bluuebunny/crossref_metadata_2025 huggingface dataset:
Clumping Factor A Interaction with Complement Factor I Increases C3b Cleavage on the Bacterial Surface ofStaphylococcus aureusand Decreases Complement-Mediated Phagocytosis
Authors: Hair Pamela S. , Echague Charlene G. , Sholl Amber M. , Watkins Justin A. , Geoghegan Joan A. , Foster Timothy J. , Cunnion Kenji M.
Published: January 2010

The human complement system is important in the immunological control ofStaphylococcus aureusinfection. We showed previously thatS. aureussurface protein clumping factor A (ClfA), when expressed in recombinant form, bound complement control protein factor I and increased factor I cleavage of C3b to iC3b. In the present study, we show that, compared to the results for the wild type, when isogenic ClfA-deficientS. aureusmutants were incubated in serum, they bound less factor I, generated less iC3b on the bacterial surface, and bound fewer C3 fragments. It has been shown previously that two amino acids in ClfA (P336and Y338) are essential for fibrinogen binding. However,S. aureusexpressing ClfA(P336A Y338S) was less virulent than ClfA-deficient strains in animal models. This suggested that ClfA contributed toS. aureusvirulence by a mechanism different than fibrinogen binding. In the present study, we showed thatS. aureusexpressing ClfA(P336A Y338S) was more susceptible to complement-mediated phagocytosis than a ClfA-null mutant or the wild type. Unlike ClfA, ClfA(P336A Y338S) did not enhance factor I cleavage of C3b to iC3b and inhibited the cofactor function of factor H. Fibrinogen enhanced factor I binding to ClfA and theS. aureussurface. Twenty clinicalS. aureusstrains all expressed ClfA and bound factor I. High levels of factor I binding by clinical strains correlated with poor phagocytosis. In summary, our results suggest that the interaction of ClfA with factor I contributes toS. aureusvirulence by a complement-mediated mechanism.
Seed size effects and competitive ability in Thlaspi arvense L. (Brassicaceae)
Authors: Susko David J. , Cavers Paul B.
Published: January 2010

We examined the effects of seed size on plant size and competitive ability of Thlaspi arvense L. grown with and without intraspecific competition under contrasting soil fertility regimes. For solitary plants from each of four half-sibship families, seed mass was positively correlated with percentage germination, cotyledon size, and plant biomass after 15 d of growth, but differences in plant biomass largely disappeared at later dates. Small and large seeds of a single maternal family were sown in uniform or mixed arrangements of seed size classes (small:large; 100%:0%; 75%:25%; 50%:50%; 25%:75%; 0%:100%) at each of two densities (8 or 16 seeds·pot–1) under low and high soil nutrient regimes. In mixtures at low density under low soil fertility, plants from small seeds had significantly lower relative yields than expected. At high density, under either low or high nutrient conditions, plants from large seeds had significantly greater relative yields than expected. Hence, under most conditions, size inequalities between plants from seeds of different size resulted in a relative competitive advantage for plants from large seeds. The duration and extent of differences in plant size arising from T. arvense seeds of contrasting size depends on maternal genetic differences, intensity of intraspecific competition, and soil fertility.
Developmentally programmed and plastic processes of growth in the multistemmed understory shrub Vaccinium hirtum (Ericaceae)
Authors: Kawamura Koji , Takeda Hiroshi
Published: January 2010

This paper investigates the developmentally programmed and plastic processes of growth in the multistemmed, deciduous shrub Vaccinium hirtum Thunb. We conducted the demographic censuses of stems and the measurements of stem growth and morphology along a natural light gradient in forest understory. With light availability from 5%–28%, the probability of sprouting new stems increased three-fold. Sprouts growing in well-lit conditions were larger than sprouts growing less light. In contrast, neither leaf area per unit aboveground biomass (LAR) nor relative growth rates of aboveground biomass (RGR) of individual stems changed significantly with light. Irrespective of light availability, LAR increased and RGR decreased with stem age. RGR approached zero in old stems > 12-years-old, and their aboveground biomass productions were mostly used to replace deciduous leaves. Our results suggest that the response of aboveground structures to increasing light availability occurs by the production of new sprouts, rather than by the increased growth of existing stems. This indicates a hierarchy of plasticities within the multistemmed structure. Age-related strong controls of stem development reflect the sprouting and multistemmed habits. This growth strategy is favorable under high-stress environments with generally low resource levels such as forest understory and with unpredictable resource pulses such as caused by canopy gap disturbances.
An issue of teamwork
Authors: Crawford Diane
Published: January 2010

This column was supposed to write itself. When Editor-in-Chief Moshe Vardi first asked me to tell readers how a typical issue of
Communications
comes together, I remember thinking "piece of cake."
Alternate interface technologies emerge
Authors: Kroeker Kirk L.
Published: January 2010

