bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineered
Streptomyces platensis
Strains That Overproduce Antibiotics Platensimycin and Platencin
Authors: Smanski Michael J. , Peterson Ryan M. , Rajski Scott R. , Shen Ben
Published: January 2009

Platensimycin, which is isolated from
Streptomyces platensis
MA7327, and platencin, which is isolated from
S. platensis
MA7339, are two recently discovered natural products that serve as important antibiotic leads. Here we report on the identification of
S. platensis
MA7327 as a dual producer of both platensimycin and platencin. A PCR-based approach was used to locate and clone the locus involved in platensimycin and platencin production, including
ptmR1
, which encodes a putative GntR-like transcriptional regulator. Deletion of this gene from the producing organism allowed us to isolate strains that overproduce platensimycin and platencin with yields of 323 ± 29 mg/liter and 255 ± 30 mg/liter, respectively. These results illustrate the effectiveness of genetic manipulation for the rational engineering of improvements in titers.
Decline in Cases of Rotavirus Gastroenteritis Presenting to The Children's Hospital of Philadelphia after Introduction of a Pentavalent Rotavirus Vaccine
Authors: Clark H Fred , Lawley Diane , Mallette Laura A. , DiNubile Mark J. , Hodinka Richard L.
Published: January 2009

A pentavalent rotavirus vaccine for infants became available in the United States in February 2006. By 2007, vaccination rates nationwide were estimated to be ∼50%. We studied the effectiveness of the vaccine in a real-world setting outside of a clinical trial. All children presenting to The Children's Hospital of Philadelphia with acute gastroenteritis have been monitored for the presence of rotavirus antigen in the stool by enzyme-linked immunosorbent assay (ELISA [followed by genotyping if ELISA positive]) since the 1994-1995 epidemic season, presenting a unique opportunity to assess the impact of the recently introduced vaccine. The annual number of community-acquired cases over the preceding 13 years had approached or exceeded 100, with 271 cases in 2005 to 2006 and 167 cases in 2006 to 2007. In the 2007-2008 season, only 36 community-acquired cases were identified, representing an 87% reduction from the same period in 2005 to 2006. G3 was the predominant serotype, accounting for 15 community cases (42%). Our study is limited by its observational design using historical comparisons. Nonetheless, the abrupt decline in rotavirus gastroenteritis cases during the 2007-2008 season likely resulted from vaccination. Because protection rates appeared to have exceeded vaccination rates, herd immunity may have contributed to some degree to the effectiveness of the vaccine.
Multiplexed Genotyping of Methicillin-Resistant
Staphylococcus aureus
Isolates by Use of Padlock Probes and Tag Microarrays
Authors: Kurt Kevin , Alderborn Anders , Nilsson Mats , Strommenger Birgit , Witte Wolfgang , Nübel Ulrich
Published: January 2009

We developed and tested a ligase-based assay for simultaneous probing of core genome diversity and typing of methicillin resistance determinants in
Staphylococcus aureus
isolates. This assay uses oligonucleotide padlock probes whose two ends are joined through ligation when they hybridize to matching target DNA. Circularized probes are subsequently amplified by PCR with common primers and analyzed by using a microarray equipped with universal tag probes. Our set of padlock probes includes oligonucleotides targeting diagnostic regions in the
mecA, ccrB
, and
ccrC
genes of the SCC
mec
cassette in methicillin-resistant
S. aureus
(MRSA). These probes determine the presence and type of SCC
mec
cassettes (i.e., SCC
mec
types I to VI). Additional oligonucleotides interrogate a number of highly informative single nucleotide polymorphisms retrieved from a multilocus sequence typing (MLST) database. These latter probes enable the exploration of isolates' phylogenetic affiliation with clonal lineages of MRSA as revealed by MLST. The described assay enables multiplexed genotyping of MRSA based on a single-tube reaction. With a set of clinical isolates of MRSA and methicillin-susceptible
S. aureus
(
n
= 66), 100% typeability and 100% accuracy were achieved. The assay described here provides valuable genotypic information that may usefully complement existing genotyping procedures. Moreover, the assay is easily extendable by incorporating additional padlock probes and will be valuable for the quick and cost-effective probing of large numbers of polymorphisms at different genomic locations, such as those ascertained through currently ongoing mutation discovery and genome resequencing projects.
Epidemiologic Study of Influenza Infection in Okinawa, Japan, from 2001 to 2007: Changing Patterns of Seasonality and Prevalence of Amantadine-Resistant Influenza A Virus
Authors: Suzuki Yasushi , Taira Katsuya , Saito Reiko , Nidaira Minoru , Okano Shou , Zaraket Hassan , Suzuki Hiroshi
Published: January 2009

