bluuebunny/crossref_metadata_2025 huggingface dataset:
ON SEMI-C-REDUCIBILITY OF (α, β)-METRICS
Authors: TAYEBI A. , PEYGHAN E. , NAJAFI B.
Published: April 2012

Every non-Riemannian (α, β)-metric on a manifold with dimension n ≥ 3 is semi-C-reducible. Thus the study on semi-C-reducible metrics will enhance our understanding on the physical meaning of (α, β)-metrics. In this paper, we study weakly Landsberg semi-C-reducible metrics with some non-Riemannian curvature properties. Then we find some conditions on semi-C-reducible manifolds under which the notions of isotropic Landsberg curvature and of isotropic mean Landsberg curvature are equivalent.
A precise analysis of Cuckoo hashing
Authors: Drmota Michael , Kutzelnigg Reinhard
Published: April 2012

Cuckoo hashing was introduced by Pagh and Rodler in 2001. Its main feature is that it provides constant worst-case search time. The aim of this article is to present a precise average case analysis of Cuckoo hashing. In particular, we determine the probability that Cuckoo hashing produces no conflicts and give an upper bound for the construction time, that is linear in the size of the table. The analysis rests on a generating function approach to the so called Cuckoo Graph, a random bipartite graph, and an application of a double saddle point method to obtain asymptotic expansions. Furthermore, we provide some results concerning the structure of these kinds of random graphs. Our results extend the analysis of Devroye and Morin [2003]. Additionally, we provide numerical results confirming the mathematical analysis.
Interactive Realizers
Authors: Berardi Stefano , de’Liguoro Ugo
Published: April 2012

We propose a realizability interpretation of a system for quantier free arithmetic which is equivalent to the fragment of classical arithmetic without
nested
quantifiers, called here
EM
1
-arithmetic. We interpret classical proofs as interactive learning strategies, namely as processes going through several stages of knowledge and learning by interacting with the “nature,” represented by the standard interpretation of closed atomic formulas, and with each other. We obtain in this way a program extraction method by proof interpretation, which is faithful with respect to proofs, in the sense that it is compositional and that it does not need any translation.
Model Checking of Recursive Probabilistic Systems
Authors: Etessami Kousha , Yannakakis Mihalis
Published: April 2012

Recursive Markov Chains (RMCs) are a natural abstract model of procedural probabilistic programs and related systems involving recursion and probability. They succinctly define a class of denumerable Markov chains that generalize several other stochastic models, and they are equivalent in a precise sense to probabilistic Pushdown Systems. In this article, we study the problem of model checking an RMC against an
ω
-regular specification, given in terms of a Büchi automaton or a Linear Temporal Logic (LTL) formula. Namely, given an RMC
A
and a property, we wish to know the probability that an execution of
A
satisfies the property. We establish a number of strong upper bounds, as well as lower bounds, both for
qualitative
problems (is the probability = 1, or = 0?), and for
quantitative
problems (is the probability ≥ 
p
?, or, approximate the probability to within a desired precision). The complexity upper bounds we obtain for automata and LTL properties are similar, although the algorithms are different.

We present algorithms for the qualitative model checking problem that run in polynomial space in the size |
A
| of the RMC and exponential time in the size of the property (the automaton or the LTL formula). For several classes of RMCs, including single-exit RMCs (a class that encompasses some well-studied stochastic models, for instance, stochastic context-free grammars) the algorithm runs in polynomial time in |
A
|. For the quantitative model checking problem, we present algorithms that run in polynomial space in the RMC and exponential space in the property. For the class of linearly recursive RMCs we can compute the exact probability in time polynomial in the RMC and exponential in the property. For deterministic automata specifications, all our complexities in the specification come down by one exponential.

For lower bounds, we show that the qualitative model checking problem, even for a fixed RMC, is already EXPTIME-complete. On the other hand, even for simple reachability analysis, we know from our prior work that our PSPACE upper bounds in
A
can not be improved substantially without a breakthrough on a well-known open problem in the complexity of numerical computation.
Annotated Probabilistic Temporal Logic
Authors: Shakarian Paulo , Simari Gerardo I. , Subrahmanian V. S.
Published: April 2012

Annotated Probabilistic Temporal (APT) logic programs support building applications where we wish to reason about statements of the form “Formula
G
becomes true with a probability in the range [
L
,
U
] within (or in exactly)
Δt
time units after formula
F
became true.” In this paper, we present a sound, but incomplete fixpoint operator that can be used to check consistency and entailment in APT logic programs. We present the first implementation of APT-logic programs and evaluate both its compute time and convergence on a suite of 23 ground APT-logic programs that were automatically learned from two real-world data sets. In both cases, the APT-logic programs contained up to 1,000 ground rules. In one data set, entailment problems were solved on average in under 0.1 seconds per ground rule, while in the other, it took up to 1.3 seconds per ground rule. Consistency was also checked in a reasonable amount of time. When discussing entailment of APT-logic formulas, convergence of the fixpoint operator refers to (
U
 − 
L
) being below a certain threshold. We show that on virtually all of the 23 automatically generated APT-logic programs, convergence was quick---often in just 2-3 iterations of the fixpoint operator. Thus, our implementation is a practical first step towards checking consistency and entailment in temporal probabilistic logics without independence or Markovian assumptions.
The Complexity of Reasoning for Fragments of Autoepistemic Logic
Authors: Creignou Nadia , Meier Arne , Vollmer Heribert , Thomas Michael
Published: April 2012

