cssi/SciSciGPT-SciSciNet huggingface dataset:
Troglitazone Inhibits Growth of MCF-7 Breast Carcinoma Cells by Targeting G1 Cell Cycle Regulators

Abstract Peroxisome proliferator activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. Ligand activation of PPARγ has been shown to cause growth arrest in several human tumor cell types, but the underlying molecular mechanism has not been elucidated. We report here that the PPARγ ligand troglitazone (TRO) inhibited MCF-7 cell proliferation by blocking events critical for G1 → S progression. Flow cytometry demonstrated that TRO at 20 μM increased the percentage of cells in G1 from 51 to 69% after 24 h. Accumulation of cells in G1 was accompanied by an attenuation of Rb protein phosphorylation associated with decreased CDK4 and CDK2 activities. Inhibition of CDK activity by TRO correlates with decreased protein levels for several G1 regulators of Rb phosphorylation (cyclin D1, and CDKs 2, 4, and 6). Overexpression of cyclin D1 partially rescued MCF-7 cells from TRO-mediated G1 arrest. Targeting of G1 regulatory proteins, particularly cyclin D1, and the resulting induction of G1 arrest by TRO may provide a novel antiproliferative therapy for human breast cancer.
Baseline data on forest loss and associated uncertainty: advances in national forest monitoring

Countries participating in climate change mitigation via the United Nations Framework Convention on Climate Change reducing emissions from deforestation and forest degradation mechanism are required to establish national forest monitoring systems. The design of national forest monitoring system includes provision of transparent, consistent and accurate estimates of emissions and removals from forests, while also taking into account national circumstances and capabilities. One key component of these systems lies in satellite remote sensing approaches and techniques to determine baseline data on forest loss against which future rates of change can be evaluated. Advances in approaches meeting these criteria for measuring, reporting and verification purposes are therefore of tremendous interest. A robust example advancing such approaches, focused on Peru, is provided in the recent paper of Potapov et al (2014 Environ. Res. Lett. 9 124012).
The detection of acetylcodeine and 6-acetylmorphine in opiate positive urines

Acetylcodeine (AC), an impurity of illicit heroin synthesis, was investigated as a urinary biomarker for detection of illicit heroin use. One hundred criminal justice urine specimens that had been confirmed positive by GC/MS for morphine at concentrations > 5000 ng/ml were analyzed for AC, 6-acetylmorphine (6AM), codeine, norcodeine and morphine. The GC/MS analysis was performed by solid phase extraction and derivatization with propionic anhydride. Total codeine and morphine concentrations were determined by acid hydrolysis and liquid/liquid extraction. AC was detected in 37 samples at concentrations ranging from 2 to 290 ng/ml (median, 11 ng/ml). 6AM was also present in these samples at concentrations ranging from 49 to 12 600 ng/ml (median, 740 ng/ml). Of the 63 specimens negative for AC, 36 were positive for 6AM at concentrations ranging from 12 to 4600 ng/ml (median, 124 ng/ml). When detected, the AC concentrations were an average of 2.2% (0.25 to 10.2%) of the 6AM concentrations. There was a positive relationship between AC concentrations and 6AM concentrations (r = 0.878). Due to its very low concentration in urine, AC was found to be a much less reliable biomarker for illicit heroin use than 6AM in workplace or criminal justice urine screening programs. However, AC detection could play an important role in determining if addicts in heroin maintenance programs are supplementing their supervised diacetylmorphine doses with illicit heroin.
Performance of Pulse Compression Code and Filter Pairs Optimized For Loss and Integrated Sidelobe Level

This paper describes a method for finding code/filter pairs with very low mismatch filter losses. These losses remain nearly constant with changing filter length. In addition it has been found that substantial improvements in sidelobe levels are obtained. The filter performance of these codes is compared to the filter performance of known codes.
Reengineering Protein Specificity By Repacking the Hydrophobic Core

Engineering of protein function frequently focuses on amino acids that directly contact the ligand or substrate. However, it seems plausible that mutating buried residues away from the binding surface could also affect protein function. Previous work in protein folding has shown that, while the core of a protein is densely packed, it can be rearranged and accommodate new compositions while preserving function. The hydrophobic core is often thought as a scaffold for the active site. We wondered if the core could have a larger role in protein activity and if rearrangements in the hydrophobic core could change function. We have taken advantage of a system developed to investigate transcription factor specificity and used it to probe the role of core repacking in evolving protein function. MarA is a small transcriptional activator that binds a range of promoters to trigger expression of genes involved in antibiotic resistance. We have made mutant libraries of MarA which represent >104 unique variants of the core of the protein. We screened our library against promoters with strong and weak affinity for wild-type MarA. Early results suggest that even minimal reorganization in the core can generate novel protein binding specificity.
Parallel program performance modeling for runtime optimization of multi-algorithm circuit simulation