Researchers working in human-computer interaction are developing new interfaces to produce greater efficiencies in personal computing and enhance miniaturization in mobile devices.
Not seeing the crime for the cameras?
Authors: Sasse M. Angela
Published: January 2010

Why it is difficult---but essential---to monitor the effectiveness of security technologies.
Why an informatics degree?
Authors: Groth Dennis P. , MacKie-Mason Jeffrey K.
Published: January 2010

Isn't computer science enough?
Taking your network's temperature
Authors: Neville-Neil George V.
Published: January 2010

A prescription for capturing data to diagnose and debug a networking problem.
Power-efficient software
Authors: Saxe Eric
Published: January 2010

Power-manageable hardware can help save energy, but what can software developers do to address the problem?
Software model checking takes off
Authors: Miller Steven P. , Whalen Michael W. , Cofer Darren D.
Published: January 2010

A translator framework enables the use of model checking in complex avionics systems and other industrial settings.
Assessing the changing U.S. IT R&D ecosystem
Authors: Benhamou Eric , Eisenberg Jon , Katz Randy H.
Published: January 2010

The National Academy of Sciences recommends what the U.S. government should do to help maintain American IT leadership.
Faster dimension reduction
Authors: Ailon Nir , Chazelle Bernard
Published: January 2010

Data represented geometrically in high-dimensional vector spaces can be found in many applications. Images and videos, are often represented by assigning a dimension for every pixel (and time). Text documents may be represented in a vector space where each word in the dictionary incurs a dimension. The need to manipulate such data in huge corpora such as the web and to support various query types gives rise to the question of how to represent the data in a lower-dimensional space to allow more space and time efficient computation. Linear mappings are an attractive approach to this problem because the mapped input can be readily fed into popular algorithms that operate on linear spaces (such as principal-component analysis, PCA) while avoiding the curse of dimensionality.

The fact that such mappings even exist became known in computer science following seminal work by Johnson and Lindenstrauss in the early 1980s. The underlying technique is often called "random projection." The complexity of the mapping itself, essentially the product of a vector with a dense matrix, did not attract much attention until recently. In 2006, we discovered a way to "sparsify" the matrix via a computational version of Heisenberg's Uncertainty Principle. This led to a significant speedup, which also retained the practical simplicity of the standard Johnson-Lindenstrauss projection. We describe the improvement in this article, together with some of its applications.
Puzzled: Breaking chocolate bars
Authors: Winkler Peter
Published: January 2010

Welcome to three new puzzles. Solutions to the first two will be published next month; the third is (as yet) unsolved. In each, the issue is how your intuition matches up with the mathematics.
ACM Fellows honored
Authors: CACM Staff
Published: January 2010

Forty-seven men and women are inducted as 2009 ACM Fellows.
It takes two to tango
Authors: Mehta Nikhil , Mehta Anju
Published: January 2010

Introduction

The IT outsourcing, industry landscape is dotted with broken contracts - results of unsuccessful client-vendor (C-V) partnerships. Approximately 78% C-V partnerships fail in the long term, inflicting high transition costs on clients. The recent economic downturn has strined C-V partnerships further. Despite the criticality of this issue, there is a relative lack of efforts to understand the issues leading to failed partnerships.

We discuss these issues in light of the clients' onus towards improving the longevity of C-V partnerships.

We adopt a two-pronged approach. First, we try to identify the client characteristics that influence their potential to forge a long-term C-V partnership. To that extent, we discuss a partnership maturity curve (PMC), which categorizes clients into three dynamic stages, and predicts their potential for developing mature partnerships based on their outsourcing objectives and their fit with vendors' capabilities (see Figure 1).

Second, we try to understand vendors' perspective on the issue. We interviewed 21 executives in nine established IT-outsourcing vendors in India. It has been recommended that vendors' perspective is critical to understanding C-V partnerships. Vendors highlighted an interesting mix of their own as well as client-generated issues, which we discuss in light of the client dynamics identified by PMC, to propse guidelines for clients interested in developing successful C-V partnerships. The study confirms existing belief that improving the longevity of C-V partnerships requires relational investments from clients. We identify various areas for clients to make such investments.
Probabilistic static pruning of inverted files
Authors: Blanco Roi , Barreiro Alvaro
Published: January 2010

Information retrieval (IR) systems typically compress their indexes in order to increase their efficiency. Static pruning is a form of lossy data compression: it removes from the index, data that is estimated to be the least important to retrieval performance, according to some criterion. Generally, pruning criteria are derived from term weighting functions, which assign weights to terms according to their contribution to a document's contents. Usually, document-term occurrences that are assigned a low weight are ruled out from the index. The main assumption is that those entries contribute little to the document content.