Autoepistemic logic extends propositional logic by the modal operator
L
. A formula
φ
that is preceded by an
L
is said to be “believed.” The logic was introduced by Moore in 1985 for modeling an ideally rational agent’s behavior and reasoning about his own beliefs. In this article we analyze all Boolean fragments of autoepistemic logic with respect to the computational complexity of the three most common decision problems expansion existence, brave reasoning and cautious reasoning. As a second contribution we classify the computational complexity of checking that a given set of formulae characterizes a stable expansion and that of counting the number of stable expansions of a given knowledge base. We improve the best known
Δ
2
p
-upper bound on the former problem to completeness for the second level of the Boolean hierarchy. To the best of our knowledge, this is the first paper analyzing counting problem for autoepistemic logic.
An Extended SystemC Framework for Efficient HW/SW Co-Simulation
Authors: Wu Meng-Huan , Wang Peng-Chih , Fu Cheng-Yang , Tsay Ren-Song
Published: April 2012

In this article, we propose an extended SystemC framework that directly enables software simulation in SystemC. Although SystemC has been widely adopted for system-level simulation of hardware designs nowadays, to complete HW/SW co-simulation, it still requires an additional instruction set simulator (ISS) for software execution. However, the heavy intercommunication overheads between the two heterogeneous simulators would significantly slow down simulation performance. To deal with this issue, our proposed approach automatically generates high-speed and equivalent SystemC models for target software applications that can be directly integrated with hardware models for complete HW/SW co-simulation. In addition, to properly handle multitasking, an efficient OS model is devised to support accurate preemptive scheduling. Since both the generated application model and the OS model are constructed in SystemC modules, our approach avoids heavy intercommunication overheads and achieves over 1,000 times faster simulation than that of the conventional ISS-SystemC approach. Experimental results demonstrate that our extended SystemC approach can perform at 50 to 220 MIPS while offering accurate simulation results.
Optimized 3D Network-on-Chip Design Using Simulated Allocation
Authors: Zhou Pingqiang , Yuh Ping-Hung , Sapatnekar Sachin S.
Published: April 2012

Three-dimensional (3D) silicon integration technologies have provided new opportunities for Network-on-Chip (NoC) architecture design in Systems-on-Chip (SoCs). In this article, we consider the application-specific NoC architecture design problem in a 3D environment. We present an efficient floorplan-aware 3D NoC synthesis algorithm based on simulated allocation (SAL), a stochastic method for traffic flow routing, and accurate power and delay models for NoC components. We demonstrate that this method finds greatly improved solutions compared to a baseline algorithm reflecting prior work. To evaluate the SAL method, we compare its performance with the widely used simulated annealing (SA) method and show that SAL is much faster than SA for this application, while providing solutions of very similar quality. We then extend the approach from a single-path routing to a multipath routing scheme and explore the trade-off between power consumption and runtime for these two schemes. Finally, we study the impact of various factors on the network performance in 3D NoCs, including the TSV count and the number of 3D tiers. Our studies show that link power and delay can be significantly improved when moving from a 2D to a 3D implementation, but the improvement flattens out as the number of 3D tiers goes beyond a certain point.
Timing Analysis of System Initialization and Crash Recovery for a Segment-Based Flash Translation Layer
Authors: Wu Chin-Hsien , Lin Hsin-Hung
Published: April 2012

Recently, the capacity of flash-memory storage systems has grown rapidly, and flash-memory technology has advanced along with the wave of consumer electronics and embedded systems. In order to properly manage product cost and initialization performance, vendors face serious challenges in system design and analysis. Thus, the timing analysis of system initialization and crash recovery for a segment-based flash translation layer has become an important research topic. This article focuses on system initialization, crash recovery, and timing analysis. The timing analysis of system initialization involves the relationship between the size of the main memory and the system initialization time. The timing analysis of crash recovery explains the worst case recovery time. The experiments in this study show that the timing analysis of system initialization and crash recovery can be applied to the segment-based flash translation layer.
Timing Optimization in Sequential Circuit by Exploiting Clock-Gating Logic
Authors: Weng Shih-Hung , Kuo Yu-Min , Chang Shih-Chieh
Published: April 2012

Clock gating is a popular technique for reducing power dissipation. In a circuit with clock gating, the clock signal can be shut off without changing the functionality under certain clock-gating conditions. In this article, we observe that the clock-gating conditions and the next-state function of a Flip-Flop (FF) are correlated and can be used for sequential circuit optimization. We also show that the implementation of the next-state function of any FF can be just an inverter if the clock signal is appropriately gated. By exploiting the flexibility between the clock-gating conditions and the next-state function, we propose an iterative optimization algorithm to improve the timing of sequential circuits. We present experimental results of a set of benchmark circuits with a timing improvement of 10.20% on average.
The Curriculum Planning Process for Undergraduate Game Degree Programs in the United Kingdom and United States
Authors: McGill Monica M.
Published: April 2012

