bluuebunny/crossref_metadata_2025 huggingface dataset:
PURA Syndrome-causing mutations impair PUR-domain integrity and affect P-body association
Authors: Proske Marcel , Janowski Robert , Bacher Sabrina , Kang Hyun-Seo , Monecke Thomas , Köhler Tony , Hutten Saskia , Tretter Jana , Crois Anna , Molitor Lena , Varela-Rial Alejandro , Fino Roberto , Donati Elisa , Fabritiis Gianni De , Dormann Dorothee , Sattler Michael , Niessing Dierk
Published: January 2024

Mutations in the human
PURA
gene cause the neuro-developmental PURA syndrome. In contrast to several other mono-genetic disorders, almost all reported mutations in this nucleic acid binding protein result in the full disease penetrance. In this study, we observed that patient mutations across PURA impair its previously reported co-localization with processing bodies. These mutations either destroyed the folding integrity, RNA binding or dimerization of PURA. We also solved the crystal structures of the N- and C-terminal PUR domains of human PURA and combined them with molecular dynamics simulations and NMR measurements. The observed unusually high dynamics and structural promiscuity of PURA indicated that this protein is particularly susceptible to mutations impairing its structural integrity. It offers an explanation why even conservative mutations across PURA result in the full penetrance of symptoms in patients with PURA syndrome.
Self-inhibiting percolation and viral spreading in epithelial tissue
Authors: Xu Xiaochan , Nielsen Bjarke Frost , Sneppen Kim
Published: January 2024

SARS-CoV-2 induces delayed type-I/III interferon production, allowing it to escape the early innate immune response. The delay has been attributed to a deﬁciency in the ability of cells to sense viral replication upon infection, which in turn hampers activation of the antiviral state in bystander cells. Here, we introduce a cellular automaton model to investigate the spatiotemporal spreading of viral infection as a function of virus and host-dependent parameters. The model suggests that the considerable person-to-person heterogeneity in SARS-CoV-2 infections is a consequence of high sensitivity to slight variations in biological parameters near a critical threshold. It further suggests that within-host viral proliferation can be curtailed by the presence of remarkably few cells that are primed for IFN production. Thus, the observed heterogeneity in defense readiness of cells reﬂects a remarkably cost-eﬃcient strategy for protection.
Climate Change Impacts and Mitigation Strategies in the Energy Sector of African Countries
Authors: Usiabulu Godsday Idanegbe , Djoï André Noukpo , Aprioku Peter Sydney , Afehikhu Otoika Tunde , Aguebor Dennis Ese , Okoye Ogechi , Ifedili Ucheana Donald , Peters Joseph Friday , Nji Christian Ayafor
Published: January 2024

Many of the Sustainable Development Goals (SDGs) require access to dependable, affordable, and sustainable energy, as it has a substantial impact on health, climate, and other sectors. This study focus on Creating an understanding of Climate Change Impacts, Identifying Mitigation Strategies as well as bringing the spot light on the Energy Sector in African Nations. Modern energy services are also required for agricultural transformation, the creation of productive firms, and the support of revenue-generating activities. As a result of energy consumption, combustion, and greenhouse impacts from emissions of environmental pollutants such as carbon monoxide, hydrocarbon compounds, sulfur oxides, nitrogen oxides, methane, and particulates are examined. Among the many pollutants that contribute to climate change, CO2 emissions have received a lot of attention as the primary cause of climate change. Special attention should be given to investments and policies that promote all three goals or at the very least, those that improve one or both without worsening the other. This report provides a (non-exhaustive) synthesis and assessment of energy consumption rates, supply, and access challenges in Africa, focusing on the connections, synergies, and conflicts with climate mitigation and adaptation strategies. Additionally, the ladder of the utilization of energy and its variety switches as income levels of individuals rise has been considered. Access to energy and its impact on the well-being of the people including the use of biomass and electricity has been expanded. Africa's energy portfolios will need to be properly calibrated to suit adequate supply, access, mitigation, and adaptation goals.
Time‐ and Velocity‐Dependent Properties of Powders Effecting Slip‐Stick Oscillations
Authors: Schulze D.
Published: October 2003

Slip‐stick behavior of powders is a phenomenon characterized by self‐excited, pulsating flow, i.e., the powder starts and stops flowing intermittently. Slip‐stick can occur both within flowing powders and with powders flowing along a rigid wall. In this study, measurements were performed in order to identify the properties of powders relevant for slip‐stick and the results interpreted on the basis of analogies to friction processes between rigid bodies. Also, findings of other fields of science (mechanics, tribology, geophysics) were considered with regard to their possible application to powders.
Hydrogenation versus Transfer Hydrogenation of Ketones: Two Established Ruthenium Systems Catalyze Both
Authors: Rautenstrauch Valentin , Hoang‐Cong Xuân , Churlaud Raphaël , Abdur‐Rashid Kamaluddin , Morris Robert H.
Published: October 2003

