bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenovirus Induction of IRF3 Occurs through a Binary Trigger Targeting Jun N-Terminal Kinase and TBK1 Kinase Cascades and Type I Interferon Autocrine Signaling
Authors: Nociari Marcelo , Ocheretina Oksana , Murphy Mary , Falck-Pedersen Erik
Published: February 2009

Pathogen recognition is a critical function of immune sentinel cells. Naïve macrophages or dendritic cells (DCs) undergo pathogen-directed activation and maturation, and as mature antigen-presenting cells (APCs), they contribute essential functions to both innate and adaptive immunity. Using recombinant adenovirus (rAdV) as a model for murine APC activation by DNA viruses, we demonstrate a critical role for stress kinase activation in cell intrinsic and extrinsic antiviral signaling cascades. We propose two viral triggers, viral capsid and viral DNA, are required for APC activation. Endosomal escape and presentation of cytosolic rAdV DNA induces phosphorylation of TANK-binding kinase 1 (TBK1) at serine 172 but does not induce IκB kinase ε activity as determined by in vitro kinase assays. However, induction of TBK1 alone is not sufficient for interferon regulatory factor 3 (IRF3) phosphorylation. We show that capsid-dependent activation of Jun N-terminal kinase (JNK) stress kinase is a necessary step, licensing TBK1 phosphorylation of IRF3 at Ser 396. A second later phase of JNK activity is required to coordinate phosphorylation of JNK-dependent transcription factors (c-Jun/ATF2) with activated IRF3 in the induction of primary IRF3-responsive transcripts. Finally, we demonstrate that maximal JNK/TBK1/IRF3 stimulation by rAdV depends on an intact type I interferon (IFN) signaling cascade. By requiring multiple viral triggers and type I IFN autocrine regulation, APCs have an inherent fail-safe mechanism against inappropriate activation and maturation.
Transcriptional Restriction of Human Immunodeficiency Virus Type 1 Gene Expression in Undifferentiated Primary Monocytes
Authors: Dong Chunsheng , Kwas Constance , Wu Li
Published: February 2009

Monocytes are critical precursors of dendritic cells and macrophages, which play an important role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1). HIV-1 postentry infection is blocked in undifferentiated monocytes in vitro, while the underlying mechanisms are not fully understood. HIV-1 Tat-mediated transactivation of the viral long terminal repeat (LTR) promoter is essential for HIV-1 transcription. Two critical cellular cofactors of HIV-1 Tat, cyclin T1 (CycT1) and cyclin-dependent kinase 9 (CDK9), are required for LTR-directed HIV-1 transcription. In addition to the previously identified restrictions in early viral life cycle, we find that HIV-1 gene expression is impaired in undifferentiated primary monocytes. Transfection of monocytes by nucleofection with HIV-1 proviral DNA could not produce infectious HIV-1. The lack of Tat transactivation of the LTR promoter correlated with the impaired HIV-1 gene expression in monocytes. Interestingly, heterokaryons between primary monocytes and a human embryonic kidney cell line restored Tat transactivation of LTR, suggesting that monocytes lack cellular factors required for Tat transactivation. CycT1 protein was undetectable in freshly isolated monocytes and induced in monocyte-differentiated macrophages, while the expression of CDK9 remained constant. Transient expression of CycT1 in undifferentiated monocytes could not rescue Tat transactivation, suggesting that CycT1 is not the only limiting factor of HIV-1 infection in monocytes. Furthermore, monocyte differentiation into macrophages appeared to enhance the phosphorylation of CDK9, which correlated with significantly increased HIV-1 infection in macrophages. Our results provide new insights into HIV-1 infection and regulation in primary monocytes and viral pathogenesis.
Donald MacDonald and the Panama Canal
Authors: Legget Robert F.
Published: February 2009

During the construction of the Panama Canal by the United States of America (1904–1914) geology was conspicuous by its absence, despite the problems with landslides, first experienced during the French construction venture (1880–1889), and especially in the Gaillard Cut through the Continental Divide. In 1913, the United States Geological Survey seconded a young geologist on their staff, Donald MacDonald, to reside on the Canal for the remainder of the construction period. Although too late to assist with the control of the slides, his studies of their causes, and of the local geology, received the highest praise from the Committee of Enquiry appointed by the United States National Academy of Sciences in 1915 after two bad slides had effectively closed the Canal for 6 months. The report of this important committee, composed equally of civil engineers and geologists, is one of the "classics" of early geotechnical literature. And MacDonald was a Canadian from Pictou County, Nova Scotia! An outline of his life is presented as a tribute to this pioneer Canadian geotechnical worker, still virtually unknown. Key words : Panama Canal, Donald MacDonald, geology, landslides, geotechnical pioneer.
Interpretation of the transient flow rate obtained from constant-head tests conducted in situ in clays
Authors: Novakowski K.S.
Published: February 2009

