cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1634: CDK4/6 inhibition directly enhances an anti-tumor immune response in breast cancer

The cyclin D:cyclin-dependent kinases 4 and 6 (CDK4/6) axis is one of the most frequently dysregulated pathways in human cancers, and CDK4/6 inhibitors have shown significant activity against a number of solid tumors, including breast cancer. Analogous to clinical experience, we found that the CDK4/6 inhibitor, abemaciclib, caused significant tumor regression in the MMTV-rtTA/tetO-HER2 mouse model of luminal breast cancer. However, as CDK4/6 inhibitors are known to block tumor cell proliferation, but not directly induce tumor cell apoptosis, as we confirmed in our study, the mechanisms by which CDK4/6 inhibition caused tumor regression were not clear. Notably, abemaciclib therapy increased total CD3+ T cells in these tumors, while decreasing the immunosuppressive CD4+ regulatory T cell population. Further investigation revealed that CDK4/6 inhibition directly suppresses regulatory T cells by inhibiting their proliferation without impacting natural regulatory T cell formation in the thymus, the differentiation of inducible regulatory T cells, or regulatory T cell apoptosis. We are currently exploring potential effects of CDK4/6 inhibition on regulatory T cell function and lineage stability. Analysis of CD8+ and CD4+ T cells in abemaciclib-treated tumors revealed a marked reduction in the expression of the inhibitory immune checkpoint receptors PD-1, Tim-3, CTLA-4, and LAG3. Specifically, the fraction of CD8+ T cells expressing known markers of T cell exhaustion (PD-1/Tim-3 double-positivity or high expression of PD-1) was decreased in abemaciclib-treated tumors. Importantly, antibody-mediated depletion of CD8+ T cells established that response of MMTV-rtTA/tetO-HER2 tumors to abemaciclib is dependent on CD8+ T cells. Finally, given the observed immunomodulatory effects of abemaciclib, we sought to determine if abemaciclib treatment would sensitize MMTV-rtTA/tetO-HER2 tumors to immune checkpoint blockade. Pretreatment with abemaciclib followed by combination abemaciclib and α-PDL1 significantly enhanced tumor regression compared to abemaciclib or α-PDL1 alone. Our studies reveal a novel mechanism by which CDK4/6 inhibitors directly elicit an anti-tumor immune response. These results provide strong rationale for further investigations into combining CDK4/6 inhibitors with immune checkpoint blockade in breast cancer. Citation Format: Molly J. DeCristo*, Shom Goel*, April C. Watt, Haley BrinJones, Jaclyn Sceneay, Ben Li, Jessalyn M. Ubellacker, Shaozhen Xie, Susanne Ramm, Hye-Jung Kim, Sandra S. McAllister, Jean J. Zhao. CDK4/6 inhibition directly enhances an anti-tumor immune response in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1634. doi:10.1158/1538-7445.AM2017-1634
Response to PCOA Letters to the Editor.

To the Editor: The purpose of our review[1][1] was to neither promulgate nor suppress the Pharmacy Curriculum Outcomes Assessment (PCOA) examination but rather to review available data and inform the Academy. We appreciate the authors’ rigorous and spirited defense of the examination and explicit
The Mindful Twenty-Something: Life Skills to Handle Stress … and Everything Else: Holly B. Rogers. 2016, Oakland, CA: New Harbinger, 186 pp., $16.95. ISBN-13: 978-1626254893

A balance of practice tips, personal reflection, science notes, and take-home messages throughout The Mindful Twenty-Something is what makes this book a well-rounded book for clients, students, and...
Alignment of Personality Is Associated With Increased Intraoperative Entrustment.

Objective:To determine the association between intraoperative entrustment and personality alignment.Summary Background Data:For surgical residents, achieving operative autonomy has become increasingly difficult. The impact of faculty-resident operative interactions in accomplishing this goal is not
Impact of Social Media on Personality Development

The aim of the study is to examine the impact of social media on personality development of adolescents and to identify social media factors that influence personality development. A qualitative approach has been adopted in order fully explore the subject matter without any constraints. Data was collected using only peer reviewed Journal Articles and articles from book sections. The grounded theory method was used to reach the conclusion. The findings show that use of social media is extreme in adolescents as they use not only for socializing, but also for communication, entertainment, and all the other activities. The four main social media factors that influence personality development include (i) Culture of Popularity, (ii) Unreal Standards of Appearance, (iii) Approval Seeking Behavior, and (iv) Prevalence of Depression and Anxiety. The research has two main limitations. The first limitation is that the study does not make use of primary data in forms of interviews or observation but it was made sure that only primary sources are used. Secondly, the use of qualitative approach which increases researcher bias. The findings of this study can be used to minimize the negative effects of social media on the personality development of adolescents through educational and intervention plans. The findings show that social media has an adverse effect on the personality development of adolescents. The study specifically identifies the four personality factors that are altered by the excessive use of social media. These findings can be used to develop interventions to minimize this negative impact on adolescents.
Wirelessly Sensing Open Parking Spaces : Accounting and Management of Parking Facility

