bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonsense but not missense mutations can decrease the abundance of nuclear mRNA for the mouse major urinary protein, while both types of mutations can facilitate exon skipping.
Authors: Belgrader P , Maquat L E
Published: January 2012

In an effort to understand the mechanisms by which nonsense codons affect RNA metabolism in mammalian cells, nonsense mutations were generated within the gene for the secretory major urinary protein (MUP) of mice. The translation of MUP mRNA normally begins within exon 1 and terminates within exon 6, the penultimate exon. Through the use of Northern (RNA) blot hybridization and assays that couple reverse transcription and PCR, a nonsense mutation within codon 50 of exon 2 or codon 143 of exon 5 was found to reduce the abundance of fully spliced, nuclear MUP mRNA to 10 to 20% of normal without an additional reduction in the abundance of cytoplasmic mRNA. In contrast, a nonsense mutation within codon 172 of exon 5 was found to have no effects on the abundance of MUP mRNA. These findings suggest that a boundary between nonsense mutations that do and do not reduce the abundance of nuclear mRNA exists within the exon preceding the exon that harbors the normal site of translation termination. In this way, the boundary is analogous to the boundary that exists within the penultimate exon of the human gene for the cytosolic enzyme triosephosphate isomerase. Assays for exon skipping, i.e., the removal of an exon as a part of the flanking introns during the process of splicing, reveal that 0.1, 2.0, and 0.1% of MUP mRNA normally lack exon 5, exon 6, and exons 5 plus 6, respectively. Relative to normal, the two nonsense mutations within exon 5 increase the abundance of RNA lacking exon 5 on average 20-fold and increase the abundance of RNA lacking exons 5 plus 6 on average 5-fold. Since only one of these nonsense mutations also reduces the abundance of fully spliced nuclear mRNA to 10 to 20% of normal, the two mechanisms by which a nonsense mutation can alter nuclear RNA metabolism must be distinct. The analysis of missense mutations within codons 143 and 172, some of which retain the nonsense mutation, indicates that the reduction in the abundance of fully spliced nuclear mRNA is dependent upon the premature termination of MUP mRNA translation, whereas skipping is attributable to nonsense mutation-mediated changes in exon 5 structure rather than to the premature termination of translation. The increase in exon 5 skipping by either the nonsense or missense mutations within codon 172 correlates with a decrease in the complementarity of exon 5 to U1 snRNA. This suggests that a 5' splice site may extend as far as 12 nucleotides into the upstream exon, which is, to our knowledge, the largest extension.
Interactions between highly conserved U2 small nuclear RNA structures and Prp5p, Prp9p, Prp11p, and Prp21p proteins are required to ensure integrity of the U2 small nuclear ribonucleoprotein in Saccharomyces cerevisiae.
Authors: Wells S E , Ares M
Published: January 2012

Binding of U2 small nuclear ribonucleoprotein (snRNP) to the pre-mRNA is an early and important step in spliceosome assembly. We searched for evidence of cooperative function between yeast U2 small nuclear RNA (snRNA) and several genetically identified splicing (Prp) proteins required for the first chemical step of splicing, using the phenotype of synthetic lethality. We constructed yeast strains with pairwise combinations of 28 different U2 alleles with 10 prp mutations and found lethal double-mutant combinations with prp5, -9, -11, and -21 but not with prp3, -4, -8, or -19. Many U2 mutations in highly conserved or invariant RNA structures show no phenotype in a wild-type PRP background but render mutant prp strains inviable, suggesting that the conserved but dispensable U2 elements are essential for efficient cooperative function with specific Prp proteins. Mutant U2 snRNA fails to accumulate in synthetic lethal strains, demonstrating that interaction between U2 RNA and these four Prp proteins contributes to U2 snRNP assembly or stability. Three of the proteins (Prp9p, Prp11p, and Prp21p) are associated with each other and pre-mRNA in U2-dependent splicing complexes in vitro and bind specifically to synthetic U2 snRNA added to crude splicing extracts depleted of endogenous U2 snRNPs. Taken together, the results suggest that Prp9p, -11p, and -21p are U2 snRNP proteins that interact with a structured region including U2 stem loop IIa and mediate the association of the U2 snRNP with pre-mRNA.
Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn.
Authors: Panchamoorthy G , Fukazawa T , Stolz L , Payne G , Reedquist K , Shoelson S , Songyang Z , Cantley L , Walsh C , Band H
Published: January 2012

