bluuebunny/crossref_metadata_2025 huggingface dataset:
Earth's Degassing: A Missing Ethane and Propane Source
Authors: Etiope Giuseppe , Ciccioli Paolo
Published: January 2009

Current emission inventories require an additional "unknown" source to balance the global atmospheric budgets of ethane (C
2
H
6
). Here, we provide evidence that a substantial part of the missing source can be attributed to natural gas seepage from petroliferous, geothermal, and volcanic areas. Such geologic sources also inject propane (C
3
H
8
) into the atmosphere. The analysis of a large data set of methane (CH
4
), ethane, and propane concentrations in surface gas emissions of 238 sites from different geographic and geologic areas, coupled with published estimates of geomethane emissions, suggests that Earth's degassing accounts for at least 17% and 10% of total ethane and propane emissions, respectively.
Alternative Zippering as an On-Off Switch for SNARE-Mediated Fusion
Authors: Giraudo Claudio G. , Garcia-Diaz Alejandro , Eng William S. , Chen Yuhang , Hendrickson Wayne A. , Melia Thomas J. , Rothman James E.
Published: January 2009

Membrane fusion between vesicles and target membranes involves the zippering of a four-helix bundle generated by constituent helices derived from target– and vesicle–soluble
N
-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs). In neurons, the protein complexin clamps otherwise spontaneous fusion by SNARE proteins, allowing neurotransmitters and other mediators to be secreted when and where they are needed as this clamp is released. The membrane-proximal accessory helix of complexin is necessary for clamping, but its mechanism of action is unknown. Here, we present experiments using a reconstituted fusion system that suggest a simple model in which the complexin accessory helix forms an alternative four-helix bundle with the target-SNARE near the membrane, preventing the vesicle-SNARE from completing its zippering.
Amiodarone Destabilizes Intracellular Ca
2+
Homeostasis and Biosynthesis of Sterols in
Leishmania mexicana
Authors: Serrano-Martín Xenón , García-Marchan Yael , Fernandez Alexis , Rodriguez Noris , Rojas Hector , Visbal Gonzalo , Benaim Gustavo
Published: January 2009

Leishmaniasis represents a serious public health problem worldwide. The first line of treatment is based on glucantime and pentostan, which generate toxic effects in treated patients. We have recently shown that amiodarone, frequently used as an antiarrhythmic, possesses activity against
Trypanosoma cruzi
through the disruption of mitochondrial Ca
2+
homeostasis and the inhibition of parasite ergosterol biosynthesis, specifically at the level of oxidosqualene cyclase activity (G. Benaim, J. Sanders, Y. Garcia-Marchan, C. Colina, R. Lira, A. Caldera, G. Payares, C. Sanoja, J. Burgos, A. Leon-Rossell, J. Concepcion, A. Schijman, M. Levin, E. Oldfield, and J. Urbina, J. Med. Chem. 49:892-899, 2006). Here we show that at therapeutic concentrations, amiodarone has a profound effect on the viability of
Leishmania mexicana
promastigotes. Additionally, its effect on the viability of the parasite was greater against intracellular amastigotes than against promastigotes, and it did not affect the host cell. Using fluorimetric and confocal microscopy techniques, we also demonstrated that the mechanism of action of amiodarone was related to the disruption of intracellular Ca
2+
homeostasis through a direct action not only on the mitochondria but also on the acidocalcisomes. On the other hand, analysis of the free sterols in promastigotes incubated with amiodarone showed that this drug also affected the biosynthesis of 5-dehydroepisterol, which results in squalene accumulation, thus suggesting that amiodarone inhibits the squalene epoxidase activity of the parasite. Taken together, the results obtained in the present work point to a more general effect of amiodarone in trypanosomatids, opening potential therapeutic possibilities for this infectious disease.
Transcriptional Signature following Inhibition of Early-Stage Cell Wall Biosynthesis in
Staphylococcus aureus
Authors: O'Neill A. J. , Lindsay J. A. , Gould K. , Hinds J. , Chopra I.
Published: January 2009

To facilitate mode of action studies on antibacterial inhibitors of early-stage cell wall biosynthesis (CWB), we determined the transcriptional response of
Staphylococcus aureus
to depletion/inhibition of enzymes in this pathway by DNA microarray analysis. We identified a transcriptional signature distinct from that previously observed following exposure to inhibitors of late-stage CWB.
Temporal Appearance of Plasmid-Mediated Quinolone Resistance Genes
Authors: Jacoby George A. , Gacharna Nancy , Black Todd A. , Miller George H. , Hooper David C.
Published: January 2009

One hundred fifty AAC(6′)-Ib-positive gram-negative isolates collected between 1981 and 1991 were examined by PCR for the presence of the
aac(6
′
)-Ib-cr
variant and other plasmid-mediated quinolone resistance (PMQR) genes. None had the
aac(6
′
)-Ib-cr
variant,
qnrA
,
qnrS
,
qnrC
, or
qepA
, but two strains collected in 1988 had
qnrB
alleles, making these the earliest known PMQR genes.
Optimization and Validation of a Multiplex, Electrochemiluminescence-Based Detection Assay for the Quantitation of Immunoglobulin G Serotype-Specific Antipneumococcal Antibodies in Human Serum
Authors: Marchese Rocio D. , Puchalski Derek , Miller Pamela , Antonello Joseph , Hammond Olivia , Green Tina , Rubinstein Leonard J. , Caulfield Michael J. , Sikkema Daniel
Published: January 2009