The established standard ketone hydrogenation (abbreviated HY herein) precatalyst [Ru(Cl)2((S)‐tolbinap){(S,S)‐dpen}] ((S),(S,S)‐1) has turned out also to be a precatalyst for ketone transfer hydrogenation (abbreviated TRHY herein) as tested on the substrate acetophenone (3) in iPrOH under standard conditions (45 °C, 45 bar H2 or Ar at atmospheric pressure). HY works at a substrate catalyst ratio (s:c) of up to 106 and TRHY at s:c<104. Both produce (R)‐1‐phenylethan‐1‐ol ((R)‐4), but the ee in HY are much higher (78–83 %) than in TRHY (4–62 %). In both modes, iPrOK is needed to generate the active catalysts, and the more there is (1–4500 equiv), the faster the catalytic reactions. The ee is about constant in HY and diminishes in TRHY as more iPrOK is added. The ketone TRHY precatalyst [Ru(Cl)2((S,S)‐cyP2(NH)2)] ((S,S)‐2), established at s:c=200, has also turned out to be a ketone HY precatalyst at up to s:c=106, again as tested on 3 in iPrOH under standard conditions. The enantioselectivity is opposite in the two modes and only high in TRHY: with (S,S)‐2, one obtains (R)‐4 in up to 98 % ee in TRHY as reported and (S)‐4 in 20–25 % ee in HY. iPrOK is again required to generate the active catalysts in both modes, and again, the more there is, the faster the catalytic reactions. The ee in TRHY are only high when 0.5–1 equivalents iPrOK are used and diminish when more is added, while the (low) ee is again about constant in HY as more iPrOK is added (0–4500 equiv). The new [Ru(H)(Cl)((S,S)‐cyP2(NH)2)] isomers (S,S)‐9 A and (S,S)‐9 B (mixture, exact structures unknown) are also precatalysts for the TRHY and HY of 3 under the same conditions, and (R)‐4 is again produced in TRHY and (S)‐4 in HY, but the lower ee shows that in TRHY (S,S)‐9 A/(S,S)‐9 B do not lead to the same catalysts as (S,S)‐2. In contrast, the ee are in accord with (S,S)‐9 A/(S,S)‐9 B leading to the same catalysts as (S,S)‐2 in HY. The kinetic rate law for the HY of 3 in iPrOH and in benzene using (S,S)‐9 A/(S,S)‐9 B/iPrOK or (S,S)‐9 A/(S,S)‐9 B/tBuOK is consistent with a fast, reversible addition of 3 to a five‐coordinate amidohydride (S,S)‐11 to give an (S,S)‐11‐substrate complex, in competition with the rate‐determining addition of H2 to (S,S)‐11 to give a dihydride [Ru(H)2((S,S)‐cyP2(NH)2)] (S,S)‐10, which in turn reacts rapidly with 3 to generate (S)‐4 and (S,S)‐11. The established achiral ketone TRHY precatalyst [Ru(Cl)2(ethP2(NH)2)] (12) has turned out to be also a powerful precatalyst for the HY of 3 in iPrOH at s:c=106 and of some other substrates. Response to the presence of iPrOK is as before, except that 12 already functions well without it at up to s:c=106.
The Austrian strategy for sustainable development: process review and policy analysis
Authors: Martinuzzi André , Steurer Reinhard
Published: October 2003

In compliance with UN requests, National Strategies for Sustainable Development (NSSDs) are emerging around the world. With these strategies, countries are supposed to halt or reverse trends that conflict with sustainable development. We begin by giving a brief overview of the history of environmental policy planning leading up to NSSDs. Afterwards, we summarize the content of the 2002 Austrian SSD and describe its making as well as implementation processes. On that basis, we proceed to analyze its respective strengths, weaknesses and the lessons learned in the process. As one of the authors took part in the making of the Austrian strategy, our process description and the subsequent analysis are able to draw upon insider knowledge. The three main conclusions of this analysis are the following: (i) the design of the implementation process is more policy relevant than NSSDs themselves; (ii) as NSSD processes, driven by bureaucracies rather than governments, will face limits in implementation, high‐level political commitment is crucial and (iii) experiences and lessons learned should not only be transferred from international organizations to individual countries but also directly between the countries themselves. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.
Peripheral lymphedema: New advances in microsurgical treatment and long‐term outcome
Authors: Campisi Corradino , Boccardo Francesco , Zilli Angelo , Macciò Alberto , Gariglio Anderson , Schenone Francesco
Published: October 2003

We report on the modern surgical management of peripheral lymphedema. An adequate diagnostic route is essential: it has to include patient history and clinical examination, an isotopic lymphography, an accurate study of the venous circulation, and in cases of angiodysplasia, an accurate study of the artery circulation. Based on over 25 years of clinical experience (more than 1,000 patients), the role of derivative and (in those cases where a venous disease is associated with lymphostatic pathology) reconstructive lymphatic microsurgery is particularly underlined, in comparison with conservative medico‐physical treatment, to which it is complementary. “Debulking” surgery can be used just in properly selected patients for minor operations with only cosmethic‐reductive purposes. With a follow‐up even over 15 years after surgery, positive results from lymphatic microsurgery can be achieved in more than 80% of cases, especially in patients at precocious stages. © 2003 Wiley‐Liss, Inc. MICROSURGERY 23:522–525 2003
Conductivity, morphology, interfacial chemistry, and stability of poly(3,4‐ethylene dioxythiophene)–poly(styrene sulfonate): A photoelectron spectroscopy study
Authors: Crispin X. , Marciniak S. , Osikowicz W. , Zotti G. , van der Gon A. W. Denier , Louwet F. , Fahlman M. , Groenendaal L. , De Schryver F. , Salaneck W. R.
Published: October 2003