The Src family protein tyrosine kinases participate in signalling through cell surface receptors that lack intrinsic tyrosine kinase domains. All nine members of this family possess adjacent Src homology (SH2 and SH3) domains, both of which are essential for repression of the enzymatic activity. The repression is mediated by binding between the SH2 domain and a C-terminal phosphotyrosine, and the SH3 domain is required for this interaction. However, the biochemical basis of functional SH2-SH3 interaction is unclear. Here, we demonstrate that when the SH2 and SH3 domains of p59fyn (Fyn) were present as adjacent domains in a single protein, binding of phosphotyrosyl peptides and proteins to the SH2 domain was enhanced, whereas binding of a subset of cellular polypeptide ligands to the SH3 domain was decreased. An interdomain communication was further revealed by occupancy with domain-specific peptide ligands: occupancy of the SH3 domain with a proline-rich peptide enhanced phosphotyrosine binding to the linked SH2 domain, and occupancy of the SH2 domain with phosphotyrosyl peptides enhanced binding of certain SH3-specific cellular polypeptides. Second, we demonstrate a direct binding between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. Heterologous binding between SH2 and SH3 domains of closely related members of the Src family, namely, Fyn, Lck, and Src, was also observed. In contrast, Grb2, Crk, Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 domains showed lower or no binding to Fyn or Lck SH3 domains. SH2-SH3 binding did not require an intact phosphotyrosine binding pocket on the SH2 domain; however, perturbations of the SH2 domain induced by specific high-affinity phosphotyrosyl peptide binding abrogated binding of the SH3 domain. SH3-SH2 binding was observed in the presence of proline-rich peptides or when a point mutation (W119K) was introduced in the putative ligand-binding pouch of the Fyn SH3 domain, although these treatments completely abolished the binding to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. These biochemical SH2-SH3 interactions suggest novel mechanisms of regulating the enzymatic activity of Src kinases and their interactions with other proteins.
Adaptive Uncertainty Resolution in Bayesian Combinatorial Optimization Problems
Authors: Guha Sudipto , Munagala Kamesh
Published: January 2012

In several applications such as databases, planning, and sensor networks, parameters such as selectivity, load, or sensed values are known only with some associated uncertainty. The performance of such a system (as captured by some objective function over the parameters) is significantly improved if some of these parameters can be probed or observed. In a resource constrained situation, deciding which parameters to observe in order to optimize system performance, itself becomes an interesting and important optimization problem. This general problem is the focus of this article.

One of the most important considerations in this framework is whether adaptivity is required for the observations. Adaptive observations introduce blocking or sequential operations in the system whereas nonadaptive observations can be performed in parallel. One of the important questions in this regard is to characterize the benefit of adaptivity for probes and observation.

We present general techniques for designing constant factor approximations to the optimal observation schemes for several widely used scheduling and metric objective functions. We show a unifying technique that relates this optimization problem to the outlier version of the corresponding deterministic optimization. By making this connection, our technique shows constant factor upper bounds for the benefit of adaptivity of the observation schemes. We show that while probing yields significant improvement in the objective function, being adaptive about the probing is not beneficial beyond constant factors.
Online Optimization with Uncertain Information
Authors: Mahdian Mohammad , Nazerzadeh Hamid , Saberi Amin
Published: January 2012

We introduce a new framework for designing online algorithms that can incorporate additional information about the input sequence, while maintaining a reasonable competitive ratio if the additional information is incorrect. Within this framework, we present online algorithms for several problems including allocation of online advertisement space, load balancing, and facility location.
Adversarial Queuing on the Multiple Access Channel
Authors: Chlebus Bogdan S. , Kowalski Dariusz R. , Rokicki Mariusz A.
Published: January 2012

We study deterministic broadcasting on multiple access channels when packets are injected continuously. The quality of service is considered in the framework of adversarial queuing. An adversary is determined by injection rate and burstiness, the latter denoting the number of packets that can be injected simultaneously in a round. We consider only injection rates that are less than 1. A protocol is stable when the numbers of packets in queues stay bounded at all rounds, and it is of fair latency when waiting times of packets in queues are
O
(burstiness/rate). For channels with collision detection, we give a full-sensing protocol of fair latency for injection rates that are at most 1 2(⌈lg
n
⌉ + 1), where
n
is the number of stations, and show that fair latency is impossible to achieve for injection rates that are
ω
(1 log
n
). For channels without collision detection, we present a full-sensing protocol of fair latency for injection rates that are at most 1
c
lg
2
n
, for some
c
> 0. We show that there exists an acknowledgment-based protocol that has fair latency for injection rates that are at most 1
cn
lg
2
n
, for some
c
> 0, and develop an explicit acknowledgment-based protocol of fair latency for injection rates that are at most 1 27
n
2
ln
n
. Regarding impossibility to achieve just stability by restricted protocols, we prove that no acknowledgment-based protocol can be stable for injection rates larger than 3 1 + lg
n
.
Iterative Expansion and Color Coding
Authors: Chen Jianer , Liu Yang , Lu Songjian , Sze Sing-Hoi , Zhang Fenghui
Published: January 2012

