bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethical aspects of clinical decision-making.
Authors: Kollemorten I , Strandberg C , Thomsen B M , Wiberg O , Windfeld-Schmidt T , Binder V , Elsborg L , Hendriksen C , Kristensen E , Madsen J R , Rasmussen M K , Willumsen L , Wulff H R , Riis P
Published: November 2008

The aim of the present investigation was to describe and to classify significant ethical problems encountered by the members of the staff during the daily clinical work at a hospital medical department. A set of definitions was prepared for the purpose, including the definition of a 'significant ethical problem'. During a three month period 426 inpatients and 173 outpatients were admitted. Significant ethical problems were encountered during the management of 106 in-patients (25 per cent) and 9 out-patients (5 per cent). No significant difference was found between the frequency of ethical problems in female and male patients, but a positive correlation was noted between the number of problems and the patients' age. The problem types were classified according to a problem list. The results of this investigation suggest that greater attention must be paid to discussions about ethical problems among doctors and other categories of health personnel and that, among others, medical students ought to be taught the analysis of ethical problems.
USES OF A SMALL FIELD VALUE WHICH FALLS FROM A METASTABLE MAXIMUM OVER COSMOLOGICAL TIMES
Authors: BARSHAY SAUL , KREYERHOFF GEORG
Published: November 2008

We consider a small, metastable maximum vacuum expectation value b0 of order of a few eV, for a pseudoscalar Goldstone-like field, which is related to the scalar inflaton field ϕ in an idealized model of a cosmological, spontaneously-broken chiral symmetry. The b field allows for relating semi-quantitatively three distinct quantities in a cosmological context.

(a) A very small, residual vacuum energy density or effective cosmological constant of [Formula: see text], for λ ~ 3×10-14, the same as an empirical inflaton self-coupling.

(b) A tiny neutrino mass, less than b0.

(c) A possible small variation downward of the proton to electron mass ratio over cosmological time. The latter arises from the motion downward of the b field over cosmological time, toward a nonzero value. Such behavior is consistent with an equation of motion.

We argue that hypothetical b quanta, potentially inducing new long-range forces, are absent, because of negative, effective squared mass in an equation of motion for b-field fluctuations. The assumed flatness of a potential maximum involves a small inverse-time parameter μ ≪ 1/t0, where t0 is the present age of the universe.
PHASES OF 4D SCALAR–TENSOR BLACK HOLES COUPLED TO BORN–INFELD NONLINEAR ELECTRODYNAMICS
Authors: ZH. STEFANOV IVAN , YAZADJIEV STOYTCHO S. , TODOROV MICHAIL D.
Published: November 2008

Recent results show that when nonlinear electrodynamics is considered, the no-scalar-hair theorems in the scalar–tensor theories (STT) of gravity, which are valid for the cases of neutral black holes and charged black holes in the Maxwell electrodynamics, can be circumvented.1,2 What is even more, in the present work, we find new non-unique, numerical solutions describing charged black holes coupled to nonlinear electrodynamics in a special class of scalar–tensor theories. One of the phases has a trivial scalar field and coincides with the corresponding solution in General Relativity. The other phases that we find are characterized by the value of the scalar field charge. The causal structure and some aspects of the stability of the solutions have also been studied. For the scalar–tensor theories considered, the black holes have a single, non-degenerate horizon, i.e. their causal structure resembles that of the Schwarzschild black hole. The thermodynamic analysis of the stability of the solutions indicates that a phase transition may occur.
VISUAL MODELING OF DEFEASIBLE LOGIC RULES WITH DR-VisMo
Authors: KONTOPOULOS EFSTRATIOS , BASSILIADES NICK , ANTONIOU GRIGORIS , SERIDOU ANNA
Published: November 2008

The standardization of the Semantic Web has reached as far as ontologies and ontology languages. However, in order for the full potential of the Semantic Web to be achieved, the ability of reasoning over the available information is also essential. Rules can assist in this affair and various logics have been proposed for the Semantic Web domain. One of them is defeasible reasoning that deals with incomplete and conflicting information. However, despite its solid mathematical notation, it may be confusing to end users. To confront this downside, we proposed a representation schema for defeasible logic rule bases, which is based on directed graphs that feature distinct node and connection types. This paper presents DR-VisMo, a defeasible logic rule base editor and visualization system that implements this representation approach. The system also features a stratification algorithm for visualizing rule bases that deals with decisions, regarding the arrangement of the various elements in the graph. DR-VisMo is implemented as part of VDR-DEVICE, an environment for modeling and deploying defeasible logic rule bases on top of RDF ontologies.
ESTABLISHING LOGICAL RULES FROM EMPIRICAL DATA
Authors: PFALTZ JOHN L.
Published: November 2008

We review a method of generating logical rules, or axioms, from empirical data. This method, using closed set properties of formal concept analysis, has been previously described and tested on rather large sets of deterministic data. In spite of the fact that formal concept techniques have been used to prune frequent set data mining results, frequency and/or statistical significance are totally irrelevant to this method. It is strictly logical and deterministic.

