bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel In Vivo Model for the Study of Human Immunodeficiency Virus Type 1 Transcription Inhibitors: Evaluation of New 6-Desfluoroquinolone Derivatives
Authors: Stevens Miguel , Pollicita Michela , Pannecouque Christophe , Verbeken Erik , Tabarrini Oriana , Cecchetti Violetta , Aquaro Stefano , Perno Carlo Federico , Fravolini Arnaldo , De Clercq Erik , Schols Dominique , Balzarini Jan
Published: January 2007

Two novel 6-desfluoroquinolone derivatives, HM-12 and HM-13, were evaluated for anti-human immunodeficiency virus (anti-HIV) activity in acutely, chronically, and latently HIV type 1 (HIV-1)-infected cell cultures and were found to behave as potent HIV-1 transcription inhibitors. In order to extend this result in vivo, we developed an artificial hu-SCID mouse model for HIV-1 latency based on SCID mice engrafted with latently HIV-1-infected promyelocytic OM-10.1 cells in which HIV-1 can be reactivated in vivo by the administration of human tumor necrosis factor alpha (hTNF-α). Treating these SCID mice with HM-12 or HM-13 prior to hTNF-α stimulation resulted in a pronounced suppressive effect on viral reactivation. Since both quinolone derivatives were able to inhibit the reactivation of HIV-1 from this artificial viral reservoir in vivo, we provide encouraging evidence for the use of quinolones in the control of HIV-1 infections.
Lactobacillus paracasei
subsp.
paracasei
B21060 Suppresses Human T-Cell Proliferation
Authors: Peluso Ilaria , Fina Daniele , Caruso Roberta , Stolfi Carmine , Caprioli Flavio , Fantini Massimo Claudio , Caspani Giorgio , Grossi Enzo , Di Iorio Laura , Paone Francesco Maria , Pallone Francesco , Monteleone Giovanni
Published: January 2007

Recent studies have shown that probiotics are beneficial in T-cell-mediated inflammatory diseases. The molecular mechanism by which probiotics work remains elusive, but accumulating evidence indicates that probiotics can modulate immune cell responses. Since T cells express receptors for bacterial products or components, we examined whether different strains of lactobacilli directly regulate the functions of human T cells. CD4
+
T cells were isolated from blood and intestinal lamina propria (LP) of normal individuals and patients with inflammatory bowel disease (IBD). Mononuclear cells were also isolated from Peyer's patches. Cells were activated with anti-CD3/CD2/CD28 in the presence or absence of
Lactobacillus paracasei
subsp.
paracasei
B21060,
L. paracasei
subsp.
paracasei
F19, or
L. casei
subsp.
casei
DG. Cell proliferation and death, Foxp3, intracellular pH, and cytokine production were evaluated by flow cytometry. We showed that
L. paracasei
subsp.
paracasei B21060
but neither
L. paracasei
subsp.
paracasei
F19 nor
L. casei
subsp.
casei
DG inhibited blood CD4
+
T-cell growth. This effect was associated with no change in cell survival, expression of Foxp3, or production of gamma interferon, interleukin-4 (IL-4), IL-5, and IL-10.
L. paracasei
subsp.
paracasei
B21060-mediated blockade of CD4
+
T-cell proliferation required a viable bacterium and was associated with decreased MCT-1 expression and low intracellular pH.
L. paracasei
subsp.
paracasei
B21060 also inhibited the growth of Peyer's patch mononuclear cells, normal lymphocytes, and IBD CD4
+
LP lymphocytes without affecting cytokine production. The data show that
L. paracasei
subsp.
paracasei
B21060 blocks T-cell growth, thus suggesting a mechanism by which these probiotics could interfere with T-cell-driven immune responses.
ON THE PRINCIPLE OF CONTROLLED L∞CONVERGENCE IMPLIES ALMOST EVERYWHERE CONVERGENCE FOR GRADIENTS
Authors: ZHANG KEWEI
Published: January 2007

Let Ω ⊂ ℝnbe a bounded open set. If a sequence fk: Ω → ℝNconverges to f in L∞in a certain "controlled" manner while bounded in W1,p(1 < p < + ∞) or BV, we show that f ∈ W1,p(respectively, f ∈ BV) and ∇fk→ ∇f almost everywhere, where ∇fkand ∇f are the usual gradients if fk∈ W1,p(respectively, the absolutely continuous part of the gradient measures if fk∈ BV). Our main theorem generalizes results for Lipschitz mappings. We show by an example that when p = 1, the limit of a sequence of increasing functions may fail to be in W1,1and can even be nowhere C1.
PREDICTION OF DNA-BINDING RESIDUES FROM SEQUENCE FEATURES
Authors: WANG LIANGJIANG , BROWN SUSAN J.
Published: January 2007

