bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of Control and Distribution of Adaptive Mutations in a Metabolic Pathway
Authors: Wright Kevin M , Rausher Mark D
Published: December 2009

In an attempt to understand whether it should be expected that some genes tend to be used disproportionately often by natural selection, we investigated two related phenomena: the evolution of flux control among enzymes in a metabolic pathway and properties of adaptive substitutions in pathway enzymes. These two phenomena are related by the principle that adaptive substitutions should occur more frequently in enzymes with greater flux control. Predicting which enzymes will be preferentially involved in adaptive evolution thus requires an evolutionary theory of flux control. We investigated the evolution of enzyme control in metabolic pathways with two models of enzyme kinetics: metabolic control theory (MCT) and Michaelis–Menten saturation kinetics (SK). Our models generate two main predictions for pathways in which reactions are moderately to highly irreversible: (1) flux control will evolve to be highly unequal among enzymes in a pathway and (2) upstream enzymes evolve a greater control coefficient then those downstream. This results in upstream enzymes fixing the majority of beneficial mutations during adaptive evolution. Once the population has reached high fitness, the trend is reversed, with the majority of neutral/slightly deleterious mutations occurring in downstream enzymes. These patterns are the result of three factors (the first of these is unique to the MCT simulations while the other two seem to be general properties of the metabolic pathways): (1) the majority of randomly selected, starting combinations of enzyme kinetic rates generate pathways that possess greater control for the upstream enzymes compared to downstream enzymes; (2) selection against large pools of intermediate substrates tends to prevent majority control by downstream enzymes; and (3) equivalent mutations in enzyme kinetic rates have the greatest effect on flux for enzymes with high levels of flux control, and these enzymes will accumulate adaptive substitutions, strengthening their control. Prediction 1 is well supported by available data on control coefficients. Data for evaluating prediction 2 are sparse but not inconsistent with this prediction.
Experimentally Increased Codon Bias in the DrosophilaAdhGene Leads to an Increase in Larval, But Not Adult, Alcohol Dehydrogenase Activity
Authors: Hense Winfried , Anderson Nathan , Hutter Stephan , Stephan Wolfgang , Parsch John , Carlini David B
Published: December 2009

Although most amino acids can be encoded by more than one codon, the synonymous codons are not used with equal frequency. This phenomenon is known as codon bias and appears to be a universal feature of genomes. The translational selection hypothesis posits that the use of optimal codons, which match the most abundant species of isoaccepting tRNAs, results in increased translational efficiency and accuracy. Previous work demonstrated that the experimental reduction of codon bias in the Drosophila alcohol dehydrogenase (Adh) gene led to a significant decrease in ADH protein expression. In this study we performed the converse experiment: we replaced seven suboptimal leucine codons that occur naturally in the Drosophila melanogaster Adh gene with the optimal codon. We then compared the in vivo ADH activities imparted by the wild-type and mutant alleles. The introduction of optimal leucine codons led to an increase in ADH activity in third-instar larvae. In adult flies, however, the introduction of optimal codons led to a decrease in ADH activity. There is no evidence that other selectively constrained features of the Adh gene, or its rate of transcription, were altered by the synonymous replacements. These results are consistent with translational selection for codon bias being stronger in the larval stage and suggest that there may be a selective conflict over optimal codon usage between different developmental stages.
Paclitaxel/Carboplatin plus Bevacizumab/Erlotinib in the First-Line Treatment of Patients with Carcinoma of Unknown Primary Site
Authors: Hainsworth John D. , Spigel David R. , Thompson Dana S. , Murphy Patrick B. , Lane Cassie M. , Waterhouse David M. , Naot Yuval , Greco F. Anthony
Published: December 2009

Introduction.

This phase II trial evaluated the efficacy and toxicity of the combination of paclitaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with carcinoma of unknown primary site (CUP).

Methods.

Patients with previously untreated CUP (adenocarcinoma, poorly differentiated carcinoma, poorly differentiated squamous carcinoma) without clinical or pathologic characteristics of a well-defined treatable subset were eligible. All patients received paclitaxel, carboplatin, bevacizumab, and erlotinib. Treatment cycles were repeated at 21-day intervals. After four cycles, paclitaxel and carboplatin were discontinued; bevacizumab–erlotinib treatment was continued until tumor progression. Patients were initially evaluated for response after completion of two treatment cycles; re-evaluations occurred every 6 weeks thereafter.

Results.

Forty-nine of 60 patients (82%) completed four cycles of therapy, and 44 patients (73%) subsequently received maintenance bevacizumab and erlotinib. Thirty-two patients (53%) had major responses to treatment; an additional 18 patients had stable disease. After a median follow-up of 19 months, the median progression-free survival time was 8 months, with 38% of patients progression free at 1 year. The median survival time and 2-year overall survival rate were 12.6 months and 27%, respectively. Treatment was generally well tolerated, with a toxicity profile as predicted based on the known toxicities of each treatment component.

Conclusions.