X‐ray photoelectron spectroscopy (XPS) has been used to characterize poly(3,4‐ethylene dioxythiophene)–poly(styrene sulfonate) (PEDT/PSS), one of the most common electrically conducting organic polymers. A correlation has been established between the composition, morphology, and polymerization mechanism, on the one hand, and the electric conductivity of PEDT/PSS, on the other hand. XPS has been used to identify interfacial reactions occurring at the polymer‐on‐ITO and polymer‐on‐glass interfaces, as well as chemical changes within the polymer blend induced by electrical stress and exposure to ultraviolet light. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 2561–2583, 2003
Dielectric and electrical properties of Sr5EuCr3Nb7O30 nanoceramics prepared using a novel chemical route
Authors: Ranga Raju M. R. , Choudhary R. N. P. , Ram S.
Published: October 2003

Polycrystalline samples of Sr5EuCr3Nb7O30, a member of the tungsten bronze (TB) family, have been prepared by a novel chemical precursor route with a chemical dispersion and mixing of the metal cations in an acidic solution. Preliminary structural studies have been carried out using X‐ray diffraction of samples heated at different temperatures, in the 973 to 1173 K range, from the precursor. They confirm the formation of the single‐phase compound in an orthorhombic structure at room temperature. The dielectric constant (ε) and tangent loss (tan δ) of the samples have been measured as a function of both frequency (102–105 kHz) and temperature (300–700 K). None of the samples shows any dielectric anomaly. Impedance spectroscopic data are explored to gain an insight into the electrical properties and the relaxation behaviors. The measurement of the conductivity as a function of temperature suggests that the samples have a negative temperature coefficient of resistivity in a typical semiconductor behavior.
Surface color perception in constrained environments
Authors: Maloney Laurence T.
Published: October 2003

Byrne & Hilbert propose that color can be identified with explicit properties of physical surfaces. I argue that this claim must be qualified to take into account constraints needed to make recovery of surface color information possible. When these constraints are satisfied, then a biological visual system can establish a correspondence between perceived surface color and specific surface properties.
Have Byrne & Hilbert answered Hardin's challenge?
Authors: Pautz Adam
Published: October 2003

I argue that Byrne & Hilbert (B&H) have not answered Hardin's objection to physicalism about color concerning the unitary-binary structure of the colors for two reasons. First, their account of unitary-binary structure seems unsatisfactory. Second, pace B&H, there are no physicalistically acceptable candidates to be the hue-magnitudes. I conclude with a question about the justification of physicalism about color.
A NOTE ON THE CONDUCTIVITY OF RANDOM TREES
Authors: Konsowa Mokhtar H.
Published: October 2003

We prove that no stochastic domination exists between the
effective resistance of a spherically symmetric random tree
and that of a branching process in a varying environments tree
if they grow according to the same law of distribution.
Dysphagia: implications for older people
Authors: Ratnaike Ranjit N
Published: October 2003

Dysphagia is defined as difficulty in swallowing solids or liquids and is distinct from odynophagia, which is pain on swallowing. Dysphagia occurs in a range of conditions that affect the oral, pharyngeal and oesophageal phase of swallowing. The problem of dysphagia assumes greater importance in older persons. Some people may not be able to communicate that a problem exists. In others the lack of nutrition due to dysphagia compounds existing undernutrition, a common problem in institutionalized older persons. This paper discusses dysphagia in the context of the older person and outlines the normal mechanism of swallowing, the important clinical distinction between oropharyngeal dysphagia and oesophageal dysphagia, the aetiology of dysphagia and issues of management.
Structure of the Hall current system in the vicinity of the magnetic reconnection site
Authors: Nagai T. , Shinohara I. , Fujimoto M. , Machida S. , Nakamura R. , Saito Y. , Mukai T.
Published: October 2003

The spacecraft Geotail has observed the Hall current system in the vicinity of the magnetic reconnection site of the near‐Earth magnetotail for substorm onsets. In the outermost region near the plasma sheet/tail lobe boundary, field‐aligned currents flow out of the magnetic reconnection site. In the adjacent region, just inside the outflowing current layer, field‐aligned currents flow into the magnetic reconnection site. Hence, the Hall current circuit forms a thin double‐sheet structure near the separatrix layer.
Dynamics Around Minimal Hyperbolic Torus in Hamiltonian Systems
Authors: Yan Jun , Cheng Chong-Qing
Published: October 2003

By investigating the topological properties of action minimal sets near a minimal hyperbolic torus in nearly integrable Hamiltonian system, a sufficient condition of existence of connections between different Mather sets is obtained.
Inverse Fractal Statistics in Turbulence and Finance
Authors: Jensen Mogens H. , Johansen Anders , Simonsen Ingve
Published: October 2003

We consider inverse statistics in turbulence and financial data. By inverse statistics, also sometimes called exit time statistics, we "turn" the variables around such that the fluctuating variable becomes the fixed variable, while the fixed variable becomes fluctuating. In that sense we can probe distinct regimes of the data sets. In the case of turbulence, we obtain a new set of (multi)-scaling exponents which monitor the dissipation regime. In the case of economics, we obtain a distribution of waiting times needed to achieve a predefined level of return. Such a distribution typically goes through a maximum at a time called the optimal investment horizon[Formula: see text], since this defines the most likely waiting time for obtaining a given return ρ. By considering equal positive and negative levels of return, we report on a quantitative gain-loss asymmetry most pronounced for short horizons.
Multistability Formation and Loss of Chaos Synchronization in Coupled Period-Doubling Systems
Authors: Uhm W. , Astakhov V. , Akopov A. , Kim S.
Published: October 2003