We present a novel pruning technique that is based on a probabilistic model of IR. We employ the Probability Ranking Principle as a decision criterion over which posting list entries are to be pruned. The proposed approach requires the estimation of three probabilities, combining them in such a way that we gather all the necessary information to apply the aforementioned criterion.

We evaluate our proposed pruning technique on five TREC collections and various retrieval tasks, and show that in almost every situation it outperforms the state of the art in index pruning. The main contribution of this work is proposing a pruning technique that stems directly from the same source as probabilistic retrieval models, and hence is independent of the final model used for retrieval.
Learning author-topic models from text corpora
Authors: Rosen-Zvi Michal , Chemudugunta Chaitanya , Griffiths Thomas , Smyth Padhraic , Steyvers Mark
Published: January 2010

We propose an unsupervised learning technique for extracting information about authors and topics from large text collections. We model documents as if they were generated by a two-stage stochastic process. An author is represented by a probability distribution over topics, and each topic is represented as a probability distribution over words. The probability distribution over topics in a multi-author paper is a mixture of the distributions associated with the authors. The topic-word and author-topic distributions are learned from data in an unsupervised manner using a Markov chain Monte Carlo algorithm. We apply the methodology to three large text corpora: 150,000 abstracts from the CiteSeer digital library, 1740 papers from the Neural Information Processing Systems (NIPS) Conferences, and 121,000 emails from the Enron corporation. We discuss in detail the interpretation of the results discovered by the system including specific topic and author models, ranking of authors by topic and topics by author, parsing of abstracts by topics and authors, and detection of unusual papers by specific authors. Experiments based on perplexity scores for test documents and precision-recall for document retrieval are used to illustrate systematic differences between the proposed author-topic model and a number of alternatives. Extensions to the model, allowing for example, generalizations of the notion of an author, are also briefly discussed.
Sparse Matrix-Vector Multiplication on a Reconfigurable Supercomputer with Application
Authors: Dubois David , Dubois Andrew , Boorman Thomas , Connor Carolyn , Poole Steve
Published: January 2010

Double precision floating point Sparse Matrix-Vector Multiplication (SMVM) is a critical computational kernel used in iterative solvers for systems of sparse linear equations. The poor data locality exhibited by sparse matrices along with the high memory bandwidth requirements of SMVM result in poor performance on general purpose processors. Field Programmable Gate Arrays (FPGAs) offer a possible alternative with their customizable and application-targeted memory sub-system and processing elements. In this work we investigate two separate implementations of the SMVM on an SRC-6 MAPStation workstation. The first implementation investigates the peak performance capability, while the second implementation balances the amount of instantiated logic with the available sustained bandwidth of the FPGA subsystem. Both implementations yield the same sustained performance with the second producing a much more efficient solution. The metrics of processor and application balance are introduced to help provide some insight into the efficiencies of the FPGA and CPU based solutions explicitly showing the tight coupling of the available bandwidth to peak floating point performance. Due to the FPGAs ability to balance the amount of implemented logic to the available memory bandwidth it can provide a much more efficient solution. Finally, making use of the lessons learned implementing the SMVM, we present a fully implemented non-preconditioned Conjugate Gradient Algorithm utilizing the second SMVM design.
Configuration Merging in Point-to-Point Networks for Module-Based FPGA Reconfiguration
Authors: Koh Shannon , Diessel Oliver
Published: January 2010

Partial runtime reconfiguration allows some circuit components to be reconfigured while the remaining circuitry continues to operate. Applications partitioned into modules have the potential to exploit this capability to virtualize hardware by swapping modules as required. One of the challenges in doing so is to provide a communication infrastructure that supports the interfaces and communication needs of a sequence of dynamic module swaps. In contrast to previous approaches which have examined the use of buses and networks-on-chip for this purpose, we examine the use of customized point-to-point wiring harnesses to provide the dynamic connections required for dynamic modular reconfiguration in an efficient manner. The COMMA methodology implements applications on tile-reconfigurable FPGAs, such as the Virtex-4, and its design flow is integrated with the early access partial reconfiguration tools from Xilinx. This article outlines the methodology and describes greedy and dynamic programming approaches to merging the communication graphs of successive configurations in order to generate effective wiring harnesses within the methodology. Our evaluation indicates merging can markedly reduce total reconfiguration delays at the cost of increased critical path delays. Application of the technique is likely to be limited to scenarios in which the execution time between reconfigurations is short.
Stopping a myth in artificial neural networks
Authors: Yang Feng-Jen
Published: January 2010

