affects the rate and extent of decidualization in women with and without inflammatory disorders. To characterize the response of the endometrium to SP and SP constituents, RNA was isolated from treated eSFs or eECs and

Objective: This prospective longitudinal cohort study at six tertiary referral centers in Canada and Denmark describes the clinical efficiency and surgical safety of cochlear implantation with the Oticon Medical Neuro cochlear implant system, including the Neuro Zti implant, the EVO electrode array, and the Neuro One sound processor. Methods: Patients were adult cochlear implant candidates with bilateral sensorineural hearing loss. Results: The mean HINT scores in quiet pre-operatively and at 3, 6, and 12 months post-activation were 13%, 58%, 67%, and 72%, respectively, and in noise (+10 dB SNR) 13%, 46%, 53%, and 59%, respectively. The mean improvement from baseline to 6 months post-activation was 54% in quiet and 40% in noise. The surgical major complication incidence rate was 0% and the post-surgical major complication incidence rate (until 12 months post-activation) was 4%. There was no adverse event that was fatal, that required explantation, or that resulted in sound processor nonuse, and no implant failure. Conclusion: Cochlear implantation with the Oticon Medical Neuro system enables speech identification both in quiet and in noise and audiologic outcomes continue to improve in the year following activation. No substantial adverse events occurred during the surgical implantation procedure and during the 12 months post-activation.

Advances in engineering biology have expanded the list of renewable compounds that can be produced at scale via biological routes from plant biomass. In most cases, these chemical products have not been evaluated for effects on biological systems, defined in the present study as bioactivity, that may be relevant to their manufacture. For sustainable chemical and fuel production, the industry needs to transition from fossil to renewable carbon sources, resulting in unprecedented expansion in the production and environmental distribution of chemicals used in biomanufacturing. Further, although some chemicals have been assessed for mammalian toxicity, environmental and agricultural hazards are largely unknown. We assessed 6 compounds that are representative of the emerging biofuel and bioproduct manufacturing process for their effect on model plants (Arabidopsis thaliana, Sorghum bicolor) and show that several alter plant seedling physiology at submillimolar concentrations. However, these responses change in the presence of individual bacterial species from the A. thaliana root microbiome. We identified 2 individual microbes that change the effect of chemical treatment on root architecture and a pooled microbial community with different effects relative to its constituents individually. The present study indicates that screening industrial chemicals for bioactivity on model organisms in the presence of their microbiomes is important for biologically and ecologically relevant risk analyses. Environ Toxicol Chem 2019;38:1911-1922. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

BACKGROUND: Patients with neurofibromatosis type 2 develop bilateral vestibular schwannomas with progressive hearing loss. Auditory brainstem implants (ABIs) stimulate hearing in the cochlear nuclei and show promise in improving hearing. Here, we assess the impact of ABI on hearing over time by systematically reviewing the literature and re-analyzing available individual patient data. METHODS: A multidatabase search identified 3 studies with individual patient data of longitudinal hearing outcomes after ABI insertion in adults. Data were collected on hearing outcomes of different sound complexities from sound to speech using an ABI +/- lip reading ability plus demographic data. Because of heterogeneity each study was analyzed separately using random effects multilevel mixed linear modeling. RESULTS: Across all 3 studies (n = 111 total) there were significant improvements in hearing over time from ABI placement (P < 0.000 in all). Improvements in comprehension of sounds, words, sentences, and speech occurred over time with ABI use + lip reading but lip reading ability did not improve over time. All categories of hearing complexity had over 50% comprehension after over 1 year of ABI use and some subsets had over 75% or near 100% comprehension. Vowel comprehension was greater than consonant, and word comprehension was greater than sentence comprehension (P < 0.0001 in both). Age and sex did not predict outcomes. CONCLUSIONS: ABIs improve hearing beyond lip reading alone, which represents baseline patient function prior to treatment, and the benefits continue to improve with time. These findings may be used to guide patient counseling regarding ABI insertion, rehabilitation course after insertion, and future studies.

Glioblastoma (GBM) is the most aggressive and common form of primary brain cancer. Several decades of research have provided great insight into GBM progression; however, the prognosis remains poor with a median patient survival time of ~ 15 months. The tumour microenvironment (TME) of GBM plays a crucial role in mediating tumour progression and thus is being explored as a therapeutic target. Progress in the development of treatments targeting the TME is currently limited by a lack of model systems that can accurately recreate the distinct extracellular matrix composition and anatomic features of the brain, such as the blood-brain barrier and axonal tracts. Biomaterials can be applied to develop synthetic models of the GBM TME to mimic physiological and pathophysiological features of the brain, including cellular and ECM composition, mechanical properties, and topography. In this Review, we summarize key features of the GBM microenvironment and discuss different strategies for the engineering of GBM TME models, including 2D and 3D models featuring chemical and mechanical gradients, interfaces and fluid flow. Finally, we highlight the potential of engineered TME models as platforms for mechanistic discovery and drug screening as well as preclinical testing and precision medicine.

