bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Microarray-Based Method for Monitoring of All Currently Known Single-Nucleotide Polymorphisms Associated with Parasite Resistance to Antimalaria Drugs
Authors: Crameri Andreas , Marfurt Jutta , Mugittu Kefas , Maire Nicolas , Regös Attila , Coppee Jean Yves , Sismeiro Odile , Burki Richard , Huber Eric , Laubscher Daniel , Puijalon Odile , Genton Blaise , Felger Ingrid , Beck Hans-Peter
Published: September 2007

Parasite drug resistance is partly conferred by single-nucleotide polymorphisms (SNPs), and monitoring them has been proposed as an alternative to monitoring drug resistance. Therefore, techniques are required to facilitate analyses of multiple SNPs on an epidemiological scale. We report a rapid and affordable microarray technique for application in epidemiological studies of malaria drug resistance. We have designed a multiwell microarray that is used in conjunction with PCR-amplified target genes implicated in the drug resistance of malaria with subsequent one-tube minisequencing using two fluorochromes. The drug-resistance-associated genes
pfdhfr, pfdhps, pfcrt, pfmdr1
, and
pfATPase
were amplified and analyzed for cultured
Plasmodium falciparum
strains and from field samples. We obtained a specificity of 94%, and comparison of field sample results to those of restriction fragment length polymorphism (RFLP) typing resulted in an overall consistency of >90%, except for
pfdhfr51
, for which most discrepancies were due to false determinations by RFLP of mixed infections. The system is sufficiently sensitive to assay parasites in clinical malaria cases and in most asymptomatic cases, and it allows high throughput with minimal hands-on time. The cost for the assay has been calculated as 0.27 euros/SNP (US$0.33), which is below the cost incurred with other systems. Due to the simplicity of the approach, newly identified SNPs can be incorporated rapidly. Such a monitoring system also makes it possible to identify the reemergence of drug-susceptible parasites once a drug has been withdrawn.
Assessment of Population Structure and Major Circulating Phylogeographical Clades of
Mycobacterium tuberculosis
Complex in Bangladesh Suggests a High Prevalence of a Specific Subclade of Ancient
M. tuberculosis
Genotypes
Authors: Rahim Zeaur , Zaman Khadiza , van der Zanden Adri G. M. , Möllers Marius J. , van Soolingen Dick , Raqib Rubhana , Zaman Khalequ , Begum Vikarunessa , Rigouts Leen , Portaels Françoise , Rastogi Nalin , Sola Christophe
Published: September 2007

Spoligotyping was performed to study the population structure of
Mycobacterium tuberculosis
complex strains (
n
= 224) from Bangladesh. Strains were split into principal genetic group 1 (PGG 1 [75.0%]) and PGG 2 and 3 (25%). Forty-nine strains with a new spoligotype signature and considered as south or southeast Asian-linked emerging clones were designated as “Matlab type.”
Differential Inhibition of Type I Interferon Induction by Arenavirus Nucleoproteins
Authors: Martínez-Sobrido Luis , Giannakas Panagiotis , Cubitt Beatrice , García-Sastre Adolfo , de la Torre Juan Carlos
Published: September 2007

We have documented that the nucleoprotein (NP) of the prototypic arenavirus lymphocytic choriomeningitis virus is an antagonist of the type I interferon response. In this study we tested the ability of NPs encoded by representative arenavirus species from both Old World and New World antigenic groups to inhibit production of interferon. We found that, with the exception of Tacaribe virus (TCRV), all NPs tested inhibited activation of beta interferon and interferon regulatory factor 3 (IRF-3)-dependent promoters, as well as the nuclear translocation of IRF-3. Consistent with this observation, TCRV-infected cells also failed to inhibit interferon production.
Crystallographic and Biochemical Analysis of Rotavirus NSP2 with Nucleotides Reveals a Nucleoside Diphosphate Kinase-Like Activity
Authors: Kumar Mukesh , Jayaram Hariharan , Vasquez-Del Carpio Rodrigo , Jiang Xiaofang , Taraporewala Zenobia F. , Jacobson Raymond H. , Patton John T. , Prasad B. V. Venkataram
Published: September 2007