Hydraulic tests conducted in situ using a source condition of constant head are frequently employed to determine the hydraulic properties of low-permeability clays. In this paper, an analytical model is developed for analyzing the results of a constant-head test conducted under conditions where the influence of finite-thickness skin and partial penetration are present at the source well. The analytical model is derived by application of the Laplace transform method with respect to time and the finite Fourier cosine transform with respect to the vertical coordinate. The solution is used to produce type curves of dimensionless flow rate versus dimensionless time so as to investigate the influence of finite thickness skin and partial penetration on the results of constant-head tests. Results show that the presence of a skin zone of finite thickness having permeability less than the formation produces an inflection point in the type curves at which point the dimensionless flow rate tends asymptotically towards a steady value. For the case where the skin and formation permeabilities are similar, these type curves can be used to uniquely define both the skin and formation properties. Where the skin zone is very thin, the shape of the type curves mimics the curve for a uniform, fully confined medium, and thus only the properties of the skin are measured using type-curve analysis. Conversely, the type curves for the case where the skin zone is of greater permeability than the formation show a unique and interpretable shape for each skin thickness and ratio of formation to skin permeability over most practical values of hydraulic diffusivity. Additional effects due to partial penetration were found to be pronounced in piezometers completed with small screen lengths. Particular conditions where the conventional steady approximation can be used are also discussed. Key words : constant-head test, flow rate, skin zone, partial penetration.
Dynamic performance of the Becker hammer drill and penetration test
Authors: Sy Alex , Campanella R.G. (Dick)
Published: February 2009

The Becker penetration test (BPT) blow counts are commonly correlated to the standard penetration test (SPT) N-values for foundation design and liquefaction potential assessment in coarse-grained soils. Most of the existing correlations, however, do not adequately account for the variable energy output of the ICE 180 diesel hammer used in the Becker system, and the shaft resistance acting on the Becker pipe is often ignored. To obtain reliable BPT–SPT correlations, an extensive study of the BPT has been conducted at several sites in British Columbia. Dynamic measurements of Becker drill rigs and penetration tests were conducted that included hammer combustion and bounce chamber pressures, as well as force and acceleration near the top of the drill pipe. The dynamic field data are presented, including the maximum energy transferred to the top of the Becker pipe (ENTHRU). An energy approach for correcting Becker blow counts to a reference ENTHRU level of 30% of the hammer-rated energy is proposed. Different combustion conditions, drill rigs, and pipe sizes are investigated in the study. The test results show that ENTHRU is a fundamental and useful parameter for normalizing the BPT blow counts to account for the variable energy transfer from the diesel hammer. Key words : penetration test, dynamic measurement, energy, pile driving, diesel hammer, stress-wave propagation.
Characterization of fracture aperture by inverse analysis
Authors: Piggott Andrew R. , Elsworth Derek
Published: February 2009

Formulation and application of a procedure for characterizing the spatial distribution of aperture within a single fracture in rock are discussed. A simultaneous-inversion approach is used to construct the aperture distribution that best replicates the variability apparent in measured hydraulic and electrical data. In this approach, aperture distributions are generated from a specified model, flow is simulated for each of multiple test types and configurations, the error of approximating the measured data with the simulated results is evaluated, and an optimization algorithm is used to minimize the error with respect to parameters regulating the aperture distribution. The procedure is applied to data obtained from laboratory tests conducted on a natural fracture in granite. Three aperture distributions with similar macroscopic characteristics are inferred from the data. Corroboration of these distributions is obtained from the simulation of tracer transport within the fracture and comparison of the simulated results with measured data. Key words : characterization, fractured rock, groundwater flow, contaminant transport, inverse analysis.
Modeling and analysis of core-centric network processors
Authors: Lin Yi-Neng , Lin Ying-Dar , Tseng Kuo-Kun , Lai Yuan-Cheng
Published: February 2009

Network processors can be categorized into two types, the coprocessors-centric model in which the data-plane is handled by coprocessors, and the core-centric model in which the core processes most of the data-plane packets yet offloading some tasks to coprocessors. While the former has been properly explored over various applications, researches regarding the latter remain limited. Based on the previous experience of prototyping the virtual private network (VPN) over the IXP425 network processor, this work aims to derive design implications for the core-centric model performing computational intensive applications. From system and IC vendors' perspectives, the continuous-time Markov chain and Petri net simulations are adopted to explore this architecture. Analytical results prove to be quite inline with those of the simulation and implementation. With subsequent investigation we find that appropriate process run lengths can improve the effective core utilization by 2.26 times, and by offloading the throughput boosts 7.5 times. The results also suggest single process programming since context switch overhead impacts considerably on the performance.
Low-latency time-portable real-time programming with Exotasks
Authors: Auerbach Joshua , Bacon David F. , Iercan Daniel , Kirsch Christoph M. , Rajan V. T. , Röck Harald , Trummer Rainer
Published: February 2009

Exotasks
are a novel Java programming construct that achieve three important goals. They achieve low latency while allowing the fullest use of Java language features, compared to previous attempts to restrict the Java language for use in the submillisecond domain. They support pluggable schedulers, allowing easy implementation of new scheduling paradigms in a real-time Java system. They can achieve deterministic timing, even in the presence of other Java threads, and across changes of hardware and software platform. To achieve these goals, the program is divided into tasks with private heaps. Tasks may be strongly isolated, communicating only with each other and guaranteeing determinism, or weakly isolated, allowing some communication with the rest of the Java application. Scheduling of the tasks' execution, garbage collection, and value passing is accomplished by the pluggable scheduler. Schedulers that we have written employ logical execution time (LET) in association with strong isolation to achieve time portability. We have also built a quad-rotor model helicopter, the JAviator, which we use to evaluate our implementation of Exotasks in an experimental embedded version of IBM's J9 real-time virtual machine. Our experiments show that we are able to maintain very low scheduling jitter and deterministic behavior in the face of variations in both software load and hardware platform. We also show that Exotasks perform nearly as well as Eventrons on a benchmark audio application.
Register coalescing techniques for heterogeneous register architecture with copy sifting
Authors: Ahn Minwook , Paek Yunheung
Published: February 2009