Niagara is currently the fastest supercomputer accessible to academics in Canada. It was deployed at the beginning of 2018 and has been serving the research community ever since. This homogeneous 60,000-core cluster, owned by the University of Toronto and operated by SciNet, was intended to enable large parallel jobs and has a measured performance of 3.02 petaflops, debuting at #53 in the June 2018 TOP500 list. It was designed to optimize throughput of a range of scientific codes running at scale, energy efficiency, and network and storage performance and capacity. It replaced two systems that SciNet operated for over 8 years, the Tightly Coupled System (TCS) and the General Purpose Cluster (GPC). In this paper we describe the transition process from these two systems, the procurement and deployment processes, as well as the unique features that make Niagara a one-of-a-kind machine in Canada., Comment: PEARC'19: "Practice and Experience in Advanced Research Computing", July 28-August 1, 2019, Chicago, IL, USA

© 2019 Hogrefe Publishing. Adaptive motivation is central to positive functioning. Social agents such as teachers play a significant role in shaping the motivation of people with whom they interact by satisfying or thwarting their psychological needs of autonomy, competence, and relatedness. The development and validation of tools that assess the types of behaviors social agents adopt to satisfy these psychological needs are important agenda items for substantive and applied researchers. In this study, we examined factorial and convergent validity evidence of a need support scale adapted from the physical education context for use in tertiary settings with health science students. Factor analyses of responses from 290 health science students indicated that need-supportive behaviors are best captured by one latent factor, rather than the a priori 4-factor structure designed to capture needs for autonomy, relatedness, and competence. Regression analyses supported the convergent validity of the unidimensional structure, such that students who perceived higher levels of need-supportive behaviors from their tutor reported higher levels of behavioral engagement, and experiences of vitality and learning. Validation of a scale that assesses need-supportive behaviors within a health science context provides researchers with a tool to employ in future research that aims to investigate the antecedents and outcomes of such behaviors, as well as the effects of interventions designed to equip educators with the skills, motivation, and knowledge to employ successfully such behaviors.

ObjectiveTo develop a protocol for cryopreservation and recovery of human endometrial epithelial cells (eECs) retaining molecular and functional characteristics of endometrial epithelium in vivo.DesignIn vitro study using human endometrial cells.SettingUniversity research laboratory.Patient(s)Endometrial biopsies were obtained from premenopausal women undergoing benign gynecologic procedures.Intervention(s)Primary eECs were cryopreserved in 1% fetal bovine serum/10% dimethylsulfoxide in Defined Keratinocyte Serum-Free Medium (KSFM). Recovered cells were observed for endometrial stromal fibroblast (eSF) contamination and subsequently evaluated for morphology, gene expression, and functional characteristics of freshly cultured eECs and in vivo endometrial epithelium.Main outcome measure(s)Analysis of eEC morphology and the absence of eSF contamination; evaluation of epithelial-specific gene and protein expression; assessment of epithelial polarity.Result(s)Endometrial epithelial cells recovered after cryopreservation (n = 5) displayed epithelial morphology and expressed E-cadherin (CDH1), occludin (OCLN), claudin1 (CLDN1), and keratin18 (KRT18). Compared with eSF, recovered eECs displayed increased (P<.05) expression of epithelial-specific genes AREG, CDH1, DEFB4A, MMP7, and WNT7A, while exhibiting low-to-undetectable (P<.05) stromal-specific genes COL6A3, HOXA11, MMP2, PDGFRB, and WNT5A. Recovered eECs secreted levels of cytokines and growth factors similarly to freshly cultured eECs. Recovered eECs could form a polarized monolayer with high transepithelial electrical resistance (TER) and impermeability to small molecules, and expressed apical/basolateral localization of CDH1 and apical localization of OCLN.Conclusion(s)We have developed a protocol for cryopreservation of eECs in which recovered cells after thawing demonstrate morphologic, transcriptomic, and functional characteristics of human endometrial epithelium in vivo.

Purification and culture of endometrial epithelial cells (eEC) and stromal fibroblasts (eSF) from endometrial biopsies allows for downstream cell-specific in vitro studies. The utility of this protocol is the ease with which cells are purified without contamination from unwanted cell types, and the ability to use patient-paired eEC and eSF in experiments. These methods have been previously published, but here the protocol has been updated for maximum efficiency.