With the increasing popularity of multi-core processors and the promise of future many-core systems, parallel CAD algorithm development has attracted a significant amount of research effort. However, a highly relevant issue, parallel program performance modeling has received little attention in the EDA community. Performance modeling serves the critical role of guiding parallel algorithm design and provides a basis for runtime performance optimization. We propose a systematic composable approach for the performance modeling of a recently developed hierarchical multi-algorithm parallel circuit simulation (HMAPS) approach. The unique integration of inter- and intra-algorithm parallelisms allows a multiplicity of parallelisms to be exploited in HMAPS and also creates interesting modeling challenges in forms of complex performance tradeoffs and large runtime configuration space. We model the performances of key subtask entities as functions of workload and parallelism. We address significant complications introduced by inter-algorithm interactions in terms of memory contention and collaborative simulation behavior via novel penalty and statistical based modeling. The proposed approach is able to accurately predict the parallel performance of a given HMAPS configuration and hence enables the runtime optimization of the parallel simulation code.
Wideband Frequency-Reconfigurable Spirograph Planar Monopole Antenna (SPMA) Operating in the UHF Band

A frequency-reconfigurable spirograph planar monopole antenna (SPMA) operating in the ultrahigh frequency (UHF) band using RF p-i-n diodes is presented, including experimental verification. The radiating element is compact (0.53λ at 3.1 GHz) such that it can be used as an array element. It has three measured frequency bands with VSWR <;2: case 1, 2.17-3.36 GHz (43.0% impedance bandwidth); case 2, 1.21-2.50 GHz (69.5%); and case 3, 1.07-2.92 GHz (92.7%). Cases 1 and 2 provide contiguous coverage, and case 3 covers almost the entire range of cases 1 and 2. Thus, this antenna provides continuous coverage for 1.07-3.36 GHz (103.4%). This antenna has acceptable omnidirectional radiation patterns with relatively low cross polarization.
Congregational intervention when the pastor has committed sexual misconduct

When a pastor has committed sexual misconduct, the congregation is impacted profoundly. Viewed as one of the pastor's primary systems, the congregation may have played a significant part in precipitating a crisis, yet also become secondary victims. Intervention with the congregation is, therefore, as crucial as with the primary victims, the pastor, and his family. The Parish Consultation Service is developing a strategy for intervention with congregations. Some preliminary research highlights many of the issues involved, and indicates the direction such intervention should take.
Thy will be done

This essay is a meditation on the idea of power in contemporary writing about management. It finds power puzzling because people think about it in natural terms of forces and resistances rather than in moral terms of authority. Authority derives ultimately from the Divine, from the author of human being and all creation. To exercise power with authority is to serve the Divine in humility by serving the human person made in the Divine image. To lead is to serve. A few of the many implications of a theological concept of power for management are considered.
Motoneuron development after deafferentation. I. Dorsal rhizotomy does not alter growth in the spinal nucleus of the bulbocavernosus (SNB)

The spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN) are sexually dimorphic motor nuclei in the rat lumbar spinal cord. During postnatal development, SNB and DLN motoneurons grow substantially in measures of soma size, dendritic length, and radial dendritic extent. SNB motoneurons exhibit a biphasic pattern of dendritic growth, where there is an initial period of exuberant growth followed by a period of retraction to mature lengths by 7 weeks. In this experiment, we examined whether primary afferent input to the SNB nucleus was necessary for the normal postnatal growth of SNB motoneurons. We partially deafferented the SNB via unilateral dorsal rhizotomy of lumbosacral dorsal roots in male rats at 1 week of age. Using cholera toxin horseradish peroxidase (BHRP) to visualize SNB motoneurons, we examined SNB motoneuron morphology at 4 and 7 weeks of age. SNB motoneurons in rhizotomized males developed normally; measures of dendritic length in rhizotomized males were typically exuberant at 4 weeks of age, and declined significantly to mature lengths by 7 weeks of age. In addition, dorsal rhizotomy did not alter the development of SNB motoneuron soma size or radial dendritic extent. These results are discussed in reference to sensorimotor connections in the SNB, the extent of the deafferentation, and dendrodendritic interactions.
Response to Comment on “Stellar activity masquerading as planets in the habitable zone of the M dwarf Gliese 581”

Anglada-Escude and Tuomi question the statistical rigor of our analysis while ignoring the stellar activity aspects that we present. Although we agree that improvements in multiparametric radial velocity (RV) modeling are necessary for the detection of Earth-mass planets, the key physical points we raised were not challenged. We maintain that activity on Gliese 581 induces RV shifts that were interpreted as exoplanets.
Word functions of pseudo-Markov chains