Optimistic coalescing has been proven as an elegant and effective technique that provides better chances of safely coloring more registers in register allocation than other coalescing techniques. Its algorithm originally assumes homogeneous registers, which are all gathered in the same register file. Although this register architecture is still common in most general-purpose processors, embedded processors often contain heterogeneous registers, which are scattered in physically different register files dedicated for each dissimilar purpose and use. In this work, we show that optimistic coalescing is also useful for an embedded processor to better handle such heterogeneity of the register architecture, and developed a modified algorithm for optimal coalescing that helps a register allocator. In the experiment, an existing register allocator was able to achieve up to 13.0% reduction in code size through our coalescing, and avoid many spills that would have been generated without our scheme.
Complexity results in revising UNITY programs
Authors: Bonakdarpour Borzoo , Ebnenasir Ali , Kulkarni Sandeep S.
Published: February 2009

We concentrate on automatic revision of untimed and real-time programs with respect to UNITY properties. The main focus of this article is to identify instances where addition of UNITY properties can be achieved efficiently (in polynomial time) and where the problem of adding UNITY properties is difficult (NP-complete). Regarding efficient revision, we present a sound and complete algorithm that adds a singleleads-toproperty (respectively,bounded-time leads-toproperty) and a conjunction ofunless, stable, andinvariantproperties (respectively,bounded-time unlessandstable) to an existing untimed (respectively, real-time) UNITY program in polynomial-time in the state space (respectively, region graph) of the given program. Regarding hardness results, we show that (1) while oneleads-to(respectively,ensures) property can be added in polynomial-time, the problem of adding two such properties (or any combination ofleads-toandensures) is NP-complete, (2) if maximum non-determinism is desired then the problem of adding even a singleleads-toproperty is NP-complete, and (3) the problem of providing maximum non-determinism while adding a singlebounded-time leads-toproperty to a real-time program is NP-complete (in the size of the program's region graph) even if the original program satisfies the correspondingunbounded leads-toproperty.
On bootstrapping topology knowledge in anonymous networks
Authors: Masuzawa Toshimitsu , Tixeuil Sébastien
Published: February 2009

In this article, we quantify the amount of “practical” information (i.e., views obtained from the neighbors, colors attributed to the nodes and links) to obtain “theoretical” information (i.e., the local topology of the network up to distance
k
) in anonymous networks. In more detail, we show that a coloring at distance 2
k
+ 1 is necessary and sufficient to obtain the local topology at distance
k
that includes outgoing links. This bound drops to 2
k
when outgoing links are not needed. A second contribution of this article deals with color bootstrapping (from which local topology can be obtained using the aforementioned mechanisms). On the negative side, we show that (
i
) with a distributed daemon, it is impossible to achieve deterministic color bootstrap, even if the whole network topology can be instantaneously obtained, and (
ii
) with a central daemon, it is impossible to achieve distance
m
when instantaneous topology knowledge is limited to
m
− 1. On the positive side, we show that (
i
) under the
k
-central daemon, deterministic self-stabilizing bootstrap of colors up to distance
k
is possible provided that
k
-local topology can be instantaneously obtained, and (
ii
) under the distributed daemon, probabilistic self-stabilizing bootstrap is possible for any range.
A security and robustness performance analysis of localization algorithms to signal strength attacks
Authors: Chen Yingying , Kleisouris Konstantinos , Li Xiaoyan , Trappe Wade , Martin Richard P.
Published: February 2009

Recently, it has been noted that localization algorithms that use signal strength are susceptible to noncryptographic attacks, which consequently threatens their viability for sensor applications. In this work, we examine several localization algorithms and evaluate their robustness to attacks where an adversary attenuates or amplifies the signal strength at one or more landmarks. We study both point-based and area-based methods that employ received signal strength for localization, and propose several performance metrics that quantify the estimator's precision, bias, and error, including Hölder metrics, which quantify the variability in position space for a given variability in signal strength space. We then conduct a trace-driven evaluation of a set of representative algorithms, where we measured their performance as we applied attacks on real data from two different buildings. We found the median error degraded gracefully, with a linear response as a function of the attack strength. We also found that area-based algorithms experienced a decrease and a spatial-shift in the returned area under attack, implying that precision increases though bias is introduced for these schemes. Additionally, we observed similar values for the average Hölder metric across most of the algorithms, thereby providing strong experimental evidence that nearly all the algorithms have similar average responses to signal strength attacks with the exception of the Bayesian Networks algorithm.
Compressive light transport sensing
Authors: Peers Pieter , Mahajan Dhruv K. , Lamond Bruce , Ghosh Abhijeet , Matusik Wojciech , Ramamoorthi Ravi , Debevec Paul
Published: February 2009