Seminal plasma (SP), the liquid fraction of semen, is not mandatory for conception, but clinical studies suggest that SP improves implantation rates. Prior in vitro studies examining the effects of SP on the endometrium, the site of implantation, surprisingly revealed that SP induces transcriptional profiles associated with neurogenesis. We investigated the presence and activity of neurogenesis pathways in the endometrium, focusing on TrkA, one of the canonical receptors associated with neurotrophic signaling. We demonstrate that TrkA is expressed in the endometrium. To determine if SP activates TrkA signaling, we isolated the two most abundant endometrial cell types-endometrial epithelial cells (eEC) and endometrial stromal fibroblasts (eSF)-and examined TrkA activity in these cells after SP exposure. While SP only moderately activated TrkA in eEC, it potently and rapidly activated TrkA in eSF. This activation occurred in both non-decidualized and decidualized eSF. Blocking this pathway resulted in dysregulation of SP-induced cytokine production by eSF. Surprisingly, while the canonical TrkA agonist nerve growth factor was detected in SP, TrkA activation was principally induced by a 30-100-kDa protein whose identity remains to be established. Our results show that TrkA signaling is highly active in eSF and is rapidly induced by SP.

Tightly regulated promoters are essential for numerous biological applications, where strong inducibility, portability, and scalability are desirable. Current systems are often incompatible with large-scale fermentations due to high inducer costs and strict media requirements. Here, we describe the bottom-up engineering of 'Jungle Express', an expression system that enables efficient gene regulation in diverse proteobacteria. This system is guided by EilR, a multidrug-binding repressor with high affinity to its optimized operator and cationic dyes that act as powerful inducers at negligible costs. In E. coli, the engineered promoters exhibit minimal basal transcription and are inducible over four orders of magnitude by 1 µM crystal violet, reaching expression levels exceeding those of the strongest current bacterial systems. Further, we provide molecular insights into specific interactions of EilR with its operator and with two inducers. The versatility of Jungle Express opens the way for tightly controlled and efficient gene expression that is not restricted to host organism, substrate, or scale.

In the original version of this Article, an incorrect URL was provided in the Data Availability Statement regarding the deposition of plasmids listed in Supplementary Table 4. The correct URL is https://public-registry.jbei.org/folders/378 . This error has been corrected in both the PDF and HTML versions of the Article.

Ventriculoperitoneal shunts are the current treatment of choice for congenital hydrocephalus. It is rare for physicians to see patients with alternative types of shunting devices. Lumboureteral shunts, once popular from the 1940s to 1960s, decompress via the genitourinary system. Immediate complications were dehydration, electrolyte imbalances, infection, and the sacrifice of a functional kidney. Long-term complications include retrograde meningitis due to urinary tract infections. Three shunt types have been documented: polyethylene, silicone rubber, and ureterodural anastomosis. Routine imaging cannot detect a ureterodural anastomosis, and if suspected, computed tomography myelogram is needed for confirmation. This article presents the case of a man with long-standing ureterodural anastomosis that required ligation after recurrent episodes of acute meningitis secondary to urinary retention.

Study questionHow does seminal plasma (SP) affect the transcriptome of human primary endometrial epithelial cells (eEC) and stromal fibroblasts (eSF)?Summary answerExposure of eEC and eSF to SP in vitro increases expression of genes and secreted proteins associated with cellular migration, proliferation, viability and inhibition of cell death.What is known alreadyStudies in both humans and animals suggest that SP can access and induce physiological changes in the upper female reproductive tract (FRT), which may participate in promoting reproductive success.Study design, size, durationThis is a cross sectional study involving control samples versus treatment. SP (pooled from twenty donors) was first tested for dose- and time-dependent cytotoxic effects on eEC and eSF (n = 4). As exposure of eEC or eSF to 1% SP for 6 h proved to be non-toxic, a second set of eEC/eSF samples (n = 4) was treated under these conditions for transcriptome, protein and functional analysis. With a third set of samples (n = 3), we further compared the transcriptional response of the cells to SP versus fresh semen.Participants/materials, setting, methodseEC and eSF were isolated from endometrial biopsies from women of reproductive age undergoing benign gynecologic procedures and maintained in vitro. RNA was isolated and processed for microarray studies to analyze global transcriptomic changes. Secreted factors in conditioned media from SP-treated cells were analyzed by Luminex and for the ability to stimulate migration of CD14+ monocytes and CD4+ T cells.Main results and the role of chancePathway identifications were determined using the Z-scoring system in Ingenuity Pathways Analysis (Z scores ≥|1.5|). SP induced transcriptomic changes (P < 0.05) associated with promoting leukocyte and endothelial cell recruitment, and proliferation of eEC and eSF. Cell viability pathways were induced, while those associated with cell death were suppressed (P < 0.05). SP and fresh semen induced similar