Protein–DNA interaction plays a pivotal role in transcriptional regulation, DNA metabolism and chromatin formation. Although structural data are available for a few hundreds of protein–DNA complexes, the molecular recognition pattern is still poorly understood. With the rapid accumulation of sequence data from many genomes, it is important to develop predictive methods for identification of potential DNA-binding residues in proteins. In this study, neural networks have been trained using five sequence-derived features for prediction of DNA-binding residues. These features include the molecular mass, hydrophobicity index, side chain p K a value, solvent accessible surface area and conservation score of an amino acid. Interestingly, the side chain p K a value appears to be the best feature for prediction, suggesting that the ionization state of amino acid side chains is important for DNA-binding. The predictive performance is enhanced by using multiple features for classifier construction. The classifier that has been constructed using all the five features predicts at 72.71% sensitivity and 67.73% specificity. This is by far the most accurate classifier reported for prediction of DNA-binding residues from sequence data. The classifier has also been evaluated by using the Receiver Operating Characteristic curve and by examining the predictions made for different classes of DNA-binding proteins. Supplementary materials including the datasets are available at .
HYPLOSP: A KNOWLEDGE-BASED APPROACH TO PROTEIN LOCAL STRUCTURE PREDICTION
Authors: CHEN CHING-TAI , LIN HSIN-NAN , SUNG TING-YI , HSU WEN-LIAN
Published: January 2007

Local structure prediction can facilitate ab initio structure prediction, protein threading, and remote homology detection. However, the accuracy of existing methods is limited. In this paper, we propose a knowledge-based prediction method that assigns a measure called the local match rate to each position of an amino acid sequence to estimate the confidence of our method. Empirically, the accuracy of the method correlates positively with the local match rate; therefore, we employ it to predict the local structures of positions with a high local match rate. For positions with a low local match rate, we propose a neural network prediction method. To better utilize the knowledge-based and neural network methods, we design a hybrid prediction method, HYPLOSP (HYbrid method to Protein LOcal Structure Prediction) that combines both methods. To evaluate the performance of the proposed methods, we first perform cross-validation experiments by applying our knowledge-based method, a neural network method, and HYPLOSP to a large dataset of 3,925 protein chains. We test our methods extensively on three different structural alphabets and evaluate their performance by two widely used criteria, Maximum Deviation of backbone torsion Angle (MDA) and QN, which is similar to Q3in secondary structure prediction. We then compare HYPLOSP with three previous studies using a dataset of 56 new protein chains. HYPLOSP shows promising results in terms of MDA and QNaccuracy and demonstrates its alphabet-independent capability.
CHARACTERIZATION OF THE EXISTENCE OF GALLED-TREE NETWORKS
Authors: GUPTA ARVIND , MAŇUCH JÁN , ZHAO XIAOHONG , STACHO LADISLAV
Published: January 2007

In this paper, we give a complete characterization of the existence of a galled-tree network in the form of simple sufficient and necessary conditions for both root-known and root-unknown cases. As a by-product we obtain a simple algorithm for constructing galled-tree networks. We also introduce a new necessary condition for the existence of a galled-tree network similar to bi-convexity.
HAAR METHOD, AVERAGED MATRIX, WAVE CANCELLATIONS, AND L1STABILITY FOR HYPERBOLIC SYSTEMS
Authors: LEFLOCH PHILIPPE G.
Published: January 2007

We develop a version of Haar and Holmgren methods which applies to discontinuous solutions of nonlinear hyperbolic systems and allows us to control the L1distance between two entropy solutions. The main difficulty is to cope with linear hyperbolic systems with discontinuous coefficients. Our main observation is that, while entropy solutions contain compressive shocks only, the averaged matrix associated with two such solutions has compressive or undercompressive shocks, but no rarefaction-shocks — which are recognized as a source for non-uniqueness and instability. Our Haar–Holmgren-type method rests on the geometry associated with the averaged matrix and takes into account adjoint problems and wave cancellations along generalized characteristics. It generalizes the method proposed earlier by LeFloch et al. for genuinely nonlinear systems. In the present paper, we cover solutions with small total variation and a class of systems with general flux that need not be genuinely nonlinear and includes for instance fluid dynamics equations. We prove that solutions generated by Glimm or front tracking schemes depend continuously in the L1norm upon their initial data, by exhibiting an L1functional controlling the distance between two solutions.
Konane as a vehicle for teaching AI
Authors: Gyllenskog Joel H.
Published: January 2007

The game of Konane is described and suggested as a suitable vehicle for use in teaching artificial intelligence in a classroom situation. Examples of programs played by computers are given. A simple technique for avoiding repeated losses by computers in games against humans is presented.
Theory and practice of cross-traffic estimation
Authors: Machiraju Sridhar , Veitch Darryl , Baccelli François , Nucci Antonio , Bolot Jean C.
Published: January 2007

Active probing heuristics are usually based on queuing systems. However, a rigorous probabilistic treatment of probing methods has been lacking. For instance, it is not known even in principle, what can and cannot be measured in general, nor the true limitations of existing methods. We provide a probabilistic treatment for the measurement of cross traffic in the 1-hop case. We derive inversion formulae for the cross traffic process, and explain their fundamental limits, using an intuitive geometric framework.
A taxonomy approach to simulation model documentation
Authors: Highland Harold Joseph
Published: January 2007

In preparing this presentation I find myself in the ineluctable position of an applications-oriented practioners espousing a pedogical approach to simulation model documentation. Although theoretically cloistered in an academic environment, my teaching is applications-oriented and not theoretical, a reflection not only of my industrial background but also my lack of a formal theoretical education in computer science.
Multi-level RAID for very large disk arrays
Authors: Thomasian Alexander
Published: January 2007