Abstract A word function is a function from the set of all words over a finite alphabet into the set of real numbers. In particular, when the blocks of a partition over the state set of a Markov chain are taken as the letters of the finite alphabet, and the function represents the probabilities that the chain will visit sequences of such blocks consecutively, then the function is a function of a Markov chain. It is known that (the rank of a function is defined in the text), a word function is of “finite rank” if and only if it is a function of a pseudo Markov chain (“pseudo” means here that the initial vector and the matrix representing the chain may have positive, negative, or zero values and are not necessarily stochastic). The aim of this note is to show that any function of a pseudo Markov chain can be represented as the difference of two functions of true Markov chains multiplied by a factor which grows exponentially with the length of the arguments (considered as words over a finite alphabet).
Atomic mass transport of carbon in the one-phase Nb-1Zr-C system under a temperature gradient

Mass transport behavior of carbon in the one-phase Nb-1wt%Zr-C system under a temperature gradient was studied using a radioactive tracer technique. Each sample was heated in an ultrahigh vacuum chamber under a pressure of the order of 10−9 Torr. Temperature gradients in different ranges were induced in separate samples to determine any possible effects of temperature on the phenomenon. Results showed that the heat of transport Q∗ of carbon in the Nb-1Zr-C system is −15.2 ± 0.2 kcalmol−1, representing carbon migration from the colder to the hotter regions of the sample. This value is greater in magnitude than Q∗ of carbon in the Nb-C system (−13.1 kcal mol−1) and is independent of temperature within the range of about 1500–2000 K.
Estimation of power-law creep parameters from bend test data

Power-law creep parameters of brittle ceramic materials are commonly deduced from load-point displacement data generated by four-point bend experiments, under the assumption that tensile and compressive behaviours obey the same constitutive law. However, because of microcracking and cavitation, it is now well recognized that this premise may not always be valid. The present paper presents an analysis which takes the differences into account. Governing equations are first derived for the location of the neutral axis of a beam under bending which does not in general pass through the centroid of the cross-section, and for the creep response in terms of both curvature rate and load-point displacement rate as functions of the applied moment and power-law creep parameters. Numerical solutions are obtained for any given set of material constants over a wide range of applied moments. It is shown from the plots of creep response against applied moment on a logarithmic scale that even linear curves over a narrow range of applied moment do not necessarily imply identical stress exponents, and that non-linear curves concave upward signify a profound difference in stress exponent between tension and compression. An example is given of applying the present analysis to a set of load-point displacement data on glass-alumina beam specimens crept at 1100° C. The results show that the conventional method over/underestimates the creep rates in compression/tension by two orders of magnitude, indicating a need for using the more accurate analysis presented here. Several recommendations are offered to improve the estimation of power-law creep parameters from bend test data.
Preconditioned conjugate gradient and finite element methods for massively data-parallel architectures

The numerical solution of partial differential equations on supercomputers has challenged many mathematicians, numerical analysts, computer scientists and engineers. Changes in the architecture from serial to parallel, and further, to the latest massively parallel machines (such as the Thinking Machines' CM-2), require new and sophisticated considerations of data structures and their optimal mapping as essential ingredients to the numerical algorithms. Only in this way can the high performance capabilities of the latest supercomputers be harnessed. For computational solution of the Navier's partial differential equations of elasticity on general domains, a finite element discretization and its implementation on a massively parallel (CM-2) architecture is investigated. The discretization leads to irregular finite element grids in order to accommodate general domains in applications. The resulting algebraic equations for those grids are found to be very amenable to element to processor mappings on data-parallel supercomputers if implemented in conjunction with conjugate gradient numerical solvers. These iterative solvers are then accelerated by the use of local type preconditioners to enable the robust solution of large scale problems. A number of actual computational tests were undertaken on the CM-2 machine. Efficient communication topology was mapped onto the finite element grids and appropriately coupled to the iterative preconditioned conjugate gradient solver. The approximate finite element solutions of Navier's equations over a wide range of domains were examined, and finally, recommendations and suggestions to advance the current numerical solution of Navier's equation on massively parallel supercomputers are outlined.
Risk Assessment for Children and Other Sensitive Populations

Abstract: Children form a unique subgroup within the population who require special consideration in risk assessment. Children are not little adults. Their tissues and organs grow rapidly, developing and differentiating. These development processes create windows of great vulnerability to environmental toxicants. Furthermore, the exposure patterns of children to environmental chemicals are very different from those of adults. Traditional risk assessment has generally failed to consider the special exposures and the unique susceptibilities of infants and children. Adoption of a new child-centered agenda for research and risk assessment is necessary if disease in children of toxic environmental origin is to be identified, understood, controlled, and prevented. This agenda needs to be multidisciplinary. Specific requirements within the agenda include: (1) exploration and quantification of unique patterns of exposure for children; (2) adoption of new, more sensitive approaches to testing chemicals that can recognize the consequences of exposure during early development; (3) identification, through clinical and epidemiologic studies, of etiologic associations between environmental exposures and pediatric diseases; and (4) elucidation, at the cellular and molecular levels, of the pathogenetic mechanisms of pediatric environmental illness. In the United States, an important start toward adoption of this new agenda has occurred since passage of the Food Quality Protection Act in 1996. A Presidential Executive Order on Children's Health and the Environment has been promulgated. This Order requires all federal agencies to make protecting the health of children against environmental hazards a high priority. A new Office of Children's Health Protection has been established at the U.S. Environmental Protection Agency. Programs in children's environmental health have been created at the Centers for Disease Control and Prevention, the Agency for Toxic Substances and Disease Registry, and the National Institute of Environmental Health Sciences. A national network of eight new Children's Environmental Health Research and Disease Prevention Centers has been formed. These developments will enhance research on previously understudied issues in the environmental health of children and will provide a scientific basis for child-centered risk assessment.
Possible vestige of early phosphatic biomineralization in gorgonian octocorals (Coelenterata)