The myth of "the more neurons, the better learning" is commonly held in artificial intelligence personnel. The side effect of having too many neurons may not be easily observed unless some active measurements and analyses are taken. In this study, I performed a series of experiments to make various neural networks learn the same quadratic equation and then analyzed three statistical data to illustrate the problems that can be caused by having more than necessary number of neurons in a neural network.
On the non-modular design of on-the-fly computations
Authors: Ginat David
Published: January 2010

On-the-fly computations are apparent in all levels of the CS studies. Yet, textbooks do not underline their characterizing design features. One of their primary features is the non-modular composition of design patterns. Additional design features involve insightful observations and the perspective of state transitions. Unfortunately, novices demonstrate limited competence with these features, even after repeatedly seeing on-the-fly designs. The objective of this paper is to shed light on the novice difficulties, and to elaborate on the above features, in advocating the importance of their explicit presentation to students.
A hands-on approach to proof and abstraction
Authors: Ensley Douglas
Published: January 2010

Abstraction is an important part of mathematics and computer science, and it is a common stumbling point for students learning how to write mathematical proofs. This article outlines simple strategies for making mathematical proof less abstract in the context of the discrete mathematics course.
Learning difficulties experienced by students in a course on formal languages and automata theory
Authors: Pillay Nelishia
Published: January 2010

Students taking courses on formal languages and automata theory (FLAT) usually do not find these courses interesting and experience difficulty in grasping the different concepts. While there has been a vast amount of research into methodologies to assist students to conceptualize FLAT topics, there has been no research into the actual learning difficulties experienced by students with the different topics. This paper reports on the findings of a study conducted to identify these learning difficulties for some of the FLAT topics.
Sorting and searching using lisp, functional programming, and recursion
Authors: Maniccam S.
Published: January 2010

This paper presents some commonly used algorithms and data structures using the Lisp language, functional programming style, and recursive thinking. Insertion sort, selection sort, quick sort, binary search tree, search, insertion, and deletion operations are presented. The algorithms are written in purely functional and recursive style using Lisp. Only a small subset of Lisp is used to write the algorithms. Various factors related to learning, teaching, and the curriculum are pointed out.
The classical/linear Hanoi hybrid problem
Authors: Minsker Steven
Published: January 2010

We continue our study, begun in [3], of the classical/linear Towers of Hanoi "hybrid" problem, in which there are three pegs arranged in a row, and the rules governing ring movement depend on ring color. Whereas [3] dealt with perfect to perfect configuration problems in a very straightforward manner, the current paper discusses deterministic and dynamic algorithms for regular to regular problems, which turn out to be far more complicated than perhaps might be expected.
A browser-based operating systems project
Authors: Labouseur Alan G.
Published: January 2010

This paper presents one educator's experience with a browser-based project for an upper-level/graduate Operating Systems course. The author explains the project goals, why the browser in general and JavaScriptin particular are so well suited for this task, challenges andtheir solutions, the incremental assignments that ultimately result in a fairly complex OS simulation by the end of the semester, the response to the project, and some ideas about where to go next.
A broken metaphor in Java
Authors: Milner Walter W.
Published: January 2010

In this paper, the matrix of metaphors in which Java is located is outlined, and the way that students understand event-handling through the EventListener metaphor is described, supported by interview extracts. This clashes both with the typical syntax of natural language imperatives, and with the actual mechanism of Java eventhandling. It is therefore a source of some confusion in students.
How should transversal competence be introduced In computing education?
Authors: Sicilia Miguel-Angel
Published: January 2010

The development of transversal or transferable competences is currently considered a key ingredient of the outcomes of Higher Education. However, course and curricula design accounting for such competences remains a challenge for which little practical guidance is available. This paper sketches a systematic procedure for introducing such competencies in courses related to engineering software by analyzing the connection of transversal abilities to specific competencies that have been recognized as important. This emphasizes the contextualization of generic skills within realistic practical activity, and avoids, at least to some extent, both overemphasis on activities oriented to developing the transversal aspects and also disconnection of these aspects with real-world performances.
An exploration of the current state of information assurance education
Authors: Cooper Stephen , Nickell Christine , Piotrowski Victor , Oldfield Brenda , Abdallah Ali , Bishop Matt , Caelli Bill , Dark Melissa , Hawthorne E. K. , Hoffman Lance , Pérez Lance C. , Pfleeger Charles , Raines Richard , Schou Corey , Brynielsson Joel
Published: January 2010

Information Assurance and computer security are serious worldwide concerns of governments, industry, and academia. Computer security is one of the three new focal areas of the ACM/IEEE's Computer Science Curriculum update in 2008. This ACM/IEEE report describes, as the first of its three recent trends, "the emergence of security as a major area of concern." The importance of Information Assurance and Information Assurance education is not limited to the United States. Other nations, including the United Kingdom, Australia, New Zealand, Canada, and other members from NATO countries and the EU, have inquired as to how they may be able to establish Information Assurance education programs in their own country.