Very Large Disk Arrays - VLDAs have been developed to cope with the rapid increase in the volume of data generated requiring ultrareliable storage. Bricks or Storage Nodes - SNs holding a dozen or more disks are cost effective VLDA building blocks, since they cost less than traditional disk arrays. We utilize the Multilevel RAID - MRAID paradigm for protecting both SNs and their disks. Each SN is a k-disk-failure-tolerant kDFT array, while replication or
l
-node failure tolerance -
l
NFTs paradigm is applied at the SN level. For example, RAID1(M)/5(N) denotes a RAID1 at the higher level with a degree of replication
M
and each virtual disk is an SN configured as a RAID5 with
N
physical disks. We provide the data layout for RAID5/5 and RAID6/5 MRAIDs and give examples of updating data and recovering lost data. The former requires
storage transactions
to ensure the atomicity of storage updates. We discuss some weaknesses in reliability modeling in RAID5 and give examples of an asymptotic expansion method to compare the reliability of several MRAID organizations. We outline the reliability analysis of Markov chain models of VLDAs and briefly report on conclusions from simulation results. In Conclusions we outline areas for further research.
The TREC 2005 robust track
Authors: Voorhees Ellen M.
Published: January 2007

The TREC robust retrieval track explores methods for improving the consistency of retrieval technology by focusing on poorly performing topics. The retrieval task in the track is a traditional ad hoc retrieval task where the evaluation methodology emphasizes a system's least effective topics. The 2005 edition of the track used 50 topics that had been demonstrated to be difficult on one document collection, and ran those topics on a different document collection. Relevance information from the first collection could be exploited in producing a query for the second collection, if desired. As in previous years, the most effective retrieval strategy was to expand queries using terms derived from additional corpora. The relative difficulty of topics differed across the two document sets.
Motivation and performance in the information systems field
Authors: Myers Martha E.
Published: January 2007

Motivation is important. In today's economy, it is vital that all scarce resources - especially human resources - be utilized efficiently and effectively. Daft and Steers state unequivocally that motivation is the foundation upon which human resources may be optimally utilized (1986).Prior studies of motivation in the information systems (IS) profession have led to inconclusive and, even contradictory results. It may be that these apparently inconsistent results are actually evidence of a rapidly changing and evolving profession. Several IS research articles have documented rapidly occurring changes within IS job environments, changes in development methodologies and IS organizational structure. Thus, an assessment of the fit between the IS professional and the changing IS work environment is a fundamental component of IS human resource management. Knowledge of job fit in this profession is crucial to each phase of human resource development, from recruitment to evaluation and training.The primary purpose of this paper is to review personnel literature within the context of a larger picture of IS motivation:• Motivation in the IS profession• The evolving IS work environment• Job fit within the IS profession• Related studies from other disciplines
SCinet '91
Authors: Nussbaum Alex
Published: January 2007

Albuquerque, NM: In a spirit of cooperation unparalleled in the computing business, technicians, company CEOs, scientists, and engineers worked together to create SCinet '91, a gigabit network designed specifically for SUPERCOMPUTING '91, the fourth conference on high-performance computing, held November 18-22 in Albuquerque. In addition to hundreds of person-hours in the past few weeks and several months of planning, donations of cable and equipment came from Cray Research, IBM, Digital Equipment, USWest Communications, Network Systems, Ultra Network Technologies, SynOptics Communications, Broadband Communications Products, Interop, Aquila Group, and Siecor to develop this unique example of the cooperation and networking envisioned in the National Research and Education Network (NREN). NREN is part of the President's High Performance Computing and Communication initiative, a bill that just passed in the House of Representatives and is currently in the Senate. The keynote address at the conference was given by D. Allan Bromley, Science Advisor to the President, who expressed strong hope that the bill would pass.
Cultural diversity in user interface design
Authors: Teasley Barbee , Leventhal Laura , Blumenthal Brad , Instone Keith , Stone Daryl
Published: January 2007

In a Communications of the ACM article of April 1993 ("Human Communications Issues in Advanced UIs," pp. 101--109), Aaron Marcus makes a number of compelling points about the design of interactive computer systems for demographically-diverse user populations. In particular, he advocates interfaces that support users by providing an "appealing perceptual experience" both in their appearance ("look") and behavior ("feel"). He contends that the path to such appealing interfaces involves developing and evaluating candidate scenarious through "either professional intuition or focus groups, [developing] prototypes quickly, [evaluating] their utility carefully through testing, and [implementing] a practical version."
Book review: Usability Inspection Methods edited by Jakob Nielsen and Robert L. Mack (John Wiley & Sons, Inc., 1994)
Authors: Merrill Douglas C.
Published: January 2007

In recent years, organizations have become more and more concerned with the concept of "usability," the ease with which customers will be able to employ an artifact, be it a computer program or a voice mail system. Usability Inspection is a rapidly growing science concerned with developing tools and techniques for identifying potential problems that will face customers using the artifact during the design process, rather than discovering them after the product has gone to market. This edited volume fills an important niche, by describing a variety of methods employed by usability engineers and comparing their effectiveness. The editors planned the volume, which arose out of a CHI 1992 workshop, to be used as a primer for students or user interface practitioners. Many of the chapters are very useful for this purpose, however the book as a whole is somewhat redundant, and some of the contributions are too vague to be of much value to a novice in the field.
A multiparadigmatic environment for interacting with databases
Authors: Catarci T. , Costabile M. F. , Massari A. , Saladini L. , Santucci G.
Published: January 2007