The contribution of this paper is a completely new extension of this method to create implications involving numeric inequalities. That is, numerical inequalities such as "age > 39" can be treated as logical predicates that have been extracted from the data itself and not postulated apriori.
A REGRESSION MIXTURE MODEL WITH SPATIAL CONSTRAINTS FOR CLUSTERING SPATIOTEMPORAL DATA
Authors: BLEKAS K. , NIKOU C. , GALATSANOS N. , TSEKOS N. V.
Published: November 2008

We present a new approach for curve clustering designed for analysis of spatiotemporal data. Such data contains both spatial and temporal patterns that we desire to capture. The proposed methodology is based on regression and Gaussian mixture modeling. The novelty of the herein work is the incorporation of spatial smoothness constraints in the form of a prior for the data labels. This allows to take into account the property of spatiotemporal data according to which spatially adjacent data points have higher probability to belong to the same cluster. The proposed model can be formulated as a Maximum a Posteriori (MAP) problem, where the Expectation Maximization (EM) algorithm is used to estimate the model parameters. Several numerical experiments with both simulated data and real cardiac perfusion MRI data are used for evaluating the methodology. The results are promising and demonstrate the value of the proposed approach.
CROSS-LAYERED MAC AND MULTIPATH ROUTING PROTOCOLS IN MULTI-HOP WIRELESS MOBILE NETWORKS
Authors: BONONI LUCIANO , DI FELICE MARCO
Published: November 2008

In this paper, we propose a multipath routing scheme for wireless mobile networks which extends the Ad Hoc On-demand Multipath Distance Vector (AOMDV) routing protocol, by introducing a novel load-balancing approach to concurrently distribute the traffic among the multiple paths. The traffic-path allocation scheme is based on cross-layer measurements of path statistics reflecting the size and congestion level of each path. In order to provide an efficient support to the proposed routing scheme at the MAC layer, we also study the composition effect of a IEEE 802.11-based enhanced MAC forwarding mechanism called Fast Forward (FF), used to reduce the effects of self-contention among frames at the MAC layer. The protocol framework has been modelled and extensively simulated for a large set of metrics and scenarios. Simulation results provide guidelines for multi-hop communication solutions under both static and mobile scenarios and different traffic loads.
A LINK STATE DEPENDENT TDMA PROTOCOL FOR INDUSTRIAL WIRELESS SENSOR NETWORK APPLICATIONS IN PERIODICALLY CHANGING ENVIRONMENTS
Authors: PHUA VALANCE , DATTA AMITAVA
Published: November 2008

Existing TDMA-based MAC protocols for wireless sensor networks are not specifically built to consider communication channels that are prone to fading. We describe the impact of periodically changing environment on small-scale fading effects in industrial indoor wireless networks. Using a site-specific ray tracer, we show that the position of nodes and the periodic movements of objects with constant velocities in the environment have significant impact on signal fading. Finding that fading is approximately periodic, we propose a TDMA-based MAC protocol for wireless sensor networks built for industrial applications that uses link state dependent scheduling. In our approach, nodes gather samples of the channel quality and generate prediction sets from the sample sets in independent slots. Using the prediction sets, nodes only wake up to transmit/receive during scheduled slots that are predicted to be clear and sleep during scheduled slots that may potentially cause a transmitted signal to fade. We simulate our proposed protocol and compare its performance with the well published Z-MAC protocol. We found that our protocol significantly improves packet throughput and energy consumption as compared to Z-MAC. We also found that in conditions which are not perfect under our assumptions, the performance of our protocol degrades gracefully.
CHRONOLOGICAL TREE — A COMPRESSED STRUCTURE FOR MINING BEHAVIORAL PATTERNS FROM WIRELESS SENSOR NETWORKS
Authors: SAMARAH SAMER , BOUKERCHE AZZEDINE
Published: November 2008

Wireless Sensor Networks (WSNs) have proven their success in a variety of applications for monitoring physical and critical environments. However, the streaming nature, limited resources, and the unreliability of wireless communication are among the factors that affect the Quality of Service (QoS) of WSNs. In this paper, we propose a data mining technique to extract behavioral patterns about the sensor nodes during their operation. The behavioral patterns, which we refer to as Chronological Patterns, can be thought of as tutorials that teach about the set of sensors that report on events within a defined time interval and the order in which the events were detected. Chronological Patterns can serve as a helpful tool for predicting behaviors in order to enhance the performance of the WSN and thus improve the overall QoS. The proposed technique consists of: a formal definition of the Chronological Patterns and a new representation structure, which we refer to as Chlorotical Tree (CT), that facilities the mining of these patterns. To report about the performance of the CT, several experiments have been conducted to evaluate the CT using different density factors.
Perfect hashing as an almost perfect subtype test
Authors: Ducournau Roland
Published: November 2008

Subtype tests are an important issue in the implementation of object-oriented programming languages. Many techniques have been proposed, but none of them perfectly fulfills the five requirements that we have identified: constant-time, linear-space, multiple inheritance, dynamic loading and inlining. In this article, we propose a subtyping test implementation that involves a combination of usual hashtables and Cohen's display, which is a well-known technique for single inheritance hierarchies. This novel approach is based on
perfect hashing
, that is, an optimized and truly constant-time variant of hashing that applies to
immutable
hashtables. We show that the resulting technique closely meets all five requirements. Furthermore, in the framework of Java-like languages—characterized by single inheritance of classes and multiple subtyping of interfaces—perfect hashing also applies to method invocation when the receiver is typed by an interface. The proposed technique is compared to some alternatives, including the proposal by Palacz and Vitek [2003]. Time-efficiency is assessed at the cycle level in the framework of Driesen's pseudo-code and the linear-space criterion is validated by statistical simulation on benchmarks consisting of large-scale class hierarchies.
CGMN Revisited
Authors: Gordon Dan , Gordon Rachel
Published: November 2008