Pneumovax 23 consists of a mixture of highly purified capsular polysaccharides (Ps) from 23 of the most prevalent serotypes of
Streptococcus pneumoniae
. Testing of vaccine immunogenicity has been historically performed on the enzyme-linked immunosorbent assay (ELISA) platform, validated to measure immunoglobulin G (IgG) antibodies to all 23 serotypes included in Pneumovax 23. In order to significantly improve the throughput of this form of testing, we have developed and validated a direct binding electrochemiluminescence (ECL)-based multiplex assay that can measure the antibody response in human serum to eight serotypes within a single microtiter well. The pneumococcal (Pn) ECL assay is based on the Meso Scale Discovery (MSD) technology which utilizes a Sulfo-Tag-labeled anti-human IgG antibody that emits light upon electrochemical stimulation. The Pn ECL assay exhibits a wide dynamic range and provides the ability to read concentrations down to the minimum reported concentration in the Merck ELISA (0.1 μg/ml). Cross-reactivity assessment using type-specific monoclonal antibodies showed no cross talk between antigen spots within a well. By use of the WHO Pn sample reference panel, the results obtained with the Pn ECL assay were compared to the results obtained with the international Pn ELISA. The results for the Pn ECL assay satisfied the WHO-recommended acceptance criterion for concordance for all seven serotypes with published Pn ELISA values, and the overall correlation (
r
value) across the seven serotypes was 0.994. The MSD methodology has great potential to be extremely useful for simultaneously quantitating IgG responses to several Pn serotypes while conserving serum volumes and laboratory testing time.
Multilocus Sequence Types Associated with Neonatal Group B Streptococcal Sepsis and Meningitis in Canada
Authors: Manning Shannon D. , Springman A. Cody , Lehotzky Erica , Lewis Maggi A. , Whittam Thomas S. , Davies H. Dele
Published: January 2009

Group B streptococci (GBS), a leading cause of neonatal sepsis and meningitis, are transferred to neonates from colonized mothers during childbirth. Prior studies using multilocus sequence typing (MLST) have found specific GBS clones (e.g., sequence type 17 [ST-17]) to be associated with neonatal disease in several geographic locations. Few population-based studies, however, have been conducted to determine the frequency of disease caused by specific GBS clones. MLST was used to assess the genetic diversity of 192 GBS strains from neonates and young children identified by population-based surveillance in Alberta, Canada, from 1993 to 2002. Comparisons were made to 232 GBS strains collected from colonized pregnant women, and all strains were characterized for one of nine capsule (
cps
) genotypes. A total of 47 STs were identified, and more than 80% of GBS strains were represented by 7 STs that have been shown to predominate in other populations. ST-17 and ST-19 were more prevalent in strains causing early onset disease (EOD) and late onset disease (LOD) than from pregnant women, whereas STs 1, 12, and 23 were more common in pregnant women. In addition, ST-17 strains and close relatives more frequently caused meningitis than sepsis and LOD versus EOD in this population of neonates. Further research is required to better understand why strains belonging to the ST-17 phylogenetic lineage are more likely to cause both LOD and meningitis and may provide clues into the pathogenesis of these conditions.
First Evaluation of the WASP, a New Automated Microbiology Plating Instrument
Authors: Bourbeau Paul P. , Swartz Brandi Lynn
Published: January 2009

Many laboratories are experiencing growing shortages of trained microbiology technologists and technicians. Consequently, there is considerable interest in new automation that could potentially lessen labor demands for specimen processing. In this study, we present the first published evaluation of a new microbiology instrument, the Walk Away Specimen Processor (WASP), manufactured by Copan, Inc., in which we evaluated cross-contamination, the accuracy of plating, and the quality of the results. The absence of cross-contamination was demonstrated by plating a total of 200 alternating inoculated and sterile specimen tubes. The ability of the WASP to subculture enrichment broths was evaluated with 106 Lim broth specimens, with the results being identical to those obtained by testing by routine methods. Plating of urine specimens with the WASP was compared to plating with the Dynacon Inoculab instrument. Three hundred specimens were plated in duplicate on both instruments with 1-μl loops, and 293 specimens were plated in duplicate on both instruments with 10-μl loops. The results of duplicate plating with the same instrument (replicate plating) and of the consensus agreement between the two instruments were compared. The replicate plating results were comparable for both instruments, while the WASP had more specimens with significant results than the Inoculab with the 1-μl loop only. Lastly, for the plating of 113 specimens in ESwab tubes, the manual method and WASP plating each yielded 90 potential pathogens. In summary, we report the first evaluation of a new microbiology specimen-plating instrument, the WASP, which offers opportunities for the automated plating of microbiology specimens to an extent that has not been possible to date.
Demonstration of Sustained Drug-Resistant Human Immunodeficiency Virus Type 1 Lineages Circulating among Treatment-Naïve Individuals
Authors: Hué Stéphane , Gifford Robert J. , Dunn David , Fernhill Esther , Pillay Deenan
Published: January 2009