We present a prototype system to be used for visually accessing heterogeneous databases. The basic idea is to provide the user with several visual representations of data as well as multiple interaction mechanisms for both querying databases and visualizing the query results. Since some visual representations better fit certain user classes, the system adapts to the user's needs by switching to the most appropriate visual representation and interaction mechanism, according to a suitable user model. The data and query representations are consistent in every paradigm. Such a notion of consistency stems from formal basis, i.e. a twofold data/representation model, namely the Graph Model, and a set of basic Graphical Primitives. This formal approach allows the user to switch from one interaction paradigm to another, always saving the query state.
Concurrency preserving partitioning (CPP) for parallel logic simulation
Authors: Kim Hong K. , Jean Jack
Published: January 2007

Based on a linear ordering of vertices in a directed graph, a linear-time partitioning algorithm for parallel logic simulation is presented. Unlike most other partitioning algorithms, the proposed algorithm preserves circuit concurrency by assigning to processors circuit gates that can be evaluated at about the same time. As a result, the concurrency preserving partitioning (CPP) algorithm can provide better load balancing throughout the period of a parallel simulation. This is especially important when the algorithm is used together with a Time Warp simulation where a high degree of concurrency can lead to fewer rollbacks and better performance. The algorithm consists of three phases, and three conflicting goals can be separately considered in each phase so to reduce computational complexity. A parallel gate-level circuit simulator is implemented on an Intel Paragon machine to evaluate the performance of the CPP algorithm. The results are compared with two other partitioning algorithms to show that reasonable speedup may be achieved with the algorithm.
Monitoring anytime algorithms
Authors: Hansen Eric A. , Zilberstein Shlomo
Published: January 2007

Anytime algorithms offer a tradeoff between solution quality and computation time that has proved useful in applying artificial intelligence techniques to time-critical problems. To exploit this tradeoff, a system must be able to determine the best time to stop deliberation and act on the currently available solution. If there is uncertainty about how much solution quality will improve with computation time, or about how the problem state may change after the start of the algorithm, monitoring the algorithm's progress and/or the problem state can make possible a better stopping decision and so improve the utility of the system. This paper analyzes the issues involved in run-time monitoring of anytime algorithms. It reviews previous work and casts the problem in a new framework from which some improved monitoring strategies emerge.
Design and code reuse based on fuzzy classification of components
Authors: Damiani E. , Fugini M. G.
Published: January 2007

A bottleneck in software reuse is the classification schema and retrieval method of components. Particularly when large repositories of components are available, classification and retrieval for reuse should be flexible to allow the selection also of components which, although not perfectly matching requirements, are adaptable with a limited effort. This paper presents a fuzzy classification model for a repository storing descriptors of components. These descriptors include fuzzy-weighted keyword pairs describing components functionalities extracted from code and its design documentation. A mechanism for semi-automatic extraction of keywords, and for automatic assignement of fuzzy weights to keyword pairs based on text retrieval algorithms is provided.
The concept of relevant time scales and its application to queuing analysis of self-similar traffic (or is Hurst naughty or nice?)
Authors: Neidhardt Arnold L. , Wang Jonathan L.
Published: January 2007

Recent traffic analyses from various packet networks have shown the existence of long-range dependence in bursty traffic. In evaluating its impact on queuing performance, earlier investigations have noted how the presence of long-range dependence, or a high value of the Hurst parameter
H
, is often associated with surprisingly large queue sizes. As a result, a common impression has been created of expecting queuing performance to be worse as
H
increases, but this impression can be misleading. In fact, there are examples in which larger values of
H
are associated with smaller queues. So the question is how can one tell whether queuing performance would improve or degrade as
H
rises? In this paper, we show that the relative queuing performance can be assessed by identifying a couple of time scales. First, in comparing a high-
H
process with a low-
H
process, there is a unique time scale

t
m

at which the variances of the two processes match (assuming exact, second-order self similarity for both processes). Second, there are time scales

t
qi

that are most relevant for queuing the arrivals of process
i
. If both of the queuing scales

t
qi

exceed the variance-matching scale

t
m

, then the high-
H
queue is worse; if the queuing scales are smaller, then the low-
H
queue is worse. However, no firm prediction can be made in the remaining case of

t
m

falling between the two queuing scales. Numerical examples are given to demonstrate our results.
Application performance pitfalls and TCP's Nagle algorithm
Authors: Minshall Greg , Saito Yasushi , Mogul Jeffrey C. , Verghese Ben
Published: January 2007

Performance improvements to networked applications can have unintended consequences. In a study of the performance of the Network News Transport Protocol (NNTP), the initial results suggested it would be useful to disable TCP's Nagle algorithm for this application. Doing so significantly improved latencies. However, closer observation revealed that with the Nagle algorithm disabled, the application was transmitting an order of magnitude more packets. We found that proper application buffer management significantly improves performance, but that the Nagle algorithm still slightly increases mean latency. We suggest that modifying the Nagle algorithm would eliminate this cost.
Hypertext '87
Authors: Nielsen Jakob
Published: January 2007