Given a linear system
Ax
 = 
b
, one can construct a related “normal equations” system
AA
T
y
 = 
b, x
 = 
A
T
y
. Björck and Elfving have shown that the SSOR algorithm, applied to the normal equations, can be accelerated by the conjugate gradient algorithm (CG). The resulting algorithm, called CGMN, is error-reducing and in theory it always converges even when the equation system is inconsistent and/or nonsquare. SSOR on the normal equations is equivalent to the Kaczmarz algorithm (KACZ), with a fixed relaxation parameter, run in a double (forward and backward) sweep on the original equations. CGMN was tested on nine well-known large and sparse linear systems obtained by central-difference discretization of elliptic convection-diffusion partial differential equations (PDEs). Eight of the PDEs were strongly convection-dominated, and these are known to produce very stiff systems with large off-diagonal elements. CGMN was compared with some of the foremost state-of-the art Krylov subspace methods: restarted GMRES, Bi-CGSTAB, and CGS. These methods were tested both with and without various preconditioners. CGMN converged in all the cases, while none of the preceding algorithm/preconditioner combinations achieved this level of robustness. Furthermore, on varying grid sizes, there was only a gradual increase in the number of iterations as the grid was refined. On the eight convection-dominated cases, the initial convergence rate of CGMN was better than all the other combinations of algorithms and preconditioners, and the residual decreased monotonically. The CGNR algorithm was also tested, and it was as robust as CGMN, but slower.
Algorithm 886
Authors: Caliari Marco , Marchi Stefanode , Vianello Marco
Published: November 2008

We present a stable and efficient Fortran implementation of polynomial interpolation at the Padua points on the square [ − 1,1]2. These points are unisolvent and their Lebesgue constant has minimal order of growth (log square of the degree). The algorithm is based on the representation of the Lagrange interpolation formula in a suitable orthogonal basis, and takes advantage of a new matrix formulation together with the machine-specific optimized BLAS subroutine for the matrix-matrix product. Extension to interpolation on rectangles, triangles and ellipses is also described.
Algorithm 889
Authors: Cazals Frédéric , Pouget Marc
Published: November 2008

Surfaces of R
3
are ubiquitous in science and engineering, and estimating the local differential properties of a surface discretized as a point cloud or a triangle mesh is a central building block in computer graphics, computer aided design, computational geometry, and computer vision. One strategy to perform such an estimation consists of resorting to polynomial fitting, either interpolation or approximation, but this route is difficult for several reasons: choice of the coordinate system, numerical handling of the fitting problem, and extraction of the differential properties.

This article presents a generic C++ software package solving these problems. On the theoretical side and as established in a companion paper, the interpolation and approximation methods provided achieve the best asymptotic error bounds known to date. On the implementation side and following state-of-the-art coding rules in computational geometry, genericity of the package is achieved thanks to four template classes accounting for, (a) the type of the input points, (b) the internal geometric computations, (c) a conversion mechanism between these two geometries, and (d) the linear algebra operations. An instantiation within the Computational Geometry Algorithms Library (CGAL, version 3.3) and using LAPACK is also provided.
Scalable on-demand media streaming for heterogeneous clients
Authors: Gill Phillipa , Shi Liqi , Mahanti Anirban , Li Zongpeng , Eager Derek L.
Published: November 2008

Periodic broadcast protocols enable efficient streaming of highly popular media files to large numbers of concurrent clients. Most previous periodic broadcast protocols, however, assume that all clients can receive at the same rate, and also assume that reception bandwidth is not time-varying. In this article, we first develop a new periodic broadcast protocol, Optimized Heterogeneous Periodic Broadcast (OHPB), that can be optimized for a given population of clients with heterogeneous reception bandwidths and quality-of-service requirements. The OHPB protocol utilizes an optimized segment size progression determined by solving a linear optimization model that takes as input the client population characteristics and an objective function such as mean client startup delay. We then develop a generalization of the OHPB linear optimization model that allows optimal server bandwidth allocation among multiple concurrent OHPB broadcasts, wherein each media file and its clients may have different characteristics. Finally, we propose complementary client protocols employing work-ahead buffering of data during playback, so as to enable more uniform playback quality when the reception bandwidth is time-varying.
Parallel algorithms for approximation of distance maps on parametric surfaces
Authors: Weber Ofir , Devir Yohai S. , Bronstein Alexander M. , Bronstein Michael M. , Kimmel Ron
Published: November 2008

We present an efficient O(
n
) numerical algorithm for first-order approximation of geodesic distances on geometry images, where
n
is the number of points on the surface. The structure of our algorithm allows efficient implementation on parallel architectures. Two implementations on a SIMD processor and on a GPU are discussed. Numerical results demonstrate up to four orders of magnitude improvement in execution time compared to the state-of-the-art algorithms.
Logarithmic perspective shadow maps
Authors: Lloyd D. Brandon , Govindaraju Naga K. , Quammen Cory , Molnar Steven E. , Manocha Dinesh
Published: November 2008