Transmission of human immunodeficiency virus (HIV) drug resistance is well-recognized and compromises response to first-line therapy. However, the population dynamics of transmitted resistance remains unclear, although previous models have assumed that such transmission reflects direct infection from treated individuals. We investigated whether population-based phylogenetic analyses would uncover lineages of resistant viruses circulating in untreated individuals. Through the phylogenetic analysis of 14,061 HIV type 1 (HIV-1)polgene sequences generated in the United Kingdom from both treatment-naïve and -experienced individuals, we identified five treatment-independent viral clusters containing mutations conferring cross-resistance to antiretroviral drugs prescribed today in the United Kingdom. These viral lineages represent sustainable reservoirs of resistance among new HIV infections, independent of treatment. Dated phylogenies reconstructed through Bayesian Markov chain Monte Carlo inference indicated that these reservoirs originated between 1997 and 2003 and have persisted in the HIV-infected population for up to 8 years. Since our cohort does not represent all infected individuals within the United Kingdom, our results are likely to underestimate the number and size of the resistant reservoirs circulating among drug-naïve patients. The existence of sustained reservoirs of resistance in the absence of treatment has the capacity to threaten the long-term efficacy of antiretroviral therapy and suggests there is a limit to the decline of transmitted drug resistance. Given the current decrease in resistance transmitted from treated individuals, a greater proportion of resistance is likely to come from drug-naïve lineages. These findings provide new insights for the planning and management of treatment programs in resource-rich and developing countries.
Dual Roles for an Arginine-Rich Motif in Specific Genome Recognition and Localization of Viral Coat Protein to RNA Replication Sites in Flock House Virus-Infected Cells
Authors: Venter P. Arno , Marshall Dawn , Schneemann Anette
Published: January 2009

Assembly of many RNA viruses entails the encapsidation of multiple genome segments into a single virion, and underlying mechanisms for this process are still poorly understood. In the case of the nodavirus
Flock House virus
(FHV), a bipartite positive-strand RNA genome consisting of RNA1 and RNA2 is copackaged into progeny virions. In this study, we investigated whether the specific packaging of FHV RNA is dependent on an arginine-rich motif (ARM) located in the N terminus of the coat protein. Our results demonstrate that the replacement of all arginine residues within this motif with alanines rendered the resultant coat protein unable to package RNA1, suggesting that the ARM represents an important determinant for the encapsidation of this genome segment. In contrast, replacement of all arginines with lysines had no effect on RNA1 packaging. Interestingly, confocal microscopic analysis demonstrated that the RNA1 packaging-deficient mutant did not localize to mitochondrial sites of FHV RNA replication as efficiently as wild-type coat protein. In addition, gain-of-function analyses showed that the ARM by itself was sufficient to target green fluorescent protein to RNA replication sites. These data suggest that the packaging of RNA1 is dependent on trafficking of coat protein to mitochondria, the presumed site of FHV assembly, and that this trafficking requires a high density of positive charge in the N terminus. Our results are compatible with a model in which recognition of RNA1 and RNA2 for encapsidation occurs sequentially and in distinct cellular microenvironments.
Peptidylproline
cis
-
trans
-Isomerase Pin1 Interacts with Human T-Cell Leukemia Virus Type 1 Tax and Modulates Its Activation of NF-κB
Authors: Peloponese Jean-Marie , Yasunaga Junichiro , Kinjo Takao , Watashi Koichi , Jeang Kuan-Teh
Published: January 2009

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus etiologically causal of adult T-cell leukemia (ATL). The virus encodes a Tax oncoprotein that functions in transcriptional regulation, cell cycle control, and transformation. ATL is a highly virulent cancer that is resistant to chemotherapeutic treatments. To understand this disease better, it is important to comprehend how HTLV-1 promotes cellular growth and survival. Tax activation of NF-κB is important for the proliferation and transformation of virus-infected cells. We show here that prolyl isomerase Pin1 is over expressed in HTLV-1 cell lines; Pin1 binds Tax and regulates Tax-induced NF-κB activation.
Differential Neutralization of Human Immunodeficiency Virus (HIV) Replication in Autologous CD4 T Cells by HIV-Specific Cytotoxic T Lymphocytes
Authors: Chen Huabiao , Piechocka-Trocha Alicja , Miura Toshiyuki , Brockman Mark A. , Julg Boris D. , Baker Brett M. , Rothchild Alissa C. , Block Brian L. , Schneidewind Arne , Koibuchi Tomohiko , Pereyra Florencia , Allen Todd M. , Walker Bruce D.
Published: January 2009