In this article we propose a new framework for capturing light transport data of a real scene, based on the recently developed theory of compressive sensing. Compressive sensing offers a solid mathematical framework to infer a sparse signal from a limited number of nonadaptive measurements. Besides introducing compressive sensing for fast acquisition of light transport to computer graphics, we develop several innovations that address specific challenges for image-based relighting, and which may have broader implications. We develop a novel hierarchical decoding algorithm that improves reconstruction quality by exploiting interpixel coherency relations. Additionally, we design new nonadaptive illumination patterns that minimize measurement noise and further improve reconstruction quality. We illustrate our framework by capturing detailed high-resolution reflectance fields for image-based relighting.
QoS for storage subsystems using IEEE-1394
Authors: Huang Chih-Yuan , Kuo Tei-Wei , Pang Ai-Chun
Published: February 2009

IEEE-1394 is widely adopted in various commercial products for computing, communication, and entertainment. Although many services with Quality-of-Service (QoS) supports are now available in systems over IEEE-1394, little work is done for QoS-based resource allocation. In this article, we aim at the design of a bandwidth reservation mechanism and its policy for isochronous requests, such as those from cameras. We then address the QoS support issue for asynchronous requests, such as those from disks, and an analytic framework for probability-based QoS guarantees. This work is concluded by the proposing of a topology configuration algorithm for IEEE-1394 devices. The capability of the proposed methodology and the analytic framework are evaluated by a series of experiments over a Linux-based system prototype.
JFTL
Authors: Choi Hyun Jin , Lim Seung-Ho , Park Kyu Ho
Published: February 2009

In flash memory-based storage, a Flash Translation Layer (FTL) manages the mapping between the logical addresses of a file system and the physical addresses of the flash memory. When a journaling file system is set up on the FTL, the consistency of the file system is guaranteed by duplications of the same file system changes in both the journal region of the file system and the home locations of the changes. However, these duplications inevitably degrade the performance of the file system. In this article we present an efficient FTL, called
JFTL
, based on a journal remapping technique. The FTL uses an address mapping method to write all the data to a new region in a process known as an out-of-place update. Because of this process, the existing data in flash memory is not overwritten by such an update. By using this characteristic of the FTL, the JFTL remaps addresses of the logged file system changes to addresses of the home locations of the changes, instead of writing the changes once more to flash memory. Thus, the JFTL efficiently eliminates redundant data in the flash memory as well as preserving the consistency of the journaling file system. Our experiments confirm that, when associated with a writeback or ordered mode of a conventional EXT3 file system, the JFTL enhances the performance of EXT3 by up to 20%. Furthermore, when the JFTL operates with a journaled mode of EXT3, there is almost a twofold performance gain in many cases. Moreover, the recovery performance of the JFTL is much better than that of the FTL.
Distributed hash sketches
Authors: Ntarmos N. , Triantafillou P. , Weikum G.
Published: February 2009

Counting items in a distributed system, and estimating the cardinality of multisets in particular, is important for a large variety of applications and a fundamental building block for emerging Internet-scale information systems. Examples of such applications range from optimizing query access plans in peer-to-peer data sharing, to computing the significance (rank/score) of data items in distributed information retrieval. The general formal problem addressed in this article is computing the network-wide distinct number of items with some property (e.g., distinct files with file name containing “spiderman”) where each node in the network holds an arbitrary subset, possibly overlapping the subsets of other nodes. The key requirements that a viable approach must satisfy are: (1) scalability towards very large network size, (2) efficiency regarding messaging overhead, (3) load balance of storage and access, (4) accuracy of the cardinality estimation, and (5) simplicity and easy integration in applications. This article contributes the DHS (Distributed Hash Sketches) method for this problem setting: a distributed, scalable, efficient, and accurate multiset cardinality estimator. DHS is based on hash sketches for probabilistic counting, but distributes the bits of each counter across network nodes in a judicious manner based on principles of Distributed Hash Tables, paying careful attention to fast access and aggregation as well as update costs. The article discusses various design choices, exhibiting tunable trade-offs between estimation accuracy, hop-count efficiency, and load distribution fairness. We further contribute a full-fledged, publicly available, open-source implementation of all our methods, and a comprehensive experimental evaluation for various settings.
Developmental changes in Ca2+homeostasis and contractility in gallbladder smooth muscle
Authors: Camello-Almaraz Cristina , Macias Beatriz , Gomez-Pinilla Pedro J. , Alcon Soledad , Martin-Cano Francisco E. , Baba Akemishi , Matsuda Toshio , Camello Pedro J. , Pozo María J.
Published: February 2009

Relatively little is known about the contribution of Ca2+-dependent and -independent mechanisms in the contractility of neonatal gastrointestinal smooth muscle. We therefore studied Ca2+homeostasis and Ca2+sensitization mechanisms in 10-day-old and adult guinea pig gallbladder smooth muscle to elucidate developmental changes in these processes. Gallbladder contractility was evaluated by isometrical tension recordings from strips, intracellular Ca2+concentration was estimated by epifluorescence microscopy of fura-2-loaded isolated cells, and protein expression and phosphorylation were assessed by Western blot analysis. The neonatal gallbladder contracted significantly less to CCK than adult tissue, but this correlated with an increased Ca2+mobilization, suggesting immaturity of Ca2+sensitization mechanisms. The enhanced Ca2+release in the newborn gallbladder was the result of the increase in the size of the releasable Ca2+pool. Moreover, in neonatal smooth muscle cells, neither the plasma membrane Ca2+pump nor the Na+/Ca2+exchanger collaborate in the extrusion of Ca2+. In contrast, in these cells, there is an increase in phospholamban phosphorylation, which could drive to an overactivity of the sarco(endo)plasmic reticulum Ca2+-ATPase pump. The reduced Ca2+sensitivity in neonatal tissues was demonstrated by the lack of effect to Y-27362, an inhibitor of Rho kinase (ROCK), and GF-109203X, an inhibitor of PKC, on agonist-induced contraction. In addition, the neonatal gallbladder showed lower levels of RhoA, ROCK, PKC, and two effectors [C-kinase-dependent inhibitor of 17 kDa (CPI-17) and myosin phosphatase targetting 1 (MYPT1)] as well as an absence of CPI-17 and MYPT1 phosphorylation in response to agonists. In conclusion, our results indicate that the main mechanisms involved in smooth muscle contractility are under developmental regulation.
Estrogen receptor β mediates increased activation of PI3K/Akt signaling and improved myocardial function in female hearts following acute ischemia
Authors: Wang Meijing , Wang Yue , Weil Brent , Abarbanell Aaron , Herrmann Jeremy , Tan Jiangning , Kelly Megan , Meldrum Daniel R.
Published: February 2009