To clarify seasonal influenza patterns and the prevalence of amantadine-resistant influenza A viruses in Okinawa, located at the southern extremity of Japan in a subtropical climate, we conducted a laboratory-based study of influenza virus infections from 2001 to 2007. The annual outbreaks tended to show two peaks in Okinawa, in summer and winter, although the main islands of Japan, located in a temperate climate area, showed only winter influenza activity. Epidemic types and subtypes in Okinawa mostly matched those on the main islands of Japan in winter and those in Taiwan in summer. Rates of amantadine resistance dramatically increased, from 7.3% in the November 2002-to-March 2003 season to 90.0% in summer 2005, and a similarly high rate of resistance continued for the rest of the study period. Phylogenetic analysis of the hemagglutinin gene of A/H3N2 isolates collected from 2002 to 2007 revealed a monophyletic lineage that was divided into four period groups. Each group included amantadine-sensitive and -resistant viruses within independent clusters. In the November 2005-to-March 2006 season, all of the amantadine-resistant viruses were clustered in clade N, with dual (position 193 and 225) amino acid mutations in their HA1 subunits. In 2005, clade N amantadine-resistant viruses existed in Okinawa several months before the circulation of this clade on the main islands of Japan. In conclusion, surveillance in Okinawa to monitor influenza virus circulation is important for elucidating the dynamics of virus transmission in a border area between temperate and subtropical areas, as Okinawa is one of the best sentinel points in Japan.
Changes in Genetic Diversity of the
Bordetella pertussis
Population in the United Kingdom between 1920 and 2006 Reflect Vaccination Coverage and Emergence of a Single Dominant Clonal Type
Authors: Litt David J. , Neal Shona E. , Fry Norman K.
Published: January 2009

Pertussis (whooping cough) is a potentially fatal respiratory disease caused by the bacterium
Bordetella pertussis
. Despite effective vaccination programs, there has been concern in some developed countries that pertussis cases are on the increase. We characterized 703 clinical
B. pertussis
isolates collected in the United Kingdom between 1920 and 2006 using multilocus variable-number tandem repeat analysis (MLVA), pertactin (
prnA
) and pertussis toxin (
ptxA
) genotyping, and serotyping. The results showed that the genetic diversity of the bacterial population decreased during periods of high vaccine coverage. However, it was elevated between 1977 and 1986, when vaccine coverage in the United Kingdom was low and epidemics occurred. A high proportion of MLVA types during this epidemic period were novel, and the
prnA
(2) and
prnA
(3) alleles were seen for the first time in the United Kingdom. MLVA-27 appeared in 1982, was codominant during the 1998-to-2001 period, and comprised ∼70% of isolates during both the 2002-to-2004 and the 2005-to-2006 periods. The United Kingdom is dominated currently by an MLVA-27
prnA
(2)
ptxA
(1) serotype Fim3 clonal type. Even during recent periods dominated by MLVA-27, many novel types were found at low frequencies, suggesting that either there are a large number of uncommon MLVA types circulating at low frequencies or new types are constantly arising. This supports a hypothesis that MLVA-27 is under some form of positive selection conferring increased survival in a highly vaccinated population. There has been no significant change to the bacterial population in the first 2 years since the United Kingdom switched from a whole-cell to an acellular vaccine.
Incidence, Virulence Factors, and Clonality among Clinical Strains of Non-O1, Non-O139
Vibrio cholerae
Isolates from Hospitalized Diarrheal Patients in Kolkata, India
Authors: Chatterjee S. , Ghosh K. , Raychoudhuri A. , Chowdhury G. , Bhattacharya M. K. , Mukhopadhyay A. K. , Ramamurthy T. , Bhattacharya S. K. , Klose Karl E. , Nandy R. K.
Published: January 2009

The incidence of
Vibrio cholerae
non-O1, non-O139 strains from hospitalized patients with acute diarrhea constituted 27.4% (
n
= 54) of the total 197
V. cholerae
strains isolated from patients in Kolkata, India, in 2003. Of 197 strains, 135 were identified as O1 serotype Ogawa and 2 were identified as O139. In the same time period, six O1 background rough strains that possessed all known virulence factors were identified. Serotype analysis of the non-O1, non-O139 strains placed 42 strains into 19 serogroups, while 12 remained O nontypeable (ONT); the existing serotyping scheme involved antisera to 206 serogroups. Detection of a good number of ONT strains suggested that additional serogroups have arisen that need to be added to the current serotyping scheme. The non-O1, non-O139 strains were nontoxigenic except for an O36 strain (SC124), which regulated expression of cholera toxin as O1 classical strains did. Additionally, strain SC124 carried alleles of
tcpA
and
toxT
that were different from those of the O1 counterpart, and these were also found in five clonally related strains belonging to different serogroups. Strains carrying
tcpA
exhibited higher colonization in an animal model compared to those lacking
tcpA
. PCR-based analyses revealed remarkable variations in the distribution of other virulence factors, including
hlyA
,
rtxA
,
Vibrio
seventh pandemic island I (VSP-I), VSP-II, and type III secretion system (TTSS). Most strains contained
hlyA
(87%) and
rtxA
(81.5%) and secreted cytotoxic factors when grown in vitro. Approximately one-third of the strains (31.5%) contained the TTSS gene cluster, and most of these strains were more motile and hemolytic against rabbit erythrocytes. Partial nucleotide sequence analysis of the TTSS-containing strains revealed silent nucleotide mutations within
vcsN2
(type III secretion cytoplasmic ATPase), indicating functional conservation of the TTSS apparatus.
Performance of Microcalorimetry for Early Detection of Methicillin Resistance in Clinical Isolates ofStaphylococcus aureus
Authors: Baldoni Daniela , Hermann Heinz , Frei Reno , Trampuz Andrej , Steinhuber Andrea
Published: January 2009