Digital games are marketed, mass-produced, and consumed by an increasing number of people and the game industry is only expected to grow. In response, postsecondary institutions in the UK and the U.S. have started to create game degree programs. Though curriculum theorists provide insight into the process of creating a new program, no formal research contextualizes curriculum planning for game degree programs. The purpose of this research was to explore these processes when planning undergraduate game degree programs. The research methodology included an explanatory mixed-methods approach, using a quantitative survey of participants in the UK and the U.S., followed by interviews with several participants selected on the basis of their institution’s demographics. Results indicate that five external factors influence the development of game programs (government, industry, other universities, society, and trade associations) and eight internal factors influence curriculum planning (facilities, faculty, institution, interdisciplinary collaboration, learners, learning time and space, originating department, and backgrounds of the planners). Results also indicate that while some differences exist in the game degree programs across countries, the vast majority of curriculum planning processes and influencing factors are the same. The study concludes with a set of recommendations for educators, trade associations, and the games industry to improve game degree programs.
Crossing the software education chasm
Authors: Fox Armando , Patterson David
Published: April 2012

An Agile approach that exploits cloud computing.
Comparative analysis of protein networks
Authors: Atias Nir , Sharan Roded
Published: April 2012

Examining tools that provide valuable insight about molecular components within a cell.
Moment distributions of phase-type (abstract only)
Authors: Bladt Mogens , Nielsen Bo Friis
Published: April 2012

Both matrix-exponential and phase-type distributions have a number of important closure properties. Among those are the distributions of the age and residual life-time of a stationary renewal process with inter-arrivals of either type. In this talk we show that the spread, which is the sum of the age an residual life-time, is also phase-type distributed. Moreover, we give some explicit representations. The spread is known to have a first order moment distribution. If X is a positive random variable and ?i is its i'th moment, then the function fi(x) = xif(x)/?i is a density function, and the corresponding distribution is called the i'th order moment distribution.

We prove that the classes of matrix-exponential or phase-type distributions are closed under the formation of moment distributions of any order. Other distributions which are closed under the formation of moment distributions are e.g. log-normal, Pareto and gamma distributions. We provide explicit representations for both the matrix-exponential class and for the phase-type distributions, where the latter class may also use the former representations, but for various reasons it is desirable to establish a phase-type representation when dealing with phase-type distributions.

For the first order distribution we present an explicit formula for the related Lorenz curve and Gini index. Moment distributions of orders one, two and three have been extensively used in areas such as economy, physics, demography and civil engineering.
Characterizing matrix-exponential distributions of order 4 (abstract only)
Authors: Fackrell Mark
Published: April 2012

The Laplace-Stieltjes transform of a matrix-exponential distribution is a rational function. If there are no common factors between the numerator and denominator polynomials, then the order of the matrix-exponential distribution is the degree of the denominator polynomial. Given a rational Laplace-Stieltjes transform, it is unknown, in general, when it corresponds to a matrix-exponential distribution. Matrix-exponential distributions of order 3 have been completely characterized in this manner, but in this talk we look at the problem of characterizing matrix-exponential distributions of order 4.
Two-dimensional fluid queues with temporary assistance (abstract only)
Authors: Latouche Guy , Nguyen Giang T. , Palmowski Zbigniew
Published: April 2012

We consider a two-dimensional stochastic fluid model with N ONOFF inputs and temporary assistance, which is an extension of the same model with N = 1 in Mahabhashyam et al. (2008). The rates of change of both buffers are piecewise constant and dependent on the underlying Markovian phase of the model, and the rates of change for Buffer 2 are also dependent on the specific level of Buffer 1. This is because both buffers share a fixed output capacity, the precise proportion of which depends on Buffer 1. The generalization of the number of ON-OFF inputs necessitates modifications in the original rules of output-capacity sharing from Mahabhashyam et al. (2008) and considerably complicates both the theoretical analysis and the numerical computation of various performance measures. We derive the marginal probability distribution of Buffer 1, and bounds for that of Buffer 2. Furthermore, restricting Buffer 1 to a finite size, we determine its marginal probability distribution in the specific case of N = 1, thus providing numerical comparisons to the corresponding results in Mahabhashyam et al. (2008) where Buffer 1 is assumed to be infinite.
An overview of multivariate gamma distributions as seen from a (multivariate) matrix exponential perspective
Authors: Bladt Mogens , Nielsen Bo Friis
Published: April 2012

Numerous definitions of multivariate exponential and gamma distributions can be retrieved from the literature [4]. These distribtuions belong to the class of Multivariate Matrix-- Exponetial Distributions (MVME) whenever their joint Laplace transform is a rational function. The majority of these distributions further belongs to an important subclass of MVME distributions [5, 1] where the multivariate random vector can be interpreted as a number of simultaneously collected rewards during sojourns in a the states of a Markov chain with one absorbing state, the rest of the states being transient. We present the corresponding representations for all such distributions. In this way we obtain a unification of the variety of existing distributions as well as a deeper understanding of their probabilistic nature and a clarification of their similarities and differences. In particular one may easily generalize or combine any of the known distributions by modifying the generators adequately. Also, it is straightforward to simulate from this class. Thus, by identifying distributions as belonging to this subclass it becomes apparent how to simulate from most previously discussed distributions with rational Laplace transform. In a longer perspective stochastic and statistical analysis for MVME will in particular apply to any of the previously defined distributions.