Metal-organic frameworks (MOFs), a new class of porous materials, are crystalline networks of metal clusters or ions connected by organic linkers through coordination bonds. These frameworks exhibit a rich diversity of structures, chemistries, and topologies, as evidenced by the explosion of new MOF structures in the last decade. However, the nearly infinite number of possible network connectivities and framework compositions, as well as the significant impact of minor changes in reaction conditions on the structure obtained, impedes optimization. Although high-throughput synthesis can greatly accelerate the discovery of new materials, the speed of subsequent characterization, such as gas adsorption measurements, limits the rate of optimization. In response to this challenge, we describe the development of a high-throughput nuclear magnetic resonance (NMR) porosity screening tool that uses NMR relaxation times of adsorbed molecules to estimate porosity. The diffusion and exchange processes uncovered during the development of this NMR screening tool highlight the lack of a molecular understanding of how adsorbed molecules, or guests, move in metal-organic frameworks. Thus, we investigate adsorbate dynamics in detail using NMR relaxation and diffusion experiments. Our relaxation experiments, combined with molecular simulations, establish the presence of a new condensation phenomenon occurring in a model adsorbate-MOF system. Our diffusion studies explore the interplay between the adsorbate-adsorbent interaction energy and this new condensation phenomenon on adsorbate diffusion in MOFs. These fundamental investigations, as well as our more practical efforts in developing a porosity screening tool, provide detailed insight into molecular dynamics in confined systems, and this knowledge possesses broad implications for applications in separations and catalysis.

ObjectiveTo determine the effects of coculturing endometrial epithelial cells (eEC) with paired endometrial stromal fibroblasts (eSF) on cell-specific gene expression and cytokine secretion patterns.DesignIn vitro study.SettingUniversity research laboratory.Patient(s)Endometrial biopsies were obtained from premenopausal women.Intervention(s)Polarized eEC and subject-paired eSF were cultured for 12.5 hours alone (monoculture) or combined in a two-chamber coculture system without cell-cell contact. Cells and conditioned media were analyzed for global gene expression and cytokine secretion, respectively. Purified, endometrial tissue-derived eEC and eSF isolated by fluorescent activated cell sorting (FACS) were used as noncultured controls.Main outcome measure(s)Cell-specific global gene expression profiling and analysis of secreted cytokines in eEC/eSF cocultures and respective monocultures.Result(s)Transepithelial resistance, diffusible tracer exclusion, expression of tight junction proteins, and apical/basolateral vectorial secretion confirmed eEC structural and functional polarization. Distinct transcriptomes of eEC and eSF were consistent with their respective lineages and their endometrial origin. Coculture of eEC with eSF resulted in altered cell-specific gene expression and cytokine secretion.Conclusion(s)This coculture model provides evidence that interactions between endometrial functionally polarized epithelium and stromal fibroblasts affect cell-specific gene expression and cytokine secretion underscoring their relevance when modeling endometrium in vitro.

Human endometrium undergoes extensive regeneration on a cyclic basis in premenopausal women and likely occurs through the contribution of stem/progenitor cells. Menopause results in the permanent cessation of menstrual cycles and is preceded by perimenopause, a period of several years in which endocrine and biological changes occur and is a period of risk for endometrial proliferative disorders. The objectives of this study were to identify endometrial mesenchymal stem cells (eMSC) and endometrial stromal fibroblasts (eSF) in endometrium of perimenopausal women and perform expression profile analysis of perimenopausal eMSC and eSF to gain insight into the biology of stem/progenitor and lineage cell populations during the transition to menopause. Endometrial tissue was collected from perimenopausal and premenopausal women (n = 9 each). Microarray analysis was performed on fluorescence-activated cell sorting-isolated eSF and eMSC, and data were validated by quantitative real-time PCR. Principal component analysis showed that cells clustered into three distinct groups in 3-dimensional space: perimenopausal eMSC and premenopausal eMSC clustered together, while perimenopausal eSF and premenopausal eSF formed two discrete clusters separate from eMSC. Hierarchical clustering revealed a branching pattern consistent with principle clustering analysis results, indicating that eMSC from premenopausal and perimenopausal women exhibit similar transcriptomic signatures. Pathway analysis revealed dysregulation of cytoskeleton, proliferation, and survival pathways in perimenopausal vs. premenopausal eSF. These data demonstrate that cell populations have altered gene expression in perimenopausal vs. premenopausal endometrium, and that perimenopausal eSF had altered pathway activation when compared to premenopausal eSF. This study provides insight into aging endometrium with relevance to function in reproductively older women.