Empiric treatment with paclitaxel, carboplatin, bevacizumab, and erlotinib is effective and well tolerated as first-line treatment for patients with CUP. Further development of this regimen is warranted.
A Case of Bullous Dermatitis Induced by Erlotinib
Authors: Oteri Alessandro , Cattaneo Maria Teresa , Filipazzi Virginio , Ferrario Sabrina , Gambaro Anna , Isabella Luigi , Tosca Nicoletta , Clementi Emilio , Radice Sonia , Piazza Elena
Published: December 2009

Herein, we report a case of bullous dermatitis that occurred in a 61-year-old woman 5 days after beginning therapy with erlotinib for the treatment of stage IV pulmonary adenocarcinoma with metastases at the hypophyseal level. Skin reactions are the most common adverse drug reactions (ADRs) associated with epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors, and acneiform rash is the most frequently reported ADR in patients treated with erlotinib. To our knowledge, this is the first case of bullous dermatitis induced by erlotinib. This report highlights the need for additional research in the field of skin toxicity of EGFR-TK inhibitors.
Selective recruitment of breast cancer anti-estrogen resistance genes and relevance for breast cancer progression and tamoxifen therapy response
Authors: van Agthoven Ton , Sieuwerts Anieta M , Meijer Danielle , Meijer-van Gelder Marion E , van Agthoven Thecla L A , Sarwari Roya , Sleijfer Stefan , Foekens John A , Dorssers Lambert C J
Published: December 2009

Although endocrine treatment of breast cancer is effective and common practice, in advanced disease the development of resistance is nearly inevitable. To get more insight into individual genes that account for resistance against hormonal agents, we have executed functional genetic screens and subsequently evaluated the clinical relevance of several identified genes with respect to tumor aggressiveness and tamoxifen resistance in estrogen receptor-positive patients. Estrogen-dependent human breast cancer cells were transduced with different retroviral cDNA expression libraries and subjected to selective cultures with various anti-estrogens. From a total of 264 resistant cell clones, 132 different genes were recovered by PCR. By applying stringent selection criteria, we identified 15 breast cancer anti-estrogen resistance (BCAR) genes individually yielding resistance. BCAR genes were recovered with differential frequencies for the diverse culture conditions and anti-estrogen drugs. Analysis of the relation of BCAR genes (EIF1, FBXL10, HRAS, NRG1, PDGFRA, PDGFRB, RAD21, and RAF1) with tamoxifen treatment in patients with advanced disease showed significant association with clinical benefit and progression-free survival for EIF1 and PDGFRA mRNA levels. Furthermore, PDGFRA and HRAS mRNA levels were significantly associated with tumor aggressiveness in lymph node-negative patients who had not received adjuvant systemic therapy. In conclusion, our functional genetic screens showed that BCAR genes differ in their ability to confer resistance towards distinct anti-estrogens. Based on the clinical relevance of several BCAR genes, further studies are warranted to characterize the underlying mechanisms, which may ultimately lead to the development of novel treatments and more individualized management of breast cancer patients.
Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells
Authors: Santer Frédéric R , Malinowska Kamilla , Culig Zoran , Cavarretta Ilaria T
Published: December 2009

Interleukin-6 (IL-6) is suggested to have a pathogenic role in the progression of prostate cancer (PC), therefore representing an attractive target for new therapies. However, due to the pleiotropy of this cytokine, targeting IL-6 results in different and unpredictable responses. In order to better understand the mechanisms underlying the different responses to the cytokine, we focused our attention on IL-6 receptors (IL-6Rs) that represent the first element in the cascade of cytokine-activated signalling pathways. IL-6 signal transduction may indeed occur through the membrane IL-6R (classical signalling) and/or through the less studied soluble IL-6R (sIL-6R; IL-6 trans-signalling (IL-6TS)). We provide the first evidence how responses to IL-6 may depend on the different content of IL-6Rs in PC. In particular, the studies of 3H-thymidine incorporation and exploitation of different approaches (i.e. activation or inhibition of IL-6TS in sIL-6R-negative and -positive cell lines and transfection of IL-6R siRNA) allowed us to demonstrate that IL-6TS specifically accounts for an anti-proliferative effect of the cytokine in three PC cell lines that are known to respond differently to IL-6. Additionally, by applying migration-, scratch- and adhesion assays, we show that IL-6TS increases motility and migration and decreases adhesion of prostate cells facilitating thereby processes that determine metastasis initiation and spread. Finally, by western analyses, we uncovered an IL-6- and sIL-6R-dependent downregulation of the tumour suppressor maspin. Collectively, these data suggest that selective targeting of IL-6TS might allow to refine the currently available experimental anti-IL-6 therapies against PC.
Predicting Two-Phase Flow Regimes in Segments of a Gas/Condensate Well
Authors: Adeyemi Williams
Published: December 2009

As the prospect of producing gas reservoirs increases and economic uncertainties become greater, a good way of predicting the two-phase flow in a gas well is very important to know what to be expected and contingency plans to be adopted.