Multivariate gamma distributions have been used in a variety of fields like hydrology, [11], [10], [6], space (wind modeling) [9] reliability [3], [7], traffic modeling [8], and, finance [2]. It is our hope that our the paper will assist practitioners in formulating and analyzing models in a much more transparent and easily accessible way.
On the recent use of email through traffic and network analysis
Authors: Aceto Giuseppe , Pescapè Antonio
Published: April 2012

Since the late 1971 -- when Ray Tomlinson invented Internetbased email and sent the first message on ARPANET -- email technology has evolved a lot, and nowadays it is one of the most widely used applications on the Internet. Despite this primacy, during the last years other ways to exchange messages have been used by Internet users (e.g. Instant Messaging, Social Networks, microblogs, etc.). In this paper we propose a methodology based on heterogeneous data sources to analyze the amount of traffic associated with emails in order to gain knowledge on the use of email by Internet users in the last years. We consider real traffic traces that are well known to the research community as well as locally captured, and discuss them in the light of other related phenomena: social networks adoption, online advertising trends, abusive email spreads, etc..We discuss the trend of email traffic in the last 10 years and we provide explanations related to the impact, on the email usage, of the utilization of other communication platforms. This work represents a first step towards a framework in which to analyze the trend of the email traffic and the associated phenomena as well as the understanding of the upcoming novel communications behavior of Internet users.
Highlights from ACM SIGSPATIAL GIS 2011: the 19th ACM SIGSPATIAL International Conference on Advances in Geographic Information Systems
Authors: Jensen Christian S. , Ofek Eyal , Tanin Egemen
Published: April 2012

ACM SIGSPATIAL GIS 2011 was the 19th gathering of the premier event on spatial information and Geographic Information Systems (GIS). It is also the fourth year that the conference was held under the auspices of ACM's most recent special interest group, SIGSPATIAL. Since its start in 1993, the conference has targeted researchers, developers, and users whose work relates to spatial information and GIS, and it has a tradition of interdisciplinary discussions and presentations. It provides a forum for original research contributions that cover conceptual, design, and implementation aspects of spatial information systems and GIS.
SPRINGL 2011 Workshop Report: the Fourth ACM SIGSPATIAL International Workshop on Security and Privacy in GIS and LBS
Authors: Ghinita Gabriel
Published: April 2012

The ACM SIGSPATIAL International Workshop on Security and Privacy in GIS (SPRINGL) has reached its fourth edition on November 1st, 2011. Held in the opening of the ACM SIGSPATIAL GIS conference in Chicago, Illinois, the one-day SPRINGL'11 event has brought together academia and industry researchers from US, Europe and the Asia-Pacific region. Similar to previous years, the main workshop themes were privacy-preserving sharing of geo-spatial data and location-based access control. It is noteworthy that this edition saw an increasing number of presentations and discussions related to the issue of location security and privacy in social networks, which was dedicated an entire session this year.
Relyzer
Authors: Hari Siva Kumar Sastry , Adve Sarita V. , Naeimi Helia , Ramachandran Pradeep
Published: April 2012

Future microprocessors need low-cost solutions for reliable operation in the presence of failure-prone devices. A promising approach is to detect hardware faults by deploying low-cost monitors of software-level symptoms of such faults. Recently, researchers have shown these mechanisms work well, but there remains a non-negligible risk that several faults may escape the symptom detectors and result in silent data corruptions (SDCs). Most prior evaluations of symptom-based detectors perform fault injection campaigns on application benchmarks, where each run simulates the impact of a fault injected at a hardware site at a certain point in the application's execution (application fault site). Since the total number of application fault sites is very large (trillions for standard benchmark suites), it is not feasible to study all possible faults. Previous work therefore typically studies a randomly selected sample of faults. Such studies do not provide any feedback on the portions of the application where faults were not injected. Some of those instructions may be vulnerable to SDCs, and identifying them could allow protecting them through other means if needed.