Objective Intrinsic inflammatory characteristics play a pivotal role in stem cell recruitment and homing through migration where the subsequent change in niche has been shown to alter these characteristics. The bone marrow mesenchymal stem cells (bmMSCs) have been demonstrated to migrate to the endometrium contributing to the stem cell reservoir and regeneration of endometrial tissue. Thus, the aim of the present study was to compare the inflammation-driven migration and cytokine secretion profile of human bmMSCs to endometrial mesenchymal stem cells (eMSCs) and endometrial fibroblasts (eSFs). Materials and methods The bmMSCs were isolated from bone marrow aspirates through culturing, whereas eMSCs and eSFs were FACS-isolated. All cell types were tested for their surface marker, proliferation profiles and migration properties towards serum and inflammatory attractants. The cytokine/chemokine secretion profile of 35 targets was analysed in each cell type at basal level along with lipopolysaccharide (LPS)-induced state. Results Both stem cell types, bmMSCs and eMSCs, presented with similar stem cell surface marker profiles as well as possessed high proliferation and migration potential compared to eSFs. In multiplex assays, the secretion of 16 cytokine targets was detected and LPS stimulation expanded the cytokine secretion pattern by triggering the secretion of several targets. The bmMSCs exhibited higher cytokine secretion of vascular endothelial growth factor (VEGF)A, stromal cell-derived factor-1 alpha (SDF)-1 alpha, interleukin-1 receptor antagonist (IL-1RA), IL-6, interferon-gamma inducible protein (IP)-10, monocyte chemoattractant protein (MCP)1, macrophage inflammatory protein (MIP) 1 alpha and RANTES compared to eMSCs and/or eSFs after stimulation with LPS. The basal IL-8 secretion was higher in both endometrial cell types compared to bmMSCs. Conclusion Our results highlight that similar to bmMSCs, the eMSCs possess high migration activity while the different

A clear understanding of the issues surrounding climate change, global warming, air and water pollution, ozone depletion, deforestation, the loss of biodiversity and global poverty is essential for every manager in the hospitality industry. Present and future hospitality executives need to know how sustainable management systems can be integrated into their businesses while maintaining and hopefully improving the bottom line. Sustainability in the Hospitality Industry explores innovative ways to tackle the ever increasing costs of energy and water as well as the moral, ethical, social and political arguments for taking action. This book uses case studies throughout to explore the following key issues:*How can hospitality properties and equipment be designed to use less resources?*What are the benefits of using more sustainable food and beverage sources?*How can environmental impacts be reduced and profitability increased?*How can properties integrate sustainability management systems and stay one step ahead of the competition?*How can the reputation of a hospitality operation be improved to attract investment by incorporating responsible marketing and corporate social responsibility policies?

Cardiovascular side effects of cancer therapeutics are the leading causes of morbidity and mortality in cancer survivors. Anthracyclines (AC) serve as the backbone of many anti-cancer treatment strategies, but dose-dependent myocardial injury limits their use. Cumulative AC exposure can disrupt the dynamic equilibrium of the myocardial microarchitecture while repeated injury and repair leads to myocyte loss, interstitial myocardial fibrosis, and impaired contractility. Although children are assumed to have greater myocardial plasticity, AC exposure at a younger age portends worse prognosis. In older patients, there is lower overall survival once they develop cardiovascular disease. Because aberrations in the myocardial architecture predispose the heart to a decline in function, early detection with sensitive imaging tools is crucial and the implications for resource utilization are substantial. As a comprehensive imaging modality, cardiac magnetic resonance (CMR) imaging is able to go beyond quantification of ejection fraction and myocardial deformation to characterize adaptive microstructural and microvascular changes that are important to myocardial tissue health. Herein, we describe CMR as an established translational imaging tool that can be used clinically to characterize AC-associated myocardial remodeling.

Human endometrium undergoes cyclic regeneration involving stem/progenitor cells, but the role of resident endometrial mesenchymal stem cells (eMSC) as progenitors of endometrial stromal fibroblasts (eSF) has not been definitively demonstrated. In endometriosis, eSF display progesterone (P4) resistance with impaired decidualization in vivo and in vitro. To investigate eMSC as precursors of eSF and whether endometriosis P4 resistance is inherited from eMSC, we analyzed transcriptomes of eutopic endometrium eMSC and eSF isolated by fluorescence-activated cell sorting (FACS) from endometriosis (eMSCendo, eSFendo) and controls (eMSCcontrol, eSFcontrol) and their derived primary cultures. Differentially expressed lineage-associated genes (LG) of FACS-isolated eMSC and eSF were largely conserved in endometriosis. In culture, eSFcontrol maintained in vitro expression of a subset of eSF LG and decidualized in vitro with P4 The eMSCcontrol cultures differentiated in vitro to eSF lineage, down-regulating eMSC LG and up-regulating eSF LG, showing minimal transcriptome differences versus eSFcontrol cultures and decidualizing in vitro. Cultured eSFendo displayed less in vitro LG stability and did not decidualize in vitro. In vitro, eMSCendo differentiated to eSF lineage but showed more differentially expressed genes versus eSFendo cultures, and did not decidualize in vitro, demonstrating P4 resistance inherited from eMSCendo Compared to controls, cultures from tissue-derived eSFendo uniquely had a pro-inflammatory phenotype not present in eMSCendo differentiated to eSF in vitro, suggesting divergent niche effects for in vivo versus in vitro lineage differentiation. These findings substantiate eMSC as progenitors of eSF and reveal eSF in endometriosis as having P4 resistance inherited from eMSC and a pro-inflammatory phenotype acquired within the endometrial niche.