Skeletal carbonate hydroxylapatite, heretofore unknown in modern coelenterates, has been found in the axes and holdfasts of the gorgonian octocoral family Gorgoniidae. This carbonate apatite is a distinctive feature of this family of octocorals and may indicate a previous history of phosphatic skeletal mineralization within this phylum.
Correlation effects in the energy bands of insulating crystals

Abstract The effect of electronic correlation on the electronic energy bands of insulating crystals has been investigated. Solid argon is treated as an example, and calculations have been performed without and with correlation, which reduces the energy gap by several eV.
A Brief Version of the Fear of Negative Evaluation Scale

Although the Fear of Negative Evaluation (FNE) Scale has widespread applicability to many areas of research in personality and social psychology, its utility is sometimes limited by its length. This article presents a brief, 12-item version of the FNE that correlates very highly (f96) with the original scale and that demonstrates psychometric properties that are nearly identical to those of the full-length scale.
How many lakes are there, and how big are they?

Because of the important role lakes play in regional and local biogeochemical cycling, including carbon storage and emissions, scientists need to know how many lakes of various sizes exist. However, determining the size distribution of lakes is more difficult than it may seem—the smallest lakes are often not recorded on maps. Some researchers have suggested that the number of small lakes is underestimated and have used size distributions to suggest that small lakes dominate the global lake surface area.
Constitutive expression and alternative splicing of the exons encoding SCRs in Sp152, the sea urchin homologue of complement factor B. Implications on the evolution of the Bf/C2 gene family.

The purple sea urchin, Strongylocentrotus purpuratus, possesses a non-adaptive immune system including elements homologous to C3 and factor B (Bf) of the vertebrate complement system. SpBf is composed of motifs typical of the Bf/C2 protein family. Expression of Sp152 (encodes SpBf) was identified in the phagocyte type of coelomocyte in addition to gut, pharynx and esophagus, which may have been due to the presence of these coelomocytes in and on all tissues of the animal. Sp152 expression in coelomocytes was constitutive and non-inducible based on comparisons between pre- and post-injection with lipopolysaccharide or sterile seawater. The pattern of five short consensus repeats (SCRs) in SpBf has been considered ancestral compared to other deuterostome Bf/C2 proteins that contain either three or four SCRs. Three alternatively spliced messages were identified for Sp152 and designated Sp152Δ1, Sp152Δ4, and Sp152Δ1+Δ4, based on which of the five SCRs were deleted. Sp152Δ4 had an in-frame deletion of SCR4, which would encode a putative SpBfΔ4 protein with four SCRs rather than five. On the other hand, both Sp152Δ1 and Sp152Δ1+Δ4 had a frame-shift that introduced a stop codon six amino acids downstream of the splice site for SCR1, and would encode putative proteins composed only of the leader. Comparisons between the full-length SpBf and its several splice variants with other Bf/C2 proteins suggested that the early evolution of this gene family may have involved a combination of gene duplications and deletions of exons encoding SCRs.
Efficacy of a new endoureterotomy balloon for the treatment of benign ureteral strictures using the porcine model.

Abstract Objectives Endoureterotomy and balloon dilation are techniques that have shown promise as treatment modalities for benign ureteral stricture disease. In this animal investigation, the results of a new endoureterotomy balloon that simultaneously incises and dilates the ureteral stricture via a retrograde approach are discussed. Methods Using the female pig model, 9 subjects with benign ureteral strictures were treated: 7 with the endoureterotomy balloon and 2 with balloon dilation only. Results Success based on radiologic parameters and Whitaker testing was obtained in 5 of the 7 animals treated by endoureterotomy. In both animals treated by balloon dilation only, recurrent ureteral stricture disease developed. Conclusions This preliminary investigation suggests that this new device may be an effective treatment for benign ureteral stricture disease and that further study in clinical trials is warranted.
Hydrocortisone acetate-induced eosinopenia in mice: Independence from the thymus