The goal of this document is to explore the space of various existing Information Assurance educational standards and guidelines, and how they may serve as a basis for helping to define the field of Information Assurance. It was necessary for this working group to study what has been done for other areas of computing. For example, computer science (CS 2008 and associate-degree CS 2009), information technology (IT 2008), and software engineering (SE 2004), all have available curricular guidelines.

In its exploration of existing government, industry, and academic Information Assurance guidelines and standards, as well as in its discovery of what guidance is being provided for other areas of computing, the working group has developed this paper as a foundation, or a starting point, for creating an appropriate set of guidelines for Information Assurance education. In researching the space of existing guidelines and standards, several challenges and opportunities to Information Assurance education were discovered. These are briefly described and discussed, and some next steps suggested.
Challenges in distributed energy adaptive computing
Authors: Kant Krishna
Published: January 2010

Fueled by burgeoning online services, energy consumption in information technology (IT) equipment is becoming a major concern from a variety of perspectives including the continuation of Moore's Law for hardware design, enabling sophisticated mobile client functionality, mounting utility costs in data centers, and increasing CO2 emissions associated with IT manufacturing, distribution, usage and disposal. This article discusses an approach where energy consumption and related issues of heat dissipation and sustainability are considered as the primary concerns that drive the way computation and communication is organized at both clients and servers. This article describes the challenges in supporting such a distributed energy adaptive computing paradigm.
NetReplay
Authors: Anand Ashok , Akella Aditya
Published: January 2010

In this paper, we describe Net-Replay, a new network primitive to help application end points conduct in-band characterization of the glitches they encountered. In Net-Replay, each network infrastructure element remembers a small amount of information for every packet observed at the element over a certain time interval. Furthermore, network elements expose a simple "packet marking" interface, using which they can indicate to end-points whether or not they had seen a particular packet in the past. When application end-points observe glitches, they replay (i.e. retransmit) the packets which observed the glitch and leverage feedback from network elements to determine the type and location of the glitch encountered by the packets. We discuss how end-host network stacks should be modified to leverage Net-Replay in this fashion. We also consider how network infrastructure can support Net-Replay in a lowoverhead fashion.

We argue that Net-Replay can enable applications to detect a variety of glitches and react to them in an accurate and informed manner, while ensuring that the infrastructure stays simple and fast. We believe that proactive support from the network in the form of Net-Replay-like functionality is crucial to ensure robust performance of future Internet applications, many of which are likely to be highly demanding and far less tolerant of network glitches than traditional applications.
A weighted spectrum metric for comparison of internet topologies
Authors: Fay Damien , Haddadi Hamed , Moore Andrew W. , Mortier Richard , Uhlig Steve , Jamakovic Almerima
Published: January 2010

Comparison of graph structures is a frequently encountered problem across a number of problem domains. Comparing graphs requires a metric to discriminate which features of the graphs are considered important. The spectrum of a graph is often claimed to contain all the information within a graph, but the raw spectrum contains too much information to be directly used as a useful metric. In this paper we introduce a metric, the weighted spectral distribution, that improves on the raw spectrum by discounting those eigenvalues believed to be unimportant and emphasizing the contribution of those believed to be important.

We use this metric to optimize the selection of parameter values for generating Internet topologies. Our metric leads to parameter choices that appear sensible given prior knowledge of the problem domain: the resulting choices are close to the default values of the topology generators and, in the case of some generators, fall within the expected region. This metric provides a means for meaningfully optimizing parameter selection when generating topologies intended to share structure with, but not match exactly, measured graphs.
Poster Abstract
Authors: Meyerowitz Joseph T. , Choudhury Romit Roy
Published: January 2010

Mobile users face privacy risks when providing their locations to untrusted location based services (LBSs). We develop CacheCloak, a system that enables realtime anonymization of location data. A trusted anonymizing server receives the location of a user, processes it using CacheCloak, and exposes the processed data to LBSs. We show that the quality of the location data does not degrade in space or time, and hence, LBSs are able to respond accurately in real time. Yet, privacy is preserved as LBSs are unable to track any given user for more than a short duration. The key is to exploit mobility patterns to intelligently extrapolate each user's path until it meets another. A snapshot of intersecting paths is sent to the LBS, preventing reliable tracking of any given user. We use stochastic methods to generate mobility predictions and entropy measurements to quantify a user's anonymity. We demonstrate a high tracking resilience against a reasonably powerful adversary. Tracebased traffic simulation using real GIS data shows that CacheCloak can achieve realtime location privacy without degrading location accuracy or service availability.
Poster abstract
Authors: Lee Jung Woo , Kusy Branislav , Levis Philip
Published: January 2010

Whirlpool Ad-hoc Routing Protocol (WARP) is a dynamic data collection protocol for wireless sensor networks. Compared to existing protocols, WARP offers order of magnitude improvements in reliability, efficiency, and routing stretch for a moving data sink. When the sink moves, nearby WARP nodes stop forwarding data directly towards the sink. Instead, they speculatively disseminate data packets along loops centered at the last location of the sink. The loop radius progressively increases searching more widely until the sink is found. Finally, WARP embeds a few bits of control information in data packets and aggressively suppresses control packets to further improve its efficiency.