We present a novel shadow map parameterization to reduce perspective aliasing artifacts for both point and directional light sources. We derive the aliasing error equations for both types of light sources in general position. Using these equations we compute tight bounds on the aliasing error. From these bounds we derive our shadow map parameterization, which is a simple combination of a perspective projection with a logarithmic transformation. We formulate several types of logarithmic perspective shadow maps (LogPSMs) by replacing the parameterization of existing algorithms with our own. We perform an extensive error analysis for both LogPSMs and existing algorithms. This analysis is a major contribution of this paper and is useful for gaining insight into existing techniques. We show that compared with competing algorithms, LogPSMs can produce significantly less aliasing error. Equivalently, for the same error as competing algorithms, LogPSMs can produce significant savings in both storage and bandwidth. We demonstrate the benefit of LogPSMs for several models of varying complexity.
Status-Based Access Control
Authors: Barker Steve , Sergot Marek J. , Wijesekera Duminda
Published: November 2008

Despite their widespread adoption, Role-based Access Control (RBAC) models exhibit certain shortcomings that make them less than ideal for deployment in, for example, distributed access control. In the distributed case, standard RBAC assumptions (e.g., of relatively static access policies, managed by human users, with complete information available about users and job functions) do not necessarily apply. Moreover, RBAC is restricted in the sense that it is based on one type of ascribed status, an assignment of a user to a role. In this article, we introduce the status-based access control (SBAC) model for distributed access control. The SBAC model (or family of models) is based on the notion of users having an action status as well as an ascribed status. A user's action status is established, in part, from a history of events that relate to the user; this history enables changing access policy requirements to be naturally accommodated. The approach can be implemented as an autonomous agent that reasons about the events, actions, and a history (of events and actions), which relates to a requester for access to resources, in order to decide whether the requester is permitted the access sought. We define a number of algebras for composing SBAC policies, algebras that exploit the language that we introduce for SBAC policy representation: identification-based logic programs. The SBAC model is richer than RBAC models and the policies that can be represented in our approach are more expressive than the policies admitted by a number of monotonic languages that have been hitherto described for representing distributed access control requirements. Our algebras generalize existing algebras that have been defined for access policy composition. We also describe an approach for the efficient implementation of SBAC policies.
A Graph Based Approach Toward Network Forensics Analysis
Authors: Wang Wei , Daniels Thomas E.
Published: November 2008

In this article we develop a novel graph-based approach toward network forensics analysis. Central to our approach is the evidence graph model that facilitates evidence presentation and automated reasoning. Based on the evidence graph, we propose a hierarchical reasoning framework that consists of two levels. Local reasoning aims to infer the functional states of network entities from local observations. Global reasoning aims to identify important entities from the graph structure and extract groups of densely correlated participants in the attack scenario. This article also presents a framework for interactive hypothesis testing, which helps to identify the attacker's nonexplicit attack activities from secondary evidence. We developed a prototype system that implements the techniques discussed. Experimental results on various attack datasets demonstrate that our analysis mechanism achieves good coverage and accuracy in attack group and scenario extraction with less dependence on hard-coded expert knowledge.
Secrecy in Multiagent Systems
Authors: Halpern Joseph Y. , O'Neill Kevin R.
Published: November 2008

We introduce a general framework for reasoning about secrecy requirements in multiagent systems. Our definitions extend earlier definitions of secrecy and nondeducibility given by Shannon and Sutherland. Roughly speaking, one agent maintains secrecy with respect to another if the second agent cannot rule out any possibilities for the behavior or state of the first agent. We show that the framework can handle probability and nondeterminism in a clean way, is useful for reasoning about asynchronous systems as well as synchronous systems, and suggests generalizations of secrecy that may be useful for dealing with issues such as resource-bounded reasoning. We also show that a number of well-known attempts to characterize the absence of information flow are special cases of our definitions of secrecy.
Tight bounds for asynchronous randomized consensus
Authors: Attiya Hagit , Censor Keren
Published: November 2008

A distributed consensus algorithm allows
n
processes to reach a common decision value starting from individual inputs.
Wait-free
consensus, in which a process always terminates within a finite number of its own steps, is impossible in an asynchronous shared-memory system. However, consensus becomes solvable using randomization when a process only has to terminate with probability 1. Randomized consensus algorithms are typically evaluated by their
total step complexity
, which is the expected total number of steps taken by all processes.

This article proves that the total step complexity of randomized consensus is Θ(
n
2
) in an asynchronous shared memory system using multi-writer multi-reader registers. This result is achieved by improving both the lower and the upper bounds for this problem.

In addition to improving upon the best previously known result by a factor of log
2
n
, the lower bound features a greatly streamlined proof. Both goals are achieved through restricting attention to a set of
layered
executions and using an isoperimetric inequality for analyzing their behavior.