The research in the parameterized
3d-matching
problem has yielded a number of new algorithmic techniques and an impressive list of improved algorithms. In this article, a new deterministic algorithm for the problem is developed that integrates and improves a number of known techniques, including greedy localization, dynamic programming, and color coding. The new algorithm, which either constructs a matching of
k
triples in a given triple set or correctly reports that no such a matching exists, runs in time
O
*
(2.80
3
k
), improving a long list of previous algorithms for the problem.
Improved Fixed-Parameter Algorithms for Minimum-Flip Consensus Trees
Authors: Böcker Sebastian , Bui Quang Bao Anh , Truss Anke
Published: January 2012

In computational phylogenetics, the problem of constructing a consensus tree for a given set of rooted input trees has frequently been addressed. In this article we study the
Minimum-Flip Problem
: the input trees are transformed into a binary matrix, and we want to find a perfect phylogeny for this matrix using a minimum number of flips, that is, corrections of single entries in the matrix. The graph-theoretical formulation of the problem is as follows: Given a bipartite graph
G
= (
Vt
∪
Vc
,
E
), the task is to find a minimum set of edge modifications such that the resulting graph has no induced path with four edges that starts and ends in
Vt
, where
Vt
corresponds to the taxa set and
Vc
corresponds to the character set.

We present two fixed-parameter algorithms for the
Minimum-Flip Problem
, one with running time
O
(4.83
k
+
poly
(
m
,
n
)) and another one with running time
O
(4.42
k
+
poly
(
m
,
n
)) for
n
taxa,
m
characters,
k
flips, and
poly
(
m
,
n
) denotes a polynomial function in
m
and
n
. Additionally, we discuss several heuristic improvements. We also report computational results on phylogenetic data.
Researchers' big data crisis; understanding design and functionality
Authors: Stonebraker Michael , Hong Jason
Published: January 2012

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Michael Stonebraker issues a call to arms about research groups' data-management problems. Jason Hong discusses the nature of functionality with respect to design
.
Peer instruction
Authors: Simon Beth , Cutts Quintin
Published: January 2012

How the computing education community can learn from physics education.
BufferBloat
Authors: CACM Staff
Published: January 2012

A discussion with Vint Cerf, Van Jacobson, Nick Weaver, and Jim Gettys.
Progress and challenges in intelligent vehicle area networks
Authors: Faezipour Miad , Nourani Mehrdad , Saeed Adnan , Addepalli Sateesh
Published: January 2012

Vehicle area networks form the backbone of future intelligent transportation systems.
Software synthesis procedures
Authors: Kuncak Viktor , Mayer Mikaël , Piskac Ruzica , Suter Philippe
Published: January 2012

Automated synthesis of program fragments from specifications can make programs easier to write and easier to reason about. To integrate synthesis into programming languages, software synthesis algorithms should behave in a predictable way: they should succeed for a well-defined class of specifications. We propose to systematically generalize decision procedures into
synthesis procedures
, and use them to compile implicitly specified computations embedded inside functional and imperative programs. Synthesis procedures are predictable, because they are guaranteed to find code that satisfies the specification whenever such code exists. To illustrate our method, we derive synthesis procedures by extending quantifier elimination algorithms for integer arithmetic and set data structures. We then show that an implementation of such synthesis procedures can extend a compiler to support implicit value definitions and advanced pattern matching.
Approximate graph clustering for program characterization
Authors: Demme John , Sethumadhavan Simha
Published: January 2012

An important aspect of system optimization research is the discovery of program traits or behaviors. In this paper, we present an automated method of program characterization which is able to examine and cluster program graphs, i.e., dynamic data graphs or control flow graphs. Our novel approximate graph clustering technology allows users to find groups of program fragments which contain similar code idioms or patterns in data reuse, control flow, and context. Patterns of this nature have several potential applications including development of new static or dynamic optimizations to be implemented in software or in hardware.

For the SPEC CPU 2006 suite of benchmarks, our results show that approximate graph clustering is effective at grouping behaviorally similar functions. Graph based clustering also produces clusters that are more homogeneous than previously proposed non-graph based clustering methods. Further qualitative analysis of the clustered functions shows that our approach is also able to identify some frequent unexploited program behaviors. These results suggest that our approximate graph clustering methods could be very useful for program characterization.
Compiler mitigations for time attacks on modern x86 processors
Authors: Cleemput Jeroen V. , Coppens Bart , De Sutter Bjorn
Published: January 2012