Abstract The eosinopenia-inducing effect of the adrenal-cortical steroid, hydrocortisone acetate (HCA), was studied with respect to the involvement of thymus-dependent lymphocytes. Thymectomized, irradiated, bone-marrow-reconstituted male B6D2F1 mice experienced as extensive an eosinopenic effect of HCA as did sham-operated, irradiated, bone-marrow reconstituted control mice. Femoral bone marrow appeared unaffected during the times studied. A similar decrease in circulating eosinophils could be induced in congenitally athymic nude (nu/nu) mice. The results argue against a role for the thymus in hydrocortisone-induced eosinopenia.
Erosive Esophagitis following Horizontal Gastroplasty for Morbid Obesity: Treatment by Gastric Bypass

We describe a patient who underwent horizontal gastroplasty for morbid obesity while exhibiting mild symptoms of gastroesophageal reflux disease. The patient lost 36.4 kg, but reflux symptoms progressed to the point of becoming almost incapacitating, associated with erosive esophagitis. The patient subsequently underwent vertical Roux-en-Y gastric bypass, becoming asymptomatic and demonstrating complete healing of the esophageal erosions. Post-operative esophageal pH monitoring demonstrated continuing pathologic reflux in this patient despite her being asymptomatic.
Acidic and basic amino acid transport systems of Penicillium chrysogenum.

Abstract Penicillium chrysogenum possesses a relatively specific constitutive transport system for the basic amino acids l -lysine and l -arginine (Km = 6 × 10−6 m , Vmax = 1 μmole/g-min). This system has a low affinity for 2,4-diaminobutryate, l -ornithine, and l -histidine. The basic amino acid transport system can be assayed readily in nutrient-sufficient mycelia where a nonspecific amino acid transport system (Benko, P. V., Wood, T. C., and Segel, I. H., Arch. Biochem. Biophys.129, 498, 1969), which also transports basic amino acids, is extremely low in activity. Nutrient-sufficient mycelia also contain a low-level lysine-insensitive arginine transport system and a low-level arginine-insensitive lysine transport system. The basic amino acid transport system can be assayed in nitrogen-starved and in carbon-starved mycelia if a large excess of, e.g., l -leucine is added to the assay mixture in order to suppress transport of the labeled substrate by the nonspecific amino acid transport system. The acidic amino acids, l -glutamate and l -aspartate, are also substrates of the general amino acid transport system. However, the preferred ionic form is the uncharged species. l -Glutamate and l -aspartate are also transported by a distinct stereospecific acidic amino acid transport system that develops along with the nonspecific system during nitrogen starvation or carbon starvation. The acidic amino acid system can be assayed at pH 6.0 in the presence of a large excess of, e.g., l -leucine. These conditions minimize the transport of glutamate and aspartate by the nonspecific system. A distinct proline transport system has also been detected in nitrogen-starved and in carbon-starved mycelia. No distinct or quantitatively significant specific systems for aromatic amino acids or histidine were detected. The general and acidic amino acid transport systems are subject to feedback inhibition (“transinhibition”) by their intracellular substrates. The transinhibition is most evident under conditions in which the amino acid is transported much faster than it is metabolized. In this respect, l -α-aminoadipate is a better transinhibitor of the acidic system than the preferred substrates, aspartate and glutamate. The feedback inhibitor of the nonspecific system has been shown to be the accumulated substrate rather than NH4+.
Altered metabolism and resistance to obesity in long-lived mice producing reduced levels of IGF-I

The extension of lifespan due to reduced insulin-like growth factor 1 (IGF-I) signaling in mice has been proposed to be mediated through alterations in metabolism. Previously, we showed that mice h...
"No—You Can't Watch That" Parental Rules and Young Children's Media Use

This study addresses the relations between parental rules regarding television use (for time and program, respectively) and television use among very young children (ages 0 to 6). Higher education level was related to rules of both types, whereas higher household income was related to having program rules. Parents with time rules reported their children watching less television, but parents with program rules reported their children watching more television. Parents with program rules were more likely to have positive attitudes toward television and more likely to be present when their children were viewing. Parents with both types of rules were more likely to see their children imitating positive behaviors from television, whereas parents with program rules were more likely to see their children imitating negative behaviors. Exploratory path models suggest that the processes by which television time rules and television program rules are related to young children’s viewing differ in important ways.
Direct measurement of methane hydrate composition along the hydrate equilibrium boundary.

The composition of methane hydrate, namely nw for CH4·nwH2O, was directly measured along the hydrate equilibrium boundary under conditions of excess methane gas. Pressure and temperature conditions ranged from 1.9 to 9.7 MPa and 263 to 285 K. Within experimental error, there is no change in hydrate composition with increasing pressure along the equilibrium boundary, but nw may show a slight systematic decrease away from this boundary. A hydrate stoichiometry of nw = 5.81−6.10 H2O describes the entire range of measured values, with an average composition of CH4·5.99(±0.07)H2O along the equilibrium boundary. These results, consistent with previously measured values, are discussed with respect to the widely ranging values obtained by thermodynamic analysis. The relatively constant composition of methane hydrate over the geologically relevant pressure and temperature range investigated suggests that in situ methane hydrate compositions may be estimated with some confidence.
Development of a hypothetical baccalaureate program in dental hygiene emphasizing the community.