Females have a lower incidence of heart failure and improved survival after myocardial ischemia-reperfusion (I/R) compared with males. Although estrogen-suppressed cardiomyocyte apoptosis may be mediated through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, it is unclear whether this action is mediated via estrogen receptor β (ERβ). Therefore, we hypothesized that ERβ mediates estrogen-induced cardioprotection through PI3K/Akt and antiapoptotic signaling in females but not in males. Isolated male and female hearts from ERβ knockout (ERβKO) and wild-type (WT) mice ( n = 5 mice/group) were subjected to 20-min ischemia followed by 60-min reperfusion (Langendorff). Ablation of ERβ significantly decreased postischemic recovery of left ventricular developed pressure in female, but not male, hearts. Reduced activation of PI3K and Akt was noted in female ERβKO hearts, which was associated with increased expression of caspase-3 and -8, as well as decreased Bcl-2 levels compared with WT. However, myocardial STAT3, SOCS3 (suppressor of cytokine signaling 3), VEGF, and TNF receptors 1 and 2 levels did not change in ERβKO of either sex following I/R. Furthermore, deficiency of ERβ increased myocardial JNK activation in females but increased ERK1/2 activity in males during acute I/R. We conclude that ERβ mediates myocardial protection via upregulation of PI3K/Akt activation, decreased caspase-3 and -8, and increased Bcl-2 in female hearts following I/R. These findings provide evidence of ERβ-mediated PI3K/Akt and antiapoptotic signaling in the myocardium and may lend insight into the mechanistic pathways behind the observed variation in clinical outcomes between males and females after myocardial infarction.
Effect of BSA-induced ER stress on SGLT protein expression levels and α-MG uptake in renal proximal tubule cells
Authors: Lee Yu Jin , Suh Han Na , Han Ho Jae
Published: February 2009

Recent studies demonstrated that endoplasmic reticulum (ER) stress regulates glucose homeostasis and that ER stress preconditioning which induces an adaptive, protective unfolded protein response (UPR) offers cytoprotection against nephrotoxins. Thus the aim of the present study was to use renal proximal tubule cells (PTCs) to further elucidate the link between the BSA-induced ER stress and α-methyl-d-glucopyranoside (α-MG) uptake and to identify related signaling pathways. Among ER stress inducers such as high glucose, BSA, H2O2, or tumicamycin, BSA pretreatment ameliorated the reduction of Na+-glucose cotransporter (SGLT) expression and α-MG uptake by gentamicin or cyclosporine A. Immunofluorescence studies revealed that BSA (10 mg/ml) stimulated the expression of glucose-regulated protein 78 (GRP78), an ER stress biomarker. In addition, BSA increased levels of GRP78 protein expression and eukaryotic initiation factor 2α (eIF2α) phosphorylation in a time-dependent manner. Furthermore, transfection with a GRP78-specific small interfering RNA (siRNA) inhibited BSA-stimulated SGLT expression and α-MG uptake. In experiments designed to unravel the mechanisms underlying BSA-induced ER stress, BSA stimulated the production of cellular reactive oxygen species (ROS), and antioxidants such as ascorbic acid or N-acetylcysteine (NAC) blocked BSA-induced increases in GRP78 activation, eIF2α phosphorylation, SGLT expression, and α-MG uptake. Moreover, the cells upregulated peroxisome proliferator-activated receptor-γ (PPARγ) mRNA levels in response to BSA or troglitazone (a PPARγ agonist), but BSA was ineffective in the presence of GW9662 (a PPARγ antagonist). In addition, both BSA and troglitazone stimulated GRP78 and eIF2α activation, SGLT expression, and α-MG uptake, whereas GW9662 inhibited the effects of BSA. BSA also stimulated phosphorylation of JNK and NF-κB, and GW9662 or GRP78 siRNA attenuated this response. Moreover, SP600125 or SN50 effectively blocked SGLT expression and α-MG uptake in BSA- or PPARγ agonists (troglitazone or PGJ2)-treated PTCs. We conclude that BSA induces ER stress through ROS production and PPARγ activation, which subsequently activates JNK/NF-κB signaling to enhance glucose uptake in renal PTCs.
Unexpected effect of angiotensin AT1receptor blockade on tubuloglomerular feedback in early subtotal nephrectomy
Authors: Singh Prabhleen , Deng Aihua , Blantz Roland C. , Thomson Scott C.
Published: February 2009