Defining the antiviral efficacy of CD8 T cells is important for immunogen design, and yet most current assays do not measure the ability of responses to neutralize infectious virus. Here we show that human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) clones and cell lines derived from infected persons and targeting diverse epitopes differ by over 1,000-fold in their ability to retard infectious virus replication in autologous CD4 T cells during a 7-day period in vitro, despite comparable activity as assessed by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Cell lines derived from peripheral blood mononuclear cells stimulated in vitro with peptides representing targeted Gag epitopes consistently neutralized HIV better than Env-specific lines from the same person, although ineffective inhibition of virus replication is not a universal characteristic of Env-specific responses at the clonal level. Gag-specific cell lines were of higher avidity than Env-specific lines, although avidity did not correlate with the ability of Gag- or Env-specific lines to contain HIV replication. The greatest inhibition was observed with cell lines restricted by the protective HLA alleles B*27 and B*57, but stimulation with targeted Gag epitopes resulted in greater inhibition than did stimulation with targeted Env epitopes even in non-B*27/B*57 subjects. These results assessing functional virus neutralization by HIV-specific CD8 T cells indicate that there are marked epitope- and allele-specific differences in virus neutralization by in vitro-expanded CD8 T cells, a finding not revealed by standard IFN-γ ELISPOT assay currently in use in vaccine trials, which may be of critical importance in immunogen design and testing of candidate AIDS vaccines.
Nucleotide Sequence Requirements at the 5′ End of the Influenza A Virus M RNA Segment for Efficient Virus Replication
Authors: Ozawa Makoto , Maeda Junko , Iwatsuki-Horimoto Kiyoko , Watanabe Shinji , Goto Hideo , Horimoto Taisuke , Kawaoka Yoshihiro
Published: January 2009

The mechanism by which the influenza A virus genome is packaged into virions is not fully understood. The coding and noncoding regions necessary for packaging of the viral RNA segments, except for the M segment, have been identified. Here, we delineate the M segment regions by incorporating a reporter viral RNA into virions and by generating viruses possessing mutations in the regions. We found that, like the other segments, the M segment coding regions are essential for virion incorporation and that the nucleotide length rather than the nucleotide sequence of the 5′ end of the coding region is important.
Stability, polarity, intramolecular interactions and π-electron delocalization for all eighteen tautomers rotamers of uracil. DFT studies in the gas phase
Authors: Raczyńska Ewa D. , Zientara Katarzyna , Stępniewski Tomasz M. , Kolczyńska Katarzyna
Published: January 2009

Complete tautomeric equilibria were investigated for uracil at the DFT(B3LYP)/6-311+G(d,p) level to establish the stability order of all possible 18 tautomers-rotamers in the gas phase and to characterize their internal effects, polarity and aromatic character. Although the di-NH form strongly predominates (100%) in the mixture, the NH–OH, di-OH and CH–NH forms can be also considered. The favored tautomer is moderately stabilized by intramolecular interactions (attractions of the NH and C=O groups); it is also moderately polar and moderately delocalized. Stability of the functional groups (both amide functions) seems to be more important than intramolecular interactions, polarity and aromaticity. This is probably the main factor that dictates the tautomeric preferences in the uracil molecule.
Multiple risk factors related to familial predisposition to anterior cruciate ligament injury: fraternal twin sisters with anterior cruciate ligament ruptures
Authors: Hewett T E , Lynch T R , Myer G D , Ford K R , Gwin R C , Heidt R S
Published: January 2009

Objective

A multifactorial combination of predictors may increase anterior cruciate ligament (ACL) injury risk in athletes. The objective of this twin study was to examine these risk factors to identify commonalities in risk factors that predisposed female fraternal twins to ACL injury.

Methods

Female twins in high-risk sports were prospectively measured prior to an injury for neuromuscular control using three-dimensional motion analysis during landing, hamstrings and quadriceps muscular strength on a dynamometer and joint laxity using a modified Beighton–Horan index and a Compu-KT arthrometer. Intraoperative measures of femoral intercondylar notch width were recorded during ACL reconstruction.

Results

Abduction angles were increased at one knee in both of the twin sister athletes relative to uninjured controls at initial contact and at maximum displacement during landing. The twin female athletes that went on to ACL injury also demonstrated decreased peak knee flexion motion at both knees than uninjured females during landing. The twin athletes also had increased joint laxity and decreased hamstrings to quadriceps (H/Q) torque ratios compared to controls. Femoral intercondylar notch widths were also below the control mean in the twin siblings.

Conclusions

Prescreened mature female twins that subsequently experienced ACL injury demonstrated multiple potential risk factors including: increased knee abduction angles, decreased knee flexion angles, increased general joint laxity, decreased H/Q ratios and femoral intercondylar notch width.
Predictive validity of health-related fitness in youth: a systematic review
Authors: Ruiz J R , Castro-Piñero J , Artero E G , Ortega F B , Sjöström M , Suni J , Castillo M J
Published: January 2009

The objective of the present systematic review was to investigate whether physical fitness in childhood and adolescence is a predictor of cardiovascular disease (CVD) risk factors, events and syndromes, quality of life and low back pain later in life. Physical fitness-related components were: cardiorespiratory fitness, musculoskeletal fitness, motor fitness and body composition. Adiposity was considered as both exposure and outcome. The results of 42 studies reporting the predictive validity of health-related physical fitness for CVD risk factors, events and syndromes as well as the results of five studies reporting the predictive validity of physical fitness for low back pain in children and adolescents were summarised. Strong evidence was found indicating that higher levels of cardiorespiratory fitness in childhood and adolescence are associated with a healthier cardiovascular profile later in life. Muscular strength improvements from childhood to adolescence are negatively associated with changes in overall adiposity. A healthier body composition in childhood and adolescence is associated with a healthier cardiovascular profile later in life and with a lower risk of death. The evidence was moderate for the association between changes in cardiorespiratory fitness and CVD risk factors, and between cardiorespiratory fitness and the risk of developing the metabolic syndrome and arterial stiffness. Moderate evidence on the lack of a relationship between body composition and low back pain was found. Due to a limited number of studies, inconclusive evidence emerged for a relationship between muscular strength or motor fitness and CVD risk factors, and between flexibility and low back pain.
Cancer risks in chemical production workers exposed to 2-mercaptobenzothiazole
Authors: Sorahan T
Published: January 2009

Objectives:

To investigate cancer risks in chemical production workers exposed to 2-mercaptobenzothiazole (MBT).