We investigate phenomena of multistability and complete chaos synchronization in coupled period-doubling systems. Bifurcational mechanisms for both a loss of chaos synchronization and multistability formation are described and their relation is uncovered. Multiparametric analysis of special families of stable and saddle periodic orbits shows generic "interior" bifurcational processes that determine a variety of complex dynamics in interacting period-doubling systems. In particular, we find that for decreasing coupling the bifurcational cascades for symmetric saddle periodic orbits determine loss of chaos synchronization and multistability formation.
Controlling Beam Halo-Chaos for ADS
Authors: Fang Jin-Qing , Zhao Geng , Zhou Liu-Lai , Chen Guanrong
Published: October 2003

Accelerator driven clean nuclear power system (ADS) as an innovative technique in the 21st century is among the most challenge of high-tech fields since it makes nuclear power system safer, cleaner, cheaper, and more reliable. ADS is very necessary option for sustainable development of nuclear energy in the 21st century. However, beam halo-chaos occurred in high-current accelerators of ADS has become a key concerned issue for many important applications of intensity ion beam.To understand the complex of beam halo-chaos, this paper analyzes one of the main physical mechanism for halo-chaos formation, i.e. nonlinear resonance overlapping routes to halo-chaos. Then some efficient nonlinear control methods of beam halo-chaos are presented. The simulation results demonstrate that the control methods we proposed are very effective for beam halo-chaos suppression.
A Transient Crisis
Authors: He Da-Ren , Wang Wen-Xiu , Lu Yun-Qing
Published: October 2003

A new kind of crisis, which is marked by a sudden change of a strange repeller, is observed in an electronic relaxation oscillator. Fist, by its simplified piecewise linear model, we show analytically that a strange repeller appears after a hole-induced crisis, and that the fractal dimension of the strange repeller and the averaged lifetime of the iterations in the region occupied by the original attractor suddenly change at a critical parameter value when the repeller disappears. Our numerical investigation convinces us that the corresponding phenomenon can be found in the original electronic relaxation oscillator.
Classification of Cellular Automata and Complexity
Authors: Jin Xiaogang , Kim Tae-Wan
Published: October 2003

Cellular automata (CA) is not only a discrete dynamical system with infinite dimension, but also an important computational model. One of the most important problems in the theory of CA is how to establish the relationship between the local rules and the global behavior and then obtain the classification of CA. In this paper, we consider previous works on the classification of CA, including dynamical, statistical and computational classification and address the significance of research on theory of CA and complexity.
Chaotic Synchronization for Scene Segmentation
Authors: Zhao Liang
Published: October 2003

In this work, we analyze the synchronization role in a 1D array of coupled continuous chaotic elements. The ordinary differential equations, which represent each chaotic element, have a stable linear part perturbed by a bounded nonlinear function. A theorem is established to give sufficient condition to obtain synchronization of the array. Then, the above results are applied to a 2D network of coupled Wilson-Cowan neural oscillators showing how to solve scene segmentation problems by rapid chaotic synchronization and desynchronization. Computer simulations confirm the mathematical analysis.
Low Frequency AC Nonlinear Dynamic Admittance in Quantum Dot Structure
Authors: Zhao Xuean , Pan Zheng-Quan
Published: October 2003

In the framework of scattering theory and in terms of the notion of local partial density of states(LPDOS), we derived the expressions of the linear and the second order nonlinear emittance, which is the imaginary part of admittance, for the quantum dot structure. With the help of discrete Hamiltonian model we obtained the linear and the second nonlinear partial density of states. By using the linear and the nonlinear emittance we could obtain expressions which can be used to detect the density of state(DOS) of the sample.
Reflection of Transient Acoustic Waves by a Continuously Layered Halfspace with Depth-Dependent Attenuation
Authors: Verweij Martin D.
Published: October 2003

An integral transformation-type method is presented for the analysis of the space-time domain acoustic wavefield that is reflected by a halfspace consisting of a continuously layered, lossy, isotropic (equivalent) fluid. The application of a vertically varying compliance memory function makes it possible to model a large class of depth-dependent loss properties. The method combines higher-order WKBJ-like asymptotics with the Cagniard-De Hoop method of inverse transformation. The coefficients that occur in the WKBJ asymptotics follow a recurrence scheme that is easy to evaluate by means of a symbolic manipulation program. The form of the transform domain expressions leads to a very fast inversion process. Numerical results are presented that show the reflections from continuously layered lossless and lossy halfspaces.
Biomechanics of the Lumbar Disc
Authors: Goel V. K. , Grosland N. M. , Scifert J.
Published: October 2003

The human disc and the facets work in unison to transmit loads across a lumbar motion segment. For this reason, if one component is affected by the degenerative process, the other follows. Modern imaging techniques and clinical observations have adequately delineated morphological changes in the spinal structures, while in vitro biomechanical studies have revealed that repetitive complex loads may lead to loosening of spinal structures, annular tears, and herniated discs. In addition to such experimental methods, analytical models have been able to explain the role of mechanical factors in producing disc degeneration and herniation. Furthermore, these techniques are applicable to investigating various surgical stabilization procedures. From a biomechanical perspective, surgical procedures such as discectomy are effective in reducing pain due to a decrease in disc bulge following surgery. Excessive instability across the disc, however, may require the use of bone grafts, cages or other types of interbody spacers to restore disc height. Efforts are currently underway to restore disc mechanics via an artificial disc. The following review is aimed at outlining the role of mechanical foctors in both inducing and stabilizing the degenerated/herniated intervertebral disc.
View-dependent displacement mapping
Authors: Wang Lifeng , Wang Xi , Tong Xin , Lin Stephen , Hu Shimin , Guo Baining , Shum Heung-Yeung
Published: October 2003