After subtotal nephrectomy (STN), the remaining nephrons engage in hyperfiltration, which may be facilitated by a reduced sensitivity of the tubuloglomerular feedback (TGF) response to increased distal delivery. However, a muted TGF response would contradict the notion of remnant kidney as a prototype of angiotensin II (ANG II) excess, since ANG II normally sensitizes the TGF response and stimulates proximal reabsorption. We examined the role of ANG II as a modulator of TGF and proximal reabsorption in 7 days after STN in male rats. Single-nephron glomerular filtration rate (SNGFR) and proximal reabsorption ( Jprox) were measured in late proximal collections while perfusing Henle's loop for minimal and maximal TGF stimulation in rats treated with the angiotensin type 1 (AT1) receptor blocker losartan or placebo in drinking water for 7 days. Perfusion of Henle's loop yielded a robust TGF response in sham-operated rats. In STN, the feedback responses were highly variable and nil, on average. Paradoxical TGF responses to augmented late proximal flow were confirmed in SNGFR measurements from the early distal nephron. Chronic losartan treatment normalized the average TGF response without reducing the variability. Jproxwas subtly affected by chronic losartan in sham surgery or STN, after controlling for differences in SNGFR. However, when administered acutely into the early S1 segment, losartan potently suppressed Jproxin STN and sham-operated rats alike. Chronic losartan stabilizes the TGF system in remnant kidneys. This cannot be explained by currently known actions of AT1receptors but is commensurate with a salutary effect of an intact TGF system on dynamic autoregulation of intraglomerular flow and pressure.
Relationship Between Spontaneous and Evoked Spike-Time Correlations in Primate Visual Cortex
Authors: Jermakowicz Walter J. , Chen Xin , Khaytin Ilya , Bonds A. B. , Casagrande Vivien A.
Published: February 2009

Coincident spikes have been implicated in vision-related processes such as feature binding, gain modulation, and long-distance communication. The source of these spike-time correlations is unknown. Although several studies have proposed that cortical spikes are correlated based on stimulus structure, others have suggested that spike-time correlations reflect ongoing cortical activity present even in the absence of a coherent visual stimulus. To examine this issue, we collected single-unit recordings from primary visual cortex (V1) of the anesthetized and paralyzed prosimian bush baby using a 100-electrode array. Spike-time correlations for pairs of cells were compared under three conditions: a moving grating at the cells’ preferred orientation, an equiluminant blank screen, and a dark condition with eyes covered. The amplitudes, lags, and widths of cross-correlation histograms (CCHs) were strongly correlated between these conditions although for the blank stimulus and dark condition, the CCHs were broader with peaks lower in amplitude. In both preferred stimulus and blank conditions, the CCH amplitudes were greater when the cells within the pair had overlapping receptive fields and preferred similar orientations rather than nonoverlapping receptive fields and different orientations. These data suggest that spike-time correlations present in evoked activity are generated by mechanisms common to those operating in spontaneous conditions.
Critical Time to Nucleation: Graphite and Silicon Nanoparticle Generation by Laser Ablation
Authors: Senadheera Sid , Tan Bo , Venkatakrishnan Krishnan
Published: February 2009

Femtosecond laser ablation hydrodynamics has been analyzed numerically. The nucleation process of two materials (silicon and graphite) in an expanding plume produced by a femtosecond laser ablation is analyzed within the framework of the Zeldovich-Raizer theory (RZ theory). RZ theory is the most appropriate theory applicable to an expanding plume created by a femtosecond laser ablation and has been used to estimate the critical times in the evolution of nanoparticle formation. However, there is no experimental result to directly substantiate the theoretical model on a fundamental level. This paper gives an experimental approach to prove theoretical predictions of critical times to nucleation in laser-ablated graphite and silicon plumes. The critical time to nucleation deduced using the RZ theory was found to be in close agreement with pulse frequency at which fibrous nanoparticle aggregates start to form for both materials. We experimentally showed that the nanoparticle aggregates were produced consistently when the pulse frequency corresponding to the femtosecond laser time interval was shorter than the critical time to begin nucleation. Therefore the nucleation time acts as a threshold time length to begin nucleation.
High Lifetime Incidence of Adult Acute Lymphoblastic Leukemia among Hispanics in California
Authors: Pullarkat Sheeja T. , Danley Kathleen , Bernstein Leslie , Brynes Russell K. , Cozen Wendy
Published: February 2009

Background: The higher incidence of acute lymphoblastic leukemia (ALL) among Hispanic children relative to that in other racial/ethnic groups is well-known. We evaluated the incidence patterns of ALL in adults.

Methods: We analyzed the incidence patterns of ALL (International Classification of Diseases for Oncology 3 codes 9835-9837) among all patients diagnosed from 1988 to 2004 in California using data from the California Cancer Registry to determine whether adult Hispanics also had higher incidence rates of ALL compared with non–Hispanic Whites (Whites). Age-adjusted incidence rates (AAIR), incidence rate ratios (IRR), and 5-year survival rates were obtained using SEER*Stat. AAIRs of other leukemia subtypes and IRRs relative to non–Hispanic Whites were also examined as references for ALL.