Driving into a parking lot only to find that all of the parking spaces are taken is frustrating. It would be very beneficial to implement a system that tracks the number of spaces left. Wireless sensors are well-fitted to do this task. Existing systems perform this task in various ways, discussed at the beginning of the paper. Taking the shortcomings of these systems into account, a new system based on signal strength is proposed and tested in a virtual environment.
Fetch limited drag coefficients

Measurements made at a tower located 2 km off the coast of Denmark inshallow water during the Riso Air Sea Experiment (RASEX) are analyzedto investigate the behaviour of the drag coefficient in the coastal zone.For a given wind speed, the drag coefficient is larger during conditions ofshort fetch (2-5 km) off-shore flow with younger growing waves than it isfor longer fetch (15-25 km) on-shore flow. For the strongest on-shorewinds, wave breaking enhances the drag coefficient. Variation of the neutral drag coefficient in RASEX is dominated byvariation of wave age, frequency bandwidth of the wave spectra and windspeed. The frequency bandwidth is proportional to the broadness of the waveheight spectra and is largest during conditions of light wind speeds. Usingthe RASEX data, simple models of the drag coefficient and roughness length are developed in terms of wind speed, wave age and bandwidth. An off-shoreflow model of the drag coefficient in terms of nondimensional fetch isdeveloped for situations when the wave state is not known.
The classification of involutions and symmetric spaces of modular groups

The involutions and the symmetric spaces associated to the family of modular groups of order 2m are explored. We begin by analyzing the structure of the automorphism group and by establishing which automorphisms are involutions. We conclude by calculating the fixed-point group and symmetric spaces determined by each involution.
Learning routing policies in a disrupted, congestible network with real-time information: An experimental approach

Abstract The roles of learning, inertia and real-time travel information on route choices in a highly disrupted network are investigated, based on data from a laboratory competitive route choice game. Routing policies instead of simple paths are treated as the subject of learning when real-time travel information is available, where a routing policy is defined as a contingency plan that maps realized traffic conditions to path choices. A learning model based on the power law of forgetting and reinforcement is applied to calculate the perceived travel times of alternative routing policies, based on which choices are made. A deterministic correction to the Logit choice model in a learning context is developed to account for overlapping routing policies. Model parameter estimates are obtained from maximizing the likelihood of making the observed choices on the current day based on choices from all previous days. Prediction performance is measured in terms of both one-step and full-trajectory predictions, based on observed choices up to today, in which one-step prediction entails predicting the next day’s choice, while full-trajectory prediction entails predicting the next K days’ choices. Three major conclusions are drawn. First, the routing policy learning model can capture travelers’ learning and choice behavior better than a path-based model under real-time travel information, as it accounts for travelers’ forward-looking capabilities. Secondly, inertia exists where travelers stick to previously chosen routes and do not necessarily minimize travel time. Inertia plays a dominant role in one-step prediction, and a less important role in full-trajectory prediction, suggesting that learning is more important in longer term prediction. Thirdly, relative importance of learning compared with inertia is more prominent in a less uncertain, but not close to deterministic, environment. Therefore, decreasing uncertainty by providing real-time information could encourage learning and potentially more optimal decisions for individuals and the system.
Approaches to Kurban Said’s Ali and Nino: Love, Identity, and Intercultural Conflict

This edited volume has two significant merits: it offers new scholarly perspectives on a fascinating work of German-language literature and it suggests ways in which this work can be incorporated i...
Single-Cell Analysis Reveals that the Enterococcal Sex Pheromone Response Results in Expression of Full-Length Conjugation Operon Transcripts in All Induced Cells

For high-frequency transfer of pCF10 between E. faecalis cells, induced expression of the pCF10 genes encoding conjugative machinery from the prgQ operon is required. This process is initiated by the cCF10 (C) inducer peptide produced by potential recipient cells. The expression timing of prgB, an "early" gene just downstream of the inducible promoter, has been studied extensively in single cells. However, several previous studies suggest that only 1 to 10% of donors induced for early prgQ gene expression actually transfer plasmids to recipients, even at a very high recipient population density. One possible explanation for this is that only a minority of pheromone-induced donors actually transcribe the entire prgQ operon. Such cells would not be able to functionally conjugate but might play another role in the group behavior of donors. Here, we sought to (i) simultaneously assess the presence of RNAs produced from the proximal (early induced transcripts [early Q]) and distal (late Q) portions of the prgQ operon in individual cells, (ii) investigate the prevalence of heterogeneity in induced transcript length, and (iii) evaluate the temporality of induced transcript expression. Using fluorescent in situ hybridization chain reaction (HCR) transcript labeling and single-cell microscopic analysis, we observed that most cells expressing early transcripts (QL, prgB, and prgA) also expressed late transcripts (prgJ, pcfC, and pcfG). These data support the conclusion that, after induction is initiated, transcription likely extends through the end of the conjugation machinery operon for most, if not all, induced cells.IMPORTANCE In Enterococcus faecalis, conjugative plasmids like pCF10 often carry antibiotic resistance genes. With antibiotic treatment, bacteria benefit from plasmid carriage; however, without antibiotic treatment, plasmid gene expression may have a fitness cost. Transfer of pCF10 is mediated by cell-to-cell signaling, which activates the expression of conjugation genes and leads to efficient plasmid transfer. Yet, not all donor cells in induced populations transfer the plasmid. We examined whether induced cells might not be able to functionally conjugate due to premature induced transcript termination. Single-cell analysis showed that most induced cells do, in fact, express all of the genes required for conjugation, suggesting that premature transcription termination within the prgQ operon does not account for failure of induced donor cell gene transfer.
Some questions about the attention schema theory