This paper presents a method of predicting the type of two-phase flow in segments of a well using a program written in FORTRAN, Bill-FlowTRAN.f95. The pressure drop across each segment was arithmetically calculated from the difference in the flowing bottomhole pressure across the segment, obtained using Cullender and Smith (Katz et al., 1957) method. Orkiszewski calculation procedures for two-phase flow and other correlations were then used to predict the two-phase flow in such a segment. The flow regimes covered are mist, transition and slug flow since bubble flow would likely not occur in a gas well.
Optimal Waterflood Management Under Geologic Uncertainty Using Rate Control: Theory and Field Applications
Authors: Alhuthali Ahmed H.
Published: December 2009

A robust and efficient approach for computing optimal injection and production rates is proposed to manage the waterflood front and maximize sweep efficiency. The work relies on equalizing the arrival times of the waterfront at all producers within selected sub-regions of a water flood project. The optimization approach proceeds smoothly toward the solution even if the initial conditions are far away because the arrival time optimization has favorable quasi-linear properties. The proposed approach also accounts for geologic uncertainty via a stochastic optimization framework using multiple realizations. Analytical forms for gradients and Hessian of the objective functions are derived, making the optimization computationally efficient for large-scale applications. In addition, optimization is performed under operational and facility constraints using a sequential quadratic programming approach.

The applicability of the approach is demonstrated using three field-scale examples. The first one is a benchmark case called ‘Brugge’ field, based on a North Sea Brent-type field. The production rate is optimized for this field as part of a closed-loop reservoir management process where the production history is matched prior to the production optimization. The optimization is performed over multiple realizations to account for geologic uncertainty. The second example is a CO2 pilot project area in the Goldsmith San Andres Unit (GSAU) in west Texas. The production rates are optimized for 31 wells while accounting for changing field condition such as shut-in and infill drilling. The third example is a super-giant middle-eastern field. The optimization is performed for a sub-region of this field which contains a large number of wells nearly 300 wells consisting of conventional vertical and horizontal wells and smart horizontal wells. The results clearly demonstrate the robustness and the efficiency of the proposed approach with considerable increase in cumulative oil production and a substantial decrease in the associated water production.
Determination of Facies From Seismic Data: A New and Improved Approach
Authors: Maria Belyanushkina
Published: December 2009

This paper describes a new computational method for facies mapping from seismic data and its application for analysis of new oil-prospective zones and projects for new exploration wells. In this paper the description of the algorithm and an opportunity of clustering of seismic data are presented. The developed algorithm allows execution of steady splitting into an automatically calculated number of clusters. In other words this algorithm enables obtaining identical results of clustering after reiteration of clustering procedure with the same parameters. A cluster's probability maps can be thus created. The evaluation procedure of the facies maps obtained can be done by means of this approach.

A system of tests was performed to check the new algorithm and to estimate its efficiency when the result of correct clustering is known in advance. Points were distributed randomly in spheres with the centers in corners of a multidimensional cube. Thus we can estimate the probability for correct calculation of the number of clusters.

Two sets of data were used: artificial (synthetic) data and real seismic data. For the synthetic data, as will be shown in the example, more reliable results were obtained when compared with the result of the well-known K-means algorithm. For real data the algorithm was applied to interesting areas for exploration of hydrocarbons deposits (traps) without using well information.
Investigation of the Mobilization of Residual Oil Using Micromodels
Authors: El Din Saad Ibrahim Ahmed Salah
Published: December 2009

The mobilization of residual oil was investigated in glass micromodels consisting of capillary networks with water-wet wettability as a function of capillary number (ratio of viscous to capillary forces). The micromodels used in this work had variable pore throat and pore body size distribution. Experimental results demonstrated that the entrapped residual oil blobs have a preferable orientation along the macroscopic flow direction of waterflooding. For substantial mobilization of the waterflood residual oil, the corresponding capillary number needs to be 100 times larger than that for the onset of mobilization of the largest blobs in place at the end of waterflooding. The reduced residual oil saturation with increasing capillary number obtained in this study is in qualitative and quantitative agreement with published capillary number curves for water-wet sandstones. A key feature of oil blob mobilization at high capillary number is the break-up of mobilized blobs to sub-pore size droplets as they flow through the pore network, some of which attach to the pore walls and thus making complete mobilization very difficult. It was concluded that class micromodels offer the potential to screen the best surfactant formulations for EOR application using residual oil mobilization experiments and for displacements of continuous oil in place.
Calculation of Permeabilities and Residual Saturations Using Invasion Percolation
Authors: Paredes Ricardo , Octavio Miguel
Published: December 2009

In this paper we describe computer simulations in two dimensions of two fluids flowing in a disordered porous media. In particular, we study the process of the displacement of a fluid by a second one in the limit of smallcapillary number. To simulate the dynamics of this process we use the invasion percolation model and represent the medium. by an array of pores with various size distributions. To assign disorder to the system, we model the presence of defects using percolating pore networks. The geometry of the disorder is characterized using concepts of the theory of fractals. The simulations yield percolating clusters of pores saturated with the invading fluid. The geometry of these clusters is characterized by its fractal dimension. This dimension depends on whether the displaced fluid is assumed to be completely incompressible or completely compressible, as well as on the fractal dimension of the porous medium. We also calculate the saturation of the fluids, which is found to be dependent on the geometry of the invader cluster and on the distribution of pore sizes. Using this invading clusters we employ a fast reduction algorithm, based on concepts of network theories, to calculate the effective permeability of the invader fluid with a variety of pore size distributions. We find that the particular size distribution and the geometry of the invading cluster determine the value of this permeability.