Bacterial biofilms underlie many persistent infections, posing major hurdles in antibiotic treatment. Here we design and demonstrate 'tug-of-war' optical tweezers that can facilitate the assessment of cell-cell adhesion-a key contributing factor to biofilm development, thanks to the combined actions of optical scattering and gradient forces. With a customized optical landscape distinct from that of conventional tweezers, not only can such 'tug-of-war' tweezers stably trap and stretch a rod-shaped bacterium in the observing plane, but, more importantly, they can also impose a tunable lateral force that pulls apart cellular clusters without any tethering or mechanical movement. As a proof of principle, we examined a Sinorhizobium meliloti strain that forms robust biofilms and found that the strength of intercellular adhesion depends on the growth medium. This technique may herald new photonic tools for optical manipulation and biofilm study, as well as other biological applications.

Epidemiological studies indicate that progestin-containing contraceptives increase susceptibility to HIV, although the underlying mechanisms involving the upper female reproductive tract are undefined. To determine the effects of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) on gene expression and physiology of human endometrial and cervical transformation zone (TZ), microarray analyses were performed on whole tissue biopsies. In endometrium, activated pathways included leukocyte chemotaxis, attachment, and inflammation in DMPA and LNG-IUS users, and individual genes included pattern recognition receptors, complement components, and other immune mediators. In cervical TZ, progestin treatment altered expression of tissue remodeling and viability but not immune function genes. Together, these results indicate that progestins influence expression of immune-related genes in endometrium relevant to local recruitment of HIV target cells with potential to increase susceptibility and underscore the importance of the upper reproductive tract when assessing the safety of contraceptive products.

Intravaginal anti-HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract might contribute to the lower-than-expected efficacy of HIV microbicides. Our objective was to study the effects of intravaginal gels on the immune microenvironment of the cervix and uterus. In this randomized crossover study, 27 healthy female volunteers used a nightly application of intravaginal nonoxynol-9 (N9) gel as a "failed" microbicide or the universal placebo gel (UPG) as a "safe" gel (intervention cycles), or nothing (control cycle) from the end of menses to the mid-luteal phase. At a specific time-point following ovulation, all participants underwent sample collection for measurements of T-cell phenotypes, gene expression, and cytokine/chemokine protein concentrations from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI) intervention effects, for N9 and UPG relative to control. Exposure to N9 gel and UPG generated a common "harm signal" that included transcriptional up-regulation of inflammatory genes chemokine (C-C motif) ligand 20 (macrophage inflammatory factor-3alpha) and interleukin 8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor, and transcriptional up-regulation of inflammatory mediators glycodelin-A and osteopontin in the endometrium. These results need to be replicated with a larger sample, but underscore the need to consider the effects of microbicide agents and gel excipients on the upper female reproductive tract in studies of vaginal microbicides.

OBJECTIVE: To describe a procedure for Leksell gamma knife (LGK) radiosurgery in a lateral position, for treatment of far-lateral intracranial lesions. METHODS: Positioning of the patient in the lateral decubitus position during LGK treatment switches the x and y axis coordinates. This increases the range of the x axis from 52 to 148 mm to 40 to 160 mm (i.e. 12 mm in each direction). RESULTS: Conversion of the coordinates of the isocenters is easily performed with simple mathematical algorithms and does not impair the precision of target positioning at the isocenters during LGK radiosurgery. CONCLUSION: LGK treatment in the lateral decubitus position is a simple accurate procedure for the treatment of far-lateral lesions that cannot be reached with normal supine positioning., SCOPUS: ar.j, info:eu-repo/semantics/published

Travel and tourism marketers face a highly competitive environment brought on by the changing demographics of the U.S. population, the most significant change being the growth in size of the mature segment of the population. In terms of market size, there are currently 73 million people age 50 and older, comprising nearly one-fourth of the U.S. population (U.S. Census Bureau 2000). That number is expected to rise to 96 million by 2010, representing one-third of the population (Rasmusson 2000). A swelling population is not the only enticement that this age group offers. It is important to note that many mature consumers have deep pockets and a strong desire to spend. In fact, they control more than three-quarters of the wealth and one-half of the discretionary income in the nation. It is also estimated that they lay claim to three-fourths of the country's financial assets and boast more than $1 trillion in annual buying power. When all is said and done, this age group accounts for 40 percent of the total consumer demand in the United States (Swartz, 1999). However, even though recognizing the significance of the mature market in terms of their market size and economic potential, little research has been conducted to identify and understand the mature travelers who use the Internet.The main purpose of this study is to profile mature travelers on the basis of Internet use. More specifically, the intention is to examine the demographic and socio-economic characteristics of mature travelers who use the Internet compared to those who do not use the Internet. In addition, the purpose of the present study is to examine whether or not differences exist between Internet users and Internet non-users among mature travelers with respect to travel behavior. Attention is paid to investigate types of trip selected, the preferred activities participated in during the travel, length of stay, travel-related expenditures, type of lodging, type of transportation, number in the travel pa