We describe a calorimetric assay for the detection of methicillin-resistantStaphylococcus aureus(MRSA) within 5 h. Microbial heat was calculated in culture with and without cefoxitin. Among 30 genetically distinct clinical isolates, 19/20 MRSA (95%) and 10/10 methicillin-susceptibleStaphylococcus aureus(100%) were correctly identified. Microcalorimetry may be useful for rapid MRSA screening.
Herpesvirus gB-Induced Fusion between the Virion Envelope and Outer Nuclear Membrane during Virus Egress Is Regulated by the Viral US3 Kinase
Authors: Wisner Todd W. , Wright Catherine C. , Kato Akihisa , Kawaguchi Yasushi , Mou Fan , Baines Joel D. , Roller Richard J. , Johnson David C.
Published: January 2009

Herpesvirus capsids collect along the inner surface of the nuclear envelope and bud into the perinuclear space. Enveloped virions then fuse with the outer nuclear membrane (NM). We previously showed that herpes simplex virus (HSV) glycoproteins gB and gH act in a redundant fashion to promote fusion between the virion envelope and the outer NM. HSV mutants lacking both gB and gH accumulate enveloped virions in herniations, vesicles that bulge into the nucleoplasm. Earlier studies had shown that HSV mutants lacking the viral serine/threonine kinase US3 also accumulate herniations. Here, we demonstrate that HSV gB is phosphorylated in a US3-dependent manner in HSV-infected cells, especially in a crude nuclear fraction. Moreover, US3 directly phosphorylated the gB cytoplasmic (CT) domain in in vitro assays. Deletion of gB in the context of a US3-null virus did not add substantially to defects in nuclear egress. The majority of the US3-dependent phosphorylation of gB involved the CT domain and amino acid T887, a residue present in a motif similar to that recognized by US3 in other proteins. HSV recombinants lacking gH and expressing either gB substitution mutation T887A or a gB truncated at residue 886 displayed substantial defects in nuclear egress. We concluded that phosphorylation of the gB CT domain is important for gB-mediated fusion with the outer NM. This suggested a model in which the US3 kinase is incorporated into the tegument layer (between the capsid and envelope) in HSV virions present in the perinuclear space. By this packaging, US3 might be brought close to the gB CT tail, leading to phosphorylation and triggering fusion between the virion envelope and the outer NM.
Robust In Vivo Transduction of a Genetically Stable Epstein-Barr Virus Episome to Hepatocytes in Mice by a Hybrid Viral Vector
Authors: Gallaher Sean D. , Gil Jose S. , Dorigo Oliver , Berk Arnold J.
Published: January 2009

To make a safe, long-lasting gene delivery vehicle, we developed a hybrid vector that leverages the relative strengths of adenovirus and Epstein-Barr virus (EBV). A fully gene-deleted helper-dependent adenovirus (HDAd) is used as the delivery vehicle for its scalability and high transduction efficiency. Upon delivery, a portion of the HDAd vector is recombined to form a circular plasmid. This episome includes two elements from EBV: an EBV nuclear antigen 1 (EBNA1) expression cassette and an EBNA1 binding region. Along with a human replication origin, these elements provide considerable genetic stability to the episome in replicating cells while avoiding insertional mutagenesis. Here, we demonstrate that this hybrid approach is highly efficient at delivering EBV episomes to target cells in vivo. We achieved nearly 100% transduction of hepatocytes after a single intravenous injection in mice. This is a substantial improvement over the transduction efficiency of previously available physical and viral methods. Bioluminescent imaging of vector-transduced mice demonstrated that luciferase transgene expression from the hybrid was robust and compared well to a traditional HDAd vector. Quantitative PCR analysis confirmed that the EBV episome was stable at approximately 30 copies per cell for up to 50 weeks and that it remained circular and extrachromosomal. Approaches for adapting the HDAd-EBV hybrid to a variety of disease targets and the potential benefits of this approach are discussed.
Self-Assembly of Epstein-Barr Virus Capsids
Authors: Henson Brandon W. , Perkins Edward M. , Cothran Jonathan E. , Desai Prashant
Published: January 2009

Epstein-Barr virus (EBV), a member of the
Gammaherpesvirus
family, primarily infects B lymphocytes and is responsible for a number of lymphoproliferative diseases. The molecular genetics of the assembly pathway and high-resolution structural analysis of the capsid have not been determined for this lymphocryptovirus. As a first step in studying EBV capsid assembly, the baculovirus expression vector (BEV) system was used to express the capsid shell proteins BcLF1 (major capsid protein), BORF1 (triplex protein), BDLF1 (triplex protein), and BFRF3 (small capsid protein); the internal scaffold protein, BdRF1; and the maturational protease (BVRF2). Coinfection of insect cells with the six viruses expressing these proteins resulted in the production of closed capsid structures as judged by electron microscopy and sedimentation methods. Therefore, as shown for other herpesviruses, only six proteins are required for EBV capsid assembly. Furthermore, the small capsid protein of EBV (BFRF3), like that of Kaposi's sarcoma-associated herpesvirus, was found to be required for assembly of a stable structure. Localization of the small capsid protein to nuclear assembly sites required both the major capsid (BcLF1) and scaffold proteins (BdRF1) but not the triplex proteins. Mutational analysis of BFRF3 showed that the N-terminal half (amino acids 1 to 88) of this polypeptide is required and sufficient for capsid assembly. A region spanning amino acids 65 to 88 is required for the concentration of BFRF3 at a subnuclear site and the N-terminal 65 amino acids contain the sequences required for interaction with major capsid protein. These studies have identified the multifunctional role of the gammaherpesvirus small capsid proteins.
Olfactory System Involvement in Natural Scrapie Disease
Authors: Corona Cristiano , Porcario Chiara , Martucci Francesca , Iulini Barbara , Manea Barbara , Gallo Marina , Palmitessa Claudia , Maurella Cristiana , Mazza Maria , Pezzolato Marzia , Acutis Pierluigi , Casalone Cristina
Published: January 2009