Introduction

In the last years, a series of new methods for studying disordered systems have shaken the investigations in porous media. The birth of new fractal geometries, which have struck a great part of natural sciences, also have begun to touch the field of reservoirs engineering. Though on a practical level, until now, fractal geometries haven't had the impact expected, on a conceptual level it has been possible to make researchers reorient their way of interpreting phenomena, from core to reservoir levels. On the other hand, stochastic type theories have also been revised with great interest by reservoir engineers. This type of theories have also been used from microscopic to reservoir scales. For example, many reservoir engineers have tought ingeostatistics as a fundamental tool in reservoir characterization.
Steam Stimulation Pilot Project in the Orinoco Belt, Zuata Area, Venezuela
Authors: Burkill Guy C.C. , Rondon Luis A.
Published: December 2009

Maraven has implemented a Pilot Project in the Zuata area of the Orinoco Belt to evaluate the following parameters in relation to a commercial development:Performance of slant wells drilled with angles of inclination up to 45degrees.Production mechanisms, particularly the possibility of reservoir compaction.Productivity of the area and well response to â??Huff and Puffâ?¿ steaminjection.Pumping efficiency as related to oil viscosity and well angle.

Twelve inclined wells (7 producers and 5 observers) have been drilled in a cluster configuration, using a slant rig with a well spacing at surface of 15metres and 300 metres in the reservoir.
Organic Food Consumption Patterns
Authors: Monier Sylvette , Hassan Daniel , Nichèle Véronique , Simioni Michel
Published: December 2009

This research addresses two important issues for the future expansion of organic consumption in France. The first one is related to knowing whether the organic choice is a permanent feature of consumer's attitude or not: Do organic buyers occasionally pick one organic product or do they choose organic for "several" categories? The second issue concerns the impact of prices on buying organics which is revisited, distinguishing between capturing new consumers and increasing the demand coming from people already involved in organic markets. These questions are examined using the market basket approach; the price issue requires further estimations of demand models. The study relies on two staple food products, eggs and milk. The findings are: (i) choosing organic for one of the two items reinforces the probability of purchasing also the organic version of the second item; (ii) marginal reductions of the organic price have no impact on the decision of buying organic rather than conventional products; (iii) when people already purchase organic products, they may be price sensitive; and (iv) organic buyers' demographic profile is not related to income neither to age nor to family size, but to the educational level.
Certification of Socially Responsible Behavior: Eco-Labels and Fair-Trade Coffee
Authors: Mason Charles F
Published: December 2009

An intriguing alternative to traditional methods for regulating externalities is the provision of information about firms' environmental attributes. An increasingly important example of this approach is "eco-labeling," where a third party certifies firms' products. This sort of approach can also be used in similar circumstances, for example providing consumers with information on the techniques used to produce the good in question (e.g., shade-grown coffee) or the nature of rent-sharing arrangements that govern the transaction (e.g., fair trade coffee). I present a model of this phenomenon. An important aspect of this scheme is that the product in question is typically a credence good (buyers cannot infer product quality from search or consumption), and hence must rely on a third-party for information about the product. But the very fact that consumers cannot infer quality from consumption implies they cannot infer accuracy about the signal; indeed, the certifying agency may not be able to perfectly determine quality at a reasonable cost. As such, the certification process is potentially noisy, albeit with green firms more likely to pass than brown firms. While it is likely to increase the fraction of green units in the market, the introduction of eco-labeling can either increase or decrease welfare. In addition, expected profits earned by green sellers are likely to be more variable in an equilibrium with certification. The paper provides some casual empirical evidence from Latin American coffee markets as a backdrop to the theoretical results.
Multiplicity of Eco-Labels, Competition, and the Environment
Authors: Ben Youssef Adel , Abderrazak Chema
Published: December 2009

This article develops a vertical differentiation model to study the competition and environmental effects of multiplicity of eco-labels within a given market. The focus is on the informational content of multiple eco-labels and whether or not they reflect the environmental qualities the labels purport to represent. Two settings are considered. In the first setting, which represents the benchmark, we assume information is complete (consumers know the true environmental qualities of the eco-labeled goods). In the second setting, information is incomplete but consumers use price as a signal for environmental qualities. Our results show that when information is complete, introduction of a second eco-label in a market improves the environmental qualities of eco-labeled goods. When information is incomplete, introduction of a second label leads to a rise in prices and a reduction in the environmental qualities of the goods. The latter setting requires specific regulation whereby information must be revealed by a benevolent social planner.
How Cognitive Biases Can Affect the Performance of Eco-Labeling Schemes
Authors: Beretti Antoine , Grolleau Gilles , Mzoughi Naoufel
Published: December 2009