The task of developing a curriculum model for baccalaureate education in community dental hygiene proved to be an assignment far more difficult than first anticipated. Hopefully, the product which resulted from those efforts will stimulate discussion here that is, after all, its primary purpose. The curriculum model proposed is essentially a dental hygiene “major” and a minor within another academic discipline preferably one of the social or behavioral sciences. Rather than examine only that final product, it seems reasonable to describe the processes by which it was created. Like a true “public healther,”my initial response to the problem of developing a curriculum was to conduct a survey. Actually, several surveys were carried out of dental hygienists, dental hygiene educators, potential employers of these “community dental hygienists,” nurses, public health workers, and, of course, books of all kinds. 5~fi~7.8~13~t5,16 Those surveying activities did not provide instant answers and, in fact, they created some new questions. The issue of training versus education was resolved by choosing to emphasize the higher cognitive process implied by the word “education” rather than the development of specific technical skills usually associated with “training.” Still, that decision could hardly be called a breakthrough, given the title of this conference.
Gene therapy for cystic fibrosis: challenges and future directions.

for gene therapy when the gene responsible for the disease was isolated in 1989 (3-5). The wide distribution of possible cellular targets for gene transfer in the CF lung and the absence of a known lung epithelial stem cell suggested that an ex vivo approach to gene therapy would not be feasible (6, 7). Research immediately focused on in vivo approaches for gene transfer that could conveniently be delivered into the airway via aerosols. The ensuing research effort has literally dominated the field ofhuman gene therapy of genetic diseases while establishing the basic principles of in vivo gene delivery. This review summarizes critical scientific issues that have emerged in the development of in vivo gene therapy for CF using adenoviral vectors as a model.
Tissue-based immune monitoring I: tumor core needle biopsies allow in-depth interrogation of the tumor microenvironment.

We sought to assess the feasibility and reproducibility of performing tissue-based immune characterization of the tumor microenvironment using CT-compatible needle biopsy material. Three independent biopsies were obtained intraoperatively from one metastatic epithelial ovarian cancer lesion of 7 consecutive patients undergoing surgical cytoreduction using a 16-gauge core biopsy needle. Core specimens were snap-frozen and subjected to immunohistochemistry (IHC) against human CD3, CD4, CD8, and FoxP3. A portion of the cores was used to isolate RNA for 1) real-time quantitative (q)PCR for CD3, CD4, CD8, FoxP3, IL-10 and TGF-beta, 2) multiplexed PCR-based T cell receptor (TCR) CDR3 Vβ region spectratyping, and 3) gene expression profiling. Pearson's correlations were examined for immunohistochemistry and PCR gene expression, as well as for gene expression array data obtained from different tumor biopsies. Needle biopsy yielded sufficient tissue for all assays in all patients. IHC was highly reproducible and informative. Significant correlations were seen between the frequency of CD3+, CD8+ and FoxP3+ T cells by IHC with CD3e, CD8A, and FoxP3 gene expression, respectively, by qPCR (r=0.61, 0.86, and 0.89; all p< 0.05). CDR3 spectratyping was feasible and highly reproducible in each tumor, and indicated a restricted repertoire for specific TCR Vβ chains in tumor-infiltrating T cells. Microarray gene expression revealed strong correlation between different biopsies collected from the same tumor. Our results demonstrate a feasible and reproducible method of immune monitoring using CT-compatible needle biopsies from tumor tissue, thereby paving the way for sophisticated translational studies during tumor biological therapy.
A Qualitative Analysis of Slot Clubs as Drivers of Casino Loyalty

The slot club is a very common type of loyalty program in the casino industry. In this research, the authors look at the deep meanings and emotions of a slot club for tourists and frequent local customers at a Las Vegas mega casino resort using an in-depth interview technique, the Zaltman Metaphor Elicitation Technique (ZMET). Results indicate that the opportunities for casino loyalty programs to establish emotional bonds with the customer lie in the capacity of reflecting human qualities in the slot club service delivery process, such as memory, creativity, and flexibility. The results also indicate that the slot club brings different meanings to different customer groups and that these emotional connections (or lack thereof) are best elucidated via this qualitative research technique that uses images, rather than words, to guide the in-depth interview. The authors discuss the implications of the results for loyalty programs as well as how this research technique might be used in other sectors of the hos...
Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells.