Hypertext '87
was the first large-scale meeting devoted to the hypertext concept. Before the workshop, hypertext had been considered a somewhat esoteric concept of interest to a few fanatics only. So just in case some readers don't know what hypertext is, let me start by defining it.
INCREASING PERSONAL PRODUCTIVITY OF ADULTS WITH BRAIN INJURIES THROUGH INTERFACE DESIGN
Authors: Cole Elliot , Bergman Marilyn M. , Bendashti Parto
Published: January 2007

This poster-session paper addresses interface issues which arise when the user has traumatic brain injury (TBI). The case study documents the failure of a commercial product's interface, and redesign of the interface to overcome failures. Quantitative data are presented on performance of both interfaces. Implications for user models and for interface management systems are discussed.
Geocast enhancements of AODV for vehicular networks
Authors: Schwingenschlogl Christian , Kosch Timo
Published: January 2007

Because of its reactive nature, AODV can handle the highly-dynamic behavior of vehicular Ad-Hoc networks relatively efficiently. However, in addition to link status information, a lot of other information is available within cars, e.g. information about speed and location as well as digital maps. The realization of some of the envisioned application scenarios depends on the additional usage of this information. In this paper, we motivate the usage of GPS- and vehicle velocity data for geocast applications in the vehicular environment. We also describe the prototype that we are developing based on NIST-AODV [4].
A concurrent migration extension to an end-to-end host mobility architecture
Authors: Tilak Sameer , Abu-Ghazaleh Nael B.
Published: January 2007

With the proliferation of mobile devices and the emergence of the internet as a global communication and business medium, there is significant interest in providing robust, high-performance, internet connectivity to protable devices. This requires seamless delivery of data between the peers even as they change location. The accepted solution for mobility is Mobile IP, an IETF standard supporting mobility in the network layer. Recently, Snoren and Balakrishnan suggested an end-to-end implementation that uses dynamic DNS updates and transport layer connection migration to implement seamless mobility. This approach has several advantages and it is conceivable that it will replace (or co-exist) with Mobile IP to implement mobility. One of the restrictions in the proposed implementation is that it does not support the case where both peers can migrate. In this note, we propose an extension to the end-to-end implementation to allow concurrent peer migration.
A survey and comparison of business-to-business e-commerce frameworks
Authors: Dogac Asuman , Cingil Ibrahim
Published: January 2007

Business-to-business (B2B) e-commerce is booming thanks to the ubiquity of the Internet, which dwarfs the coverage of EDI VANs. B2B e-commerce needs to seamlessly and dynamically handle the interactions among a vast variety of organizations without ad hoc and proprietary integrations. A number of B2B e-commerce frameworks have emerged as a result. In this paper we present a brief survey and a comparison of some of these frameworks.
Mobilization of osmotically inactive Na+ by growth and by dietary salt restriction in rats
Authors: Schafflhuber Markus , Volpi Nicola , Dahlmann Anke , Hilgers Karl F. , Maccari Francesca , Dietsch Peter , Wagner Hubertus , Luft Friedrich C. , Eckardt Kai-Uwe , Titze Jens
Published: January 2007

The idea that an osmotically inactive Na+ storage pool exists that can be varied to accommodate states of Na+ retention and/or Na+ loss is controversial. We speculated that considerable amounts of osmotically inactive Na+ are lost with growth and that additional dietary salt excess or salt deficit alters the polyanionic character of extracellular glycosaminoglycans in osmotically inactive Na+ reservoirs. Six-week-old Sprague-Dawley rats were fed low-salt (0.1%; LS) or high-salt (8%; HS) diets for 1 or 4 wk. At their death, we separated the tissues and determined their Na+, K+, and water content. Three weeks of growth reduced the total body Na+ content relative to dry weight (rTBNa+) by 23%. This “growth-programmed” Na+ loss originated from the bone and the completely skinned and bone-removed carcasses. The Na+ loss was osmotically inactive (45–50%) or osmotically active (50–55%). In rats aged 10 wk, compared with HS, 4 wk of LS reduced rTBNa+ by 9%. This dietary-induced Na+ loss was osmotically inactive (≈50%) and originated largely from the skin, while ≈50% was osmotically active. LS for 1 wk did not reduce skin Na+ content. The mobilization of osmotically inactive skin Na+ with long-term salt deprivation was associated with decreased negatively charged skin glycosaminoglycan content and thereby a decreased water-free Na+ binding capacity in the extracellular matrix. Our data not only serve to explain discrepant results in salt balance studies but also show that glycosaminoglycans may provide an actively regulated interstitial cation exchange mechanism that participates in volume and blood pressure homeostasis.
Size at Birth and Autonomic Function During Psychological Stress
Authors: Jones Alexander , Beda Alessandro , Ward Alexandra M.V. , Osmond Clive , Phillips David I.W. , Moore Vivienne M. , Simpson David M.
Published: January 2007