Rotavirus, the major pathogen of infantile gastroenteritis, carries a nonstructural protein, NSP2, essential for viroplasm formation and genome replication/packaging. In addition to RNA-binding and helix-destabilizing properties, NSP2 exhibits nucleoside triphosphatase activity. A conserved histidine (H225) functions as the catalytic residue for this enzymatic activity, and mutation of this residue abrogates genomic double-stranded RNA synthesis without affecting viroplasm formation. To understand the structural basis of the phosphatase activity of NSP2, we performed crystallographic analyses of native NSP2 and a functionally defective H225A mutant in the presence of nucleotides. These studies showed that nucleotides bind inside a cleft between the two domains of NSP2 in a region that exhibits structural similarity to ubiquitous cellular HIT (
hi
stidine
t
riad) proteins. Only minor conformational alterations were observed in the cleft upon nucleotide binding and hydrolysis. This hydrolysis involved the formation of a stable phosphohistidine intermediate. These observations, reminiscent of cellular nucleoside diphosphate (NDP) kinases, prompted us to investigate whether NSP2 exhibits phosphoryl-transfer activity. Bioluminometric assay showed that NSP2 exhibits an NDP kinase-like activity that transfers the bound phosphate to NDPs. However, NSP2 is distinct from the highly conserved cellular NDP kinases in both its structure and catalytic mechanism, thus making NSP2 a potential target for antiviral drug design. With structural similarities to HIT proteins, which are not known to exhibit NDP kinase activity, NSP2 represents a unique example among structure-activity relationships. The newly observed phosphoryl-transfer activity of NSP2 may be utilized for homeostasis of nucleotide pools in viroplasms during genome replication.
Efficient Thymopoiesis Contributes to the Maintenance of Peripheral CD4 T Cells during Chronic Human Immunodeficiency Virus Type 2 Infection
Authors: Gautier David , Beq Stéphanie , Cortesão Catarina S. , Sousa Ana E. , Cheynier Rémi
Published: September 2007

Human immunodeficiency virus type 2 (HIV-2) infection leads to a lifelong asymptomatic period in the majority of patients. Even in patients with progressive disease, a slow CD4 count decline characterizes the chronic phase of HIV-2 infection, suggesting that peripheral T-cell homeostasis is controlled better following HIV-2 infection than following HIV-1 infection. Herein we showed that, in contrast to HIV-1-infected patients, HIV-2-infected patients demonstrate enhanced thymic function compared to age-matched healthy individuals. The correlation between higher thymic production and lower CD4 T-cell loss in these patients suggests that efficient thymopoiesis is implicated in the long-lasting maintenance of CD4 T-cell counts in HIV-2 disease.
A Single-Amino-Acid Substitution in the P2 Domain of VP1 of Murine Norovirus Is Sufficient for Escape from Antibody Neutralization
Authors: Lochridge Vance P. , Hardy Michele E.
Published: September 2007

Noroviruses cause epidemic outbreaks of acute viral gastroenteritis worldwide, and the number of reported outbreaks is increasing. Human norovirus strains do not grow in cell culture. However, murine norovirus (MNV) replicates in the RAW 264.7 macrophage cell line and thus provides a tractable model to investigate norovirus interactions with host cells. Epitopes recognized by monoclonal antibodies (MAbs) against the human norovirus strains Norwalk virus and Snow Mountain virus (SMV) identified regions in the P domain of major capsid protein VP1 important for interactions with putative cellular receptors. To determine if there was a relationship between domains of MNV VP1 and VP1 of human norovirus strains involved in cell binding, epitope mapping by phage display was performed with an MNV-1-neutralizing MAb, A6.2.1. A consensus peptide, GWWEDHGQL, was derived from 20 third-round phage clones. A synthetic peptide containing this sequence and constrained through a disulfide linkage reacted strongly with the A6.2.1 MAb, whereas the linear sequence did not. Four residues in the A6.2.1-selected peptide, G327, G333, Q334, and L335, aligned with amino acid residues in the P2 domain of MNV-1 VP1. This sequence is immediately adjacent to the epitope recognized by anti-SMV MAb 61.21. Neutralization escape mutants selected with MAb A6.2.1 contained a leucine-to-phenylalanine substitution at position 386 in the P2 domain. The predicted location of these residues on VP1 suggests that the phage peptide and the mutation in the neutralization-resistant viruses may be in close proximity to each other and to residues reported to be important for carbohydrate binding to VP1 of human norovirus strains.
Claudin-6 and Claudin-9 Function as Additional Coreceptors for Hepatitis C Virus
Authors: Zheng Aihua , Yuan Fei , Li Yanqin , Zhu Fangfang , Hou Pingping , Li Jianqing , Song Xijun , Ding Mingxiao , Deng Hongkui
Published: September 2007

Hepatitis C virus (HCV) is a global challenge to public health. Several factors have been proven to be critical for HCV entry, including the newly identified claudin-1 (CLDN1). However, the mechanism of HCV entry is still obscure. Presently, among the 20 members of the claudin family identified in humans so far, CLDN1 has been the only member shown to be necessary for HCV entry. Recently, we discovered that Bel7402, an HCV-permissive cell line, does not express CLDN1 but expresses other members of claudin family. Among these claudins, CLDN9 was able to mediate HCV entry just as efficiently as CLDN1. We then examined if other members of the claudin family could mediate entry. We show that CLDN6 and CLDN9, but not CLDN2, CLDN3, CLDN4, CLDN7, CLDN11, CLDN12, CLDN15, CLDN17, and CLDN23, were able to mediate the entry of HCV into target cells. We found that CLDN6 and CLDN9 are expressed in the liver, the primary site of HCV replication. We also showed that CLDN6 and CLDN9, but not CLDN1, are expressed in peripheral blood mononuclear cells, an additional site of HCV replication. Through sequence comparison and mutagenesis studies, we show that residues N38 and V45 in the first extracellular loop (EL1) of CLDN9 are necessary for HCV entry.
Ternary Complex Formation on the Adenovirus Packaging Sequence by the IVa2 and L4 22-Kilodalton Proteins
Authors: Ewing Sean G. , Byrd Serena A. , Christensen Joan B. , Tyler Ryan E. , Imperiale Michael J.
Published: September 2007