This paper studies and evaluates the extent to which automated compiler techniques can defend against timing-based side channel attacks on modern x86 processors. We study how modern x86 processors can leak timing information through side channels that relate to data flow. We study the efficiency, effectiveness, portability, predictability and sensitivity of several mitigating code transformations that eliminate or minimize key-dependent execution time variations. Furthermore, we discuss the extent to which compiler backends are a suitable tool to provide automated support for the proposed mitigations.
Hardware transactional memory with software-defined conflicts
Authors: Titos-Gil Ruben , Acacio Manuel E. , Garcia Jose M. , Harris Tim , Cristal Adrian , Unsal Osman , Hur Ibrahim , Valero Mateo
Published: January 2012

In this paper we investigate the benefits of turning the concept of transactional conflict from its traditionally fixed definition into a variable one that can be dynamically controlled in software. We propose the extension of the
atomic
language construct with an attribute that specifies the definition of conflict, so that programmers can write code which adjusts what kinds of conflicts are to be detected, relaxing or tightening the conditions according to the forms of interference that can be tolerated by a particular algorithm. Using this performance-motivated construct, specific conflict information can be associated with portions of code, as each transaction is provided with a local definition that applies while it executes. We find that defining conflicts in software makes possible the removal of dependencies which arise as a result of the coarse synchronization style encouraged by the TM programming model. We illustrate the use of the proposed construct in a variety of use cases with real applications, showing how programmers can take advantage of their knowledge about the problem and other global information not available at run-time. We describe how to implement a hardware TM design that utilizes this software construct. Our experiments reveal that leveraging software-defined conflicts, the programmer is able to achieve significant reductions in the number of aborts--over 50% for most applications. At 16 threads, our system with software-defined conflicts outperforms LogTM-SE in nearly all benchmarks, reaching an average reduction in execution time of 18%.
Improving performance of nested loops on reconfigurable array processors
Authors: Kim Yongjoo , Lee Jongeun , Mai Toan X. , Paek Yunheung
Published: January 2012

Pipelining algorithms are typically concerned with improving only the steady-state performance, or the kernel time. The pipeline setup time happens only once and therefore can be negligible compared to the kernel time. However, for Coarse-Grained Reconfigurable Architectures (CGRAs) used as a coprocessor to a main processor, pipeline setup can take much longer due to the communication delay between the two processors, and can become significant if it is repeated in an outer loop of a loop nest. In this paper we evaluate the overhead of such non-kernel execution times when mapping nested loops for CGRAs, and propose a novel architecture-compiler cooperative scheme to reduce the overhead, while also minimizing the number of extra configurations required. Our experimental results using loops from multimedia and scientific domains demonstrate that our proposed techniques can greatly increase the performance of nested loops by up to 2.87 times compared to the conventional approach of accelerating only the innermost loops. Moreover, the mappings generated by our techniques require only a modest number of configurations that can fit in recent reconfigurable architectures.
On the evaluation of the impact of shared resources in multithreaded COTS processors in time-critical environments
Authors: Radojković Petar , Girbal Sylvain , Grasset Arnaud , Quiñones Eduardo , Yehia Sami , Cazorla Francisco J.
Published: January 2012

Commercial Off-The-Shelf (COTS) processors are now commonly used in real-time embedded systems. The characteristics of these processors fulfill system requirements in terms of time-to-market, low cost, and high performance-per-watt ratio. However, multithreaded (MT) processors are still not widely used in real-time systems because the timing analysis is too complex. In MT processors, simultaneously-running tasks share and compete for processor resources, so the timing analysis has to estimate the possible impact that the inter-task interferences have on the execution time of the applications.

In this paper, we propose a method that quantifies the slowdown that simultaneously-running tasks may experience due to collision in shared processor resources. To that end, we designed benchmarks that stress specific processor resources and we used them to (1) estimate the upper limit of a slowdown that simultaneously-running tasks may experience because of collision in different shared processor resources, and (2) quantify the sensitivity of time-critical applications to collision in these resources. We used the presented method to determine if a given MT processor is a good candidate for systems with timing requirements. We also present a case study in which the method is used to analyze three multithreaded architectures exhibiting different configurations of resource sharing. Finally, we show that measuring the slowdown that real applications experience when simultaneously-running with resource-stressing benchmarks is an important step in measurement-based timing analysis. This information is a base for incremental verification of MT COTS architectures.
SYRANT: SYmmetric resource allocation on not-taken and taken paths
Authors: Premillieu Nathanael , Seznec Andre
Published: January 2012

In the multicore era, achieving ultimate single process performance is still an issue e.g. for single process workload or for sequential sections in parallel applications. Unfortunately, despite tremendous research effort on branch prediction, substantial performance potential is still wasted due to branch mispredictions. On a branch misprediction resolution, instruction treatment on the wrong path is essentially thrown away. However, in most cases after a conditional branch, the taken and the not-taken paths of execution merge after a few instructions. Instructions that follow the reconvergence point are executed whatever the branch outcome is.