This study investigates how tourism affects the quality of life of residents in tourism destinations that vary in the stage of development. The proposed model in this study structurally depicts that satisfaction with life in general derives from the satisfaction with particular life domains. Overall life satisfaction is derived from material well-being, which includes the consumer's sense of well being as it is related to material possessions, community well-being, emotional well-being, and health and safety well-being domains. The model also posits that residents' perception of tourism impacts (economic, social, cultural, and environmental) affects their satisfaction of particular life domains. Lastly, this study investigates that tourism development stages moderate the relationship between residents' perception of tourism impacts and their satisfaction with particular life domains. Accordingly, the study proposed four major hypotheses: (1) residents' perception of tourism impacts affects their QOL in the community, (2) residents' satisfaction with particular life domains is affected by the perception of particular tourism impact dimensions, (3) residents' satisfaction with particular life domains affects residents' life satisfaction in general, and (4) the relationship between residents' perception of tourism impacts and their satisfaction with particulate life domains is moderated by tourism development stages. The sample population consisting of residents residing in Virginia was surveyed. The sample was proportionally stratified on the basis of tourism development stages covering counties and cities in the state. Three hundreds and twenty-one respondents completed the survey. Structural Equation Modeling and Hierarchical Multiple Regression were used to test study hypotheses. The results revealed that the residents' perception of tourism impacts did affect their satisfaction with particular life domains significantly, and their satisfaction with particular life

This study was conducted to theoretically develop and empirically test a structural equation model of tourism destination competitiveness from the tourism stakeholders'perspective. The proposed hypotheses that attempted to identify the structural relationships among the five constructs in the model were examined through a series of analyses in LISREL: 1) perceived tourism development impacts, 2) environmental attitudes, 3) place attachment, 4) development preferences about destination attractions/resources, and 5) support for destination competitive strategies The principle guideline of this study was that the support of tourism stakeholders for tourism planning and development is a key element for the successful operation, management, and long-term sustainability of tourism destinations. Tourism stakeholders' solid knowledge and experiences in tourism management and industry, professional involvement and participation in tourism planning and development, and long-term community observation and interactions have played an important role in tourism destination management. A total of 646 usable questionnaires were collected from randomly selected tourism stakeholders in the state of Virginia. From the results of hypotheses tests, tourism stakeholders' preferences about tourism attractions/ resources development are a function of perceived tourism development impacts as well as place attachment. The more stakeholders' preference for developing tourism attractions/resources, the more likely they were to support destination competitive strategies such as marketing efforts and activities, and destination management organizations' role. An additional finding that was not hypothesized indicated that tourism stakeholders, who have perceived benefits from tourism development, particularly in its economic and cultural aspects, are likely to support enhancement strategies for destination competitiveness. The implications of these findings can be applied to the enhancement of to

In the dynamic global environment of today, understanding how travelers acquire information is important for marketing management decisions (Srinivasan 1990; Wilkie and Dickson 1985). For destination marketing managers, understanding information search behavior of travelers is crucial for designing effective marketing communication campaigns because information search represents the primary stage at which marketing can provide information and influence travelers' vacation decisions. Therefore, conceptual and empirical examinations of tourist information search behavior have a long tradition in tourism marketing literature (Etzel and Wahlers, 1985; Fodness and Murray, 1997, 1998, 1999; Perdue, 1985; Schul and Crompton, 1983; Snepenger and Snepenger 1993; Woodside and Ronkainen, 1980). Even though several studies examined travelers information search behavior and the factors that are likely to affect it, they all examined travelers' prior product knowledge as a uni-dimensional construct, most often referred to as destination familiarity or previous trip experiences (Woodside and Ronkainen, 1980). However, consumer behavior literature suggests that the prior product knowledge is not a uni-dimensional construct (Alba and Hutchinson). Alba and Hutchinson (1987) propose that prior product knowledge has two major components, familiarity and expertise, and cannot be measured by a single indicator. In addition, in tourism, little research has been done on the factors that are likely to influence travelers' prior product knowledge and, therefore, their information search behavior. The purpose of this study is to examine travelers' information search behavior by studying the effects of travelers' familiarity and expertise on their information search behavior and identifying the factors that are likely to influence travelers' familiarity and expertise and their information search behavior. A travelers' information search behavior model and a measurement instrument to assess the