Results: AAIRs of ALL in Hispanic males and females ages 20 to 54 years were higher compared with those in White males and females (IRR, 1.99; 95% confidence interval, 1.74-2.28 and IRR, 1.91; 95% confidence interval, 1.60-2.25, respectively). A higher AAIR of ALL was also observed among older (55+ years) Hispanic females (IRR, 1.84; 95% confidence interval, 1.52-2.21), but not in males (IRR, 1.07; 95% confidence interval, 0.84-1.34). Among Hispanics, low socioeconomic status was associated with a higher AAIR compared with high/middle socioeconomic status (IRR, 1.33; 95% confidence interval, 1.04-1.70). The respective 5-year survival rates among ALL patients were 38% and 30% for Whites and Hispanics ages 20 to 54 years, and 8% and 12% for patients 55 years of age or older. Compared with other racial/ethnic groups, Hispanics did not have an increased IRR of the other major leukemia subtypes.

Conclusion: Hispanics experience a higher incidence of ALL throughout life, but not other subtypes. (Cancer Epidemiol Biomarkers Prev 2009;18(2):611–5)
Serum High-Density Lipoprotein Cholesterol and Breast Cancer Risk by Menopausal Status, Body Mass Index, and Hormonal Receptor in Korea
Authors: Kim Yeonju , Park Sue K. , Han Wonshik , Kim Dong-Hyun , Hong Yun-Chul , Ha Eun Hee , Ahn Sei-Hyun , Noh Dong-Young , Kang Daehee , Yoo Keun-Young
Published: February 2009

High-density lipoprotein cholesterol (HDL-C) has been suggested to be associated with breast cancer. However, the roles of HDL-C and hypertriglyceridemia on breast cancer still have been controversial. The goal of this study was to investigate the association between HDL-C with breast cancer risk, stratifying by menopausal status, and body mass index. The hormonal receptor status of breast has been proposed to modify the effect of HDL-C on breast cancer. Multicenter hospital-based case-control study was conducted from November 2004 to December 2005 in Korea. After one to two individual matchings by age (±5 years) and menopausal status, 690 cases and 1,380 controls were included in the analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by conditional, unconditional, and multinomial logistic regressions. Protective effect of HDL-C on breast cancer was only observed among premenopausal women with an OR (95% CI) of 0.49 (0.33-0.72) for HDL-C ≥60 versus <50 mg/dL (Ptrend < 0.01). Only nonobese premenopausal women had a significant decreased risk (OR, 0.34; 95% CI, 0.22-0.53). OR (95% CI) of low HDL-C (<50 mg/dL) and high triglyceride (TG; ≥150 mg/dL) category was 2.20 (1.32-3.67) on estrogen receptor-negative and progesterone receptor-negative breast cancer compared with high HDL-C (≥50 mg/dL) and low TG (<150 mg/dL) category. This study suggests that higher level of HDL-C may reduce breast cancer risk among premenopausal women. Estrogen receptor-negative and progesterone receptor-negative breast cancer was associated with dyslipidemia, which implicates that association among HDL-C, TG, and breast cancer may be modified by receptor status. (Cancer Epidemiol Biomarkers Prev 2009;18(2):508–15)
The Impact of Human Papillomavirus Information on Perceived Risk of Cervical Cancer
Authors: Marlow Laura A.V. , Waller Jo , Wardle Jane
Published: February 2009

There is a need to develop public education about the link between human papillomavirus (HPV) and cervical cancer. Explaining that a sexually transmitted virus causes cervical cancer may affect perceived risk of cervical cancer. We hypothesized that presenting HPV information would have differential effects depending on age and screening attendance. Data were collected during face-to-face interviews with a sample of British women age 16 to 75 years who had not heard of HPV before (n = 965). A repeated measures design was used, assessing perceived risk of cervical cancer before and after providing information about HPV. Perceived risk was assessed using a comparative risk measure with a five-point response scale. Preinformation, the mean perceived risk score was 2.64 (SE, 0.03). Overall, presentation of HPV information did not have an effect on perceived risk of cervical cancer [χ2(1) = .72; P = 0.396], but as expected, there was a significant time by age interaction for the change in perceived risk [χ2(5) = 33.56; P < 0.001], which increased in the youngest age group (16-25 years) and decreased in the oldest age group (65-75 years). In a separate analysis with women in the screening age range (25-64 years; n = 709), there was a significant time by screening attendance interaction [χ2(1) = 5.25; P = 0.022], with an increase in perceived risk among women who did not regularly attend screening. This is the first study to examine the effect of HPV information on perceived risk across different population groups. Interventions to increase awareness of HPV could benefit from tailoring information to prescreening age, screening age, and postscreening age women. (Cancer Epidemiol Biomarkers Prev 2009;18(2):373–6)
Serum Levels of Soluble Mesothelin-Related Peptides in Malignant and Nonmalignant Asbestos-Related Pleural Disease: Relation with Past Asbestos Exposure
Authors: Rodríguez Portal José A. , Rodríguez Becerra Eulogio , Rodríguez Rodríguez David , Alfageme Michavila Inmaculada , Quero Martínez Aida , Diego Roza Carmen , León Jiménez Antonio , Isidro Montes Isabel , Cebollero Rivas Pilar
Published: February 2009

Background: Malignant pleural mesothelioma (MPM) results from malignant transformation of mesothelial cells. Past asbestos exposure represents a major risk factor for MPM and other benign pleural disease. Soluble mesothelin-related peptides (SMRP) have been regarded as a promising serum biomarker for MPM. The aim of this study was to investigate serum levels of SMRP in malignant and nonmalignant asbestos-related pleural disease.