We present SYRANT (SYmmetric Resource Allocation on Not-taken and Taken paths), a new technique for exploiting control independence. SYRANT essentially uses the same pipeline structure as a conventional processor. SYRANT tries to enforce the allocation of the exact same resources on the out-of-order execution mechanism (physical register, load/store queue and reorder buffer) for both the taken and not-taken paths. Thus, on a branch misprediction, the result of an instruction already executed on the wrong path after the reconvergence point can be conserved in the same structure when it is data independent. Adding SYRANT on top of an aggressive superscalar execution core allows to improve performance for applications suffering a significant branch misprediction rate.

As a side, but important extra contribution, we introduce ABL/SBL a simple and non-intrusive hardware reconvergence detection mechanism. ABL/SBL can be used in a conventional superscalar processor to improve branch prediction accuracy by exploiting the execution of branches along the wrong path.
The migration prefetcher
Authors: Lira Javier , Jones Timothy M. , Molina Carlos , González Antonio
Published: January 2012

The exponential increase in multicore processor (CMP) cache sizes accompanied by growing on-chip wire delays make it difficult to implement traditional caches with a single, uniform access latency. Non-Uniform Cache Architecture (NUCA) designs have been proposed to address this problem. A NUCA divides the whole cache memory into smaller banks and allows banks nearer a processor core to have lower access latencies than those further away, thus mitigating the effects of the cache's internal wires. Determining the best placement for data in the NUCA cache at any particular moment during program execution is crucial for exploiting the benefits that this architecture provides. Dynamic NUCA (D-NUCA) allows data to be mapped to multiple banks within the NUCA cache, and then uses data migration to adapt data placement to the program's behavior. Although the standard migration scheme is effective in moving data to its optimal position within the cache, half the hits still occur within non-optimal banks. This paper reduces this number by anticipating data migrations and moving data to the optimal banks in advance of being required. We introduce a prefetcher component to the NUCA cache that predicts the next memory request based on the past. We develop a realistic implementation of this prefetcher and, furthermore, experiment with a perfect prefetcher that always knows where the data resides, in order to evaluate the limits of this approach. We show that using our realistic data prefetching to anticipate data migrations in the NUCA cache can reduce the access latency by 15% on average and achieve performance improvements of up to 17%.
Toward high-throughput algorithms on many-core architectures
Authors: Orozco Daniel , Garcia Elkin , Khan Rishi , Livingston Kelly , Gao Guang R.
Published: January 2012

Advanced many-core CPU chips already have a few hundreds of processing cores (e.g., 160 cores in an IBM Cyclops-64 chip) and more and more processing cores become available as computer architecture progresses. The underlying runtime systems of such architectures need to efficiently serve hundreds of processors at the same time, requiring all basic data structures within the runtime to maintain unprecedented throughput. In this paper, we analyze the throughput requirements that must be met by algorithms in runtime systems to be able to handle hundreds of simultaneous operations in real time.

We reach a surprising conclusion: Many traditional algorithm techniques are poorly suited for highly parallel computing environments because of their low throughput. We reach the conclusion that the intrinsic throughput of a parallel program depends on both its algorithm and the processor architecture where the program runs. We provide theory to quantify the intrinsic throughput of algorithms, and we provide a few examples, where we describe the intrinsic throughput of existing, common algorithms. Then, we go on to explain how to follow a
throughput-oriented
approach to develop algorithms that have very high intrinsic throughput in many core architectures. We compare our throughput-oriented algorithms with other well known algorithms that provide the same functionality and we show that a throughput-oriented design produces algorithms with equal or faster performance in highly concurrent environments. We provide both theoretical and experimental evidence showing that our algorithms are excellent choices over other state of the art algorithms.

The major contributions of this paper are (1) motivating examples that show the importance of throughput in concurrent algorithms; (2) a mathematical framework that uses queueing theory to describe the intrinsic throughput of algorithms; (3) two highly concurrent algorithms with very high intrinsic throughput that are useful for task management in runtime systems; and (4) extensive experimental and theoretical results that show that for highly parallel systems, our proposed algorithms allow greater or at least equal scalability and performance than other well-known similar state-of-the-art algorithms.
Utilizing RF-I and intelligent scheduling for better throughput/watt in a mobile GPU memory system
Authors: Therdsteerasukdi Kanit , Byun Gyungsu , Cong Jason , Chang M. Frank , Reinman Glenn
Published: January 2012

Smartphones and tablets are becoming more and more powerful, replacing desktops and laptops as the users' main computing system. As these systems support higher and higher resolutions with more complex 3D graphics, a high-throughput and low-power memory system is essential for the mobile GPU. In this article, we propose to improve throughput/watt in a mobile GPU memory system by using intelligent scheduling to reduce power and multi-band radio frequency interconnect (MRF-I) to offset any throughput degradation caused by our intelligent scheduling. Overall, we are able to improve throughput 17% up to 66% while increasing throughput per watt by an average of 18% up to 26%.
sFtree
Authors: Bogdanski Bartosz , Reinemo Sven-Arne , Sem-Jacobsen Frank Olaf , Gran Ernst Gunnar
Published: January 2012