Significant visual effects arise from surface mesostructure, such as fine-scale shadowing, occlusion and silhouettes. To efficiently render its detailed appearance, we introduce a technique called view-dependent displacement mapping (VDM) that models surface displacements along the viewing direction. Unlike traditional displacement mapping, VDM allows for efficient rendering of self-shadows, occlusions and silhouettes without increasing the complexity of the underlying surface mesh. VDM is based on per-pixel processing, and with hardware acceleration it can render mesostructure with rich visual appearance in real time.
Bi-scale radiance transfer
Authors: Sloan Peter-Pike , Liu Xinguo , Shum Heung-Yeung , Snyder John
Published: October 2003

Radiance transfer represents how generic source lighting is shadowed and scattered by an object to produce view-dependent appearance. We generalize by rendering transfer at two scales. A macro-scale is coarsely sampled over an object's surface, providing global effects like shadows cast from an arm onto a body. A meso-scale is finely sampled over a small patch to provide local texture. Low-order (25D) spherical harmonics represent low-frequency lighting dependence for both scales. To render, a coefficient vector representing distant source lighting is first transformed at the macro-scale by a matrix at each vertex of a coarse mesh. The resulting vectors represent a spatially-varying hemisphere of lighting incident to the meso-scale. A 4D function, called a radiance transfer texture (RTT), then specifies the surface's meso-scale response to each lighting basis component, as a function of a spatial index and a view direction. Finally, a 25D dot product of the macro-scale result vector with the vector looked up from the RTT performs the correct shading integral. We use an id map to place RTT samples from a small patch over the entire object; only two scalars are specified at high spatial resolution. Results show that bi-scale decomposition makes preprocessing practical and efficiently renders self-shadowing and interreflection effects from dynamic, low-frequency light sources at both scales.
Simplifying complex environments using incremental textured depth meshes
Authors: Wilson Andrew , Manocha Dinesh
Published: October 2003

We present an incremental algorithm to compute image-based simplifications of a large environment. We use an optimization-based approach to generate samples based on scene visibility, and from each viewpoint create textured depth meshes (TDMs) using sampled range panoramas of the environment. The optimization function minimizes artifacts such as skins and cracks in the reconstruction. We also present an encoding scheme for multiple TDMs that exploits spatial coherence among different viewpoints. The resulting simplifications, incremental textured depth meshes (ITDMs), reduce preprocessing, storage, rendering costs and visible artifacts. Our algorithm has been applied to large, complex synthetic environments comprising millions of primitives. It is able to render them at 20 -- 40 frames a second on a PC with little loss in visual fidelity.
The origins of digital computing in Europe
Authors: Goodman Seymour
Published: October 2003

Retracing the paths of influential, but often isolated, computer pioneers.
Computing the distribution function of a conditional expectation via monte carlo
Authors: Lee Shing-Hoi , Glynn Peter W.
Published: October 2003

We examine different ways of numerically computing the distribution function of conditional expectations where the conditioning element takes values in a finite or countably infinite outcome space. Both the conditional expectation and the distribution function itself are computed via Monte Carlo simulation. Given a limited (and fixed) computer budget, the quality of the estimator is gauged by the inverse of its mean square error. It is a function of the fraction of the budget allocated to estimating the conditional expectation versus the amount of sampling done relative to the "conditioning variable." We will present the asymptotically optimal rates of convergence for different estimators and resolve the trade-off between the bias and variance of the estimators. Moreover, central limit theorems are established for some of the estimators proposed. We will also provide algorithms for the practical implementation of two of the estimators and illustrate how confidence intervals can be formed in each case. Major potential application areas include calculation of Value at Risk (VaR) in the field of mathematical finance and Bayesian performance analysis.
Business-oriented management of Web services
Authors: Casati Fabio , Shan Eric , Dayal Umeshwar , Shan Ming-Chien
Published: October 2003

Using tools and abstractions for monitoring and controlling Web services.
Efficient multiply-with-carry random number generators with maximal period
Authors: Goresky Mark , Klapper Andrew
Published: October 2003

In this (largely expository) article, we propose a simple modification of the multiply-with-carry random number generators of Marsaglia [1994] and Couture and L'Écuyer [1997]. The resulting generators are both efficient (since they may be configured with a base
b
which is a power of 2) and exhibit maximal period. These generators are analyzed using a simple but powerful algebraic technique involving
b
-adic numbers.
Can Renin Status Predict the Antihypertensive Efficacy of Eplerenone Add‐On Therapy?
Authors: Prisant L. Michael , Krum Henry , Roniker Barbara , Krause Scott L. , Fakouhi Kaffa , He Weizhong
Published: October 2003

Since neither angiotensin‐converting enzyme inhibitors (ACE‐I) nor angiotensin II receptor blockers (ARB) can completely suppress aldosterone levels, there is a need for alternative/supplementary antihypertensive medications, such as the selective aldosterone blocker eplerenone (Inspra™). This multicenter study measured the safety and efficacy of add‐on eplerenone therapy to reduce blood pressure not controlled by ACE‐I or ARB monotherapy. An ad hoc analysis evaluated whether active plasma renin or serum aldosterone levels could predict blood pressure response to eplerenone therapy. Patients (N = 341) with a diastolic blood pressure > 95 mmHg on a fixed dose of ACE‐I or ARB were randomized to 8 weeks of double‐blind treatment with eplerenone 50 mg qd or placebo. If blood pressure remained uncontrolled following 2, 4, or 6 weeks of treatment, the eplerenone dose was increased to 100 mg qd. In a combined cohort analysis of these patients, the placebo‐adjusted change in systolic and diastolic blood pressure was −5.9/‐2.4 mmHg (p < 0.001 and p = 0.006, respectively). While adding eplerenone to an ACE‐I or ARB is safe and effective for blood pressure reduction, there was no baseline value or range of values of active plasma renin, serum aldosterone, or their ratio that predicted a favorable response to either of these drug combinations.
Interferon Alfa-2b Three Times Daily and Thalidomide in the Treatment of Metastatic Renal Cell Carcinoma
Authors: Hernberg Micaela , Virkkunen Pekka , Bono Petri , Ahtinen Henna , Mäenpää Hanna , Joensuu Heikki
Published: October 2003