Individuals exhibit systematic cognitive biases which make their behavior 'deviant' when compared to the benchmark of perfectly rational individuals. The person's tendency to make errors in judgment based on cognitive factors, are thought to be based upon heuristics and lead to decisions that are sub-optimal. Ignoring cognitive biases can affect diverse dimensions of eco-labeling policies and lead to flawed prescriptions. We review several cognitive biases that affect eco-labeling related behaviors and show how taking them into account allows a better understanding of eco-labeling schemes and informs policy makers in order to design and implement more effective eco-labeling policies.
Standards, Voluntary Labels, and International Trade
Authors: De Freitas Jenny , Bottega Lucie
Published: December 2009

We develop a vertical differentiation model for the setting of standards and labeling in an international economy with two countries, North (N) and South (S) under two regimes: Autarky and International Trade. We assume that a firm in country S has a comparative advantage in producing low quality goods while a firm in country N has comparative advantage in producing high quality goods. Under Autarky each country sets a specific standard and the domestic firm behaves as a monopolist. Under International Trade both countries agree on harmonized standards and firms compete in the unified market. We show that standards harmonization is welfare enhancing compared to the Autarky scenario and that the introduction of a national label in country N does not lead to a Pareto improvement in country S. Consumers in both countries will be worse off with the introduction of the label, for low levels of firm S's comparative advantage.
Quality Promotion through Eco-Labeling: Introduction to the Special Issue
Authors: Costa Sandine , Ibanez Lisette , Loureiro Maria L. , Marette Stéphan
Published: December 2009

This special issue is a collection of papers that address three questions of critical importance to the design of eco-labeling marketing strategies and policies. These three questions deal respectively with the efficiency of eco-labels when considering market structure and trade, the credibility of eco-labels, and consumer attitudes towards eco-labels.
Globalization and Government Short-Term Room to Maneuver in Economic Policy: An Empirical Analysis of Reactions to Currency Crises
Authors: Sattler Thomas , Walter Stefanie
Published: December 2009

This article assesses the popular view that currency crises represent a prime example of the constraints that globalization imposes on government room to maneuver. We show that governments in fact have the possibility to respond to speculative pressure in different ways. Whether or not policymakers succumb to this pressure is not solely determined by economic factors but also a question of political considerations. Political preferences, institutions, and events significantly affect policy responses to currency crises. Our results suggest that national governments retain substantial short-run policy autonomy even in highly internationalized policy areas such as monetary and exchange rate policy.
The Case Against Mass E‐mails: Perverse Incentives and Low Quality Public Participation in U.S. Federal Rulemaking
Authors: Shulman Stuart W
Published: December 2009

Large‐scale e‐mail campaigns are a staple in the modern environmental movement. Interest groups increasingly use online mobilizations as a way to raise awareness, money, and membership. There are legitimate political, economic, and organizational reasons for doing so, but these gains may come at the expense of a more substantial and efficacious role for citizens who wish to use e‐mail to engage in public participation. This paper situates a close examination of the 1000 longest modified MoveOn. Org‐generated e‐mails sent to the Environmental Protection Agency (EPA) about its 2004 mercury rulemaking, in the broader context of online grassroots lobbying. The findings indicate that only a tiny portion of these public comments constitute potentially relevant new information for the EPA to consider. The vast majority of Move On comments are either exact duplicates of a two‐sentence form letter, or they are variants of a small number of broad claims about the inadequacy of the proposed rule. This paper argues that norms, rules, and tools will emerge to deal with the burden imposed by these communications. More broadly, it raises doubts about the notion that online public participation is a harbinger of a more deliberative and democratic era.
Early Adolescents' Use of Social Networking Sites to Maintain Friendship and Explore Identity: Implications for Policy
Authors: Clarke Barbie H
Published: December 2009

This paper considers 10‐14 year olds' adoption of digital technology, and the way in which the developmental tasks of early adolescence are played out within their everyday lives through their widespread interaction with digital media, considering both the social and the psychological processes that take place. It reflects on the concerns that have been expressed about children's use of digital social networking, but also looks at the benefits to children of using the media, and the implications for policymaking. The paper recognises that the widespread adoption of digital technology at this age is deeply embedded in the social context of early adolescents' lives. While the mental processes that take place and the developmental stages have not changed, it may be that digital technology is being used to process some of the tasks of early adolescence, especially in identity formation, the importance and the influence of peers, and the way that emotional support is given and received. An ethnographic study was carried out over two years in the homes of twenty‐eight children living in the south‐east of England. Research included over 30 hours of filmed observation, diaries, friendship maps, individual interviews, friendship focus groups and an online bulletin board. Early adolescence is viewed as a key stage in which emotional development can affect children's level of wellbeing, and friendship is especially important as they turn from their family to the outside world. In playing with identity, building relationships, maintaining friendships and turning to each other for encouragement and companionship, children gain ‘digital agency’. This process may be beneficial and an important source of support and comfort to the young adolescent who is experiencing transition both cognitively, physically, and through change of school. Policy decisions need to be based on a sound understanding of how children use digital technology, raising awareness of the benefits as well as the potential risks, encouraging peer communication and support, and informing parents and teachers of children's digital world.
An Economic Perspective on a U.S. National Broadband Plan
Authors: Hahn Robert , Wallsten Scott J.
Published: December 2009