We have implementedWARP in TinyOS and evaluated it against the Collection Tree Protocol (CTP) [2], the state-of-art collection protocol for WSNs. For a mobile sink, WARP had significantly better reliability and efficiency, achieving over 90% reliability for a wide range of speeds and data rates, compared to below 10% reliability of CTP.
Therapeutic Approaches for Women Predisposed to Breast Cancer
Authors: Nathanson Katherine L. , Domchek Susan M.
Published: January 2010

The medical management of women at an increased risk of breast cancer has substantially changed over the past few years, with improvements in screening, cancer prevention, and treatment, and is best defined for women with mutations in BRCA1 and BRCA2. Screening techniques, such as breast magnetic resonance imaging, enable early detection of cancers in high-risk women. Prophylactic salpingo-oophorectomy has been demonstrated to decrease the risk of breast and ovarian cancers, as well as mortality in BRCA1/2 mutation carriers. Most recently, there have been considerable strides in the treatment of cancers in BRCA1/2 mutation carriers. Breast cancer patients with BRCA1/2 mutations treated with systemic therapy do not appear to have excess toxicity, and have similar relapse-free and overall survival compared to noncarriers. Preclinical and early clinical research suggests that specific classes of chemotherapy may be more effective in mutation carriers. PARP inhibitors represent a novel therapeutic strategy that exploits the weaknesses of BRCA1/2-associated malignancies.
The Brain-Gut Axis in Abdominal Pain Syndromes
Authors: Mayer Emeran A. , Tillisch Kirsten
Published: January 2010

The importance of bidirectional brain-gut interactions in gastrointestinal (GI) illness is increasingly recognized, most prominently in the area of functional GI syndromes such as irritable bowel syndrome (IBS), functional dyspepsia, and functional chest pain. The brain receives a constant stream of interoceptive input from the GI tract, integrates this information with other interoceptive information from the body and with contextual information from the environment, and sends an integrated response back to various target cells within the GI tract. This system is optimized to assure homeostasis of the GI tract during physiological perturbations and to adapt GI function to the overall state of the organism. In health, the great majority of interoceptive information reaching the brain is not consciously perceived but serves primarily as input to autonomic reflex pathways. In patients with functional abdominal pain syndromes, conscious perception of interoceptive information from the GI tract, or recall of interoceptive memories of such input, can occur in the form of constant or recurrent discomfort or pain. This is often associated with alterations in autonomic nervous system output and with emotional changes. A model is proposed that incorporates reported peripheral and central abnormalities in patients with IBS, extrapolates similar alterations in brain-gut interactions to patients with other chronic abdominal pain syndromes, and provides novel treatment targets.
Kawasaki Disease: Novel Insights into Etiology and Genetic Susceptibility
Authors: Rowley Anne H.
Published: January 2010

Kawasaki disease (KD) is a vasculitis of young childhood that particularly affects the coronary arteries. Molecular analysis of the oligoclonal IgA response in acute KD led to production of synthetic KD antibodies. These antibodies identify intracytoplasmic inclusion bodies in acute KD tissues. Light and electron microscopic studies indicate that the inclusion bodies are consistent with aggregates of viral proteins and RNA. Advances in molecular genetic analysis and completion of the Human Genome Project have sparked a worldwide effort to identify genes associated with KD. A polymorphism of one such gene, ITPKC, a negative regulator of T cell activation, confers susceptibility to KD in Japanese populations and increases the risk of developing coronary artery abnormalities in both Japanese and U.S. children. Identification of the etiologic agent and of genes conferring KD susceptibility are the best means of improving diagnosis and therapy and enabling prevention of this important disorder of childhood.
HIV Infection, Inflammation, Immunosenescence, and Aging
Authors: Deeks Steven G.
Published: January 2010