Purpose: The antiangiogenic effect of interferon (IFN) may improve with frequent dosing and by combination with other agents with antiangiogenic activity. To evaluate this potential, we treated patients with metastatic renal cell carcinoma (RCC) with frequently dosed IFN and thalidomide.

Patients and Methods: Thirty patients were given IFN-α-2b 0.9 MU subcutaneously three times daily for 1 month and subsequently 1.2 MU tid unless serious toxicity was encountered. Thalidomide was first given 100 mg/d for 1 week and 300 mg/d thereafter. Sera were collected before and during treatment for serum vascular endothelial growth factor (S-VEGF) analyses performed using enzyme-linked immunosorbent assay.

Results: The intention-to-treat response rate was 20% (95% CI, 6% to 34%) and response rate for assessable patients (n = 27) was 22% (95% CI, 6% to 38%). All responses were partial. In addition, 17 patients (63%; 95% CI, 45% to 81%) had stable disease for 3 months or longer. The median time to treatment failure was 7.7 months, and median survival time was 14.9 months. The most common cause of thalidomide discontinuation was neuropathy. S-VEGF levels decreased more in patients who responded to therapy compared with those in patients whose condition had stabilized or who had progressive disease (P = .036).

Conclusion: The combination of frequently dosed IFN-α-2b and low-dose thalidomide is feasible and active in advanced RCC, but the clinical benefit may remain small compared with that of IFN alone. Results from an ongoing phase III trial comparing IFN-α with or without thalidomide need to be analyzed before this combination can be recommended for use outside clinical studies.
Immunohistochemical fiber typing of harbor seal skeletal muscle
Authors: Watson Rebecca R. , Miller Todd A. , Davis Randall W.
Published: October 2003

There is strong evidence that pinnipeds maintain a lipid-based, aerobic metabolism during diving. However, the few fiber-typing studies performed on pinniped skeletal muscles are not consistent with an aerobic physiological profile. The objective of this study was to reexamine the fiber type distribution throughout the primary locomotory muscles of the harbor seal Phoca vitulina. Results from immunohistochemical (IHC) fiber typing indicated that harbor seal swimming muscles (the epaxial muscles) are composed of 47.4% type I (slow twitch, oxidative) fibers and 52.8% IIa (fast twitch,oxidative) fibers, which are homogeneously distributed throughout the muscle. Harbor seal pectoralis, a secondary swimming muscle, was composed of 16.2%type I and 84.3% type IIa fibers. No fast twitch, glycolytic (type IIb) fibers were detected in either muscle, in contrast to published data on fiber typing of harbor seal epaxial muscles using traditional histochemical techniques. The extreme specificity inherent in the IHC fiber typing procedure leads us to conclude that harbor seal swimming muscle is entirely composed of oxidative fibers. Our results are consistent with the enzymatic analyses of pinniped skeletal muscle that support the use of lipid-derived aerobic catabolism to fuel working muscle during diving in these marine mammals.
Metal‐Free, Selective Alkane Functionalizations
Authors: Fokin Andrey A. , Schreiner Peter R.
Published: September 2003

The present overview of alkane functionalization reactions presents comparisons between radical and metal‐initiated (sometimes metal‐catalyzed) methodologies. While metal‐catalyzed processes are excellent approaches to this problem, metal‐free alternatives are equally if not, at least from an environmental and cost perspective, more useful. This conclusion is supported by the fact that many so‐called metal‐catalyzed reactions also work without the metal present, and the large variety of metals showing the same product distributions emphasizes that the metal often just aids in the generation of the active species, i.e., the metal itself is not participating in the crucial CH activation step. Highly selective alkane functionalization reactions such as those derived from nitroxyl and related radicals as well as through radical reactions conducted in phase‐transfer catalyzed systems are available but generally underutilized. These systems, in contrast to typical metal‐catalyzed approaches, are also applicable to highly strained alkanes and offer the highest 3°/2° CH selectivities reported to date in a radical reaction. The article closes with representative experimental protocols for the PTC bromination of cubane as an example of the applicability of this method to strained hydrocarbons and the direct iodination of cyclohexane as well as adamantane as typical alkanes bearing secondary and tertiary CH bonds.
Mixed Phosphite‐Phosphine and Phosphinite‐Phosphine Palladacyclic Complexes as Highly Active Catalysts for the Amination of Aryl Chlorides
Authors: Bedford Robin B. , Blake Michael E.
Published: September 2003

Tri‐tert‐butylphosphine adducts of ortho‐palladated phosphite and phosphinite complexes formed in situ are excellent catalysts for the Buchwald–Hartwig amination of aryl chloride substrates.
Reversible CH Bond Activation Reactions of the N‐Heterocyclic Carbene Ligands in Ru(Ph2PCH2CH2CH2PPh2)(IMes)(CO)H2 and Ru(Ph2AsCH2CH2PPh2)(IMes)(CO)H2 (IMes=1,3‐Dimesityl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene)
Authors: Chilvers Mark J. , Jazzar Rodolphe F. R. , Mahon Mary F. , Whittlesey Michael K.
Published: September 2003