Small size at birth is associated with exaggerated blood pressure responses to psychological stressors, which increase the risk of developing sustained hypertension in adult life. Explanatory mechanisms for this association are not well characterized. We investigated the hypothesis that an adverse fetal environment, reflected by small size at birth, persistently alters autonomic nervous system and baroreflex control of cardiovascular function, resulting in exaggerated blood pressure and heart rate responses to stressors. Men and women from an Australian prospective cohort study underwent a series of 3 psychological stressors (Stroop, mirror-tracing, and speech) while their blood pressure was recorded continuously using a Portapres. Indices of autonomic function were derived using spectrum analysis (wavelet packet transform), and baroreflex function was estimated using an adaptive autoregressive model. We found that women who were small at birth demonstrated increased levels of low-frequency blood pressure variability at rest (
r
=−0.28;
P
<0.05) and during stress (
r
=−0.42;
P
<0.001), reduced levels of high-frequency heart period variability (
r
=0.22;
P
<0.05), and reduced baroreflex sensitivity (
r
=0.34;
P
<0.01). These findings were not present in the men. This study provides evidence that markers of impaired fetal growth are related to autonomic cardiovascular control involving modulation of both sympathetic and parasympathetic function but in a sex-specific manner. We also provide the first human evidence of a relationship between size at birth and baroreflex function.
Satellite and Buoy Observations of Boreal Summer Intraseasonal Variability in the Tropical Northeast Pacific
Authors: Maloney Eric D. , Esbensen Steven K.
Published: January 2007

Tropical intraseasonal variability in the eastern North Pacific during June–September of 2000–03 is analyzed using satellite and buoy observations. Quick Scatterometer ocean vector winds and the Tropical Rainfall Measuring Mission (TRMM) precipitation indicate that periods of anomalous surface westerly flow over the east Pacific warm pool during a summertime intraseasonal oscillation (ISO) life cycle are generally associated with an enhancement of convection to the east of 120°W. An exception is a narrow band of suppressed precipitation along 8°N that is associated with negative column-integrated precipitable water anomalies and anticyclonic vorticity anomalies. Periods of surface easterly anomalies are generally associated with suppressed convection to the east of 120°W. Summertime wind jets in the Gulfs of Tehuantepec and Papagayo exhibit heightened activity during periods of ISO easterly anomalies and suppressed convection. Strong variations in east Pacific warm pool wind speed occur in association with the summertime ISO. Anomalous ISO westerly flow is generally accompanied by enhanced wind speed to the east of 120°W, while anomalous easterly flow is associated with suppressed wind speed. Intraseasonal vector wind anomalies added to the climatological flow account for the bulk of the wind speed enhancement in the warm pool during the westerly phase, while the easterly phase shows strong contributions to the negative wind speed anomaly from both intraseasonal vector wind anomalies and suppressed synoptic-scale eddy activity. An analysis using Tropical Atmosphere Ocean buoys and TRMM precipitation suggests that wind–evaporation feedback is important for supporting summertime intraseasonal convection over the east Pacific warm pool. A statistically significant correlation of 0.6 between intraseasonal latent heat flux and precipitation occurs at the 12°N, 95°W buoy. Correlations between precipitation and latent heat flux at the 10°N, 95°W and 8°N, 95°W buoys are positive (0.4), but not statistically significant. Intraseasonal latent heat flux anomalies at all buoys are primarily wind induced. Consistent with the suppressed convection there during the ISO westerly phase, a negative but not statistically significant correlation (−0.3) occurs between precipitation and latent heat flux at the 8°N, 110°W buoy.
Effect of a Single Cyclosporine Dose on the Single‐Dose Pharmacokinetics of Sitagliptin (MK‐0431), a Dipeptidyl Peptidase‐4 Inhibitor, in Healthy Male Subjects
Authors: Krishna Rajesh , Bergman Arthur , Larson Patrick , Cote Josee , Lasseter Kenneth , Dilzer Stacey , Wang Amy , Zeng Wei , Chen Li , Wagner John , Herman Gary
Published: January 2007

Sitagliptin (MK‐0431) is an orally active, potent, and selective dipeptidyl peptidase‐4 inhibitor used for the treatment of patients with type 2 diabetes mellitus. Sitagliptin has been shown to be a substrate for P‐glycoprotein in preclinical studies. Cyclosporine was used as a probe P‐glycoprotein inhibitor at a high dose to evaluate the potential effect of potent P‐glycoprotein inhibition on single‐dose sitagliptin pharmacokinetics in healthy male subjects. Eight healthy young men received a single oral 600‐mg dose of cyclosporine with a single 100‐mg oral sitagliptin dose and a single oral 100‐mg sitagliptin dose alone in an open‐label, randomized, 2‐period, crossover study. Single doses of sitagliptin with or without single doses of cyclosporine were generally well tolerated. The sitagliptin AUC0‐∞ geometric mean ratio was 1.29 with a 90% confidence interval of (1.24, 1.34). The sitagliptin Cmax geometric mean ratio was 1.68 with a 90% confidence interval of (1.35, 2.08). Cyclosporine coadministration did not appear to affect apparent sitagliptin renal clearance, t1/2, or C24 h, suggesting that effects of these high doses of cyclosporine are more likely due to enhanced absorption of sitagliptin, potentially through inhibition of intestinal P‐glycoprotein. These results rationalize the use of a single high‐dose cyclosporine as a probe inhibitor of P‐glycoprotein for compound candidates whose elimination is less dependent on CYP3A4‐mediated metabolism.
Examining the Original Grasmick Scale
Authors: Higgins George E.
Published: January 2007