There are a number of overlapping themes in the target article by Graziano and colleagues (Graziano et al. 2020), such as a defense of their attention schema theory (or AST), how people’s understan...
The ABCs of ERM: Demystifying Electronic Resource Management for Public and Academic Librarians

People at all stages experience imposter syndrome, but it is especially prominent when a person is first starting a new role. eResources are no longer novel but many library staff members who take ...
Controlling electrochemical growth of metallic zinc electrodes: Toward affordable rechargeable energy storage systems.

Scalable approaches for precisely manipulating the growth of crystals are of broad-based science and technological interest. New research interests have reemerged in a subgroup of these phenomena—electrochemical growth of metals in battery anodes. In this Review, the geometry of the building blocks and their mode of assembly are defined as key descriptors to categorize deposition morphologies. To control Zn electrodeposit morphology, we consider fundamental electrokinetic principles and the associated critical issues. It is found that the solid-electrolyte interphase (SEI) formed on Zn has a similarly strong influence as for alkali metals at low current regimes, characterized by a moss-like morphology. Another key conclusion is that the unique crystal structure of Zn, featuring high anisotropy facets resulting from the hexagonal close-packed lattice with a c/a ratio of 1.85, imposes predominant influences on its growth. In our view, precisely regulating the SEI and the crystallographic features of the Zn offers exciting opportunities that will drive transformative progress.
Transcriptomic response patterns of hornyhead turbot (Pleuronichthys verticalis) dosed with polychlorinated biphenyls and polybrominated diphenyl ethers

Abstract To evaluate the impact of environmental contaminants on aquatic health, extensive surveys of fish populations have been conducted using bioaccumulation as an indicator of impairment. While these studies have reported mixtures of chemicals in fish tissues, the relationship between specific contaminants and observed adverse impacts remains poorly understood. The present study aimed to characterize the toxicological responses induced by persistent organic pollutants in wild-caught hornyhead turbot (P. verticalis). To do so, hornyhead turbot were interperitoneally injected with a single dose of PCB or PBDE congeners prepared using environmentally realistic mixture proportions. After 96-hour exposure, the livers were excised and analyzed using transcriptomic approaches and analytical chemistry. Concentrations of PCBs and PBDEs measured in the livers indicated clear differences across treatments, and congener profiles closely mirrored our expectations. Distinct gene profiles were characterized for PCB and PBDE exposed fish, with significant differences observed in the expression of genes associated with immune responses, endocrine-related functions, and lipid metabolism. Our findings highlight the key role that transcriptomics can play in monitoring programs to assess chemical-induced toxicity in heterogeneous group of fish (mixed gender and life stage) as is typically found during field surveys. Altogether, the present study provides further evidence of the potential of transcriptomic tools to improve aquatic health assessment and identify causative agents.
Neural reward circuit dysfunction as a risk factor for bipolar spectrum disorders and substance use disorders: A review and integration

Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are associated with neural reward dysfunction. However, it is unclear what pattern of neural reward function underlies pre-existing vulnerability to BSDs and SUDs, or whether neural reward function explains their high co-occurrence. The current paper provides an overview of the separate literatures on neural reward sensitivity in BSDs and SUDs. We provide a systematic review of 35 studies relevant to identifying neural reward function vulnerability to BSDs and SUDs. These studies include those examining neural reward processing on a monetary reward task with prospective designs predicting initial onset of SUDs, familial risk studies that examine unaffected offspring or first-degree relatives of family members with BSDs or SUDs, and studies that examine individuals with BSDs or SUDs who are not currently in an episode of the disorder. Findings from the review highlight that aberrant responding and connectivity across neural regions associated with reward and cognitive control confers risk for the development of BSDs and SUDs. Discussion focuses on limitations of the extant literature. We conclude with an integration and theoretical model for understanding how aberrant neural reward responding may constitute a vulnerability to the development of both BSDs and SUDs.
Community Health Centers' Practices, Barriers, and Facilitators for Providing a 1-Year Supply of Oral Contraception on Site