Benzyl isothiocyanate (BITC), a cruciferous vegetablederived compound, has been shown to inhibit chemically induced cancer in animal models. Moreover, epidemiological studies have provided compelling evidence to suggest that cruciferous vegetables may be protective against cancer risk. Here, we report that BITC significantly inhibits growth of human pancreatic cancer BxPC-3 cells in a concentration-dependent manner with an IC50 of ~8 mM, a concentration that can be generated through dietary intake of cruciferous vegetables. Treatment of BxPC-3 cells with growth suppressive concentrations of BITC resulted in G2/ M phase cell cycle arrest that was associated with a marked decline in protein levels of G2/M regulatory proteins including cyclin-dependent kinase 1 (Cdk1), cyclin B1 and cell division cycle 25B (Cdc25B). Further, BITC-mediated growth inhibition of BxPC-3 cells correlated with apoptosis induction that was characterized by an increase in Bax/ Bcl-2 ratio, cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP), and an increase in cytoplasmic histone-associated DNA fragmentation. Interestingly, BITC treatment caused inhibition of nuclear factor kB (NF-kB) activation, which is constitutively activated in human pancreatic cancer. Western blotting revealed concentration-dependent decrease in NF-kB/Rel-p65 protein level in BxPC-3 cells upon exposure to BITC. An increase in protein level of inhibitory subunit k B( I kBa) in association with reduced serine-32 phosphorylation was also observed in BITC-treated BxPC-3 cells. Consistent with these findings, BITC treatment caused a decrease in nuclear translocation of NF-kB as reflected by reduced DNA-binding capacity of NF-kB. Furthermore, the protein level of cyclin D1, a transcriptional target of NF-kB, was reduced significantly in BITC-treated BxPC-3 cells. To the best of our knowledge, this study is the first published report to implicate suppression of NF-kB activation as a potential mechanism for anti-proliferative activity of BITC against human pancreatic cancer cells.
Beam displacement and distortion effects in narrowband optical thin-film filters.

A three-dimensional model for beam propagation through optical interference filters is presented. The model predicts a wavelength-dependent lateral beam displacement of tens or hundreds of micrometers in narrowband filters at an angle of incidence of only 3° to 5°. The effects of filter bandwidth, wavelength offset, angle of incidence, and beam size are investigated. The effect is experimentally confirmed for a 100 GHz filter at a 3.5° angle of incidence.
New Models of Frontal-Subcortical Skeletomotor Circuit Pathology in Tardive Dyskinesia

Tardive dyskinesia (TD) is a hyperkinetic movement disorder that can occur as a side effect of treatment with antipsychotic medications. Because antipsychotics block the D2 family of dopamine receptors in the striatum, it has long been suspected this blockade contributes to the development of TD. Specifically, increased sensitivity of the dopamine receptors following chronic blockade has been thought to result in abnormal functioning of the frontal-subcortical (FSC) skeletomotor circuit and the symptoms of TD. However, this hypothesis remains unproven. In recent years, substantial research has focused on the basal ganglia and FSC circuits. This research has resulted in the development of the focused selection model of skeletomotor circuit function. This hypothesis provides a compelling model of neurocircuit abnormalities in TD. A greater understanding of the neuropathology of TD may lead to the development of better treatment and prevention strategies for this disorder. Furthermore, this information may c...
Habitat and infauna prey availability for flatfishes in the northern Bering Sea

Yellowfin sole (Limanda aspera), northern rock sole (Lepidopsetta polyxystra), and Alaska plaice (Pleuronectes quadrituberculatus) are valuable flatfishes in the southeastern Bering Sea (EBS) bottom trawl fishery. The northern Bering Sea (NBS) is near their northern distribution limit. We conducted the first assessment of NBS habitat suitability for these benthivorous flatfishes from the perspective of prey availability in 2010. Benthic samples were collected at 12 trawl stations along a meridional transect extending from 60.5°N to 64.5°N east of St. Lawrence Island to characterize the prey environment. Stomach contents from the flatfishes were concomitantly collected to relate diets to prey fields. The diet compositions did not correspond spatially with the infauna communities. The flatfishes elected a prey group regardless of its relative availability. The spatial mismatch between diet and infauna compositions suggests that prey availability was high in the NBS. The flatfishes generally have versatile diets, but they were more selective of their prey here than in the EBS. The biomass and the abundance of the infauna along the transect were comparable with the EBS. Although niche overlap was high in the NBS, competition for food was likely lower than in the EBS because of the lower density of flatfish. The bottom temperatures in the NBS were in the same range as the EBS during the summer of 2010. The NBS appears to be suitable flatfish habitat at least during the summer ice-free period. The effects of climate warming on the prey environment and on the production and distribution of flatfish are complex and difficult to predict, but if the NBS were to shift over time toward milder winter conditions that more resemble the EBS, its suitability as flatfish habitat would presumably increase based on the present prey availability.
Non-carious cervical lesions

Non-carious cervical lesions are commonly encountered in clinical practice and present in a variety of forms. A knowledge of the aetiology of these lesions is important for preventing further lesions, halting progression of lesions already present, and determining appropriate treatment. The most commonly cited aetiological factors thought to lead to the development of cervical lesions are erosion, abrasion and tooth flexure. Evidence supports a multifactorial aetiology for non-carious cervical lesions. The purpose of this paper is to review the evidence for each of these aetiological factors as it relates to the development of non-carious cervical lesions. Specific features of cervical lesions linked to these factors, including their morphology, location, prevalence and distribution by age and sex will be discussed. Suggestions for future research into the cause and prevention of non-carious cervical lesions will be presented.
Fast hybrid method for modeling scattering from doubly periodic dielectric structure in 3-D