The olfactory system (OS) is involved in many infectious and neurodegenerative diseases, both human and animal, and it has recently been investigated in regard to transmissible spongiform encephalopathies. Previous assessments of nasal mucosa infection by prions following intracerebral challenge suggested a potential centrifugal spread along the olfactory nerve fibers of the pathological prion protein (PrPSc). Whether the nasal cavity may be a route for centripetal prion infection to the brain has also been experimentally studied. With the present study, we wanted to determine whether prion deposition in the OS occurs also under field conditions and what type of anatomical localization PrPScmight display there. We report here on detection by different techniques of PrPScin the nasal mucosa and in the OS-related brain areas of sheep affected by natural scrapie. PrPScwas detected in the perineurium of the olfactory nerve bundles in the medial nasal concha and in nasal-associated lymphoid tissue. Olfactory receptor neurons did not show PrPScimmunostaining. PrPScdeposition was found in the brain areas of olfactory fiber projection, chiefly in the olfactory bulb and the olfactory cortex. The prevalent PrPScdeposition patterns were subependymal, perivascular, and submeningeal. This finding, together with the discovery of an intense PrPScimmunostaining in the meningeal layer of the olfactory nerve perineurium, at the border with the subdural space extension surrounding the nerve rootlets, strongly suggests a probable role of cerebrospinal fluid in conveying prion infectivity to the nasal submucosa.
Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells
Authors: Jonsson Mari I. , Lenman Annasara E. , Frängsmyr Lars , Nyberg Cecilia , Abdullahi Mohamed , Arnberg Niklas
Published: January 2009

Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on target cells in vitro, but recent research has shown that adenoviruses can also use soluble components in body fluids for indirect binding to target cells. These mechanisms have been identified upon addressing the questions of how to de- and retarget adenovirus-based vectors for human gene and cancer therapy, but the newly identified mechanisms also suggest that the role of body fluids and their components may also be of importance for natural, primary infections. Here we demonstrate that plasma, saliva, and tear fluid promote binding and infection of adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which corresponds to the natural tropism of most adenoviruses, and that plasma promotes infection by Ad31. By using a set of binding and infection experiments, we also found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just FIX, respectively, for efficient binding and infection. The concentrations of these factors that were required for maximum binding were 1/100th of the physiological concentrations. Preincubation of virions with heparin or pretreatment of cells with heparinase I indicated that the role of cell surface heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is mechanistically serotype specific. We conclude that the use of coagulation factors by adenoviruses may be of importance not only for the liver tropism seen when administering adenovirus vectors to the circulation but also during primary infections by wild-type viruses of their natural target cell types.
The impact of smoking and quitting on household expenditure patterns and medical care costs in China
Authors: Xin Y , Qian J , Xu L , Tang S , Gao J , Critchley J A
Published: January 2009

Background:

Smoking remains very common in Chinese men, and the economic burden caused by cigarette consumption on smokers and their families may be substantial. Using a large nationally representative household survey, the third National Health Services Survey (NHSS, 2003), we estimated the economic impact of smoking on households.

Methods:

Smoking status of all household members (over 15 years) was collected by interview for the NHSS, and households classified into one of seven categories based on their smoking status. Information on household income and expenditure, and use of health services was also obtained. We assessed both the “direct” costs (reducing funds available for spending on other commodities such as food, education, medical care, etc, using a fractional logit model), and “indirect costs” (increasing medical expenditures, using a log-linear model).

Results:

Every five packets of cigarettes consumed per capita per month reduces household spending on other commodities, most notably on education (by about 17 yuan per capita per annum) and medical care (11 yuan). The effects are greatest among low-income rural households. Households with quitters spend substantially more on medical care than never-smoking households (64 yuan for households with two or more quitters).

Conclusions:

If a household member smokes, there is less money available for commodities such as education and medical care. Medical care expenditure is substantially higher among households with quitters, as ill-health is the main reason for quitting smoking in China. Smoking impoverishes a substantial number of poorer rural households.
THE INFLUENCE OF RECONSTRUCTION CRITERIA ON THE SENSITIVE PROBES OF THE SYMMETRY POTENTIAL
Authors: LI QINGFENG
Published: January 2009

Different criteria of constructing clusters and tracing back Δ resonances from the intermediate-energy neutron-rich HICs are discussed by employing the updated UrQMD transport model. It is found that both the phase-space and the coordinate-density criteria affect the single and the double neutron/proton ratios of free nucleons at small transverse momenta, but the influence becomes invisible at large transverse momenta. The effect of different methods of reconstructing freeze-out Δs on the Δ0/Δ++ ratio is strong in a large kinetic energy region.
ELIMINATION OF TIME DELAY IN DIGITAL CONTROL LOOP OF SWITCHING DC–DC CONVERTERS
Authors: HE MINGZHI , XU JIANPING
Published: January 2009