Thermolysis of Ru(IMes)(dppp)(CO)H2 (1, IMes=1,3‐dimesityl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene; dppp=Ph2PCH2CH2CH2PPh2) in the presence of trimethylvinylsilane yields Ru(IMes')(dppp)(CO)H (2) resulting from intramolecular ArCH2–H CH bond activation of the N‐heterocyclic carbene ligand. The structures of 1 and 2 have been established by X‐ray crystallography. Treatment of Ru(IMes)(arphos)(CO)H2 (3, arphos=Ph2AsCH2CH2PPh2) with CH2CHSiMe3 at 85 °C produces a mixture of three CH activated products 4a–c. The CH activated complexes 2 and 4a–c reform their dihydride precursors upon heating under hydrogen.
New Aspects of Synthesis and Properties of Arylated Cyclopentadienes
Authors: Dyker Gerald , Heiermann Jörg , Miura Masahiro
Published: September 2003

The multifold palladium‐catalysed arylation is a suitable method for the synthesis of sterically crowded cyclopentadienes bearing up to five ortho‐substituted aryl groups. A maximum of four mesitylene groups can be introduced. While penta(para‐xylyl)cyclopentadiene and pentakis(2‐chlorophenyl)cyclopentadiene exhibit at least six rotamers in the proton NMR spectrum, only two rotamers are registered for the tetra(2‐chlorophenyl)cyclopentadiene; the all‐trans isomer is identified as the major one both by spectroscopy and by semi‐empirical calculations.
Activation of Molecular Nitrogen: Coordination, Cleavage and Functionalization of N2 Mediated By Metal Complexes
Authors: Shaver Michael P. , Fryzuk Michael D.
Published: September 2003

Recent developments in the activation and reactivity of coordinated dinitrogen are reviewed. Examples of weakly activated dinitrogen metal complexes, strongly reduced nitrogen‐nitrogen bonds and N2 cleavage reactions are discussed. Protonation reactions to form ammonia or hydrazido derivatives are covered along with processes in which nitrogen‐boron, nitrogen‐silicon or nitrogen‐carbon bonds can form. Although this review builds on previous publications, a general introduction to this field is included.
Influence of a β‐Alkoxy Substituent on the CH Activation Chemistry of Alkyl Ethers
Authors: Davies Huw M. L. , Yang Jaemoon
Published: September 2003

CH activation reactions of 1,2‐dimethoxyethane and methyl tert‐butyl ether with methyl aryldiazoacetates or styryldiazoacetate catalyzed by Rh2(S‐DOSP)4 result in the formation of 2‐aryl‐ or 2‐styryl‐substituted propanoic acids with asymmetric induction up to 95% ee.
Room Temperature Activation of Aromatic CH Bonds by Non‐Classical Ruthenium Hydride Complexes Containing Carbene Ligands
Authors: Giunta Daniela , Hölscher Markus , Lehmann Christian W. , Mynott Richard , Wirtz Cornelia , Leitner Walter
Published: September 2003

Non‐classical ruthenium hydride complexes are promising lead structures for the CH bond activation and functionalization of aromatic compounds. In the present paper, the preparation and crystallographic characterisation of the first organometallic complexes bearing dihydrogen ligands and N‐heterocyclic carbene ligands in the same coordination sphere are described. The mixed phosphine/carbene complex [(IMes)Ru(H)2(H2)2(PCy3)] (IMes=1,3‐dimesityl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene; 3a) shows a unique reactivity pattern in the inter‐ and intramolecular activation of CH bonds. In particular, complex 3a effects a rapid and remarkably selective intermolecular activation of sp2 CH bonds in simple aromatic compounds at room temperature.
Catalytic Methods for CH Bond Functionalization: Application in Organic Synthesis
Authors: Kakiuchi Fumitoshi , Chatani Naoto
Published: September 2003

The development of catalytic reactions involving carbon‐hydrogen bond cleavage is currently one of the most attractive research subjects in organic and organometallic chemistry. About 40 years have past since the pioneering report of the cleavage of CH bonds with transition metal complexes. Since that time, a vast number of studies of the cleavage of CH bonds, using stoichiometric amounts of transition metal complexes has appeared. In the last decade, a variety of catalytic reactions involving CH bond cleavage has been reported. In this review we briefly survey the results of these research activities with respect to the catalytic use of unreactive CH bonds in organic synthesis.
Unexpected Formation of Bis(1H‐7‐azaindol‐3‐yl)(2,4,5‐trimethylphenyl)methane by Erbium Metal‐Induced CH Activation
Authors: Deacon Glen B. , Junk Peter C. , Leary Stuart G.
Published: September 2003

Reaction of 7‐azaindole (azinH) and 1,2,4,5‐tetramethylbenzene (durene) in the presence of erbium metal and mercury at 170 °C under vacuum induced an unusual CC bond formation between a methyl group of durene and C3 of two azinH molecules yielding bis(1H‐7‐azaindol‐3‐yl)(2,4,5‐trimethylphenyl)methane {2: IUPAC name 3‐[1H‐pyrrolo[2,3‐b]pyridin‐3‐yl(2,4,5‐trimethylphenyl)methyl]‐1H‐pyrrolo[2,3‐b]pyridine}. The structure of 2 was established by X‐ray crystallography and supported by IR, NMR and mass spectroscopy.
Neuronal dysplasia: A controversial pathological correlate of intestinal pseudo‐obstruction
Authors: Kapur Raj P.
Published: September 2003