Methods:

The mortality (1955–2005) and cancer morbidity experience (1971–2005) of a cohort of 363 male production workers exposed to MBT while employed at a chemical factory in north Wales were investigated. Two analytical approaches were used, indirect standardisation and Poisson regression.

Results:

Based on national mortality rates, significant excess mortality was found for cancers of the large intestine (observed; Obs 8, standardised mortality ratio (SMR) 232, 95% CI 100 to 457) and bladder (Obs 8, SMR 374, 95% CI 162 to 737). Non-significant excesses were shown for lung cancer (Obs 27, SMR 138, 95% CI 91 to 201) and multiple myeloma (Obs 3, SMR 440, 95% CI 91 to 1287). Based on national cancer incidence rates, significant excess morbidity was found for cancer of the bladder (Obs 12, standardised registration ratio (SRR) 253, 95% CI 131 to 441) and multiple myeloma (Obs 4, SRR 465, 95% CI 127 to 1191). Non-significant excesses were shown for cancers of the large intestine (Obs 9, SRR 181, 95% CI 83 to 344) and lung (Obs 26, SRR 152, 95% CI 99 to 223). In analyses that included follow-up information on an additional 1797 plant employees not exposed to MBT, Poisson regression showed significant positive trends both for risks of cancer of the large intestine and for risks of multiple myeloma in relation to estimated cumulative exposure to MBT.

Conclusions:

MBT may be a human carcinogen; confident evaluation awaits findings from other studies.
ON SPIN-2 ELECTROMAGNETIC INTERACTIONS
Authors: ZINOVIEV YU. M.
Published: January 2009

In this paper we (re)consider the problem of electromagnetic interactions for massless spin-2 particles and show that in (A)dS spaces with nonzero cosmological constant it is indeed possible (at least in linear approximation) to switch on minimal electromagnetic interactions supplemented by third derivative non-minimal ones which are necessary to restore gauge invariance.
A HIGH-ORDER RECURSIVE QUADRATIC ALGORITHM FOR LINEAR-IN-THE-PARAMETER MODELS
Authors: ZHU QI , QIAO YING , TAN SHAOHUA
Published: January 2009

In this paper, a high-order Recursive Quadratic (RQ) algorithm is introduced, and the features of this algorithm are thoroughly studied and illustrated. In addition, a robust RQ algorithm is also developed in the presence of general bounded noisy data to enhance model robustness. A numerical example is included to demonstrate the efficiency of RQ algorithms by comparing the results with both the projection algorithm and the conventional recursive least squares algorithm. Also some simulations are carried out to illustrate the effectiveness of the RQ and robust RQ algorithms.
A LOG-DOMAIN WAVE POSITIVE IMPEDANCE INVERTER
Authors: FRAGOULIS NIKOS , SOULIOTIS GEORGE , GIANNAKOPOULOS KONSTANTINE
Published: January 2009

A new log-domain building block for log-domain filter design is proposed in this paper. This block realizes a positive impedance inverter (gyrator) by using the log-domain wave method. A simple procedure for log-domain filter development, using the proposed block, is outlined. This method results in circuits, which are simple in structure and very easy to design. An example of a second-order bandpass filter is given and its functionality is verified through simulations.
SENSOR PLACEMENT FOR COMPLETE INFORMATION COVERAGE IN DISTRIBUTED SENSOR NETWORKS
Authors: WANG BANG
Published: January 2009

The sensor placement problem for complete information coverage in a distributed sensor network is studied. Sensors are assumed to be placed on the grid points of a grid in the sensor field and complete information coverage is claimed if all the grid points are information covered. This sensor placement problem is formulated as a constrained optimization problem where the objective is to minimize the total cost while guaranteeing certain coverage requirement. We propose a greedy algorithm to solve this problem. Computational results show that the proposed algorithm can efficiently obtain a good quality solution with greatly reduced computation complexity and the number of sensors can be greatly reduced for information coverage.
COMPLEXITY-DRIVEN RELIABILITY MODEL
Authors: SCHNEIDEWIND NORMAN
Published: January 2009

A model of software complexity and reliability is developed that uses an evolutionary process to transition from one software system to the next while complexity metrics are used to predict the reliability for each system. Systems are tested until the software passes defect presence criteria and is released. Testing criteria are based on defect count, defect density, and testing efficiency predictions exceeding specified thresholds. In addition, another type of testing efficiency — a directed graph representing the complexity of the software and defects embedded in the code — is used to evaluate the efficiency of defect detection in NASA satellite system software. Complexity metrics were found to be good predictors of defects and testing efficiency in this evolutionary process.
Exploring the Root-Leaf Relationship between the Manufacturing and Financial Services Industry in Taiwan
Authors: Chien Chin-Chen , Lee Cheng-Few , Cheng Ya-Yun
Published: January 2009