This paper responds to the U.S. Federal Communications Commission's request for guidance in designing a national broadband plan. We argue that the U.S. market for Internet services is working well overall, as evidenced by nearly ubiquitous coverage, rapid adoption, large investments, and increasing speeds. Still, the market is not working well for all people in all places, and we offer a framework for considering policies intended to mitigate those issues. The core of the paper consists of nine recommendations. Two of our recommendations are general. First, the government should ensure that its interventions do more good than harm. Second, the government should define clear, measurable, goals that do not benefit particular firms, technologies, or regions. The remaining seven recommendations provide specific guidance for a U.S. broadband plan. They include: liberalizing spectrum, gathering and analyzing data on broadband demand, targeting resources to where they are most needed, defining broadband access to maximize social gain, designing mechanisms that will achieve the government's broadband goals at the lowest social cost, vigorous antitrust enforcement, and designing policies to facilitate rigorous evaluation.
The Internet and Public Policy
Authors: Margetts Helen Z
Published: December 2009

This article looks at the role of the Internet in policymaking, identifying potential policy effects of widespread use of the Internet by citizens, firms, governments and voluntary organizations. It considers how the Internet and Internet‐enabled social change might impact upon each of the four ‘tools’ of government policy — nodality, authority, treasure and organization — and how it might impact upon the mix of tools that policymakers select. It suggests a number of values normally associated with the Internet — innovation, trust, openness and equity — that might be expected to emerge in policy trends. It discusses the implications of Internet‐driven change for public policy research, pinpointing some key methodologies that will become increasingly important; generation of large‐scale transactional data; network analysis and experimental methods. The article argues that we cannot understand, analyse or make public policy without understanding the technological, social and economic shifts associated with the Internet — a task that the journal Policy & Internet is poised to undertake.
Rapunzel syndrome — a case report
Authors: Stojanovic Miroslava , Slavkovic Andjelka , Marjanovic Zoran , Stojanovic Miroslav , Zivanovic Dragoljub
Published: December 2009

Bezoars are collections of indigestible materials found in the gastrointestinal tract. Rapunzel syndrome is a rare complication of a gastric trichobezoar in which the mass of hair extends through the pylorus into the small bowel and can even reach the colon. A 12-year-old girl with severe pain and a feeling of “fullness” in the upper abdomen was admitted to Pediatric Surgery. Two days before admission, the patient presented with vague abdominal pain, vomiting with a little blood, and black stool. On physical examination she was pale and listless with patchy alopecia. Abdominal examination showed a mobile, palpable mass in the epigastrium. The initial hematocrit was 7,1%, and the erythrocyte count was 1,12×1012 cells per liter. Abdominal ultrasound and computed tomographic (CT) examinations confirmed the presence of a tumor-like formation in stomach. A giant bezoar with ulceration on the back wall of the stomach was verified by upper gastrointestinal endoscopy. Endoscopic extraction was not possible because of the size of the bezoar. Gastrotomy was performed to remove the bezoar that occupied most of the stomach, with a long tail that extended deeply into the duodenum (Rapunzel syndrome). The bezoar, 35 by 10 cm in diameter, was black and consisted of hair and synthetic fibers. Prompt diagnosis and treatment of trichobezoars are important to avoid a possible fatal outcome.
Molecular mechanisms of toxicity of simvastatin, widely used cholesterol-lowering drug. A review
Authors: Kaminsky Yury , Kosenko Elena
Published: December 2009

Statins are widely used and well tolerated cholesterol-lowering drugs, and when used for therapy purposes reduce morbidity and mortality from coronary heart disease. Simvastatin is one of nine known statins, specific inhibitors of hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting step of cholesterol biosynthesis, and is believed to reduce plasma cholesterol levels by decreasing the activity of this enzyme. Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Although statins are generally safe, minor and severe adverse reactions are well known complications of statin use. Adverse events associated with simvastatin therapy are uncommon, but potentially serious. In this review some details about statins including their adverse effects in humans and animals, the effects of simvastatin on various intracellular and mitochondrial processes, and molecular mechanisms underlying simvastatin cytotoxicity are discussed.
“Does chronic kidney disease define a particular risk pattern of cerebral vessels modifications in patients with symptomatic ischemic cerebrovascular disease?”
Authors: Petrica Ligia , Petrica Maxim , Gheorghe Gluhovschi , Liviu Matcau , Florica Gadalean , Sorin Ursoniu , Catalin Jianu , Silvia Velciov , Flaviu Bob , Cristina Gluhovschi , Virginia Trandafirescu , Diana Matcau , Gheorghe Bozdog , Carmina Muresan
Published: December 2009