Abstract Introduction High-quality family planning services help women to achieve their preferred family size and birth spacing, which in turn leads to improved health outcomes and better quality of life. This study investigates whether women have access to a 1-year supply of oral contraceptives (OCs) on site when they receive care at community health centers and whether states require coverage for a 1-year supply. Methods This study used a concurrent, mixed-methods approach, with a single phase of quantitative research (survey of health centers) and two phases of qualitative research (50-state policy environment scan and in-depth interviews). Results Only three states require coverage for a 1-year supply of OCs under all Medicaid and private insurance coverage mechanisms; the majority of states limit it through at least one mechanism. The survey found that 50.9% of health centers provided OCs on site, and of these, only 29.9% offered up to a 1-year supply at a time. An analysis of interviews revealed that clinician and pharmacist preferences and the organization's overall approach to family planning played a role in these practices. Conclusion This study finds that that only a minority of health centers provide a 1-year supply on site and that a minority of states have rules requiring coverage for a 1-year supply of OCs. To remedy these gaps, change is needed at multiple levels, including health center practices, clinician knowledge and beliefs, federal agency guidance, and state-level insurance policy.
Evidence for impaired chronotropic responses to and recovery from 6-minute walk test in women with post-acute COVID-19 syndrome.

NEW FINDINGS: What is the central question of this study? Are chronotropic responses to a 6-minute walk test different in women with post-acute coronavirus disease 2019 (COVID-19) syndrome compared with control subjects? What is the main finding and its importance? Compared with control subjects, the increase in heart rate was attenuated and recovery delayed after a 6-minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Such alterations have potential to constrain not only exercise tolerance but also participation in free-living physical activity in women during post-acute recovery from COVID-19. ABSTRACT: The short-term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well defined. However, the implications of cardiopulmonary sequelae, persisting beyond acute illness, on physical function are largely unknown. Herein, we characterized heart rate responses to and recovery from a 6-minute walk test (6MWT) in women â¼3 months after mild-to-moderate SARS-CoV-2 infection compared with non-infected control subjects. Forty-five women (n = 29 SARS-CoV-2; n = 16 controls; age = 56 ± 11 years; body mass index = 25.8 ± 6.0 kg/m2 ) completed pulmonary function testing and a 6MWT. The SARS-CoV-2 participants demonstrated reduced total lung capacity (84 ± 8 vs. 93 ± 13%; P = 0.006), vital capacity (87 ± 10 vs. 93 ± 10%; P = 0.040), functional residual capacity (75 ± 16 vs. 88 ± 16%; P = 0.006) and residual volume (76 ± 18 vs. 93 ± 22%; P = 0.001) compared with control subjects. No between-group differences were observed in 6MWT distance (P = 0.194); however, the increase in heart rate with exertion was attenuated among SARS-CoV-2 participants compared with control subjects (+52 ± 20 vs. +65 ± 18 beats/min; P = 0.029). The decrease in heart rate was also delayed for minutes 1-5 of recovery among SARS-CoV-2 participants (all P < 0.05). Women reporting specific symptoms at the time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Our findings provide evidence for marked differences in chronotropic responses to and recovery from a 6MWT in women several months after acute SARS-CoV-2 infection.
Multi-Zone DI Diesel Spray Combustion Model for Cycle Simulation Studies of Engine Performance and Emissions

A quasi -dimensional, multi-zone, direct injection (DI) diesel combustion model has been developed and implemented in a full cycle simulation of a turbocharged engine. The combustion model accounts for transient fuel spray evolution, fuel-air mixing, ignition, combustion and NO and soot pollutant formation. In the model, the fuel spray is divided into a number of zones, which are treated as open systems. While mass and energy equations are solved for each zone, a simplified momentum conservation equation is used to ca lculate the amount of air entrained into each zone. Details of the DI spray, combustion model and its implementation into the cycle simulation of Assanis and Heywood [1] are described in this paper. The model is validated with experimental data obtained in a constant volume chamber and engines. First, predictions of spray penetration and spray angle are validated against measurements in a pressurized constant volume chamber. Subsequently, predictions of heat release rate, as well as NO and soot emissions are compared with experimental data obtained from representative heavy-duty, turbocharged diesel engines. It is demonstrated that the model can predict the rate of heat release and engine performance with high fidelity. However, additional effort is require d to enhance the fidelity of NO and soot predictions across a wide range of operating conditions.
Managing Carbon Regulatory Risk in Utility Resource Planning: Current Practices in the Western United States

Concerns about global climate change have substantially increased the likelihood that future policy will seek to minimize carbon dioxide emissions. As such, even today, electric utilities are making resource planning and investment decisions that consider the possible implications of these future carbon regulations. In this article, we examine the manner in which utilities assess the financial risks associated with future carbon regulations within their long-term resource plans. We base our analysis on a review of the most recent resource plans filed by fifteen electric utilities in the Western United States. Virtually all of these utilities made some effort to quantitatively evaluate the potential cost of future carbon regulations when analyzing alternate supply- and demand-side resource options for meeting customer load. Even without Federal climate regulation in the U.S., the prospect of that regulation is already having an impact on utility decision-making and resource choices. That said, the methods and assumptions used by utilities to analyze carbon regulatory risk, and the impact of that analysis on their choice of a particular resource strategy, vary considerably, revealing a number of opportunities for analytic improvement. Though our review focuses on a subset of U.S. electric utilities, this work holds implications for all electric utilities and energy policymakers who are seeking to minimize the compliance costs associated with future carbon regulations.
Calibrated micropost arrays for biomechanical characterisation of cardiomyocytes