The purpose of this study was to identify the impact of interpersonal working relationships on employees' justice perceptions and the effects of those perceptions on employees' work-related attitudes and behavior in the hospitality industry. This study examined the mediating role played by distributive and procedural justice in linking leader-member exchange and job satisfaction, organizational commitment, and turnover intentions in the hospitality industry. The model was evaluated using structural equation modeling (SEM). The results indicated that distributive justice had a direct positive influence on job satisfaction and was negatively related to turnover intentions. Distributive justice was also found to have a strong impact on procedural justice. Procedural justice had a direct positive influence on job satisfaction. However, procedural justice was negatively related to organizational commitment, and was positively associated with turnover intentions. Thus, distributive justice played a more vital role in employees' work-related outcomes than did procedural justice. This study also indicated empirical evidence of the impact of interpersonal working relationships on employees' justice perceptions. That is, the quality of interpersonal working relationships promoted employees' perceptions of fairness. Therefore, both distributive and procedural justice played a vital mediating role in the relationships among LMX, and job satisfaction, organizational commitment, and turnover intentions. This study provides guidelines to help managers better understand how to reduce employee turnover, increase job satisfaction and organizational commitment, and make better decisions about outcomes and procedures for their employees.

Motivations behind heritage site selection was researched to glean information regarding heritage site selection. The objectives of the study were to determine: (1) The type of experience someone with an environmental preservationist and historic preservationist attitude seeks at a heritage site and (2) If the type of experience sought at a heritage site is related to the type of services and benefits sought at a heritage. Data was collected by utilizing a mailed questionnaire. Correlation analysis was used to determine if there were any relationships between Environmental Preservationist Attitude, Historic Preservationist Attitude, Benefits Sought at a Heritage Site, and Service Sought at a Heritage Site and the type of Heritage Experience preferred. The sample size consisted of 197 respondents or 29% of the 679 surveys successfully mailed. Of these respondents 37% were male and 67% were female. Most of the respondents were married (74%) and travel with their family (83%). Although no statistically significant relationships were found concerning the research hypotheses some interesting relationships surfaced relating to the value society has placed on heritage site visitation. Mainly, the great interest in a more authentic and rugged experience at a heritage site was a pattern found in the responses. This study gave a basis in which to build future research efforts in the area of heritage tourism.

The existing research in the field of tourism has exhibited a clearer understanding of how residents perceive the dynamic and complex phenomena of tourism. Since the goals of tourism planning and development are to seek maximization of benefits and minimization of the costs of tourism, it is apparent that the effective evaluation of tourism impacts will be valuable information in successful strategies for tourism product development and operation. With these perspectives, this study attempted to investigate the underlying dimensions explaining residents' perceived tourism impacts and to identify relationships between determinants and residents' perceived tourism impacts. The social exchange theory provided a fundamental framework for this study. The dimensions of the tourism impacts were addressed by explicating economic, social/cultural, environmental/physical impacts of tourism development from literature review. Ten determinants which affect residents' perception were identified from past research on tourism impacts: birthplace, length of residency, community attachment, tourism related jobs, recreational activity, tourist contacts, tourism policy participation, travel experience, levels of tourism development, and growth of community. Norfolk/Virginia Beach/Newport News MSAs areas were selected as the study area because these areas provide fine multifaceted tourism attractions, generates many tourists, and influences the host community' life. A total of 316 useful respondents (13.2%) were analyzed by using the SPSS program. Two research questions were proposed. Factor analysis, multiple regression analysis, and multivariate analysis of variance (MANAOVA) were performed. From the findings of this study, residents perceived the impacts of tourism as five different dimensions embodying economic benefits, social costs, cultural enrichment, environmental deterioration, and physical enhancement. Their perceptions were affected by eight out of ten determinants. General

In constitutive modeling, one of important tasks is to calibrate the model. To calibrate a model is to find out the values of the model parameters for a material whose stress-strain behavior is to be simulated by the model. Conventional approach is to find certain well-defined states ill certain tests where behavior of a material is controlled by those parameters and then the stress and strain and other history parameters at those states can be used to find them. However, as the model evolves more sophisticated, such as the Disturbed State Concept Model (DSC), in which a greater number of parameters are introduced to account for behavior of the material under various stress conditions, it is not possible to find an easy way to calibrate, mainly due to certain stress-strain states are difficult to be isolated out. In this study an optimization approach is proposed by using quasi-Newton method with BFGS up-dating scheme. Contrary to the conventional approach which determines parameter values by averaging values of laboratory tests or by simple data fitting of the assumed parameter relations, the optimization approach is to find the best agreement of the model simulation with the experimental observation, then gives a set of parameter values for the best agreement which is quantitatively measured by the least error residual. Weight is used in the optimization procedure to emphasize on better simulation agreement with the observation for certain stress path conditions. This weight can be decided based on the engineering judgment for certain practical problems. By using the DSC model to simulate stress-strain response of various laboratory tests of sands, and by using the DSC model in a finite element analysis to simulate dynamic soil-structure interaction response of a shaking table test for saturated soil, it is shown that the optimization approach yields closer agreement with the observation. Based on the proposed optimization approach, a computer program DSCOPT is de