Cardiovascular complications, including stroke, may be attributed the highest rate of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of our study was to evaluate the prevalence of CKD in patients with symptomatic ischaemic cerebrovascular disease and to establish of whether CKD may define a particular risk pattern of cerebral vessels modifications in this category of patients. The prevalence of CKD was evaluated in 590 consecutive patients with symptomatic ischaemic cerebrovascular disease admitted to a department of neurology. The types of stroke, the vascular territories, the vascular modifications and the haemodynamic changes (resistance index- RI) found by neurosonology (extracranial and transcranial Doppler ultrasound) were analysed in relation to classic and non-classic cerebrovascular risk factors, as well as to stages of CKD (defined by estimated glomerular filtration rate-eGFR-MDRD4 formula-K/DOQI 2002). The prevalence of CKD in the studied patients was 70.84%. Atherosclerosis in a diffuse pattern was detected in 79.7% of CKD patients, while carotid artery stenoses were found in 10% of cases, occlusions- 5.3%, stenoses + occlusions-1.2%, and multiple stenoses- 3.8% of cases. The RI evaluated in the internal carotid arteries correlated with fibrinogen(P<0.0001) and GFR(P<0.0001), while IR in the middle cerebral arteries correlated with fibrinogen(P<0.05), C-reactive protein(P<0.0001), and GFR(P<0.0001). There is a strong relation between symptomatic cerebrovascular disease and CKD, a fact demonstrated by the increased prevalence of CKD in these patients and by the severity of the cerebral vessels lesions.
Evaluation of fixed sources of variation and estimation of genetic parameters for incidence of bovine respiratory disease in preweaned calves and feedlot cattle12
Authors: Schneider M. J. , Tait R. G. , Ruble M. V. , Busby W. D. , Reecy J. M.
Published: December 2009

The primary objective of this study was to estimate variance components and heritability of bovine respiratory disease (BRD) incidence in beef calves before weaning and during the finishing phase. The second objective was to investigate the impact of BRD incidence and treatment frequency on performance and carcass traits. Bovine respiratory disease is the biggest and most costly health challenge facing the cattle industry. The 2 populations used consisted of 1,519 preweaned calves and 3,277 head of feedlot cattle. The incidence rate of BRD in preweaned calves was 11.39%, and among treated cattle, 82.1% were treated once, 13.9% were treated twice, and 4.0% were treated 3 times or more. The incidence of BRD (P = 0.35) and the number of treatments (P = 0.77) had no significant effect on weaning BW. Heritability estimates of the entire preweaned population for BRD resistance and number of treatments were 0.11 ± 0.06 and 0.08 ± 0.05, respectively. The genetic correlation estimates for BRD incidence with weaning BW and birth BW were low (−0.02 ± 0.32 and 0.07 ± 0.27, respectively). The same estimate for the number of BRD treatments with weaning BW and birth BW was 0.25 ± 0.35 and 0.30 ± 0.27, respectively. The observed BRD incidence rate for feedlot cattle was observed at 9.43%. Incidence of BRD significantly (P < 0.01) decreased overall and acclimation ADG by 0.06 ± 0.01 kg/d and 0.28 ± 0.03 kg/d, respectively. Carcass traits were also significantly (P < 0.05) affected by BRD incidence; untreated cattle had a 9.1 ± 1.7-kg heavier HCW. Results were similar in the analysis of treatment frequency. The heritability estimate of BRD incidence and the number of treatments were 0.07 ± 0.04 and 0.02 ± 0.03, respectively. Estimates of genetic correlations of BRD incidence with production traits were −0.63 ± 0.22 for acclimation ADG, −0.04 ± 0.23 for on-test ADG, −0.31 ± 0.21 for overall ADG, −0.39 ± 0.21 for final BW, −0.22 ± 0.22 for HCW, −0.03 ± 0.22 for LM area, 0.24 ± 0.25 for fat, and −0.43 ± 0.20 for marbling score. Similar results for the number of treatments and production traits were −1.00 ± 0.68 for acclimation ADG, −0.04 ± 0.39 for on-test ADG, −0.47 ± 0.41 for overall ADG, −0.66 ± 0.40 for final BW, −0.58 ± 0.45 for HCW, −0.12 ± 0.38 for LM area, 0.42 ± 0.50 for fat, and −0.32 ± 0.37 for marbling score. Because of the high economic cost associated with BRD incidence, even these modest estimates for heritability of BRD resistance should be considered for incorporation into beef cattle breeding programs.
The Transformation and Storage of Solar Energy: Progress Towards Visible-Light Induced Water Splitting
Authors: Cline Eric D. , Bernhard Stefan
Published: December 2009