The matching algorithm decreases the expected total step complexity by a log
n
factor, by leveraging the multi-writing capability of the shared registers. Its correctness proof is facilitated by viewing each execution of the algorithm as a stochastic process and applying Kolmogorov's inequality.
A fixed-parameter algorithm for the directed feedback vertex set problem
Authors: Chen Jianer , Liu Yang , Lu Songjian , O'sullivan Barry , Razgon Igor
Published: November 2008

The (parameterized) FEEDBACK VERTEX SET problem on directed graphs (i.e., the DFVS problem) is defined as follows: given a directed graph
G
and a parameter
k
, either construct a feedback vertex set of at most
k
vertices in
G
or report that no such a set exists. It has been a well-known open problem in parameterized computation and complexity whether the DFVS problem is fixed-parameter tractable, that is, whether the problem can be solved in time
f
(
k
)
n

O
(1)

for some function
f
. In this article, we develop new algorithmic techniques that result in an algorithm with running time 4

k

k
!
n

O
(1)

for the DFVS problem. Therefore, we resolve this open problem.
Aggregating inconsistent information
Authors: Ailon Nir , Charikar Moses , Newman Alantha
Published: November 2008

We address optimization problems in which we are given contradictory pieces of input information and the goal is to find a globally consistent solution that minimizes the extent of disagreement with the respective inputs. Specifically, the problems we address are rank aggregation, the feedback arc set problem on tournaments, and correlation and consensus clustering. We show that for all these problems (and various weighted versions of them), we can obtain improved approximation factors using essentially the same remarkably simple algorithm. Additionally, we almost settle a long-standing conjecture of Bang-Jensen and Thomassen and show that unless NP⊆BPP, there is no polynomial time algorithm for the problem of minimum feedback arc set in tournaments.
Introduction to special issue
Authors: Cesar Pablo , Bulterman Dick C. A. , Soares Luiz Fernando Gomes
Published: November 2008

The research area of interactive digital TV is in the midst of a significant revival. Unlike the first generation of digital TV, which focused on producer concerns that effectively limited (re)distribution, the current generation of research is closely linked to the role of the user in selecting, producing, and distributing content. The research field of interactive digital television is being transformed into a study of human-centered television. Our guest editorial reviews relevant aspects of this transformation in the three main stages of the content lifecycle: content production, content delivery, and content consumption. While past research on content production tools focused on full-fledged authoring tools for professional editors, current research studies lightweight, often informal end-user authoring systems. In terms of content delivery, user-oriented infrastructures such as peer-to-peer are being seen as alternatives to more traditional broadcast solutions. Moreover, end-user interaction is no longer limited to content selection, but now facilitates nonlinear participatory television productions. Finally, user-to-user communication technologies have allowed television to become a central component of an interconnected social experience. The background context given in this article provides a framework for appreciating the significance of four detailed contributions that highlight important directions in transforming interactive television research.
PicoServer
Authors: Kgil Taeho , Saidi Ali , Binkert Nathan , Reinhardt Steve , Flautner Krisztian , Mudge Trevor
Published: November 2008

This article extends our prior work to show that a straightforward use of 3D stacking technology enables the design of compact energy-efficient servers. Our proposed architecture, called PicoServer, employs 3D technology to bond one die containing several simple, slow processing cores to multiple memory dies sufficient for a primary memory. The multiple memory dies are composed of DRAM. This use of 3D stacks readily facilitates wide low-latency buses between processors and memory. These remove the need for an L2 cache allowing its area to be re-allocated to additional simple cores. The additional cores allow the clock frequency to be lowered without impairing throughput. Lower clock frequency means that thermal constraints, a concern with 3D stacking, are easily satisfied. We extend our original analysis on PicoServer to include: (1) a wider set of server workloads, (2) the impact of multithreading, and (3) the on-chip DRAM architecture and system memory usage. PicoServer is intentionally simple, requiring only the simplest form of 3D technology where die are stacked on top of one another. Our intent is to minimize risk of introducing a new technology (3D) to implement a class of low-cost, low-power compact server architectures.
Investigating the effects of fine-grain three-dimensional integration on microarchitecture design
Authors: Ma Yuchun , Liu Yongxiang , Kursun Eren , Reinman Glenn , Cong Jason
Published: November 2008

In this article we propose techniques that enable efficient exploration of the 3D design space, where each logical block can span more than one silicon layer. Fine-grain 3D integration provides reduced intrablock wire delay as well as improved power consumption. However, the corresponding power and performance advantage is usually underutilized, since various implementations of multilayer blocks require novel physical design and microarchitecture infrastructure to explore 3D microarchitecture design space. We develop a cubic packing engine which can simultaneously optimize physical and architectural design for efficient vertical integration. This technique selects the individual unit designs from a set of single-layer or multilayer implementations to get the best microarchitectural design in terms of performance, temperature, or both. Our experimental results using a design driver of a high-performance superscalar processor show a 36% performance improvement over traditional 2D for 2--4 layers and 14% over 3D with single-layer unit implementations. Since thermal characteristics of 3D integrated circuits are among the main challenges, thermal-aware floorplanning and thermal via insertion techniques are employed to keep the peak temperatures below threshold.
Parametric yield management for 3D ICs
Authors: Ferri Cesare , Reda Sherief , Bahar R. Iris
Published: November 2008