The infant or child with intestinal pseudo‐obstruction poses many challenges for geneticists and other specialists. Although a well‐defined anatomic diagnosis (e.g., Hirschsprung disease) can be established for a subset of patients, the pathological correlates for many patients are non‐existent or controversial. Intestinal neuronal dysplasia (IND) is frequently considered in the differential diagnosis, despite the fact that existence and significance of the abnormal histopathological features that characterize IND are hotly debated. This review highlights some of the concerns regarding this diagnosis including problems with the diagnostic criteria, the manner in which these criteria are applied in contemporary pathology practices, and the likelihood that many of the pathological findings are secondary consequences of impaired motility with no other clear clinical significance. Possible genetic and developmental bases for IND are also discussed. © 2003 Wiley‐Liss, Inc.
Feingold syndrome: Clinical review and genetic mapping
Authors: Celli Jacopo , van Bokhoven Hans , Brunner Han G.
Published: September 2003

Feingold syndrome is characterized by autosomal dominant inheritance of microcephaly and limb malformations, notably hypoplastic thumbs, and clinodactyly of second and fifth fingers. Syndactyly frequently involves the second and third, as well as the fourth and fifth toes. Approximately one in three Feingold syndrome patients have esophageal or duodenal atresia or both. Anal atresia has been reported in a single case. At least 79 patients in 25 families have been reported. The syndrome has autosomal dominant inheritance with full penetrance, and variable expressivity. Vertebral anomalies, cardiac malformations, and deafness have been noted in a minority of patients. Here, we report a patient with hydronephrosis of one kidney and cystic dysplasia of the other, necessitating nephrectomy. The overall pattern of malformations in Feingold syndrome shows considerable overlap with the VATER/VACTERL association. The gene for Feingold syndrome maps to 2p23‐p24, but remains to be identified. Comparison of the pattern of anomalies that occurs in the Feingold syndrome in humans and malformations that are present in mice with mutations of genes in the sonic hedgehog signaling pathway suggest, that the elusive Feingold syndrome gene may involve this signaling pathway as well. © 2003 Wiley‐Liss, Inc.
Molecular dimensions of gastrointestinal tumors: Some thoughts for digestion
Authors: Cohen, M. Michael
Published: September 2003

Topics discussed here includePTENmutations and colonic polyps; WNT signaling, APC, β‐catenin, and gastrointestinal neoplasms; mismatch‐repair genes (MLH1,MSH2,PMS1,MSH6) and hereditary nonpolyposis colorectal cancer;MYHmutations and autosomal recessive colorectal tumors;STK11mutations and Peutz‐Jeghers syndrome; TGFβ and gastrointestinal cancer;BMPR1Amutations and juvenile polyposis; FGF/FGFR alterations in gastrointestinal neoplasms;PTCHmutations and gastrointestinal neoplasms; RUNX3 expression and gastric cancer; role of mucins in gastric carcinogenesis; KIT, PDGFRα, and gastrointestinal stromal tumors; intestinal neurofibromatosis; and gastrointestinal tumors in other disorders. © 2003 Wiley‐Liss, Inc.
Hereditary nonpolyposis colorectal cancer and related conditions
Authors: Lucci‐Cordisco Emanuela , Zito Ilaria , Gensini Francesca , Genuardi Maurizio
Published: September 2003

Hereditary nonpolyposis colorectal cancer (HNPCC) is a cancer‐predisposing condition caused by inactivating mutations in at least four genes (MSH2, MLH1, MSH6, and PMS2) belonging to the mismatch repair system. At present, availability of the microsatellite instability (MSI) test allows screening of a relevant fraction of patients with a constellation of features suggestive of HNPCC. By analogy with several other genetic disorders, it is clearly emerging that the term HNPCC encompasses a wide spectrum of different clinical presentations, including Muir‐Torre syndrome, Turcot syndrome, and the neurofibromatosis‐hematological malignancy association. Notwithstanding the remarkable genetic and allelic heterogeneity, a few consistent phenotype‐genotype associations can be recognized. Mutations in the MSH2 gene entail higher risks of developing cancer, including extraintestinal ones, than MLH1 alterations. MSH2 also accounts for most cases of Muir‐Torre syndrome, which is characterized by the presence of sebaceous skin tumors. The few known PMS2 mutations show a striking association with the presence of gliomas, which are the hallmark of the Turcot variant of HNPCC. Homozygotes for mismatch repair gene mutations present with stigmata of neurofibromatosis 1 and usually die in childhood due to a variety of leukemias and lymphomas. While such correlations are being defined, the underlying reasons have only partially been elucidated, and may include heterogeneous gene functions and properties; types of mutation, some of which may exert dominant negative effects; and genetic and environmental modifiers. © 2003 Wiley‐Liss, Inc.
Gastrointestinal polyposis syndromes
Authors: Bronner Mary P.
Published: September 2003

Numerous polyposis syndromes involve the gastrointestinal (GI) tract, including both non‐hereditary and hereditary types. Causative genes are now known for the seven major syndromes. Genetic and clinicopathologic features are reviewed here and cancer predisposition is emphasized. Genetic testing is available for the GI polyposis syndromes, and can be accessed through GeneTests‐GeneClinics on the Internet at http://www.genetests.org/. The website is available at no cost and is a publicly funded medical genetics resource for health care providers and researchers. © 2003 Wiley‐Liss, Inc.