This paper presents Relyzer, an approach that systematically analyzes all application fault sites and carefully picks a small subset to perform selective fault injections for transient faults. Relyzer employs novel fault pruning techniques that prune faults that need detailed study by either predicting their outcomes or showing them equivalent to other faults. We find that Relyzer prunes about 99.78% of the total faults across twelve applications studied here, reducing the faults that require detailed simulation by 3 to 5 orders of magnitude for most of the applications. Fault injection simulations on the remaining faults can identify SDC causing faults in the entire application. Some of Relyzer's techniques rely on heuristics to determine fault equivalence. Our validation efforts show that Relyzer determines fault outcomes with 96% accuracy, averaged across all the applications studied here.
Aikido
Authors: Olszewski Marek , Zhao Qin , Koh David , Ansel Jason , Amarasinghe Saman
Published: April 2012

Despite a burgeoning demand for parallel programs, the tools available to developers working on shared-memory multicore processors have lagged behind. One reason for this is the lack of hardware support for inspecting the complex behavior of these parallel programs. Inter-thread communication, which must be instrumented for many types of analyses, may occur with any memory operation. To detect such thread communication in software, many existing tools require the instrumentation of all memory operations, which leads to significant performance overheads. To reduce this overhead, some existing tools resort to random sampling of memory operations, which introduces false negatives. Unfortunately, neither of these approaches provide the speed and accuracy programmers have traditionally expected from their tools. In this work, we present Aikido, a new system and framework that enables the development of efficient and transparent analyses that operate on shared data. Aikido uses a hybrid of existing hardware features and dynamic binary rewriting to detect thread communication with low overhead. Aikido runs a custom hypervisor below the operating system, which exposes per-thread hardware protection mechanisms not available in any widely used operating system. This hybrid approach allows us to benefit from the low cost of detecting memory accesses with hardware, while maintaining the word-level accuracy of a software-only approach. To evaluate our framework, we have implemented an Aikido-enabled vector clock race detector. Our results show that the Aikido enabled race-detector outperforms existing techniques that provide similar accuracy by up to 6.0x, and 76% on average, on the PARSEC benchmark suite.
Green-Marl
Authors: Hong Sungpack , Chafi Hassan , Sedlar Edic , Olukotun Kunle
Published: April 2012

The increasing importance of graph-data based applications is fueling the need for highly efficient and parallel implementations of graph analysis software. In this paper we describe Green-Marl, a domain-specific language (DSL) whose high level language constructs allow developers to describe their graph analysis algorithms intuitively, but expose the data-level parallelism inherent in the algorithms. We also present our Green-Marl compiler which translates high-level algorithmic description written in Green-Marl into an efficient C++ implementation by exploiting this exposed data-level parallelism. Furthermore, our Green-Marl compiler applies a set of optimizations that take advantage of the high-level semantic knowledge encoded in the Green-Marl DSL. We demonstrate that graph analysis algorithms can be written very intuitively with Green-Marl through some examples, and our experimental results show that the compiler-generated implementation out of such descriptions performs as well as or better than highly-tuned hand-coded implementations.
Health Status and Patient Satisfaction after Corneal Graft: Results from the Corneal Transplant Epidemiological Study
Authors: Fasolo Adriano , Capuzzo Cristina , Fornea Michela , Frigo Anna Chiara , Monterosso Cristina , Zampini Alfonso , Avarello Antonio , Galan Alessandro , Sbordone Sandro , Ragucci Adele Elisabetta , Gorla Claudio , Grigoletto Francesco , Ponzin Diego
Published: April 2012

Purpose. To evaluate effects of corneal transplantation on the health-related quality of life and patients’ satisfaction.Methods. Patients scheduled for elective penetrating or anterior lamellar keratoplasty completed by telephone interview the SF-12 Health Survey, before and one year after surgery, and a 6-item questionnaire on the satisfaction for graft outcomes.Results. The two questionnaires were answered by 1,223 patients. Transplantation did not influence the PCS-12 in males (ES=−0.01) and had a negative effect in females (ES=−0.18). Both sexes improved their MCS-12 (ES=0.18and 0.23, resp.). The majority of patients (83.1%) were satisfied by the outcome of the graft.Conclusions. This is the first report on the use of the SF-12 and one of the few that assess quality of life in patients after corneal transplantation. We showed that grafting improves patients' health-related quality of life results of patients, influencing mental health (i.e., psychological attitude, social interaction, and emotions) with minor effects on physical health (limitation, pain, and vitality).
Development of an IgG4-RD Responder Index
Authors: Carruthers Mollie N. , Stone John H. , Deshpande Vikram , Khosroshahi Arezou
Published: April 2012

IgG4-related disease (IgG4-RD) is a multiorgan inflammatory disease in which diverse organ manifestations are linked by common histopathological and immunohistochemical features. Prospective studies of IgG4-RD patients are required to clarify the natural history, long-term prognosis, and treatment approaches in this recently recognized condition. Patients with IgG4-RD have different organ manifestations and are followed by multiple specialties. Divergent approaches to the assessment of patients can complicate the interpretation of studies, emphasizing the critical need for validated outcome measures, particularly assessments of disease activity and response to treatment. We developed a prototype IgG4-RD Responder Index (IgG4-RD RI) based on the approach used in the development of the Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG). The IgG4-RD RI was refined by members of the International IgG4-RD Symposium Organizing Committee in a paper case exercise. The revised instrument was applied retrospectively to fifteen IgG4-RD patients at our institution. Those scores were compared to physician’s global assessment scale for the same visits. This paper describes the philosophy and goals of the IgG4-RD RI, the steps in the development of this instrument to date, and future plans for validation of this instrument as an outcome measure.
The Current Role of Androgen Deprivation in Patients Undergoing Dose-Escalated External Beam Radiation Therapy for Clinically Localized Prostate Cancer
Authors: Smith Michael J. , Akhtar Naveed H. , Tagawa Scott T.
Published: April 2012