The original Grasmick, Tittle, Bursik, and Arneklev self-control scale is frequently used in self-control theory studies. Examining self-control requires precision in measurement. Using the Rasch rating scale model analysis, the Grasmick et al. scale is evaluated for construct validity in a college student sample. The results show that the 4-point Likert-type format response categories are not suitable for the scale. The distribution of the measures does not align with the distribution of the item measures in the original Grasmick et al. scale. The items do not fit the Rasch model, they do not form a unidimensional trait, and they function differently for males and females. Thus, the original Grasmick et al. scale does not have construct validity. A revised scale is presented that meets the standards of the Rasch model.
Analysis of mitotic phosphorylation of Borealin
Authors: Kaur Harpreet , Stiff Andrew C , Date Dipali A , Taylor William R
Published: January 2007

Background

The main role of the chromosomal passenger complex is to ensure that Aurora B kinase is properly localized and activated before and during mitosis. Borealin, a member of the chromosomal passenger complex, shows increased expression during G2/M phases and is involved in targeting the complex to the centromere and the spindle midzone, where it ensures proper chromosome segregation and cytokinesis. Borealin has a consensus CDK1 phosphorylation site, threonine 106 and can be phosphorylated by Aurora B Kinase at serine 165 in vitro.

Results

Here, we show that Borealin is phosphorylated during mitosis in human cells. Dephosphorylation of Borealin occurs as cells exit mitosis. The phosphorylated form of Borealin is found in an INCENP-containing complex in mitosis. INCENP-containing complexes from cells in S phase are enriched in the phosphorylated form suggesting that phosphorylation may encourage entry of Borealin into the chromosomal passenger complex. Although Aurora B Kinase is found in complexes that contain Borealin, it is not required for the mitotic phosphorylation of Borealin. Mutation of T106 or S165 of Borealin to alanine does not alter the electrophoretic mobility shift of Borealin. Experiments with cyclohexamide and the phosphatase inhibitor sodium fluoride suggest that Borealin is phosphorylated by a protein kinase that can be active in interphase and mitosis and that the phosphorylation may be regulated by a short-lived phosphatase that is active in interphase but not mitosis.

Conclusion

Borealin is phosphorylated during mitosis. Neither residue S165, T106 nor phosphorylation of Borealin by Aurora B Kinase is required to generate the mitotic, shifted form of Borealin. Suppression of phosphorylation during interphase is ensured by a labile protein, possibly a cell cycle regulated phosphatase.
Experimental validation of novel genes predicted in the un-annotated regions of the Arabidopsis genome
Authors: Moskal William A , Wu Hank C , Underwood Beverly A , Wang Wei , Town Christopher D , Xiao Yongli
Published: January 2007

Background

Several lines of evidence support the existence of novel genes and other transcribed units which have not yet been annotated in the Arabidopsis genome. Two gene prediction programs which make use of comparative genomic analysis, Twinscan and EuGene, have recently been deployed on the Arabidopsis genome. The ability of these programs to make use of sequence data from other species has allowed both Twinscan and EuGene to predict over 1000 genes that are intergenic with respect to the most recent annotation release. A high throughput RACE pipeline was utilized in an attempt to verify the structure and expression of these novel genes.

Results

1,071 un-annotated loci were targeted by RACE, and full length sequence coverage was obtained for 35% of the targeted genes. We have verified the structure and expression of 378 genes that were not present within the most recent release of the Arabidopsis genome annotation. These 378 genes represent a structurally diverse set of transcripts and encode a functionally diverse set of proteins.

Conclusion

We have investigated the accuracy of the Twinscan and EuGene gene prediction programs and found them to be reliable predictors of gene structure in Arabidopsis. Several hundred previously un-annotated genes were validated by this work. Based upon this information derived from these efforts it is likely that the Arabidopsis genome annotation continues to overlook several hundred protein coding genes.
The 2′-O-methyltransferase responsible for modification of yeast tRNA at position 4
Authors: Wilkinson Martha L. , Crary Sharon M. , Jackman Jane E. , Grayhack Elizabeth J. , Phizicky Eric M.
Published: January 2007

The methylation of the ribose 2′-OH of RNA occurs widely in nature and in all stable RNAs and occurs at five positions in yeast tRNA. 2′-O-methylation of tRNA at position 4 is interesting because it occurs in the acceptor stem (which is normally undermodified), it is the only 2′-O-methylation that occurs in the middle of a duplex region in tRNA, the modification is conserved in eukaryotes, and the features of the tRNA necessary for substrate recognition are poorly defined. We show here that Saccharomyces cerevisiae ORF YOL125w (TRM13) is necessary and sufficient for 2′-O-methylation at position 4 of yeast tRNA. Biochemical analysis of the S. cerevisiae proteome shows that Trm13 copurifies with 2′-O-methylation activity, using tRNAGly(GCC) as a substrate, and extracts made from a trm13-Δ strain have undetectable levels of this activity. Trm13 is necessary for activity in vivo because tRNAs isolated from a trm13-Δ strain lack the corresponding 2′-O-methylated residue for each of the three known tRNAs with this modification. Trm13 is sufficient for 2′-O-methylation at position 4 in vitro since yeast Trm13 protein purified after expression in Escherichia coli has the same activity as that produced in yeast. Trm13 protein binds substrates tRNAHis and tRNAGly(GCC) with KD values of 85 ± 8 and 100 ± 14 nM, respectively, and has a KM for tRNAHis of 10 nM, but binds nonsubstrate tRNAs very poorly (KD > 1 μM). Trm13 is conserved in eukaryotes, but there is no sequence similarity between Trm13 and other known methyltransferases.
Structure and thermodynamics of a conserved U2 snRNA domain from yeast and human
Authors: Sashital Dipali G. , Venditti Vincenzo , Angers Cortney G. , Cornilescu Gabriel , Butcher Samuel E.
Published: January 2007