Existing fat-tree routing algorithms fully exploit the path diversity of a fat-tree topology in the context of compute node traffic, but they lack support for deadlock-free and fully connected switch-to-switch communication. Such support is crucial for efficient system management, for example, in InfiniBand (IB) systems. With the general increase in system management capabilities found in modern InfiniBand switches, the lack of deadlock-free switch-to-switch communication is a problem for fat-tree-based IB installations because management traffic might cause routing deadlocks that bring the whole system down. This lack of deadlock-free communication affects all system management and diagnostic tools using LID routing.

In this paper, we propose the sFtree routing algorithm that guarantees deadlock-free and fully connected switch-to-switch communication in fat-trees while maintaining the properties of the current fat-tree algorithm. We prove that the algorithm is deadlock free and we implement it in OpenSM for evaluation. We evaluate the performance of the sFtree algorithm experimentally on a small cluster and we do a large-scale evaluation through simulations. The results confirm that the sFtree routing algorithm is deadlock-free and show that the impact of switch-to-switch management traffic on the end-node traffic is negligible.
Efficient hole bypass routing scheme using observer packets for geographic routing in wireless sensor networks
Authors: Choo Hyunseung , Choi Mooshik , Shon Minhan , Kim Doogsoo Stephen
Published: January 2012

Greedy forwarding fails due to void area (called hole) where no nodes can be deployed in realistic wireless sensor networks. This is known as the local minimum problem. In this paper, we propose
BHOP-GR(Bypassing Hole Scheme Using Observer Packets for Geographic Routing)
that selects the optimum bypassing path while minimizing overhead to maintain hole boundary information. Several schemes have been recently proposed to solve this problem. However, they have overhead about nodes that are adjacent to the hole that have to maintain hole boundary information and increase hop count due to additional data packet transmission.
BHOP-GR
detects the hole boundary using an observer packet previously. When it transmits the data packet using a time delay, this can be arranged to decrease the average hop counts and routing path length. Also, using a virtual regular hexagon model, which can exactly cover a hole to be detoured, minimizes overhead to maintain hole boundary information. In the performance evaluation, we show that
BHOP-GR
has at least 34% and 25% of the average hop counts and routing path length compared to SLGF(Safety Information based Limited Geographic greedy Forwarding) and Virtual Circle, respectively.
Template-based autonomous navigation and obstacle avoidance in urban environments
Authors: Souza Jefferson R. , Sales Daniel O. , Shinzato Patrick Y. , Osorio Fernando S. , Wolf Denis F.
Published: January 2012

Autonomous navigation is a fundamental task in mobile robotics. In the last years, several approaches have been addressing the autonomous navigation in outdoor environments. Lately it has also been extended to robotic vehicles in urban environments. This paper presents a vehicle control system capable of learning behaviors based on examples from human driver and analyzing different levels of memory of the templates, which are an important capability to autonomous vehicle drive. Our approach is based on image processing, template matching classification, finite state machine, and template memory. The proposed system allows training an image segmentation algorithm and a neural network to work with levels of memory of the templates in order to identify navigable and non-navigable regions. As an output, it generates the steering control and speed for the Intelligent Robotic Car for Autonomous Navigation (CaRINA). Several experimental tests have been carried out under different environmental conditions to evaluate the proposed techniques.
Constraining the Stellar Mass Function in the Galactic Center via Mass Loss from Stellar Collisions
Authors: Rubin Douglas , Loeb Abraham
Published: January 2012

The dense concentration of stars and high-velocity dispersions in the Galactic center imply that stellar collisions frequently occur. Stellar collisions could therefore result in significant mass loss rates. We calculate the amount of stellar mass lost due to indirect and direct stellar collisions and find its dependence on the present-day mass function of stars. We find that the total mass loss rate in the Galactic center due to stellar collisions is sensitive to the present-day mass function adopted. We use the observed diffuse X-ray luminosity in the Galactic center to preclude any present-day mass functions that result in mass loss rates>10-5M⨀yr−1in the vicinity of~1″. For present-day mass functions of the form,dN/dM∝M-α, we constrain the present-day mass function to have a minimum stellar mass≲7M⨀and a power-law slope≳1.25. We also use this result to constrain the initial mass function in the Galactic center by considering different star formation scenarios.
CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis
Authors: Pender Michael P.
Published: January 2012

CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti-EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.
Survey: Discovery in Wireless Sensor Networks
Authors: Galluzzi Valerie , Herman Ted
Published: January 2012