Purpose. To review existing literature on the role of androgen deprivation therapy (ADT) with dose escalated radiation therapy.Methods and Materials. A PubMed search was undertaken to identify relevant articles.Results. Multiple recent studies were identified examining the role of ADT in the current era of radiation dose-escalation. Among the reviewed studies, varying radiation doses and techniques, ADT regimens, and patient selection criteria were utilized. Conflicting results were reported, with some studies demonstrating a benefit of delivering a higher radiation dose with ADT. Other studies failed to show significant benefits with the addition of ADT to dose-escalated RT.Conclusions. The benefit of adding ADT to dose-escalated RT is still uncertain. Prospective randomized trials, several of which are ongoing, are necessary to more adequately examine this issue. In the interim, physicians and patients should continue to utilize the existing data to weigh the risks and benefits of each approach to therapy.
A Micro-RNA Connection inBRafV600E-Mediated Premature Senescence of Human Melanocytes
Authors: Ren Gang , Feng Jingwei , Datar Ila , Yeung Aaron H. , Saladi Srinivas Vinod , Feng Yongqing , de la Serna Ivana , Yeung Kam C.
Published: April 2012

Recent high-throughput-sequencing of the cancer genome has identified oncogenic mutations inBRafgenetic locus as one of the critical events in melanomagenesis. In normal cells, the activity ofBRafis tightly regulated. Gain-of-function mutations like those identified in melanoma frequently lead to enhanced cell-survival and unrestrained growth. The activating mutation ofBRafwill also induce the cells to senesce. However, the mechanism by which the oncogenicBRafinduces the senescent barrier remains poorly defined. microRNAs have regulatory functions toward the expression of genes that are important in carcinogenesis. Here we show that expression of several microRNAs is altered when the oncogenic version ofBRafis introduced in cultured primary melanocytes and these cells undergo premature cellular senescence. These include eight microRNAs whose expression rates are significantly stimulated and three that are repressed. While most of the induced microRNAs have documented negative effects on cell cycle progression, one of the repressed microRNAs has proven oncogenic functions. Ectopic expression of some of these induced microRNAs increased the expression of senescence markers and induced growth arrest and senescence in primary melanocytes. Taken together, our results suggest that the change in microRNA expression rates may play a vital role in senescence induced by the oncogenicBRaf.
Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition) onAulacomya ater(Molina, 1782) (Bivalvia: Mytilidae) as a Criteria for Effects of Organophosphate Pesticide Exposition
Authors: Führer Eduardo , Rudolph Anny , Espinoza Claudio , Díaz Rodrigo , Gajardo Marisol , Camaño Nuria
Published: April 2012

The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E) on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the musselAulacomya aterwas analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L-1(LC50-96 hours). Concentrations between 0.2 and 1.61 μg L-1were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L-1stimulate ammonia excretion and decrease oxygen : ammonia-N (O : N) ratio, with respect to the control group.A. aterproved to be a species sensitive to pesticide exposure and easy to handle in lab conditions. Thus, it is recommended as a bioindicator for use in programs of environmental alertness in the Eastern South Pacific coastal zone.
Mcl-1 Phosphorylation Defines ABT-737 Resistance That Can Be Overcome by Increased NOXA Expression in Leukemic B cells
Authors: Mazumder Suparna , Choudhary Gaurav S. , Al-harbi Sayer , Almasan Alexandru
Published: April 2012

ABT-737 is a small molecule Bcl-2 homology (BH)-3 domain mimetic that binds to the Bcl-2 family proteins Bcl-2 and Bcl-xL and is currently under investigation in the clinic. In this study, we investigated potential mechanisms of resistance to ABT-737 in leukemia cell lines. Compared with parental cells, cells that have developed acquired resistance to ABT-737 showed increased expression of Mcl-1 in addition to posttranslational modifications that facilitated both Mcl-1 stabilization and its interaction with the BH3-only protein Bim. To sensitize resistant cells, Mcl-1 was targeted by two pan–Bcl-2 family inhibitors, obatoclax and gossypol. Although gossypol was effective only in resistant cells, obatoclax induced cell death in both parental and ABT-737–resistant cells. NOXA levels were increased substantially by treatment with gossypol and its expression was critical for the gossypol response. Mechanistically, the newly generated NOXA interacted with Mcl-1 and displaced Bim from the Mcl-1/Bim complex, freeing Bim to trigger the mitochondrial apoptotic pathway. Together, our findings indicate that NOXA and Mcl-1 are critical determinants for gossypol-mediated cell death in ABT-737–resistant cells. These data therefore reveal novel insight into mechanisms of acquired resistance to ABT-737. Cancer Res; 72(12); 3069–79. ©2012 AACR.
Feasibility and Reproducibility of Fetal Lung Texture Analysis by Automatic Quantitative Ultrasound Analysis and Correlation with Gestational Age
Authors: Cobo Teresa , Bonet-Carne Elisenda , Martínez-Terrón Mónica , Perez-Moreno Alvaro , Elías Núria , Luque Jordi , Amat-Roldan Ivan , Palacio Montse
Published: April 2012