The sun is a plentiful source of clean, renewable power, and the direct conversion of solar to chemical energy is a desirable goal. The collective efforts of the Bernhard group to develop molecular catalytic systems for visible-light water splitting are reviewed. Combinatorial synthesis
and high-throughput screening techniques enabled the development of a series of photosensitizers with a wide range of photophysical and electrochemical properties. Parallel evaluation of the iridium(III) photosensitizers in photocatalytic water reduction systems utilizing cobalt-, platinum-,
or rhodium-based water reduction catalysts resulted in systems that exhibited more than 5000 turnovers with quantum yields of 34% and turnover frequencies of 500 hr?1. For the complementary water oxidation system, the catalysts based on cyclometallated iridium complexes are
robust and tunable, which allows for the rapid study of water oxidation reactions through targeted ligand modification.
Fluorescent Probes and Labels for Cellular Imaging
Authors: Fahrni Christoph J.
Published: December 2009

Metal-responsive fluorescent indicators are powerful tools for visualizing trace metals with subcellular resolution. By taking advantage of the diverse photophysical properties of organic fluorophores, metal ion-selective fluorescent indicators have been rationally designed and tailored
towards cellular applications. This review summarizes challenges associated with the probe design and describes recent efforts in our research group in developing selective and sensitive reagents for the detection of zinc and copper in mammalian cells.
Polynuclear Photocatalysts in Nanoporous Silica for Artificial Photosynthesis
Authors: Frei Heinz
Published: December 2009

In this article, recent progress towards robust photocatalysts for the visible light-driven reduction of CO2 by H2O is presented. All-inorganic polynuclear photocatalysts consisting of an oxo-bridged binuclear charge-transfer chromophore (metal-to-metal charge-transfer)
coupled to a multi-electron transfer catalyst anchored in a nanoporous silica scaffold have been developed. Mild synthetic methods afford assembly, on silica nanopore surfaces, of heterobinuclear units with donor and acceptor metal centers selected for optimum solar coverage and photon to
chemical energy conversion efficiency. A photocatalyst featuring a TiOCrIII group coupled to an IrO2 nanocluster on MCM-41 silica support is shown to function as an efficient visible light water oxidation unit. Nanostructured Co3O4 clusters in mesoporous
silica SBA-15 constitute the first example of a nanometer-sized multi-electron catalyst made of an earth-abundant metal oxide that evolves oxygen from water efficiently. For carbon dioxide reduction, a binuclear unit consisting of a Zr acceptor and a CuI donor (ZrOCuI)
acts as light absorber as well as redox site, splitting CO2 to CO and H2O upon excitation of the charge-transfer transition. Structural and mechanistic insights of the photocatalytic units based on static and time-resolved optical, FT-infrared, FT-Raman, EPR, X-ray absorption
spectroscopy and transmission electron microscopy are critical for improving designs. The photocatalytic units presented here form the basis for developing robust and efficient artificial photosynthetic systems for the conversion of carbon dioxide and water to a liquid fuel.
Unusual DNA Structure and DNA Damage Recognition: Structure and Dynamic Markers
Authors: Germann Markus W. , Johnson Christopher N. , Spring Alexander M.
Published: December 2009

Nucleic acids play a central role in many biological processes, including information storage, gene expression, serving as messengers or structural components and even catalysis. Their diverse roles have made them targets of interest to diagnose and treat an array of human disorders
such as infections, degenerative diseases and cancer. Nature has evolved proteins and ligands that recognize specific nucleic acid sequences or structures and control their function, demonstrating that this can be efficiently accomplished. This has led to the development of wide variety of
synthetic molecules that selectively bind to nucleic acids. In turn, this has precipitated numerous studies which showed that nucleic acid structures and their dynamic properties must be understood in order to efficiently target specific sequences or structures.
Engineering Kinases to Phosphorylate Nucleoside Analogs for Antiviral and Cancer Therapy
Authors: Lutz Stefan , Liu Lingfeng , Liu Yichen
Published: December 2009

Enzyme engineering by directed evolution presents a powerful strategy for tailoring the function and physicochemical properties of biocatalysts to therapeutic and industrial applications. Our laboratory's research focuses on developing novel molecular tools for protein engineering,
as well as on utilizing these methods to customize enzymes and to study fundamental aspects of their structure and function. Specifically, we are interested in nucleoside and nucleotide kinases which are responsible for the intracellular phosphorylation of nucleoside analog (NA) prodrugs to
their biologically active triphosphates. The high substrate specificity of the cellular kinases often interferes with prodrug activation and consequently lowers the potency of NAs as antiviral and cancer therapeutics. A working solution to the problem is the co-adminstration of a promiscuous
kinase from viruses, bacteria, and other mammals. However, further therapeutic enhancements of NAs depend on the selective and efficient prodrug phosphorylation. In the absence of true NA kinases in nature, we are pursuing laboratory evolution strategies to generate efficient phosphoryl-transfer
catalysts. This review summarizes some of our recent work in the field and outlines future challenges.