In this paper, we present an efficient hybrid method based on finite element (FE) and rigorous coupled wave analysis (RCWA) to model scattering from 3-D doubly periodic dielectric structures. The mode expansion technique is used as boundary truncation scheme. This scheme allows truncation boundaries to be placed close to dielectric grating, thus significantly reduces the size of the problem. Comparisons with finite element/boundary integral method, as well as, FE/RCWA with perfectly matched layer (PML), will be given for accuracy validation.
GOVERNING STANDARDS OF MEDICAL CARE: State Courts Interpret the Locality Rule

This article analyzes a significant, but little researched, form of legal involvement in the medical profession—state appellate court opinions. Analyzing 100 years of state appellate court decisions on a legal rule called the “locality rule,” the author presents four distinct judicial interpretations of the rule. Each has distinctive policy implications for law and medicine pertaining to the setting of standards for professional competency in medicine. Three of the judicial interpretations provide for increasing amounts of judicial deference to the professional autonomy of the medical community. A fourth interpretation within the last decade, however, upholds a judicial prerogative for establishing standards of professional competency. The author concludes that the fourth interpretation is not an aberration and signals a change in the relationship between law and medicine for the future.
An alternative multi‐language structure for personality attributes:

A scientific taxonomy of human personality attributes should optimally be based on studies from multiple languages and cultures. Study 1 demonstrates convergence between seven‐factor structures fou...
An Airspace Planning and Collaborative Decision-Making Model: Part I--Probabilistic Conflicts, Workload, and Equity Considerations

We present a large-scale, airspace planning and collaborative decision-making model (APCDM) to enhance the management of the U.S. National Airspace System (NAS). Given a set of flights that must be scheduled during some planning horizon, along with alternative surrogate trajectories for each flight as prompted by various airspace restriction scenarios imposed by dynamic severe weather systems or space launch special use airspaces (SUA), we develop a mixed-integer programming model to select a set of flight plans from among these alternatives, subject to flight safety, air traffic control workload, and airline equity constraints. The model includes a three-dimensional probabilistic conflict analysis, the derivation of valid inequalities, the development of air traffic control workload metrics, and the consideration of equity among airline carriers in absorbing costs related to rerouting, delays, and possible cancellations. The resulting APCDM model has potential use for both tactical and strategic applications, such as air traffic control in response to severe weather phenomena or spacecraft launches, FAA policy evaluation (separation standards, workload restrictions, sectorization strategies), Homeland Defense contingency planning, and military air campaign planning. The model can also serve a useful role in augmenting the FAA'sNational Playbook of standardized flight profiles in different disruption-prone regions of the national airspace. The present paper focuses on the theory and model development; Part II of this paper will address model parameter estimations and implementation test results.
Effects of clutter on information processing deficits in individuals with hoarding disorder

Abstract Background Current cognitive behavioral models of hoarding view hoarding as a multifaceted problem stemming from various information processing deficits. However, there is also reason to suspect that the consequences of hoarding may in turn impact or modulate deficits in information processing. The current study sought to expand upon the existing literature by manipulating clutter to examine whether the presence of a cluttered environment affects information processing. Methods Participants included 34 individuals with hoarding disorder. Participants were randomized into a clutter or non-clutter condition and asked to complete various neuropsychological tasks of memory and attention. Results Results revealed that hoarding severity was associated with difficulties in sustained attention. However, individuals in the clutter condition relative to the non-clutter condition did not experience greater deficits in information processing. Limitations Limitations include the cross-sectional design and small sample size. Conclusions The current findings add considerably to a growing body of literature on the relationships between information processing deficits and hoarding behaviors. Research of this type is integral to understanding the etiology and maintenance of hoarding.
Resting metabolic rate and postprandial thermogenesis in highly trained and untrained males

The purpose was to compare the resting metabolic rate (RMR) and thermic effect of a meal (TEM) in exercise trained and untrained individuals. TEM was measured for 180 min and blood samples were drawn for determination of plasma insulin, glucose, triiodothyronine (T3) and thyroxine (T4). Results indicated that highly trained subjects demonstrated a higher RMR when expressed in kilocalories per minute and per kilogram fat-free weight (FFW) than do untrained subjects. TEM was lower in trained (55.8 +/- 3.1 kcal) than in untrained (79.2 +/- 3.7 kcal) subjects. No differences were noted between the two groups for plasma levels of insulin, glucose, T3, and T4. A higher RMR and lower TEM persisted in the trained group compared with the untrained group when groups were matched for FFW and body fat. Results support a higher RMR in endurance athletes and a lower TEM even after control is exerted over differences in body composition.