Objective: To evaluate the feasibility and reproducibility of fetal lung texture analysis using a novel automatic quantitative ultrasound analysis and to assess its correlation with gestational age. Methods: Prospective cross-sectional observational study. To evaluate texture features, 957 left and right lung images in a 2D four-cardiac-chamber view plane were previously delineated from fetuses between 20 and 41 weeks of gestation. Quantification of lung texture was performed by the Automatic Quantitative Ultrasound Analysis (AQUA) software to extract image features. A standard learning approach composed of feature transformation and a regression model was used to evaluate the association between texture features and gestational age. Results: The association between weeks of gestation and fetal lung texture quantified by the AQUA software presented a Pearson correlation of 0.97. The association was not influenced by delineation parameters such as region of interest (ROI) localization, ROI size, right/left lung selected or sonographic parameters such as ultrasound equipment or transducer used. Conclusions: Fetal lung texture analysis measured by the AQUA software demonstrated a strong correlation with gestational age. This supports further research to explore the use of this technology to the noninvasive prediction of fetal lung maturity.
Extragenital Endometrial Stromal Sarcoma Arising in Endometriosis
Authors: Alcázar Juan Luis , Guerriero Stefano , Ajossa Silvia , Parodo Giuseppina , Piras Bruno , Peiretti Michele , Jurado Matías , Idoate Miguel Ángel
Published: April 2012

The diagnosis rate of deep pelvic endometriosis is increasing. Endometrial stromal sarcoma (ESS) is a rare neoplasm. Extragenital ESS is an extremely uncommon event. Very few cases of extragenital ESS have been reported to date. The diagnosis of this entity is very difficult in some instances. Knowledge about its management is also limited. In this paper, we review the current literature on the clinical management, histology, immunohistochemistry, treatment and outcome of ESS arising in pelvic endometriosis.
Prevalence of Dementia and Mild Cognitive Impairment in the Rural Island Town of Ama-cho, Japan
Authors: Wada-Isoe Kenji , Uemura Yusuke , Nakashita Satoko , Yamawaki Mika , Tanaka Kenichiro , Yamamoto Mikie , Shimokata Hiroshi , Nakashima Kenji
Published: April 2012

Aims: In order to determine the prevalence of dementia and mild cognitive impairment (MCI), we conducted a population-based study in Japan. Methods: Participants included 924 subjects aged 65 years or older who resided in the town of Ama-cho. In phase 1 of the study, the Mini-Mental State Examination and Clinical Dementia Rating were administered for screening purposes. In phase 2 of the study, the subjects who screened positive were further examined by neurologists. Dementia and MCI were diagnosed by means of DSM-IV and International Working Group on MCI criteria, respectively. Results: By the prevalence date of June 1, 2010, 24 subjects had deceased or lived outside the town. In total, 723 of the remaining 900 subjects received a phase 1 test. In phase 2, 98 subjects were diagnosed with amnestic MCI, 113 subjects with non-amnestic MCI, and 82 subjects with dementia. Of the subjects who did not receive the phase 1 test, 66 subjects were diagnosed as having dementia according to data from their town medical card or the Long-term Care Insurance System. The crude prevalence of amnestic MCI, non-amnestic MCI, and dementia were 10.9, 12.6, and 16.4%, respectively. Conclusion: Consistent with the striking increase in the number of elderly individuals, we report higher prevalence of MCI and dementia in Japan than previously described.
Membrane Estrogen Receptor Regulation of Hypothalamic Function
Authors: Micevych Paul E. , Kelly Martin J.
Published: April 2012

Over the decades, our understanding of estrogen receptor (ER) function has evolved. Today we are confronted by at least two nuclear ERs, ERα and ERβ, and a number of putative membrane ERs, including ERα, ERβ, ER-X, GPR30 and Gq-mER. These receptors all bind estrogens or at least estrogenic compounds and activate intracellular signaling pathways. In some cases, a well-defined pharmacology and physiology has been discovered. In other cases, the identity or the function remains to be elucidated. This mini-review attempts to synthesize our understanding of 17β-estradiol membrane signaling within hypothalamic circuits involved in homeostatic functions, focusing on reproduction and energy balance.
Neuroprotection and Estrogen Receptors
Authors: Simpkins James W. , Singh Meharvan , Brock Courtney , Etgen Anne M.
Published: April 2012