Although antiretroviral therapy for HIV infection prevents AIDS-related complications and prolongs life, it does not fully restore health. Long-term treated patients remain at higher than expected risk for a number of complications typically associated with aging, including cardiovascular disease, cancer, osteoporosis, and other end-organ diseases. The potential effect of HIV on health is perhaps most clearly exhibited by a number of immunologic abnormalities that persist despite effective suppression of HIV replication. These changes are consistent with some of the changes to the adaptive immune system that are seen in the very old (“immunosenescence”) and that are likely related in part to persistent inflammation. HIV-associated inflammation and immunosenescence have been implicated as causally related to the premature onset of other end-organ diseases. Novel therapeutic strategies aimed at preventing or reversing these immunologic defects may be necessary if HIV-infected patients are to achieve normal life span.
Advances in Palliative Medicine and End-of-Life Care
Authors: Abrahm Janet L.
Published: January 2010

Palliative care improves the quality and cost-effectiveness of adult and pediatric patient care, and it decreases unwanted hospitalizations and aggressive care at the end of life. National palliative care quality standards and preferred practices can be used for benchmarking by institutions, health care systems, and accrediting bodies. Pain and symptom management and the management of delirium for patients is now possible for the vast majority of patients, even those with advanced disease. However, because of shortages of specialists providing “tertiary” palliative care, significant improvements are needed in generalist-level palliative care among oncologists, intensivists, and specialists caring for patients with advanced cardiac, pulmonary, renal, and hepatic diseases. POLST (Physician Orders for Life-Sustaining Treatment) forms are a major advance in end-of-life care. They enable patients' advance directives to be valid wherever they are cared for (home, hospital, or nursing facility).
Antiestrogens and Their Therapeutic Applications in Breast Cancer and Other Diseases
Authors: Ali Simak , Buluwela Laki , Coombes R. Charles
Published: January 2010

The identification of the link between breast cancer and estrogens has led to the development of antiestrogens, in particular tamoxifen, to inhibit the activities of estrogen receptors (ERs) in breast cancer cells. The clinical use of tamoxifen has played a major part in decreasing breast cancer mortality over the past 30 years. Though antiestrogenic in the breast, some antiestrogens have estrogen-like actions in other tissues, acting to promote bone density and protect against cardiovascular disease, thus raising the possibility of their use in counteracting the effects of estrogen loss following menopause. Moreover, antiestrogens show efficacy as chemopreventive agents in women at high risk of developing breast cancer. Thus, antiestrogens define an important and well-understood class of cancer drug, which continue to be a mainstay in breast cancer treatment.
Role of Postmarketing Surveillance in Contemporary Medicine
Authors: Woodcock Janet , Behrman Rachel E. , Dal Pan Gerald J.
Published: January 2010

Contemporary medicine is a large and complex system involving many participants, all of whom play a critical role in managing the risks intrinsic to medical product use. Despite the robust premarket review and approval process of the U.S. Food and Drug Administration (FDA), new information will inevitably be learned in the postmarketing period about the safety of medicines and how they are and should be used. For much of this information, FDA relies on public reports about possible adverse events. In turn, the public depends on FDA to communicate the most up-to-date safety information on medical products to better inform treatment decisions. Expanding the scope and strengthening the capabilities of the drug safety surveillance system are among key FDA projects designed to reduce avoidable injury and death from medication use. Although improving drug safety is our goal and obligation to the public, FDA cannot protect the public adequately without the active involvement of all participants in healthcare.
Novel Oral Factor Xa and Thrombin Inhibitors in the Management of Thromboembolism
Authors: Eriksson Bengt I. , Quinlan Daniel J. , Eikelboom John W.
Published: January 2010

The last decade has seen the evaluation of several new oral anticoagulants that directly target thrombin or activated factor X (FXa). All demonstrate a rapid onset of action, a low potential for food and drug interactions, and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. Those agents at the most advanced stages of clinical development are a direct thrombin inhibitor, dabigatran, and direct FXa inhibitors, rivaroxaban and apixaban. Dabigatran and rivaroxaban are approved in more than 70 countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty, and apixaban is being considered for approval by regulatory agencies for this indication. Dabigatran was shown in a large phase III trial to be more effective and safer than warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation and has recently been approved for this indication. Edoxaban, an oral FXa inhibitor, is also being evaluated in phase III clinical trials. This review summarizes the pharmacology, clinical trial results, and future role of the new oral anticoagulants in clinical practice.
Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest
Authors: Zacharia Brad E. , Hickman Zachary L. , Grobelny Bartosz T. , DeRosa Peter A. , Ducruet Andrew F. , Connolly E. Sander
Published: January 2010

Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.
Asymptotically Sufficient Statistics in Nonparametric Regression Experiments with Correlated Noise
Authors: Carter Andrew V.
Published: January 2010