Patients: Four groups of patients were investigated: group 1 composed of 48 healthy subjects, group 2 composed of 177 patients with previous asbestos exposure and no pleural disease, group 3 composed of 36 patients with MPM, and group 4 composed of 101 patients with previous asbestos exposure and benign pleural disease. Serum SMRP levels were determined by ELISA.

Results: Serum SMRP levels were significantly higher among group 3 than the other three groups. There were no differences in SMRP concentrations between groups 2 and 4. Subjects exposed to asbestos had higher SMRP concentrations than normal control subjects regardless of the presence of pleural disease. The area under the receiver operating characteristic curve for SMRP values was 0.75 (95% confidence interval, 0.68-0.83). The SMRP level at 0.55 nmol/L/L was determined as the most optimal cutoff value with resulting sensitivity and specificity of 72% and 72% for the diagnosis of MPM.

Conclusions: These data attest to good diagnostic sensitivity and specificity of SMRP for the diagnosis of malignant mesothelioma. We have also shown that serum SMRP levels might serve as a marker of asbestos exposure. (Cancer Epidemiol Biomarkers Prev 2009;18(2):646–50)
Telomere Length, Current Perceived Stress, and Urinary Stress Hormones in Women
Authors: Parks Christine G. , Miller Diane B. , McCanlies Erin C. , Cawthon Richard M. , Andrew Michael E. , DeRoo Lisa A. , Sandler Dale P.
Published: February 2009

Telomeres are repetitive DNA sequences that cap and protect the ends of chromosomes; critically short telomeres may lead to cellular senescence or carcinogenic transformation. Previous findings suggest a link between psychosocial stress, shorter telomeres, and chronic disease risk. This cross-sectional study examined relative telomere length in relation to perceived stress and urinary stress hormones in a sample of participants (n = 647) in the National Institute of Environmental Health Sciences Sister Study, a cohort of women ages 35 to 74 years who have a sister with breast cancer. Average leukocyte telomere length was determined by quantitative PCR. Current stress was assessed using the Perceived Stress Scale and creatinine-adjusted neuroendocrine hormones in first morning urines. Linear regression models estimated differences in telomere length base pairs (bp) associated with stress measures adjusted for age, race, smoking, and obesity. Women with higher perceived stress had somewhat shorter telomeres [adjusted difference of −129bp for being at or above moderate stress levels; 95% confidence interval (CI), −292 to 33], but telomere length did not decrease monotonically with higher stress levels. Shorter telomeres were independently associated with increasing age (−27bp/year), obesity, and current smoking. Significant stress-related differences in telomere length were seen in women ages 55 years and older (−289bp; 95% CI, −519 to −59), those with recent major losses (−420bp; 95% CI, −814 to −27), and those with above-average urinary catecholamines (e.g., epinephrine: −484bp; 95% CI, −709 to −259). Although current perceived stress was only modestly associated with shorter telomeres in this broad sample of women, our findings suggest the effect of stress on telomere length may vary depending on neuroendocrine responsiveness, external stressors, and age. (Cancer Epidemiol Biomarkers Prev 2009;18(2):551–60)
Nuclear Overexpression of Mitotic Regulatory Proteins in Biliary Tract Cancer: Correlation with Clinicopathologic Features and Patient Survival
Authors: Shen Ying-Chun , Hu Fu-Chang , Jeng Yung-Ming , Chang Yu-Ting , Lin Zhong-Zhe , Chang Ming-Chu , Hsu Chiun , Cheng Ann-Lii
Published: February 2009

Mitosis dysregulation is common in cancers. This study explored the nuclear expression patterns and prognostic significance of mitotic regulatory proteins, including Aurora kinases, survivin, and p53, in biliary tract cancer (BTC). Archival tumor samples from 161 BTC patients who underwent surgery were tested for the expression of Aurora-A, Aurora-B, survivin, and p53 by immunohistochemistry. The potential endogeneity among the clinicopathologic variables and survival outcome was assessed by a generalized simultaneous equations model. Nuclear overexpression of Aurora-A, Aurora-B, survivin, and p53 was found in 79 (49.1%), 45 (28.0%), 55 (34.2%), and 55 (34.2%) patients, respectively. Intrahepatic cholangiocarcinoma, compared with the other two subtypes, had significantly higher proportions of nuclear overexpression of Aurora-B and survivin (37.8% and 47.3%, respectively). Simultaneous overexpression of Aurora-A and Aurora-B was correlated with that of p53. Overexpression of Aurora-B was also correlated with that of survivin and tumor grade. Our data indicate that simultaneous overexpression of Aurora-A and Aurora-B, suggesting dysregulated mitosis is associated with worse survival in patients with BTC. Independent prognostic factors for poor overall survival included simultaneous overexpression of Aurora-A and Aurora-B (hazard ratio, 1.997; 95% confidence interval, 1.239-3.219; P = 0.0045) and tumor grade (hazard ratio, 2.117; 95% confidence interval, 1.339-3.348; P = 0.0013) assessed by a multivariate analysis stratified by American Joint Committee on Cancer stage and p53 overexpression. Endogeneity testing suggested that nuclear overexpression of p53 and tumor type may influence patient survival through their interactions with Aurora-A/Aurora-B expression and tumor grade. (Cancer Epidemiol Biomarkers Prev 2009;18(2):417–23)