This review is intended to assess the state of current knowledge on the role of estrogen receptors (ERs) in the neuroprotective effects of estrogens in models for acute neuronal injury and death. We evaluate the overall evidence that estrogens are neuroprotective in acute injury and critically assess the role of ERα, ERβ, GPR 30, and nonreceptor-mediated mechanisms in these robust neuroprotective effects of this ovarian steroid hormone. We conclude that all three receptors, as well as nonreceptor-mediated mechanisms can be involved in neuroprotection, depending on the model used, the level of estrogen administrated, and the mode of administration of the steroid. Also, the signaling pathways used by both ER-dependent and ER-independent mechanisms to exert neuroprotection are considered. Finally, further studies that are needed to parse out the relative contribution of receptor versus nonreceptor-mediated signaling are discussed.
Blood Pressure Change in Normotensive, Gestational Hypertensive, Preeclamptic, and Essential Hypertensive Pregnancies
Authors: Macdonald-Wallis Corrie , Lawlor Debbie A. , Fraser Abigail , May Margaret , Nelson Scott M. , Tilling Kate
Published: April 2012

We compared patterns of blood pressure (BP) change among normotensive women, women who developed gestational hypertension or preeclampsia, and women who had essential hypertension to examine how distinct these conditions are and whether rates of BP change may help to identify women at risk for hypertensive disorders. We used antenatal clinic BP measurements (median, 14 per woman) of 13016 women from the Avon Longitudinal Study of Parents and Children who had a singleton or twin live birth surviving until ≥1 year. Linear spline models were used to describe changes in systolic and diastolic BPs in different periods of pregnancy (8–18, 18–30, 30–36, and ≥36 weeks' gestation). Women who had essential hypertension and those who developed gestational hypertension or preeclampsia had higher BP at 8 weeks' gestation (baseline) compared with normotensive women. The decrease in BP until 18 weeks was smaller in gestational hypertensive compared with normotensive pregnancies. BP rose more rapidly from 18 weeks onward in gestational hypertensive and preeclamptic pregnancies and from 30 weeks onward in essential hypertensive compared with normotensive pregnancies. Women who developed preeclampsia had a more rapid increase in BP from 30 weeks onward than those who developed gestational hypertension or had essential hypertension. Our findings indicate notable patterns of BP change that distinguish women with essential hypertension, gestational hypertension, and preeclampsia from each other and from normotensive women, even from early pregnancy. These distinct patterns may be useful for identifying women at risk of developing a hypertensive disorder later in pregnancy.
Psychiatric diagnoses are not mental processes: Wittgenstein on conceptual confusion
Authors: Rosenman Stephen , Nasti Julian
Published: April 2012

Background:

Empirical explanation and treatment repeatedly fail for psychiatric diagnoses. Diagnosis is mired in conceptual confusion that is illuminated by Ludwig Wittgenstein’s later critique of philosophy ( Philosophical Investigations). This paper examines conceptual confusions in the foundation of psychiatric diagnosis from some of Wittgenstein’s important critical viewpoints.

Argument:

Diagnostic terms are words whose meanings are given by usages not definitions. Diagnoses, by Wittgenstein’s analogy with ‘games’, have various and evolving usages that are connected by family relationships, and no essence or core phenomenon connects them. Their usages will change according to the demands and contexts in which they are employed. Diagnoses, like many psychological terms, such as ‘reading’ or ‘understanding’, are concepts that refer not to fixed behavioural or mental states but to complex apprehensions of the relationship of a variety of behavioural phenomena with the world. A diagnosis is a sort of concept that cannot be located in or explained by a mental process.

Conclusion:

A diagnosis is an exercise in language and its usage changes according to the context and the needs it addresses. Diagnoses have important uses but they are irreducibly heterogeneous and cannot be identified with or connected to particular mental processes or even with a unity of phenomena that can be addressed empirically. This makes understandable not only the repeated failure of empirical science to replicate or illuminate genetic, neurophysiologic, psychic or social processes underlying diagnoses but also the emptiness of a succession of explanatory theories and treatment effects that cannot be repeated or stubbornly regress to the mean. Attempts to fix the meanings of diagnoses to allow empirical explanation will and should fail as there is no foundation on which a fixed meaning can be built and it can only be done at the cost of the relevance and usefulness of diagnosis.
Contextual Influences on Faculty Diversity Conceptualizations When Working With Trainee Competence Problems
Authors: Shen-Miller David S. , Forrest Linda , Burt Michelle
Published: April 2012

Trainees with problems of professional competence (TPPC) present trainers with unique challenges. When TPPC situations include diversity issues, the complexity of such challenges increases. Although attention to such intersections is important, little is known about what influences faculty thinking about diversity issues when trainee competence problems are identified. The authors analyzed 22 faculty interviews using grounded theory to explore contextual influences on faculty interactions. Participants described program commitments to diversity conversations, consultations, and examination of biases as important positive influences. Participants described historic conflicts (e.g., interpersonal and programwide) and within-faculty differences (e.g., differences in multicultural training, assumptions about diversity-related conflict) that made faculty interactions more difficult. New instances of competence problems that involved differences in opinion about the influence of diversity variables exacerbated existing conflicts and created new tensions among faculty. Implications for training and research are discussed.