The study of biomechanics of isolated cardiomyocytes can allow us to understand the cardiac function and disease development in the absence of viscoelastic or contractile properties of the surrounding tissue. However, popular techniques such as micropipettes and carbon fibre-based measurements require serial, single-cell measurements and limit the amount of data passing through a system or process. The authors utilise elastomer micropost arrays microfabricated by a replica molding technique for precise and quantitative force measurements of cardiomyocytes with the potential for high throughput. The authors also present a calibration system using a piezoresistive force sensor and video-analysis technique to improve the resolution and validate the analysis of these low-force measurements. Calibrated microposts arrays are applied to measure the contractile forces of rat neonatal cardiomyocytes. Using image processing, the contractile forces for a sample of cardiomyocytes are extracted. It was found that isolated rat neonatal myocytes generate 39 ± 5 nN average contractile force per post and an integrated axial contractile force of 189 ± 20 nN, which is four times smaller than isolated adult Wistar rat cardiomyocytes and 30 times smaller than isolated adult rat cardiomyocytes. With calibration and quantitative image analysis, this study demonstrates that micropost systems can provide precise high-throughput test beds for myocyte mechanics using pharmacologic, small peptide, gene therapies or heart disease models.
An Exploratory Study of Gender and Age Matching in the Salesperson-Prospective Customer Dyad: Testing Similarity-Performance Predictions

The increasingly diversified composition of the sales force poses one of the most challenging organizational issues of our time. Employing similarity-attraction theory and social identity theory, this study provides theoretical foundations for: (1) investigating salesperson preferences for selling to similar others; and (2) exploring the dynamic nature of these preferences as they relate to sales performance. The results of an empirical study using a sample drawn from insurance sales indicated that salespeople are primarily attracted to prospects who are similar to themselves in terms of age and gender. However, contrary to predictions, buyer/seller age similarity was found to have no impact on sales performance, while gender mismatch in the sales dyad was found to actually enhance performance.
Twice Upon a Time: Women Writers and the History of the Fairy Tale

Reviewed Medium: book Authors: Elizabeth Wanning Harries Year: 2001 Pages: xiv + 216 Publisher: Princeton University Press Prices: $18.75 US
Why implicit attitudes are (probably) not beliefs

Should we understand implicit attitudes on the model of belief? I argue that implicit attitudes are (probably) members of a different psychological kind altogether, because they seem to be insensitive to the logical form of an agent’s thoughts and perceptions. A state is sensitive to logical form only if it is sensitive to the logical constituents of the content of other states (e.g., operators like negation and conditional). I explain sensitivity to logical form and argue that it is a necessary condition for belief. I appeal to two areas of research that seem to show that implicit attitudes fail spectacularly to satisfy this condition—although persistent gaps in the empirical literature leave matters inconclusive. I sketch an alternative account, according to which implicit attitudes are sensitive merely to spatiotemporal relations in thought and perception, i.e., the spatial and temporal orders in which people think, see, or hear things.
Human intestinal brush border angiotensin-converting enzyme activity and its inhibition by antihypertensive Ramipril.

Abstract Angiotensin-converting enzyme (ACE) has been identified as a prominent brush border membrane-bound enzyme of human jejunum. In this study, we purified brush border membrane vesicles enriched in ACE, and characterized the ACE with regard to (a) its stability in the membrane, (b) substrate hydrolysis kinetics compared with pulmonary endothelial ACE, and (c) pharmacologic interaction with Ramipril. These investigations resulted in the following findings. The uninhibited enzyme is stable in native membranes in vitro, with a half-life of 195 ± 7 h. Kinetic analysis of ACE hydrolysis activity revealed the presence of a single enzyme species, which yielded a high V max and displayed a K m similar to purified ACE from lung endothelium. Brush border ACE was inhibited by Ramipril, one of the most specific and potent orally administered ACE inhibitors indicated for hypertension. We determined the brush border ACE value of IC 50 = 3 × 10 −9 M Ramipril-diacid, which is the same value for serum and lung ACE. Brush border ACE remains 100% inhibited by 10 μM Ramipril during at least 8 days in vitro. The data indicate that ACE is a prominent jejunal brush border enzyme that behaves pharmacologically and kinetically like its peripheral circulation counterpart. This study suggests that high doses of orally administered ACE inhibitors may affect intestinal epithelial function.
The power of search engine ranking for tourist destinations