Three-Dimensional (3D) Integrated Circuits (ICs) that integrate die with Through-Silicon Vias (TSVs) promise to continue system and functionality scaling beyond the traditional geometric 2D device scaling. 3D integration also improves the performance of ICs by reducing the communication time between different chip components through the use of short TSV-based vertical wires. This reduction is particularly attractive in processors where it is desirable to reduce the access time between the main logic die and the L2 cache or the main memory die. Process variations in 2D ICs lead to a drop in parametric yield (as measured by speed, leakage and sales profits), which forces manufacturers to speed bin their chips and to sell slow chips at reduced prices. In this paper we develop a model to quantify the impact of process variations on the parametric yield of 3D ICs, and then we propose a number of integration strategies that use a graph-theoretic framework to maximize the performance, parametric yield and profits of 3D ICs. Comparing our proposed strategies to current yield-oblivious methods, it is demonstrated that it is possible to increase the number of 3D ICs in the fastest speed bins by almost 2×, while simultaneously reducing the number of slow ICs by 29.4%. This leads to an improvement in performance by up to 6.45% and an increase of about 12.48% in total sales revenue using up-to-date market price models.
Inhibition of serine/threonine phosphatase enhances arachidonic acid-induced [Ca2+]ivia protein kinase A
Authors: Saino Tomoyuki , Watson Eileen L.
Published: November 2008

Arachidonic acid (AA) regulates intracellular calcium concentration ([Ca2+]i) in a variety of cell types including salivary cells. In the present study, the effects of serine/threonine phosphatases on AA-induced Ca2+signaling in mouse parotid acini were determined. Mice were euthanized with CO2. Treatment of acini with the serine/threonine phosphatase inhibitor calyculin A blocked both thapsigargin- and carbachol-induced Ca2+entry but resulted in an enhancement of AA-induced Ca2+release and entry. Effects were mimicked by the protein phosphatase-1 (PP1) inhibitor tautomycin but were inhibited by the PP2A inhibitor okadaic acid. The protein kinase A (PKA) inhibitor PKI(14-22)significantly attenuated AA-induced enhancement of Ca2+release and entry in the presence of calyculin A, whereas it had no effect on calyculin A-induced inhibition of thapsigargin-induced Ca2+responses. The ryanodine receptor (RyR) inhibitor, tetracaine, and StHt-31, a peptide known to competitively inhibit type II PKA regulatory subunit binding to PKA-anchoring protein (AKAP), abolished calyculin A enhancement of AA-induced Ca2+release and entry. StHt-31 also abolished forskolin potentiation of 4-chloro-3-ethylphenol (4-CEP) and AA on Ca2+release but had no effect on 8-(4-methoxyphenylthio)-2′- O-methyladenosine-3′,5′-cAMP potentiation of 4-CEP responses. Results suggest that inhibition of PP1 results in an enhancement of AA-induced [Ca2+]ivia PKA, AKAP, and RyRs.
Regulation of placental amino acid transporter activity by mammalian target of rapamycin
Authors: Roos S. , Kanai Y. , Prasad P. D. , Powell T. L. , Jansson T.
Published: November 2008

The activity of placental amino acid transporters is decreased in intrauterine growth restriction (IUGR), but the underlying regulatory mechanisms have not been established. Inhibition of the mammalian target of rapamycin (mTOR) signaling pathway has been shown to decrease the activity of the system L amino acid transporter in human placental villous fragments, and placental mTOR activity is decreased in IUGR. In the present study, we used cultured primary trophoblast cells to study mTOR regulation of placental amino acid transporters in more detail and to test the hypothesis that mTOR alters amino acid transport activity by changes in transporter expression. Inhibition of mTOR by rapamycin significantly reduced the activity of system A (−17%), system L (−28%), and taurine (−40%) amino acid transporters. mRNA expression of isoforms of the three amino acid transporter systems in response to mTOR inhibition was measured using quantitative real-time PCR. mRNA expression of l-type amino acid transporter 1 (LAT1; a system L isoform) and taurine transporter was reduced by 13% and 50%, respectively; however, mTOR inhibition did not alter the mRNA expression of system A isoforms (sodium-coupled neutral amino acid transporter-1, -2, and -4), LAT2, or 4F2hc. Rapamycin treatment did not significantly affect the protein expression of any of the transporter isoforms. We conclude that mTOR signaling regulates the activity of key placental amino acid transporters and that this effect is not due to a decrease in total protein expression. These data suggest that mTOR regulates placental amino acid transporters by posttranslational modifications or by affecting transporter translocation to the plasma membrane.
Role of HIF-1α and VEGF in human mesenchymal stem cell proliferation by 17β-estradiol: involvement of PKC, PI3K/Akt, and MAPKs
Authors: Yun Seung Pil , Lee Min Yong , Ryu Jung Min , Song Chang Hun , Han Ho Jae
Published: November 2008