We find asymptotically sufficient statistics that could help
simplify inference in nonparametric regression problems with correlated errors. These statistics are derived from a wavelet decomposition that is used to whiten the noise process and to effectively separate high‐resolution and low‐resolution components. The lower‐resolution components contain nearly all the available information about the mean function, and the higher‐resolution components can be used to estimate the error
covariances. The strength of the correlation among the errors is related to the speed at which the variance of the higher‐resolution components shrinks, and this is considered an additional nuisance parameter in the model. We show that the NPR experiment with correlated noise is asymptotically equivalent to an experiment that observes the mean function in the presence of a continuous Gaussian process that is similar to a fractional
Brownian motion. These results provide a theoretical motivation for some commonly proposed wavelet estimation techniques.
Factors Associated with Coverage and Usage of Long-Lasting Insecticidal Nets in Madagascar
Authors: Thawani Neeta , Kulkarni Manisha A. , Sohani Salim
Published: January 2010

In October 2007, long-lasting insecticidal nets (LLINs) were distributed in 59 of the 111 districts in Madagascar as part of a nationwide child survival campaign. A community-based cross-sectional survey was conducted six months post-campaign to evaluate net ownership, use and equity. Here, we examined the effects of socioeconomic factors on LLIN ownership and usage in districts with and without net distribution during the campaign. Our data demonstrated that in districts with LLIN distribution, LLIN ownership was similar across all wealth groups in households with at least one child under the age of five years (90.5% versus 88.6%); in districts without net distribution, 57.8% of households in the poorest tertile compared to 90.1% of households in the least poor tertile owned at least one LLIN. In contrast, in LLIN-owning households, both in districts with and without net distribution, higher socio-economic status was not associated with use among children under five years. These findings suggest that socio-economic status contributes to the household net ownership but once a household owns a net, socio-economic status is not associated with net use.
Leukotrienes in Atherosclerosis: New Target Insights and Future Therapy Perspectives
Authors: Riccioni Graziano , Zanasi Alessandra , Vitulano Nicola , Mancini Barbara , D'Orazio Nicolantonio
Published: January 2010

Atherosclerosis represents an important chronic inflammatory process associated with several pathophysiological reactions in the vascular wall. The arachidonic acid, released by phospholipase A2, is an important substrate for the production of a group of lipid mediators known as leukotrienes, which induce proinflammatory signaling through the activation of specific BLT and CysLT receptors. The interaction of these substances in the vascular wall determines important morphological alterations like the early lipid retention and the accumulation of foam cells, the development of intimal hyperplasia, and advanced atherosclerotic lesions, and it plays an important role in the rupture of atherosclerotic plaque. Many studies regarding myocardial ischemia and reperfusion show that leukotriene signaling may be involved in the development of ischemic injury. For these, reasons both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested for inducing beneficial effects at different stages of the atherosclerosis process and may represent a new therapeutic target in the treatment of atherosclerotic vessel diseases, in particular in acute coronary syndrome.
Leptin Induces an Inflammatory Phenotype in Lean Wistar Rats
Authors: Allman Monique , Wallace Mathew , Gaskin Latausha , Rivera Chantal A.
Published: January 2010

The present study addressed the hypothesis that leptin promotes leukocyte trafficking into adipose tissue. Accordingly, male Wistar rats were treated with saline or recombinant rat leptin (1 mg/kg) via the tail vein. Leukocyte trafficking in mesenteric venules was quantified by intravital microscopy. Treatment with leptin resulted in a 3- and 5-fold increases in rolling and firm adhesion, respectively. Compared to vehicle controls, leptin enhanced mRNA levels of IL-6 (8-fold) and MCP-1 (5-fold) in mesenteric adipose tissue (MAT). Similar increases in these markers were observed in mesenteric venules and in liver. Finally, the direct effect of leptin was assessed in C3A hepatocytes treated with leptin for 24 hours (7.8 ng/mL–125 ng/mL). Consistent with observations in vivo, production of ICAM-1, MCP-1, and IL-6 by hepatocytes was increased significantly. These findings support the hypothesis that leptin directly initiates inflammation in the local environment of mesenteric adipose tissue as well as systemically.
Hardware Accelerated Sequence Alignment with Traceback
Authors: Lloyd Scott , Snell Quinn O.
Published: January 2010

Biological sequence alignment is an essential tool used in molecular biology and biomedical applications. The growing volume of genetic data and the complexity of sequence alignment present a challenge in obtaining alignment results in a timely manner. Known methods to accelerate alignment on reconfigurable hardware only address sequence comparison, limit the sequence length, or exhibit memory and I/O bottlenecks. A space‐efficient, global sequence alignment algorithm and architecture is presented that accelerates the forward scan and traceback in hardware without memory and I/O limitations. With 256 processing elements in FPGA technology, a performance gain over 300 times that of a desktop computer is demonstrated on sequence lengths of 16000. For greater performance, the architecture is scalable to more processing elements.