Neighbor discovery is a component of communication and access protocols for ad hoc networks. Wireless sensor networks often must operate under a more severe low-power regimen than do traditional ad hoc networks, notably by turning off radio for extended periods. Turning off a radio is problematic for neighbor discovery, and a balance is needed between adequate open communication for discovery and silence to conserve power. This paper surveys recent progress on the problems of neighbor discovery for wireless sensor networks. The basic ideas behind these protocols are explained, which include deterministic schedules of waking and sleeping, randomized schedules, and combinatorial methods to ensure discovery.
Triple-Negative Breast Cancer: An Update on Neoadjuvant Clinical Trials
Authors: Amos Keith D. , Adamo Barbara , Anders Carey K.
Published: January 2012

Triple-negative breast cancer (TNBC) is an aggressive malignancy with a poor prognosis despite the high rates of response to chemotherapy. This scenario highlights the need to develop novel therapies and/or treatment strategies to reduce the mortality associated with TNBC. The neoadjuvant setting provides a model for rapid assessment of treatment efficacy with smaller patient accruals and over shorter periods of time compared to the traditional adjuvant setting. In addition, a clear surrogate endpoint of improved survival, known as pathologic complete response, already exists in this setting. Here, we review current data from completed and ongoing neoadjuvant clinical trials for TNBC.
Neisseria gonorrhoeaePilus Attenuates Cytokine Response of Human Fallopian Tube Explants
Authors: Velasquez Luis , García Katherine , Morales Francisco , Heckels John E. , Orihuela Pedro , Rodas Paula I. , Christodoulides Myron , Cardenas Hugo
Published: January 2012

Background. A role for pilus during attachment ofNeisseria gonorrhoeaeto epithelia of the female reproductive tract is currently assumed. However, Pil−gonococci have been observed during infection of the reproductive tract, which prompted us to examine the effect of pili on the dynamics of infection and the inflammatory responses of mucosal explants of the human Fallopian tube.Methods. Mucosal explants were infected in vitro with Opa negative Pil−and Pil+N. gonorrhoeaestrains.Results. Piliation enhanced gonococcal adherence to the epithelium within 3 h of infection (P<0.05) but thereafter did not offer advantage to gonococci to colonize the epithelial cell surface (P>0.05). No differences were found between the strains in numbers of gonococci inside epithelial cells. Pil−bacteria induced higher levels (P<0.05) of IL-1β, TNF-α, GM-CSF, MCP-1, and MIP-1β than Pil+bacteria. There were no differences between both strains in LOS pattern, and Pil expression did not change after coincubation with mucosal strips.Conclusions. Results show that gonococcal invasion of the human Fallopian tube can occur independently of pilus or Opa expression, and suggest that pilus, by inhibition of several key elements of the initial inflammatory response, facilitates sustained infection of this organ.
PPARs in Regulation of Paraoxonases: Control of Oxidative Stress and Inflammation Pathways
Authors: Camps Jordi , García-Heredia Anabel , Rull Anna , Alonso-Villaverde Carlos , Aragonès Gerard , Beltrán-Debón Raúl , Rodríguez-Gallego Esther , Joven Jorge
Published: January 2012

The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR.
Cervical Spondylotic Myelopathy: Factors in Choosing the Surgical Approach
Authors: Yalamanchili Praveen K. , Vives Michael J. , Chaudhary Saad B.
Published: January 2012

Cervical spondylotic myelopathy is a progressive disease and a common cause of acquired disability in the elderly. A variety of surgical interventions are available to halt or improve progression of the disease. Surgical options include anterior or posterior approaches with and without fusion. These include anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, cervical disc replacement, laminoplasty, laminectomy with and without fusion, and combined approaches. Recent investigation into the ideal approach has not found a clearly superior choice, but individual patient characteristics can guide treatment.
Serum IL-33 Levels Are Associated with Liver Damage in Patients with Chronic Hepatitis C
Authors: Wang Juan , Zhao Pingwei , Guo Hui , Sun Xiguang , Jiang Zhenyu , Xu Lijun , Feng Junyan , Niu Junqi , Jiang Yanfang
Published: January 2012

Interleukin-33 (IL-33) is associated with the development of Th2 responses. This study examined the potential role of IL-33 in the pathogenic process of chronic hepatitis C (CHC) in Chinese patients. The levels of serum IL-33 and sST2 in 154 patients with CHC, 24 with spontaneously resolved HCV (SR-HCV) infection and 20 healthy controls (HC), were analyzed by ELISA. The concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, and IL-10, HCV loads, ALT, AST, and HCV-Ab were measured. We found that the levels of serum IL-33 in CHC patients were significantly higher than those of SR-HCV and HC but decreased after treatment with interferon for 12 weeks. More importantly, the levels of serum IL-33 were correlated with the concentrations of ALT and AST in CHC patients. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHC and SR-CHC patients than those in HC, and there was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum IFN-γ and IL-6 in CHC patients were significantly lower than those of SR-HCV. These data suggest that IL-33 may be a pathogenic factor contributing to CHC-related liver injury.
In SilicoIdentification and Comparative Genomics of Candidate Genes Involved in Biosynthesis and Accumulation of Seed Oil in Plants
Authors: Sharma Arti , Chauhan Rajinder Singh
Published: January 2012