17β-Estradiol (E2) is a steroid hormone well known for its roles in the regulation of various cell functions. However, the precise role that E2 plays in the proliferation of human mesenchymal stem cells (hMSCs) has not been completely elucidated. In the present study, we examined the effects of E2 on cell proliferation and the related signaling pathways using hMSCs. We showed that E2, at ≥10−9 M, significantly increased [3H]thymidine incorporation after 24 h of incubation, and E2 also increased [3H]thymidine incorporation at >6 h. Also, E2 significantly increased the percentage of the cell population in the S phase based on FACS analysis. Moreover, E2 increased estrogen receptor (ER), PKC, phosphatidylinositol 3-kinase (PI3K)/Akt, and MAPK phosphorylation. Subsequently, these signaling molecules were involved in an E2-induced increase of [3H]thymidine incorporation. E2 also increased hypoxia-inducible factor (HIF)-1α and VEGF protein levels. These levels of protein expression were inhibited by ICI-182,780 (10−6 M, an ER antagonist), staurosporine and bisindolylmaleimide I (10−6 M, a PKC inhibitor), LY-294002 (10−6 M, a PI3K inhibitor), Akt inhibitor (10−5 M), SP-600125 (10−6 M, a SAPK/JNK inhibitor), and PD-98059 (10−5 M, a p44/42 MAPKs inhibitor). In addition, HIF-1α small interfering (si)RNA and ICI-182,780 inhibited E2-induced VEGF expression and cell proliferation. VEGF siRNA also significantly inhibited E2-induced cell proliferation. In conclusion, E2 partially stimulated hMSC proliferation via HIF-1α activation and VEGF expression through PKC, PI3K/Akt, and MAPK pathways.
Effect of interleukin-15 on depressed splenic dendritic cell functions following trauma-hemorrhage
Authors: Kawasaki Takashi , Choudhry Mashkoor A. , Schwacha Martin G. , Bland Kirby I. , Chaudry Irshad H.
Published: November 2008

Although trauma-hemorrhage (T-H) induces suppressed splenic dendritic cell (DC) maturation and antigen presentation capacity, it remains unclear whether IL-15 modulates splenic DC functions. The aim of this study therefore was to investigate the effect of IL-15 on splenic DC functions after T-H. Male C3H/HeN mice (6–8 wk old) were randomly assigned to T-H or sham operation. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× the shed blood volume in the form of Ringer lactate). Two hours later, mice were killed, splenic DCs were isolated, and the effects of exogenous IL-15 on their costimulatory factors, major histocompatibility class II expression, ability to produce cytokines, and antigen presentation were measured. The results indicate that IL-15 production capacity of splenic DCs was reduced following T-H. Ex vivo exposure to IL-15 attenuated the suppressed production of TNF-α, IL-6, and IFN-γ from splenic DCs following T-H. In addition, expression of surface antigen studies demonstrate that exogenous IL-15 attenuated T-H-induced downregulation of the activation of DC. The suppressed splenic DC antigen presentation function following T-H was also attenuated by IL-15 treatment. Moreover, IL-15 enhanced IL-12-induced IFN-γ production and antigen presentation by splenic DCs. These data suggest that ex vivo treatment with IL-15 following T-H provides beneficial effects on splenic DCs. The depression in IL-15 production by splenic DCs could contribute to the host's enhanced susceptibility to infections following T-H.
Lipid rafts mediate internalization of β1-integrin in migrating intestinal epithelial cells
Authors: Vassilieva Elena V. , Gerner-Smidt Kirsten , Ivanov Andrei I. , Nusrat Asma
Published: November 2008

Intestinal mucosal inflammation is associated with epithelial wounds that rapidly reseal by migration of intestinal epithelial cells (IECs). Cell migration involves cycles of cell-matrix adhesion/deadhesion that is mediated by dynamic turnover (assembly and disassembly) of integrin-based focal adhesions. Integrin endocytosis appears to be critical for deadhesion of motile cells. However, mechanisms of integrin internalization during remodeling of focal adhesions of migrating IECs are not understood. This study was designed to define the endocytic pathway that mediates internalization of β1-integrin in migrating model IECs. We observed that, in SK-CO15 and T84 colonic epithelial cells, β1-integrin is internalized in a dynamin-dependent manner. Pharmacological inhibition of clathrin-mediated endocytosis or macropinocytosis and small-interfering RNA (siRNA)-mediated knock down of clathrin did not prevent β1-integrin internalization. However, β1-integrin internalization was inhibited following cholesterol extraction and after overexpression of lipid raft protein, caveolin-1. Furthermore, internalized β1-integrin colocalized with the lipid rafts marker cholera toxin, and siRNA-mediated knockdown of caveolin-1 and flotillin-1/2 increased β1-integrin endocytosis. Our data suggest that, in migrating IEC, β1-integrin is internalized via a dynamin-dependent lipid raft-mediated pathway. Such endocytosis is likely to be important for disassembly of integrin-based cell-matrix adhesions and therefore in regulating IEC migration and wound closure.
Enteral feeding induces diet-dependent mucosal dysfunction, bacterial proliferation, and necrotizing enterocolitis in preterm pigs on parenteral nutrition
Authors: Bjornvad Charlotte R. , Thymann Thomas , Deutz Nicolaas E. , Burrin Douglas G. , Jensen Søren K. , Jensen Bent B. , Mølbak Lars , Boye Mette , Larsson Lars-Inge , Schmidt Mette , Michaelsen Kim F. , Sangild Per T.
Published: November 2008