Abstract Most online travelers in the United States use search engines to seek out travel information. Thus, Destination Marketing Organizations (DMOs) need to attract clicks through returned results on search engines. We modeled clickthrough rates (CTRs) of several published clickthrough reports and investigate the CTRs of a DMO's webpages on different ranks of different properties (web, image, and mobile searches) on a search engine. The results validated the power-law distribution of CTRs on different ranks: the top results attract high CTRs but the rates decrease precipitously when the ranks go down. However, top ranks are a necessary condition but not a sufficient one: many top ranked results have low CTRs. Image search and mobile search have different CTR curves, providing different opportunities for tourism destinations and businesses.
A procedural route toward understanding aspects of proof: Case studies from real analysis

In this paper, I describe how some students can successfully develop their understanding of proof techniques by viewing the act of proving as a procedure. This learning route is discussed within the context of a study in which I investigated the learning of six undergraduates in a first course in real analysis. These undergraduates first understood proof as an algorithm—or a step-by-step mechanical prescription for proving certain types of statements. They then condensed this algorithm into a process—or a shorter list of global, qualitative steps. By reflecting on the process, the successful students in this study viewed proving as forming an argument, or as an act that establishes the veracity of a mathematical statement. I illustrate this learning route by presenting a detailed analysis of two of the students from this study. Finally, I note that many of the students in this study who viewed proof as a process failed to view proof as an argument by the end of the course and I discuss the consequences of these students’ narrow view of proof.
Contrasting patterns of mitochondrial redistribution in the early lineages of Caenorhabditis elegans and Acrobeloides sp. PS1146.

Abstract We compared the redistribution of mitochondria in the early embryos of Caenorhabditis elegans (C. elegans) and Acrobeloides sp. PS1146 (Acrobeloides)—two nematode species where the mechanisms for embryonic axis specification are different even though subsequent development is remarkably similar (Goldstein et al., 1998) . During the first cell cycle of C. elegans, mitochondria move with the bulk cytoplasmic flows that are directed toward the sperm pronucleus and aggregate at the posterior cortex during the period known as “pseudocleavage.” In contrast, in Acrobeloides embryos, where prominent cytoplasmic rearrangements are absent, mitochondria that are initially distributed loosely around the pronuclei and the cytoplasm are relocated around the mitotic spindle prior to cell division. Interestingly, this rearrangement is reiterated only in the germline and not the somatic lineage. In both species, the location of the mitochondria immediately prior to cell division correlates with the known location of the germline determinants, P granules, leading us to speculate that they may be associated.
Hydrogen inhalation for detecting intracardiac left-to-right shunting in adults

Abstract The hydrogen inhalation technique is easily performed and exquisitely sensitive for detecting intracardiac left-to-right shunting. Previous studies of this technique relied heavily on data from infants and children, and the distinction between “normal” and “abnormal” was imprecise and somewhat arbitrary. The present study was done to assess the results of hydrogen inhalation in adults with and without intracardiac left-tonight shunting. In 45 adult subjects (15 men, 30 women, aged 18 to 72 years) (18 without and 27 with intracardiac left-to-right shunting), the elapsed time from hydrogen inhalation to its appearance in the pulmonary artery was measured. The 18 patients without shunting had an appearance time of 12 ± 3 (mean ± SD) seconds, and it was ≥9 seconds in all. In contrast, the 27 subjects with shunting had an appearance time of 1.5 ± 0.7 second, with only 1 of 27 being ≥3 seconds. There was no relation between the magnitude of left-to-right shunting and the hydrogen appearance time. Thus, the hydrogen inhalation technique easily and reliably separates adult subjects with and without intracardiac left-to-right shunting, with no overlap between the 2 groups.
Effect of interference on the performance of glucose enzyme electrodes using Nafion® coatings

Abstract The negatively charged perfluorinated ionomer Nafion® was used as a coating on hydrogen peroxide detecting platinum electrode as well as on a polycarbonate diffusion membrane in the construction of a glucose amperometric enzyme electrode. The current response of these electrodes to hydrogen peroxide, ascorbic acid, acetaminophen, uric acid and glucose was studied and the coating procedure was optimized. It was confirmed that the Nafion® coating prevents interference by anionic substances such as ascorbic acid and uric acid, and decreases acetaminophen interference. In this regard it was shown that coating the glucose diffusion membrane (polycarbonate) was more effective than coating the platinum wire itself, because of the prevention of the homogeneous redox reaction of the interference species with hydrogen peroxide, as well as the additional diffusional resistance to the glucose flux. The glucose levels in serum samples were estimated and the stability of the enzyme electrodes during continuous operation in serum was studied. An enzyme electrode with constant sensitivity of ca. 1 μA/m m and a linear range of up to 15 m m , unaffected by contact with serum, is reported.
Business Architecture Elicitation for Enterprise Architecture: VMOST versus Conventional Strategy Capture