The spliceosome is a dynamic ribonucleoprotein complex responsible for the removal of intron sequences from pre-messenger RNA. The highly conserved 5′ end of the U2 small nuclear RNA (snRNA) makes key base-pairing interactions with the intron branch point sequence and U6 snRNA. U2 stem I, a stem–loop located in the 5′ region of U2, has been implicated in spliceosome assembly and may modulate the folding of the U2 and U6 snRNAs in the spliceosome active site. Here we present the NMR structures of U2 stem I from human and Saccharomyces cerevisiae. These sequences represent the two major classes of U2 stem I, distinguished by the identity of tandem wobble pairs (UU/UU in yeast and CA/GU in human) and the presence of post-transcriptional modifications (four 2′-O-methyl groups and two pseudouracils in human). The structures reveal that the UU/UU and CA/GU tandem wobble pairs are nearly isosteric. The tandem wobble pairs separate two thermodynamically distinct regions of Watson–Crick base pairs, with the modified nucleotides in human stem I conferring a significant increase in stability. We hypothesize that the separate thermodynamic stabilities of U2 stem I exist to allow the structure to transition through different folded conformations during spliceosome assembly and catalysis.
The Role of Liver Transplantation in the Management of Paediatric Liver Tumours
Authors: Stringer Mark D
Published: January 2007

In recent years, considerable progress has been made in the treatment of children with hepatoblastoma largely due to effective pre-operative chemotherapy. Total hepatectomy and liver transplantation has emerged as an effective treatment for the small proportion of children with unresectable hepatoblastoma limited to the liver. A 5-year survival of 70% can be achieved in such cases. In contrast, the results of liver transplantation in children with hepatocellular cancer remain poor because these tumours are usually advanced with evidence of major vascular invasion and/or extrahepatic spread at the time of presentation. An exception is those children in whom the hepatocellular carcinoma is detected during surveillance of chronic liver disease – they typically have smaller tumours and frequently have a good prognosis after liver transplantation. The role of liver transplantation in children with other primary hepatic malignancies remains uncertain because experience is very limited. Liver transplantation is rarely needed in the management of children with benign liver tumours but, if other treatments have failed, it can be a life-saving intervention.
Orientation relations between four phases of AgI
Authors: Sowa Heidrun
Published: January 2007

Starting with wurtzite-type single crystals, AgI was investigated at room temperature and pressures up to 0.5 GPa by means of a polarizing light microscope and with the precession technique. Distinct orientation relations were observed between four different AgI phases that occur suc cessively under increasing pressure. At 0.35 GPa a reverse-obverse (111) twin of zincblende-type AgI is formed with twin plane parallel to the (001) plane of the wurtzite-type structure. The antilitharge type of AgI occurs at 0.39 GPa. Its tetragonal [001] direction runs parallel to one of the (100) directions of the zincblende type. At almost the same pres sure the transformation to the NaCl-type form takes place. This AgI modification shows also twinning on (111) and the basis vectors are oriented parallel to those of the zincblende type. The transition between the zincblende- and the anti litharge-type phase shows a hysteresis: The back transfor mation occurs at 0.35 GPa. NaCl-type AgI transforms di rectly to the zincblende-type form at approximately 0.2 GPa when pressure is released.

The observed orientation relations between zincblende-, antilitharge- and NaCl-type AgI support transition mecha nisms that have been proposed earlier [Keen & Hull, J. Phys.: Condens. Matter5(1993) 23–32].
Crystal structure of potassium and ammonium tetraperoxovanadates (V)
Authors: Grzywa Maciej , Łasocha Wieslaw
Published: January 2007

Powder diffraction measurements are fast, and sample preparation does not require time consuming manipulations what is very important for toxic, unstable or explosive samples. In addition, very good results can be also obtained at structure solution level by nowadays methods. Unfortunately, structure solution results can sometimes be biased towards assumed structure models in most popular nowadays ‘direct space search procedures’. However, in typical applications crystal structure studies can be performed using ‘ab initio’ methods. Using this approach the crystal structures of two very unstable tetraperoxovanadates (V) — (NH4)3[V(O2)4] and K3[V(O2)4] — have been ab initio solved from powder diffraction data by direct methods. The two ammonium and potassium salts are isotypic with lattice parameters: a = 6.9769(5), c = 8.211(1) and a = 6.6861(4), c = 7.708(2) Å, V = 399.68(7) Å3 and 344.6(6) Å3, respectively. The space group is I-42m (No. 121) with Z = 2 for both compounds.