Preterm neonates have an immature gut and metabolism and may benefit from total parenteral nutrition (TPN) before enteral food is introduced. Conversely, delayed enteral feeding may inhibit gut maturation and sensitize to necrotizing enterocolitis (NEC). Intestinal mass and NEC lesions were first recorded in preterm pigs fed enterally (porcine colostrum, bovine colostrum, or formula for 20–40 h), with or without a preceding 2- to 3-day TPN period ( n = 435). Mucosal mass increased during TPN and further after enteral feeding to reach an intestinal mass similar to that in enterally fed pigs without TPN (+60–80% relative to birth). NEC developed only after enteral feeding but more often after a preceding TPN period for both sow's colostrum (26 vs. 5%) and formula (62 vs. 39%, both P < 0.001, n = 43–170). Further studies in 3-day-old TPN pigs fed enterally showed that formula feeding decreased villus height and nutrient digestive capacity and increased luminal lactic acid and NEC lesions, compared with colostrum (bovine or porcine, P < 0.05). Mucosal microbial diversity increased with enteral feeding, and Clostridium perfringens density was related to NEC severity. Formula feeding decreased plasma arginine, citrulline, ornithine, and tissue antioxidants, whereas tissue nitric oxide synthetase and gut permeability increased, relative to colostrum (all P < 0.05). In conclusion, enteral feeding is associated with gut dysfunction, microbial imbalance, and NEC in preterm pigs, especially in pigs fed formula after TPN. Conversely, colostrum milk diets improve gut maturation and NEC resistance in preterm pigs subjected to a few days of TPN after birth.
Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection
Authors: Larmonier C. B. , Uno J. K. , Lee Kang-Moon , Karrasch T. , Laubitz D. , Thurston R. , Midura-Kiela M. T. , Ghishan F. K. , Sartor R. B. , Jobin C. , Kiela P. R.
Published: November 2008

Curcumin (diferulolylmethane) demonstrates profound anti-inflammatory effects in intestinal epithelial cells (IEC) and in immune cells in vitro and exhibits a protective role in rodent models of chemically induced colitis, with its presumed primary mechanism of action via inhibition of NF-κB. Although it has been demonstrated effective in reducing relapse rate in ulcerative colitis patients, curcumin's effectiveness in Crohn's disease (CD) or in Th-1/Th-17 mediated immune models of CD has not been evaluated. Therefore, we investigated the effects of dietary curcumin (0.1–1%) on the development of colitis, immune activation, and in vivo NF-κB activity in germ-free IL-10−/−or IL-10−/−;NF-κBEGFPmice colonized with specific pathogen-free microflora. Proximal and distal colon morphology showed a mild protective effect of curcumin only at 0.1%. Colonic IFN-γ and IL-12/23p40 mRNA expression followed similar pattern (∼50% inhibition at 0.1%). Secretion of IL-12/23p40 and IFN-γ by colonic explants and mesenteric lymph node cells was elevated in IL-10−/−mice and was not decreased by dietary curcumin. Surprisingly, activation of NF-κB in IL-10−/−mice (phospho-NF-κBp65) or in IL-10−/−;NF-κBEGFPmice (whole organ or confocal imaging) was not noticeably inhibited by curcumin. Furthermore, we demonstrate that IL-10 and curcumin act synergistically to downregulate NF-κB activity in IEC and IL-12/23p40 production by splenocytes and dendritic cells. In conclusion, curcumin demonstrates limited effectiveness on Th-1 mediated colitis in IL-10−/−mice, with moderately improved colonic morphology, but with no significant effect on pathogenic T cell responses and in situ NF-κB activity. In vitro studies suggest that the protective effects of curcumin are IL-10 dependent.
Chronic high-NaCl intake prolongs the cardiorenal responses to central N/OFQ and produces regional changes in the endogenous brain NOP receptor system
Authors: Wainford Richard D. , Kapusta Daniel R.
Published: November 2008

Intracerebroventricular nociceptin/orphanin FQ (N/OFQ) produces cardiovascular depressor, diuretic, and renal sympathoinhibitory responses in conscious rats. These studies examined how a chronic high-NaCl intake alters these peptide-evoked responses and the activity of the endogenous central N/OFQ peptide (NOP) receptor system. In normotensive Sprague-Dawley rats fed a chronic (3-wk) high (8%)-NaCl diet, intracerebroventricular N/OFQ (5.5 nmol) produced prolonged bradycardic, hypotensive, and diuretic responses but failed to suppress renal sympathetic nerve activity. In a separate group of rats maintained on a high-NaCl diet, intracerebroventricular infusion of the NOP receptor antagonist UFP-101 significantly decreased urine output. At the tissue level, high-NaCl treatment of rats significantly increased NOP receptor density, without altering endogenous N/OFQ peptide levels in whole hypothalamus (control, 712 ± 35 fmol/mg vs. 8% NaCl, 883 ± 49 fmol/mg, P < 0.05) and paraventricular nucleus. Furthermore, in the hypothalamus, basal GTPγS binding was increased without altering the sensitivity of N/OFQ-stimulated G protein coupling. In contrast, in whole medulla and the ventrolateral medulla (VLM), high-NaCl treatment decreased NOP receptor density (medulla: control, 1,473 ± 131 fmol/mg vs. 8% NaCl, 327 ± 31 fmol/mg, P < 0.05) and endogenous N/OFQ peptide levels (medulla: control, 35.3 ± 2 fmol/mg vs. 8% NaCl, 11.9 ± 3 fmol/mg, P < 0.05), while increasing the sensitivity of G protein signaling pathways to N/OFQ stimulation. Together, these findings suggest that during a chronic high-salt intake, regional changes in the activity of the N/OFQ-NOP system in the brain may contribute to the tonic regulation of cardiovascular function and urine output and to the altered physiological responses to exogenous central N/OFQ.