Genes involved in fatty acids biosynthesis, modification and oil body formation are expected to be conserved in structure and function in different plant species. However, significant differences in the composition of fatty acids and total oil contents in seeds have been observed in different plant species. Comparative genomics was performed on 261 genes involved in fatty acids biosynthesis, TAG synthesis, and oil bodies formation in Arabidopsis,Brassica rapa, castor bean and soybean.In silicoexpression analysis revealed that stearoyl desaturase, FatB, FAD2, oleosin and DGAT are highly abundant in seeds, thereby considered as ideal candidates for mining of favorable alleles in natural population. Gene structure analysis for major genes, ACCase, FatA, FatB, FAD2, FAD3 and DGAT, which are known to play crucial role in oil synthesis revealed that there are uncommon variations (SNPs and INDELs) which lead to varying content and composition of fatty acids in seed oil. The predicted variations can provide good targets for seed oil QTL identification, understanding the molecular mechanism of seed oil accumulation, and genetic modification to enhance seed oil yield in plants.
Cotrimoxazole Prophylaxis Specifically Selects for Cotrimoxazole Resistance inStreptococcus mutansandStreptococcus sobrinuswith Varied Polymorphisms in the Target GenesfolAandfolP
Authors: William Buwembo , Rwenyonyi Charles Mugisha , Swedberg Göte , Kironde Fred
Published: January 2012

The selection of antibiotic resistance by cotrimoxazole prophylaxis was evaluated, and we characterized the mechanism of cotrimoxazole resistance inStreptococcus mutansandStreptococcus sobrinus.In vitrosusceptibility to six antibiotics was evaluated on 64 mutans streptococci group (MSG) isolates from a cotrimoxazole prophylaxis group and compared to 84 MSG isolates from a nonprophylaxis group. ThefolAandfolPgenes were sequenced and compared with reference sequences at NCBI. Only resistance to cotrimoxazole was significantly higher in the prophylaxis group (54.7% versus 15.5%,OR=6.59, 95% CI: 2.89–15.3,P<0.05). Resistance to amoxicillin, ceftriaxone, chloramphenicol, erythromycin, and tetracycline was 1.4%, 25.5%, 6.2%, 6.5%, and 29.6% of the isolates, respectively. Considerable polymorphisms were found in thefolPgene inS. mutans, but this could not be linked to sulfonamide drug resistance. No variation was seen infolPorfolAgenes ofS. sobrinus. Genetic transfer of folate pathway genes seems unlikely in these isolates.
CD44 Proteolysis Increases CREB Phosphorylation and Sustains Proliferation of Thyroid Cancer Cells
Authors: De Falco Valentina , Tamburrino Anna , Ventre Simona , Castellone Maria Domenica , Malek Mouhannad , Manié Serge N. , Santoro Massimo
Published: January 2012

CD44 is a marker of cancer stem-like cells and epithelial–mesenchymal transition that is overexpressed in many cancer types, including thyroid carcinoma. At extracellular and intramembranous domains, CD44 undergoes sequential metalloprotease- and γ-secretase–mediated proteolytic cleavage, releasing the intracellular protein fragment CD44-ICD, which translocates to the nucleus and activates gene transcription. Here, we show that CD44-ICD binds to the transcription factor CREB, increasing S133 phosphorylation and CREB-mediated gene transcription. CD44-ICD enhanced CREB recruitment to the cyclin D1 promoter, promoting cyclin D1 transcription and cell proliferation. Thyroid carcinoma cells harboring activated RET/PTC, RAS, or BRAF oncogenes exhibited CD44 cleavage and CD44-ICD accumulation. Chemical blockade of RET/PTC, BRAF, metalloprotease, or γ-secretase were each sufficient to blunt CD44 processing. Furthermore, thyroid cancer cell proliferation was obstructed by RNA interference–mediated knockdown of CD44 or inhibition of γ-secretase and adoptive CD44-ICD overexpression rescued cell proliferation. Together, these findings reveal a CD44-CREB signaling pathway that is needed to sustain cancer cell proliferation, potentially offering new molecular targets for therapeutic intervention in thyroid carcinoma. Cancer Res; 72(6); 1449–58. ©2012 AACR.