We employ the concept of Granger causality to investigate the root-leaf relationship between the manufacturing and financial services industry in Taiwan's economy. Our empirical results show that manufacturing led finance for the last half century, which is consistent with the pattern of other emerging economies. However, the liberalization of the financial services industry in the 1980s changed the relationship from "manufacturing leads, finance follows" to a feedback system. Accordingly, the financial services industry should play a more important role than previously for Taiwan to maintain its economic growth.
Agency Theory and Flotation Methods in Seasoned Equity Offerings: The Case in Taiwan
Authors: Wang Kehluh , Chen Yi-Hsuan , Huang Szu-Wei
Published: January 2009

The purpose of this study is to examine the impacts of alternative flotation methods on price performance of seasoned equity offerings, and to compare the competing hypotheses supported by asymmetric information theory and agency theory. Based on 385 sample issues which were listed in Taiwan Stock Exchange from 1996 to 2006, we find that the bookbuilding flotation method demonstrates significant positive abnormal returns for issuing firms, whereas the fixed-price method exhibits negative results. The empirical findings support the agency theory in the sense that the bookbuilding procedure offers a mechanism to strengthen the external monitoring provided by blockholders, which can subsequently reduce the agency cost and thus increase the share price. Further cross sectional analysis confirms this argument. The result of the study implies that the governments should take effective actions to help regulate agency problems in emerging markets such as Taiwan.
A STUDY OF THE ASSOCIATION BETWEEN DOWNSIZING AND INNOVATION DETERMINANTS
Authors: MELLAHI KAMEL , WILKINSON ADRIAN
Published: January 2009

Using a survey data of UK firms that engaged in downsizing, this paper explores the link between downsizing and innovation determinants. We suggest that the relationship between downsizing and innovation determinants is contingent upon the speed of implementing the downsizing and the severity of downsizing. Overall, the results confirm our general proposition and shed new light on the relationship between downsizing and innovation enhancers, and barriers to innovation.
LIMITATIONS AND APPLICATIONS OF ICA FOR SURFACE ELECTROMYOGRAM FOR IDENTIFYING HAND GESTURES
Authors: DJUWARI DJUWARI , KUMAR DINESH K. , ARJUNAN SRIDHAR P. , NAIK GANESH R.
Published: January 2009

Surface electromyogram (SEMG) has numerous applications, but the presence of artifacts and cross talk especially at low level of muscle activity makes the recordings unreliable. Spectral and temporal overlap can make the removal of artifacts and noise, or separation of relevant signals from other bioelectric signals extremely difficult. Identification of hand gestures using low level of SEMG is one application that has a number of applications but the presence of high level of cross talk makes such an application highly unreliable. Individual muscles may be considered as independent at the local level and this makes an argument for separating the signals using independent component analysis (ICA). In the recent past, due to the easy availability of ICA tools, a number of researchers have attempted to use ICA for this application. This paper reports research conducted to evaluate the use of ICA for the separation of muscle activity and removal of the artifacts from SEMG. It discusses some of the conditions that could affect the reliability of the separation and evaluates issues related to the properties of the signals and a number of sources. This paper also identifies the lack of suitable measure of quality of separation for bioelectric signals and it recommends and tests a more robust measure of separation. This paper also proposes semi-blind ICA approach with the combination of prior knowledge of SEMG sources with ICA to identify hand gestures using low level of SEMG recordings. The theoretical analysis and experimental results demonstrate that ICA is suitable for SEMG signals. The results demonstrate the limitations of such applications due to the inability of the system to identify the correct order and magnitude of the signals. This paper determines the suitability of the use of error between estimated and actual mixing matrix as a mean for identifying the quality of separation of the output. This work also demonstrates that semi-blind ICA can accurately identify complex hand gestures from the low-level SEMG recordings.
SVM MODELS FOR DIAGNOSING BALANCE PROBLEMS USING STATISTICAL FEATURES OF THE MTC SIGNAL
Authors: LAI DANIEL T. H. , BEGG REZAUL , PALANISWAMI MARIMUTHU
Published: January 2009

Trip-related falls are a major problem in the elderly population and research in the area has received much attention recently. The focus has been on devising ways of identifying individuals at risk of sustaining such falls. The main aim of this work is to explore the effectiveness of models based on Support Vector Machines (SVMs) for the automated recognition of gait patterns that exhibit falling behavior. Minimum toe clearance (MTC) during continuous walking on a treadmill was recorded on 10 healthy elderly and 10 elderly with balance problems and with a history of tripping falls. Statistical features obtained from MTC histograms were used as inputs to the SVM model to classify between the healthy and balance-impaired subjects. The leave-one-out technique was utilized for training the SVM model in order to find the optimal model parameters. Tests were conducted with various kernels (linear, Gaussian and polynomial) and with a change in the regularization parameter, C, in an effort to identify the optimum model for this gait data. The receiver operating characteristic (ROC) plots of sensitivity and specificity were further used to evaluate the diagnostic performance of the model. The maximum accuracy was found to be 90% using a Gaussian kernel with σ2 = 10 and the maximum ROC area 0.98 (80% sensitivity and 100% specificity), when all statistical features were used by the SVM models to diagnose gait patterns of healthy and balance-impaired individuals. This accuracy was further improved by using a feature selection method in order to reduce the effect of redundant features. It was found that two features (standard deviation and maximum value) were adequate to give an improved accuracy of 95% (90% sensitivity and 100% specificity) using a polynomial kernel of degree 2. These preliminary results are encouraging and could be useful not only for diagnostic applications but also for evaluating improvements in gait function in the clinical/rehabilitation contexts.
Regulation of homocysteine homeostasis through the transcriptional coactivator PGC-1α
Authors: Li Siming , Arning Erland , Liu Chang , Vitvitsky Victor , Hernandez Carlos , Banerjee Ruma , Bottiglieri Teodoro , Lin Jiandie D.
Published: January 2009