The goal of enterprise architecture (EA) artifacts is to create an information technology (IT) infrastructure that aligns with the institution's business environment. To facilitate this, enterprise architecture frameworks (EAF) have been used to understand an enterprise's strategy and business architecture to synthesize a supporting IT strategy. This understanding is critical to the success of an EA. This paper contrasts the use of a systematic elicitation approach, VMOST, to recently completed strategy capture artifacts. We assess our approach through interviews with a number of employees across several departments within a University library, then comparing the interview responses to the conventionally compiled Strategic Plan. Placing data gathered by the two efforts side by side will allow coverage comparison of EA-unguided artifacts against a lightweight-guidance method and determine the usefulness of a non-EA strategy effort in completing an EAF. Insights into the utility of the two methods will be provided by completing relevant aspects of the Zachman Framework, which will further the understanding of the use of EA methods and tools within organizations without EA expertise or significant experience.
Contentious Language: South Park and the Transformation of Meaning

Abstract Disputes over language and meaning are central themes in South Park. The show pushes the boundaries of acceptable communication and challenges censorship. This article explores the show's treatment of language. It focuses on one episode, “The F Word,” to illustrate how the show uses sophisticated strategies of contesting meaning.
Contrasting simulated and empirical experiments in crime prevention

This paper argues that simulated experiments of crime prevention interventions are an important class of research methods that compare favorably with empirical experiments. It draws on Popper’s demarcation between science and non-science (Conjectures and refutations: the growth of scientific knowledge. Routledge, London, 1992) and Epstein’s principle of generative explanation (Generative social science: studies in agent-based computational modeling. Princeton University Press, Princeton, NJ, 2006) to show how simulated experiments can falsify theory. The paper compares simulated and empirical experiments and shows that simulations have strengths that empirical methods lack, but they also have important relative weaknesses. We identify three threats to internal validity and two forms of external validity peculiar to simulated experiments. The paper also looks at the problem of validating simulations with crime data and suggests that simulations need to mimic the error production processes involved in the creation of empirical data. It concludes by listing ways simulations can be used to improve empirical experiments and discussing the differing operating assumption of empirical and simulation experimentalists.
Hepatic targeting of transplanted liver sinusoidal endothelial cells in intact mice

Targeting of cells to specific tissues is critical for cell therapy. To study endothelial cell targeting, we isolated mouse liver sinusoidal endothelial cells (LSEC) and examined cell biodistributions in animals. To identify transplanted LSEC in tissues, we labeled cells metabolically with DiI-conjugated acetylated low density lipoprotein particles (DiI-Ac-LDL) or (111)Indium-oxine, used LSEC from Rosa26 donors expressing beta-galactosidase or Tie-2-GFP donors with green fluorescent protein (GFP) expression, and tranduced LSEC with a GFP-lentiviral vector. LSEC efficiently incorporated (111)Indium and DiI-Ac-LDL and expressed GFP introduced by the lentiviral vector. Use of radiolabeled LSEC showed differences in cell biodistributions in relation to the cell transplantation route. After intraportal injection, LSEC were largely in the liver (60 +/- 13%) and, after systemic intravenous injection, in lungs (67 +/- 9%); however, after intrasplenic injection, only some LSEC remained in the spleen (29 +/- 10%; P < .01), whereas most LSEC migrated to the liver or lungs. Transplanted LSEC were found in the liver, lungs, and spleen shortly after transplantation, whereas longer-term cell survival was observed only in the liver. Transplanted LSEC were distinct from Kupffer cells with expression of Tie-2 promoter-driven GFP and of CD31, without F4/80 reactivity. In further studies using radiolabeled LSEC, we established that the manipulation of receptor-mediated cell adhesion in liver sinusoids or the manipulation of blood flow-dependent cell exit from sinusoids improved intrahepatic retention of LSEC to 89 +/- 7% and 89 +/- 5%, respectively (P < .01). In conclusion, the targeting of LSEC to the liver and other organs is directed by vascular bed-specific mechanisms, including blood flow-related processes, and cell-specific factors. These findings may facilitate analysis of LSEC for cell and gene therapy applications.
Pregnancy, labor, delivery, and pelvic organ prolapse.

Abstract OBJECTIVE: To compare 1) the occurrence of pelvic organ prolapse after vaginal and cesarean delivery, and 2) the susceptibility of black and white women to developing prolapse during childbirth. METHODS: Ninety-four nulliparous women were evaluated for pelvic organ prolapse at their 36-week antepartum and 6-week postpartum visits using the International Continence Society staging system. A change in International Continence Society stage from 36 weeks antepartum to 6 weeks postpartum was considered pelvic organ prolapse that developed during childbirth. RESULTS: Forty-three (46%) of 94 nulliparous women had pelvic organ prolapse at their 36-week antepartum visit. Twenty-four (26%) had a stage II prolapse. Six weeks postpartum, 13 of 41 (32%) who had spontaneous vaginal delivery and nine of 26 (35%) who had cesarean delivery during active labor developed a new prolapse (P = .805). Seven (17%) who had spontaneous vaginal delivery and two (8%) who had cesarean delivery during active labor revealed a more severe prolapse (P = .237). Eighteen (33%) of 54 black and 17 (43%) of 40 white women developed a new prolapse during childbirth (P = .363). Eight (15%) black and six (15%) white women revealed a more severe prolapse (P = .980). CONCLUSION: Our data suggest that elective cesarean is only partially effective in preventing pelvic organ prolapse. Cesarean delivery during active labor and vaginal delivery had a similar effect on the maternal pelvic support. This indicates that prolapse developed during the first and not the second stage of labor. Black women are as susceptible to developing prolapse during childbirth as their white counterparts.
Relationship of chemiluminescence and electron spin resonance of plasma irradiated saccharides