Time delay introduced by sampling and calculation exists between the perturbation and the duty ratio updating in the digital control loop. This time delay degrades the transient performance of digital control switching power supplies. By overcoming the sampling and calculation time effect and to calibrate the ripple that occurs during switching cycles, new control algorithm is proposed in this paper to improve the transient performance of switching power supplies by eliminating the time delay in the control loop. Simulation results show the improvement of load transient performance by the proposed algorithms. Experimental system is also set up to verify the analysis and computer simulation results.
A TUNABLE CIRCUIT FOR REALIZING ARBITRARY FLOATING IMPEDANCES
Authors: MINAEI SHAHRAM , YUCE ERKAN
Published: January 2009

In this paper, an active-C circuit for realizing lossless floating inductor (FI) or series/parallel R–L impedances depending on the externally applied bias currents, is presented. The proposed simulator circuit employs only three plus-type second-generation current controlled conveyors (CCCII+s) as active elements and a single capacitor as passive element. SPICE simulation and experimental results are given to verify the theory.
ECONOMIC ENVIRONMENTAL DISPATCH BY A MODE TECHNIQUE
Authors: PANIGRAHI C. K. , CHAKRABARTI R. , CHATTOPADHYAY P. K.
Published: January 2009

Multi-objective differential evolution (MODE) is proposed to handle economic environmental dispatch problem, which is a multi-objective optimization problem (MOOPs) with competing and noncommensurable objectives. The proposed approach has a good performance in finding a diverse set of solutions and in converging near the true Pareto-optimal set. Numerical results for two sample test systems have been presented to demonstrate the capabilities of the proposed approach to generate well-distributed Pareto-optimal solutions of economic environmental dispatch problem in one single run. Simulation results with the proposed approach have been validated with Non-dominated Sorting Genetic Algorithm-II.
POWER GRIDS ANALYSIS IN COMPRESSED KRYLOV-SUBSPACE METHODS
Authors: SU HAOHANG , ZHANG YIMEN , ZHANG YUMING , MAN JINCAI
Published: January 2009

An improved method is proposed based on compressed and Krylov-subspace iterative approaches to perform efficient static and transient simulations for large-scale power grid circuits. It is implemented with CG and BiCGStab algorithms and an excellent result has been obtained. Extensive experimental results on large-scale power grid circuits show that the present method is over 200 times faster than SPICE3 and around 10–20 times faster than ICCG method in transient simulations. Furthermore, the presented algorithm saves the memory usage over 95% of SPICE3 and 75% of ICCG method, respectively while the accuracy is not compromised.
REVERSIBLE SYSTOLIC ARRAYS: m-ARY BIJECTIVE SINGLE-INSTRUCTION MULTIPLE-DATA (SIMD) ARCHITECTURES AND THEIR QUANTUM CIRCUITS
Authors: AL-RABADI ANAS N.
Published: January 2009

New type of m-ary systolic arrays called reversible systolic arrays is introduced in this paper. The m-ary quantum systolic architectures' realizations and computations of the new type of systolic arrays are also introduced. A systolic array is an example of a single-instruction multiple-data (SIMD) machine in which each processing element (PE) performs a single simple operation. Systolic devices provide inexpensive but massive computation power, and are cost-effective, high-performance, and special-purpose systems that have wide range of applications such as in solving several regular and compute-bound problems containing repetitive multiple operations on large arrays of data. Similar to the classical case, information in a reversible and quantum systolic circuit flows between cells in a pipelined fashion, and communication with the outside world occurs only at the boundary cells. Since basic PEs used in the construction of arithmetic systolic arrays are the add–multiply cells, the results introduced in this paper are general and apply to a very wide range of add–multiply-based systolic arrays. Since the reduction of power consumption is a major requirement for the circuit design in future technologies, such as in quantum computing, the main features of several future technologies will include reversibility. Consequently, the new systolic circuits can play an important task in the design of future circuits that consume minimal power. It is also shown that the new systolic arrays maintain the high level of regularity while exhibiting the new fundamental bijectivity (reversibility) and quantum superposition properties. These new properties will be essential in performing super-fast arithmetic-intensive computations that are fundamental in several future applications such as in multi-dimensional quantum signal processing (QSP).
A METHODOLOGY FOR SUPPORTING SYSTEM-LEVEL DESIGN SPACE EXPLORATION AT HIGHER LEVELS OF ABSTRACTION
Authors: DEDIC JOZE , FINC MATJAZ , TROST ANDREJ
Published: January 2009

The complexity of modern embedded systems requires a revised and systematic approach to efficient and concurrent management of hardware (HW) and software (SW) parts in a codesign process. In order to optimally meet the ever-increasing design requirements and at the same time leverage design productivity, higher level aspects need to be addressed before worrying about the HW/SW boundary. This paper deals with high-level aspects of system-level modeling and provides modeling extension, from which contemporary related methodologies can greatly benefit. High-level aspects, their influence on the entire design flow, and systematic integration into the codesign environment are presented. An approach is proposed with a higher level of abstraction that helps bridge the gap between informal and formal system specifications. Higher level design decisions are enabled, avoiding premature ad hoc design decisions. Applicability of the proposed high-level codesign concepts is illustrated with a case study.
A VERY LOW POWER BANDPASS FILTER FOR LOW-IF APPLICATIONS
Authors: FATIN Gh. ZAREH , KANANI Z. D. KOOZEH
Published: January 2009