Plasma homocysteine (Hcy) is an independent risk factor for cardiovascular disease. Hcy is a nonprotein amino acid derivative that is generated from the methionine cycle, which provides the methyl group for essentially all biological methylation reactions. Although plasma Hcy levels are elevated in patients with cardiovascular disease, the mechanisms that regulate Hcy homeostasis remain poorly defined. In this study, we found that the expression of key enzymes involved in Hcy metabolism is induced in the liver in response to fasting. This induction coincides with increased expression of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, a transcriptional coactivator that regulates hepatic gluconeogenesis and mitochondrial function. PGC-1α stimulates the expression of genes involved in Hcy metabolism in cultured primary hepatocytes as well as in the liver. Adenoviral-mediated expression of PGC-1α in vivo leads to elevated plasma Hcy levels. In contrast, mice deficient in PGC-1α have lower plasma Hcy concentrations. These results define a novel role for the PGC-1α coactivator pathway in the regulation of Hcy homeostasis and suggest a potential pathogenic mechanism that contributes to hyperhomocysteinemia.
Estrogens exert a rapid apoptotic action in anterior pituitary cells
Authors: Zárate S. , Jaita G. , Zaldivar V. , Radl D. B. , Eijo G. , Ferraris J. , Pisera D. , Seilicovich A.
Published: January 2009

It is now accepted that estrogens not only stimulate lactotrope proliferation but also sensitize anterior pituitary cells to proapoptotic stimuli. In addition to their classical mechanism of action through binding to intracellular estrogen receptors (ERs), there is increasing evidence that estrogens exert rapid actions mediated by cell membrane-localized ERs (mERs). In the present study, we examined the involvement of membrane-initiated steroid signaling in the proapoptotic action of estradiol in primary cultures of anterior pituitary cells from ovariectomized rats by using estren, a synthetic estrogen with no effect on classical transcription and a cell-impermeable 17β-estradiol conjugate (E2-BSA). Both compounds induced cell death of anterior pituitary cells after 60 min of incubation as assessed by flow cytometry and the [3-(4,5-dimethylthiazol-2-yl)]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Estren, E2, and E2-BSA induced apoptosis of lactotropes and somatotropes as evaluated by the deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and immunodetection of prolactin (PRL) and growth hormone (GH). The proapoptotic effect of E2-BSA was abrogated by ICI-182,780, an antagonist of ERs. The expression of membrane-associated ERα was observed in PRL- and GH-bearing cells. Our results indicate that estradiol is able to exert a rapid apoptotic action in anterior pituitary cells, especially lactotropes and somatotropes, by a mechanism triggered by mERs. This mechanism could be involved in anterior pituitary cell turnover.
Intestinal lipid absorption
Authors: Iqbal Jahangir , Hussain M. Mahmood
Published: January 2009

Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins has advanced considerably. Researchers have identified several new mechanisms by which lipids are taken up by enterocytes and packaged as chylomicrons for export into the lymphatic system or clarified the actions of mechanisms previously known to participate in these processes. Fatty acids are taken up by enterocytes involving protein-mediated as well as protein-independent processes. Net cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and ABCG8 present in the apical membrane. We have considerably more detailed information about the uptake of products of lipid hydrolysis, the active transport systems by which they reach the endoplasmic reticulum, the mechanisms by which they are resynthesized into neutral lipids and utilized within the endoplasmic reticulum to form lipoproteins, and the mechanisms by which lipoproteins are secreted from the basolateral side of the enterocyte. apoB and MTP are known to be central to the efficient assembly and secretion of lipoproteins. In recent studies, investigators found that cholesterol, phospholipids, and vitamin E can also be secreted from enterocytes as components of high-density apoB-free/apoAI-containing lipoproteins. Several of these advances will probably be investigated further for their potential as targets for the development of drugs that can suppress cholesterol absorption, thereby reducing the risk of hypercholesterolemia and cardiovascular disease.
Interstrain variation in cardiac and respiratory adaptation to repeated ozone and particulate matter exposures
Authors: Hamade Ali K. , Tankersley Clarke G.
Published: January 2009