Abstract Electron spin resonance (ESR) and chemiluminescence (CL) were measured on six saccharide samples irradiated in argon plasma and on celluloses from six sources irradiated in plasma of a nitrogen-hydrogen mixture. ESR readings were taken immediately after irradiation on samples kept under argon. The statistical relationship between the maximum levels of CL for irradiated samples exposed to air and their ESR signal intensities was determined by regression analysis. A relationship of CL to ESR was shown to exist within each of the two sets of samples and the linear regression equation was developed for each set so that the CL intensity could be predicted if the ESR intensity was known. The correlation between CL and ESR was 0·85 (significant at p
Thiophosphorylation and phosphorylation of saponin-permeabilized cultured chromaffin cells

Abstract There is increasing evidence that phosphorylation of cellular proteins plays a role in the control of events surrounding secretion in neurons and chromaffin cells. In previous studies, we have used thiophosphorylation of cell proteins as a means of fixing cellular phosphorylation reactions in the phosphorylated state. Thiophosphorylation of permeabilized chromaffin cells with adenosine-5′-O-(3-thiotriphosphate) results in irreversible inhibition of secretion. Thiophosphate is incorporated primarily by two cellular proteins of 58 and 47 kDa. Calcium enhanced thiophosphorylation of the 47 kDa protein but not the 54 kDa protein. This pattern of thiophosphorylation differed markedly from that for phosphorylation under similar treatment conditions. The phosphoprotein composition of the cells depended upon the medium calcium and ATP concentration. In the absence of exogenous ATP, fewer phosphoproteins were seen in calcium stimulated cells than in unstimulated cells. Proteins labelled with 32P or 35S migrated to the same position on polyacrylamide gels containing sodium dodecyl sulfate. In the presence of exogenous ATP, 32P incorporation was similar for both control and calcium-stimulated cells and was found primarily in a 64 kDa protein. Incorporation of [32P]phosphate by calcium-stimulated cells was reduced to the same extent by pretreatment of the cells with either adenosine-5′-O-(3-thiotriphosphate) or ATP. The different electrophoretic banding patterns for thiophosphorylation and phosphorylation are likely due to the irreversibility of the thiophosphorylation reaction and reversibility of the phosphorylation reaction. The inability to turn over thiophosphate groups, in association with changes in secretion, may permit identification of those phosphoproteins that are putatively involved in secretion.
Monolithic Silicon Probes with Flexible Parylene Cables for Neural Prostheses

This work presents the first parylene-insulated silicon probes, which are used for neural prostheses to record high-level cognitive neural signals. With parylene technology, our probes have several advantages compared with the current devices. First, instead of inorganic materials (e.g. silicon dioxide, silicon nitride), the electrodes and conduction traces on the probes are insulated by parylene, an easily-deposited polymer with mechanical flexibility and biocompatibility. As a result, the probes exhibit better electrical and mechanical properties. Second, flexible parylene cables are monolithically integrated with the probes, which arm the probes with very high flexibility to be easily assembled to a high density 3-D array and at the same time provide an ideal method to transmit neural signals through skull during chronic recording. The all dry fabrication process and a 4times4 probe array (64 electrodes) were demonstrated. The probes were successfully tested electrically and mechanically in rat cortex. Neural signals were properly recorded
Spatial relationships: a framework for understanding the relationships between real and virtual spaces

In this paper, I describe how representation, mapping, and interaction create the basis of a framework for discussing the relationships between real and virtual spaces and describe the design of an installation to illustrate these concepts.
Moving an incisor across the midline: A treatment alternative in an adolescent patient

A 13-year-old sought treatment for a severely compromised maxillary left central incisor and an impacted fully developed left canine. Extraction of both teeth became necessary. As the key component of the revised comprehensive treatment plan, the right maxillary central incisor was moved into the position of the left central incisor. All other maxillary teeth were moved mesially to close any gaps. Active orthodontic treatment was completed after 34 months. Frenectomy, minor periodontal surgeries, and bonded lingual retainers were used to improve aesthetics and stabilize the tooth positions. The patient was pleased with the treatment outcome. Cone-beam computed tomography provided evidence that the tooth movement was accompanied by a deviation of the most anterior portion of the median palatine suture. This observation may make relapse more likely if long-term retention cannot be ensured. Root resorption was not observed as a consequence of the major tooth movement.