This paper presents a second-order bandpass filter for IF frequencies in the range of 500 kHz–2 MHz. By using a single Gm–cell as a biquad filter, considerable saving in area and power is feasible. Higher order structures can be achieved by cascading this second-order block. This Gm-C filter achieves a dynamic range of 37 dB for 1% IM3 in Bluetooth while dissipating only 10.5 mW from 3.3 power supply in 0.35 μm CMOS process. The on-chip indirect automatic tuning circuit sets the filter center frequency to an external reference clock.
DESIGN OF DIGITAL MULTI-RATE CONTROLLER USING FREQUENCY DOMAIN ANALYSIS
Authors: LAVANYA K. , UMAMAHESWARI B. , PANDA RAMES C.
Published: January 2009

Multi-rate controllers are useful in providing fast control updates using slow measurements. The multi-rate control loop involves up-sampling, down-sampling, and systems considered at different timescales. The challenge is then, to present complete frequency domain model of the loop. This paper presents the frequency domain model of the loop which is suitable for analysis and design of controllers. The approach is illustrated through a numerical example.
PROBABILISTIC OPTIMIZATION OF PARTIAL SAFETY FACTORS FOR THE DESIGN OF INDUSTRIAL BUILDINGS
Authors: SADOVSKÝ ZOLTÁN , PÁLEŠ DUŠAN
Published: January 2009

By probabilistic optimization of partial safety factors for a class of structures a more uniform reliability of practical design of individual cases within the class is aimed at. The paper deals with an ultimate limit state design of a class of low rise industrial buildings subject to climatic loads and permanent loads. The optimization is carried out on selected representative structures, the reliability of which is calculated by the level II reliability method FORM. Probabilistic models of cross section resistance and of climatic loads pertinent to a continental climate are based on measurements. Peculiarities of the optimization procedure, particularly optimization stages in conjunction with the choice and possible differentiation of partial factors are discussed.
AN APPROACH FOR HUMAN ERROR MODES AND EFFECTS ANALYSIS USING HTA+ETA
Authors: ZHIQIANG SUN , HONGWEI XIE , XIUJIAN SHI , FENGQIANG LIU , ZHENGYI LI
Published: January 2009

A framework for human error modes and effects analysis is presented. The methods of hierarchical task analysis and event tree analysis are introduced as the basic analytical tools, and a novel generic framework for human errors classification is presented as the guidance to identify human errors. Firstly, the process of human error modes and effects analysis is discussed, and the hierarchical task analysis method is introduced briefly. Secondly, the framework for human errors classification is discussed in detail. Thirdly, the multi-states event tree is designed to model the accident scenario. Finally, two scenarios are selected as the examples to illustrate the proposed process of human error modes and effects analysis.
Volatility Persistence of High-Frequency Returns in the Japanese Government Bond Futures Market
Authors: Shi Weihua , Lee Cheng-Few
Published: January 2009

The availability of a two-year high-frequency transaction data of the Japanese Government Bond (JGB) futures provides us with an opportunity to uncovering volatility persistence in high-frequency returns and testing the mixed-distribution-hypothesis (MDH) in this market. Both time-domain and frequency domain methods show that the degrees of volatility persistence are very similar across various frequencies, which supports the MDH. The result also shows that the method of filtering out the intraday pattern annihilates the complex interaction of the intraday periodicity and the volatility persistent process, and effectively uncovers volatility persistence phenomenon in the high-frequency data.
A Study on Stock-Selection and Market-Timing Performance: Evidence from Hong Kong Mandatory Provident Funds (MPF)
Authors: Chu Patrick Kuok-kun , McKenzie Michael
Published: January 2009

This paper presents the first comprehensive study of the performance and market timing ability of the equity funds that comprise the Hong Kong Mandatory Provident Funds (MPF) scheme. In general, our results suggest that US equity funds consistently underperform relative to the market, while the other fund groups consistently outperform the market. The stock-selection ability of MPF constituent equity funds in times of changing economic condition is also investigated. The evidence is consistent with previous studies, which suggest that the conditional models decrease the individual fund traditional alpha measure. The market timing models of Treynor–Mazuy and Henriksson–Merton provide evidence of superior market timing ability.
A STUDY ON HOW TO ELEVATE ORGANISATIONAL CREATIVITY IN TAIWANESE DESIGN ORGANISATION
Authors: CHANG WEN-CHIH , CHIANG ZUN-HWA
Published: January 2009