Increased ambient particulate matter (PM) is associated with adverse cardiovascular and respiratory outcomes, as demonstrated by epidemiology studies. Several studies have investigated the role of copollutants, such as ozone (O3), in this association. It is accepted that physiological adaptation involving the respiratory system occurs with repeated exposures to O3. We hypothesize that adaptation to PM and O3 varies among different inbred mouse strains, and cardiopulmonary adaptation to O3 is a synchronized response between the cardiac and respiratory systems. Heart rate (HR), HR variability (HRV), and the magnitude and pattern of breathing were simultaneously measured by implanted telemeters and by plethysmography in three inbred mouse strains: C57Bl/6J (B6), C3H/HeJ (HeJ), and C3H/HeOuJ (OuJ). Physiological responses were assessed during dual exposures to filtered air (FA), O3 (576 ± 32 parts/billion), and/or carbon black (CB; 556 ± 34 μg/m3). Exposures were repeated for 3 consecutive days. While each strain showed significant reductions in HR during CB with O3 preexposure (O3CB) on day 1, prominent HRV responses were observed in only HeJ and OuJ mice. Each strain also differed in their adaptation profile in response to repeated O3CB exposures. Whereas B6 mice showed rapid adaptation in HR after day 1, HeJ mice generally showed more moderate HR and HRV adaptation after day 2 of exposure. Unlike either B6 or HeJ strains, OuJ mice showed little evidence of HR or HRV adaptation to repeated O3CB exposure. Adaptation profiles between HR regulation and breathing characteristics were strongly correlated, but these associations also varied significantly among strains. These findings suggest that genetic factors determine the responsivity and adaptation of the cardiac and respiratory systems to repeated copollutant exposures. During O3CB exposure, adaptation of cardiac and respiratory systems is markedly synchronized, which may explain a potential mechanism for adverse effects of PM on heart function.
Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro
Authors: Byerly Mardi S. , Simon Jean , Lebihan-Duval Elisabeth , Duclos Michel J. , Cogburn Larry A. , Porter Tom E.
Published: January 2009

Hypothalamic neuropeptides, neurotrophins, and systemic hormones modulate food intake and body composition. Although advances toward elucidating these interactions have been made, many aspects of the underlying mechanisms remain vague. Hypothalami from fat and lean chicken lines were assessed for differential expression of anabolic/orexigenic and catabolic/anorexigenic genes. Effects of triiodothyronine (T3), corticosterone (Cort), and brain-derived neurotrophic factor (BDNF) on expression of anabolic/orexigenic and catabolic/anorexigenic genes were tested in cultures of hypothalamic neurons. From this, we found that BDNF increased and T3decreased gene expression for BDNF, leptin receptor (LEPR), pro-opiomelanocortin (POMC), thyrotropin releasing hormone (TRH), and agouti-related protein (AGRP). Thyroid hormone levels were manipulated during development to show that T3inhibited BDNF, TRH, and BDNF receptor gene expression. Delivery of T3, Cort, T3plus Cort, or vehicle in vivo continuously for 72 h indicated that Cort and T3have overlapping roles in regulating TRH, LEPR, and POMC gene expression and that Cort and T3regulate BDNF, neuropeptide Y, and AGRP in opposite directions. Collectively, these findings suggest that interactions between the neuropeptide BDNF and the hormones T3and/or Cort may constitute a homeostatic mechanism that links hypothalamic energy regulation controlling body composition.
PERP, a p53 proapoptotic target, mediates apoptotic cell death in renal ischemia
Authors: Singaravelu Kurinji , Devalaraja-Narashimha Kishor , Lastovica Brynn , Padanilam Babu J.
Published: January 2009

The p53 tumor suppressor gene plays a crucial role in mediating apoptotic cell death in renal ischemia-reperfusion injury (IRI). To further elucidate the p53-dependent pathway, we investigated the role of the p53 apoptosis effector related to PMP-22 (PERP), an apoptosis-associated p53 transcriptional target. PERP mRNA and protein are highly induced in the outer medullary proximal tubular cells (PTC) of ischemic kidneys postreperfusion at 3, 12, and 24 h in a p53-dependent manner. In PTC, overexpression of PERP augmented the rate of apoptosis following hypoxia by inducing mitochondrial permeability and subsequent release of cytochrome c, apoptosis-inducing factor (AIF), and caspase 9 activation. In addition, silencing of the PERP gene with short hairpin RNA prevented apoptosis in hypoxia-mediated injury by precluding mitochondrial dysfunction and consequent cytochrome c and AIF translocation. These data suggest that PERP is a key effector of p53-mediated apoptotic pathways and is a potential therapeutic target for renal IRI.
Functional TRP and ASIC-like channels in cultured urothelial cells from the rat
Authors: Kullmann F. Aura , Shah M. A. , Birder L. A. , de Groat W. C.
Published: January 2009

Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in sensory neurons. They have been identified in the urothelium, a tissue considered part of bladder sensory pathways, where they might play a role in bladder function. This study investigated functional properties of TRP and ASIC channels in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca2+ imaging techniques. The TRPV4 agonist 4α-phorbol-12,13 didecanoate (4α-PDD; 1–5 μM) and the TRPA1/TRPM8 agonist icilin (50–100 μM) elicited transient currents in a high percentage of cells (>70%). 4α-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 μM). The TRPV1 agonist capsaicin (1–100 μM) and the TRPA1/TRPM8 agonist menthol (5–200 μM) elicited transient currents in a moderate percentage of cells (∼25%). All of these agonists increased intracellular calcium concentration ([Ca2+]i). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4α-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 μM), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca2+]i (pH 6.5) in ∼50% of cells. Changes in pH using acetic acid (pH 5.5) elicited biphasic-like currents. Responses induced by acid were sensitive to amiloride (10 μM). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca2+ influx. These “neuron-like” properties might be involved in transmitter release, such as ATP, that can act on afferent nerves or smooth muscle to modulate their responses to different stimuli.