This research focuses on exploring which factors influence organisational creativity the most, and what actions are the most effective to enhance organisational creativity of design companies and departments in Taiwan. The survey showed that the most influential five factors to organisational creativity were in the order of design environment, team climate, group/organisation culture, design process and motive of work. The survey also showed that the most effective ways of improving organisational creativity were in the order of effective knowledge/experience sharing among colleagues, cultivating the designers' world view, accumulations of team design experiences, visiting domestic and foreign design exhibitions and diversified design work experiences. After the data from the questionnaire were further analysed by t-test, one-way ANOVA and Scheffé post hoc multiple comparisons, the study also showed that the most effective ways of improving organisational creativity were in the significant difference between the design company and design department. Furthermore, in terms of demographic variables of gender, employees' education, professional training, age and working experiences, the study result also implied that the most effective ways of improving organisational creativity could be different under different situations. With follow-up interview, we also found that due to the differences of business conditions, interviewees also had different perspectives referring to the definitions of good ideas. It drew various degrees of attentions when valuating creativity and improving it in the organisation. Thus, in order to get an effective creative performance, while facing different layout strategies and environments, administrators must adjust these measures to fit into their own need according to the conditions or restrictions of the organisations.
ADAPTIVE FILTERING ALGORITHMS ENHANCE THE ACCURACY OF LOW-COST INERTIAL/MAGNETIC SENSING IN PEDESTRIAN NAVIGATION SYSTEMS
Authors: SABATINI ANGELO MARIA
Published: January 2009

The availability of inexpensive, miniaturized sensors and the development of efficient and accurate filtering algorithms are important elements in order that pedestrian navigation system (PNS) will become an enabling technology for monitoring unconstrained daily living activities of human subjects.

In this paper, we develop and test a computational method that estimates the path traveled by a walker from in-shoe mounted tri-axis inertial and magnetic sensors. The interest for inertial and magnetic sensors stems from their low cost, suitable form factors, small power consumption, which may give rise to self-contained, portable PNS whose hindrance to walking is limited.

An important element in our approach is represented by an extended Kalman filter (EKF), whose aim is to estimate the body part orientation and to perform the in-line calibration of the tri-axis magnetometer. Two validation tests are applied to either acceleration or magnetic vector measurements, in order to adapt the measurement noise covariance matrix against the effects of body motion and external magnetic fields on the sensed gravity and earth's magnetic fields involved in orientation determination. Additionally, some biomechanical facts about how humans normally move are exploited to enhance the positioning performance of the developed method.
Phospholemman regulates cardiac Na+/Ca2+ exchanger by interacting with the exchanger's proximal linker domain
Authors: Zhang Xue-Qian , Wang JuFang , Carl Lois L. , Song Jianliang , Ahlers Belinda A. , Cheung Joseph Y.
Published: January 2009

Phospholemman (PLM) belongs to the FXYD family of small ion transport regulators. When phosphorylated at Ser68, PLM inhibits cardiac Na+/Ca2+ exchanger (NCX1). We previously demonstrated that the cytoplasmic tail of PLM interacts with the proximal intracellular loop (residues 218–358), but not the transmembrane (residues 1–217 and 765–938) or Ca2+-binding (residues 371–508) domains, of NCX1. In this study, we used intact Na+/Ca2+ exchanger with various deletions in the intracellular loop to map the interaction sites with PLM. We first demonstrated by Western blotting and confocal immunofluorescence microscopy that wild-type (WT) NCX1 and its deletion mutants were expressed in transfected HEK-293 cells. Cotransfection with PLM and NCX1 (or its deletion mutants) in HEK-293 cells did not decrease expression of NCX1 (or its deletion mutants). Coexpression of PLM with WT NCX1 inhibited NCX1 current ( INaCa). Deletion of residues 240–679, 265–373, 250–300, or 300–373 from WT NCX1 resulted in loss of inhibition of INaCa by PLM. Inhibition of INaCa by PLM was preserved when residues 229–237, 270–300, 328–330, or 330–373 were deleted from the intracellular loop of NCX1. These results suggest that PLM mediated inhibition of INaCa by interacting with two distinct regions (residues 238–270 and 300–328) of NCX1. Indeed, INaCa measured in mutants lacking residues 238–270, 300–328, or 238–270 + 300–328 was not affected by PLM. Glutathione S-transferase pull-down assays confirmed that PLM bound to fragments corresponding to residues 218–371, 218–320, 218–270, 238–371, and 300–373, but not to fragments encompassing residues 250–300 and 371–508 of NCX1, indicating that residues 218–270 and 300–373 physically associated with PLM. Finally, acute regulation of INaCa by PLM phosphorylation observed with WT NCX1 was absent in 250–300 deletion mutant but preserved in 229–237 deletion mutant. We conclude that PLM mediates its inhibition of NCX1 by interacting with residues 238–270 and 300–328.
Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry
Authors: Pagano Mario , Clynes Michael A. , Masada Nanako , Ciruela Antonio , Ayling Laura-Jo , Wachten Sebastian , Cooper Dermot M. F.
Published: January 2009

Adenylyl cyclases (ACs) are a family of critically important signaling molecules that are regulated by multiple pathways. Adenylyl cyclase 8 (AC8) is a Ca2+stimulated isoform that displays a selective regulation by capacitative Ca2+entry (CCE), the process whereby the entry of Ca2+into cells is triggered by the emptying of intracellular stores. This selectivity was believed to be achieved through the localization of AC8 in lipid raft microdomains, along with components of the CCE apparatus. In the present study, we show that an intact leucine zipper motif is required for the efficient N-linked glycosylation of AC8, and that this N-linked glycosylation is important to target AC8 into lipid rafts. Disruption of the leucine zipper by site-directed mutagenesis results in the elimination of N-glycosylated forms and their exclusion from lipid rafts. Mutants of AC8 that cannot be N-glycosylated are not demonstrably associated with rafts, although they can still be regulated by CCE; however, raft integrity is required for the regulation of these mutants. These findings suggest that raft localized proteins in addition to AC8 are needed to mediate its regulation by CCE.
Renal NHE3 and NaPi2 partition into distinct membrane domains
Authors: Riquier Anne D. M. , Lee Donna H. , McDonough Alicia A.
Published: January 2009

Hypertension provokes differential trafficking of the renal proximal tubule Na+/H+ exchanger 3 (NHE3) to the base of the apical microvilli and Na+-Pi cotransporter 2 (NaPi2) to endosomes. The resultant diuresis and natriuresis are key to blood pressure control. We tested the hypothesis that this differential trafficking of NHE3 vs. NaPi2 was associated with partitioning to distinct membrane domains. In anesthetized rats, arterial pressure was increased (104 ± 2 to 142 ± 4 mmHg, 15 min) by arterial constriction and urine output increased 23-fold. Renal membranes were fractionated by cold 1% Triton X-100 extraction then centrifugation through OptiPrep flotation gradients. In controls, 84 ± 9% of NHE3 localized to flotillin-enriched lipid raft domains and 69 ± 5% of NaPi2 localized to transferrin receptor-enriched nonrafts. MyosinVI and dipeptidyl peptidase IV, associated with NHE3 regulation, coenriched in lipid rafts with NHE3, while NHE regulatory factor-1 coenriched in nonrafts with NaPi2. Partitioning was not altered by hypertension. Detergent insoluble membranes were pelleted after detergent extraction. NHE3 detergent insolubility decreased as it redistributed from body (80 ± 10% detergent insoluble) to base (75 ± 3%) of the apical microvilli, while NaPi2 partitioned into more insoluble domains as it moved from the microvilli (45 ± 7% detergent insoluble) to endosomes (82 ± 1%). In conclusion, NHE3 and NaPi2, while both localized to apical microvilli, are segregated into domains: NHE3 to lipid rafts and NaPi2 to nonrafts. These domain properties may play a role in the distinct trafficking patterns observed during elevated pressures: NHE3 remains in rafts and settles to the base of the microvilli while NaPi2 is freely endocytosed.
Angiotensin-converting enzyme inhibitor-enhanced MR renography: repeated measures of GFR and RPF in hypertensive patients
Authors: Zhang Jeff L. , Rusinek Henry , Bokacheva Louisa , Lim Ruth P. , Chen Qun , Storey Pippa , Prince Keyma , Hecht Elizabeth M. , Kim Danny C. , Lee Vivian S.
Published: January 2009

This study aims to assess the feasibility of a protocol to diagnose renovascular disease using dual MR renography acquisitions: before and after administration of angiotensin-converting enzyme inhibitor (ACEi). Results of our simulation study aimed at testing the reproducibility of glomerular filtration rate (GFR) and renal plasma flow demonstrate that for a fixed overall dose of 12 ml gadolinium-based contrast material (500 mmol/l), the second dose should be approximately twice as large as the first dose. A three-compartment model for analyzing the second-injection data was shown to appropriately handle the tracer residue from the first injection. The optimized protocol was applied to 18 hypertensive patients without renovascular disease, showing minimal systematic difference in GFR measurements before and after ACEi of 0.8 ± 4.4 ml/min or 2.7 ± 14.9%. For 10 kidneys with significant renal artery stenosis, GFR decreased significantly after ACEi ( P < 0.001, T value = 3.79), and the difference in GFR measurements before and after ACEi averaged 8.3 ± 6.9 ml/min or 26.2 ± 43.9%. Dual-injection MRI with optimized dose distribution appears promising for ACEi renography by offering measures of GFR changes with clinically acceptable precision and accuracy.
Deep Brain Stimulation of the Globus Pallidus Internus in the Parkinsonian Primate: Local Entrainment and Suppression of Low-Frequency Oscillations
Authors: McCairn Kevin W. , Turner Robert S.
Published: January 2009

Competing theories seek to account for the therapeutic effects of high-frequency deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically intractable Parkinson's disease. To investigate this question, we studied the spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques rendered parkinsonian by administration of MPTP. Stimulation through macroelectrodes in the GPi (≥200 μA at 150 Hz for 30 s) reduced rigidity in one animal and increased spontaneous movement in both. Novel artifact subtraction methods allowed uninterrupted single-unit recording during stimulation. GPiDBS induced phasic (78% of cells) or sustained (22%) peristimulus changes in firing in both pallidal segments. A subset of cells responded at short latency (<2 ms) in a manner consistent with antidromic driving. Later phasic increases clustered at 3- to 5-ms latency. Stimulation-induced decreases were either phasic, clustered at 1–3 ms, or sustained, showing no peristimulus modulation. Response latency and magnitude often evolved over 30 s of stimulation, but responses were relatively stable by the end of that time. GPiDBS reduced mean firing rates modestly and only in GPi (−6.9 spikes/s). Surprisingly, GPiDBS had no net effect on the prevalence or structure of burst firing. GPiDBS did reduce the prevalence of synchronized low-frequency oscillations. Some cell pairs became synchronized instead at the frequency of stimulation. Suppression of low-frequency oscillations did not require high-frequency synchronization, however, or even the presence of a significant peristimulus response. In summary, the therapeutic effects of GPiDBS may be mediated by an abolition of low-frequency synchronized oscillations as a result of phasic driving.