Assembly of infectious adenovirus particles requires seven functionally redundant elements at the left end of the genome, termed A repeats, that direct packaging of the DNA. Previous studies revealed that the viral IVa2 protein alone interacts with specific sequences in the A repeats but that additional IVa2-containing complexes observed during infection require the viral L4 22-kDa protein. In this report, we purified a recombinant form of the 22-kDa protein to characterize its DNA binding properties. In electrophoretic mobility shift assay analyses, the 22-kDa protein alone did not interact with the A repeats but it did form complexes on them in the presence of the IVa2 protein. These complexes were identical to those seen in extracts from infected cells and had the same DNA sequence dependence. Furthermore, we provide data that the 22-kDa protein enhances binding of the IVa2 protein to the A repeats and that multiple binding sites in the packaging sequence augment this activity. These data support a cooperative role of the IVa2 and 22-kDa proteins in packaging and assembly.
Signal Peptide Requirements for Lymphocytic Choriomeningitis Virus Glycoprotein C Maturation and Virus Infectivity
Authors: Schrempf Sabrina , Froeschke Marc , Giroglou Tsanan , von Laer Dorothee , Dobberstein Bernhard
Published: September 2007

Insertion of the lymphocytic choriomeningitis virus (LCMV) precursor glycoprotein C (GP-C) into the membrane of the endoplasmic reticulum is mediated by an unusual signal peptide (SP
GP-C
). It is comprised of 58 amino acid residues and contains an extended hydrophilic N-terminal region, two hydrophobic regions, and a short C-terminal region. After cleavage by signal peptidase, SP
GP-C
accumulates in cells and virus particles. In the present study, we identified the LCMV SP
GP-C
as being an essential component of the GP complex and show that the different regions of SP
GP-C
are required for distinct steps in GP maturation and virus infectivity. More specifically, we show that one hydrophobic region of SP
GP-C
is sufficient for the membrane insertion of GP-C, while both hydrophobic regions are required for the processing and cell surface expression of the GPs. The N-terminal region of SP
GP-C
, on the other hand, is essential for pseudoviral infection of target cells. Furthermore, we show that unmyristoylated SP
GP-C
exposes its N-terminal region to the exoplasmic side. This SP
GP-C
can promote GP-C maturation but is defective in pseudoviral infection. Myristoylation and topology of SP
GP-C
in the membrane may thus hold the key to an understanding of the role of SP
GP-C
in GP-C complex maturation and LCMV infectivity.
Escape from the Dominant HLA-B27-Restricted Cytotoxic T-Lymphocyte Response in Gag Is Associated with a Dramatic Reduction in Human Immunodeficiency Virus Type 1 Replication
Authors: Schneidewind Arne , Brockman Mark A. , Yang Ruifeng , Adam Rahma I. , Li Bin , Le Gall Sylvie , Rinaldo Charles R. , Craggs Sharon L. , Allgaier Rachel L. , Power Karen A. , Kuntzen Thomas , Tung Chang-Shung , LaBute Montiago X. , Mueller Sandra M. , Harrer Thomas , McMichael Andrew J. , Goulder Philip J. R. , Aiken Christopher , Brander Christian , Kelleher Anthony D. , Allen Todd M.
Published: September 2007

Human leukocyte antigen (HLA)-B27-positive subjects are uncommon in their ability to control infection with human immunodeficiency virus type 1 (HIV-1). However, late viral escape from a narrowly directed immunodominant Gag-specific CD8+T-lymphocyte (CTL) response has been linked to AIDS progression in these individuals. Identifying the mechanism of the immune-mediated control may provide critical insights into HIV-1 vaccine development. Here, we illustrate that the CTL escape mutation R264K in the HLA-B27-restricted KK10 epitope in the capsid resulted in a significant defect in viral replication in vitro. The R264K variant was impaired in generating late reverse transcription products, indicating that replication was blocked at a postentry step. Notably, the R264K mutation was associated in vivo with the development of a rare secondary mutation, S173A, which restored viral replication in vitro. Furthermore, infectivity of the R264K variant was rescued by the addition of cyclosporine A or infection of a cyclophilin A-deficient cell line. These data demonstrate a severe functional defect imposed by the R264K mutation during an early step in viral replication that is likely due to the inability of this variant to replicate efficiently in the presence of normal levels of cyclophilin A. We conclude that the impact of the R264K substitution on capsid structure constrains viral escape and enables long-term maintenance of the dominant CTL response against B27-KK10, providing an explanation for the protective effect of HLA-B27 during HIV infection.
Digital rectal examination: national survey of undergraduate medical training in Ireland
Authors: Fitzgerald Deirdre , Connolly Stephen S , Kerin Michael J
Published: September 2007

Objective

To assess the experience gained in digital rectal examination (DRE) by medical students in the Republic of Ireland by the completion of undergraduate training.

Methods

A national survey was conducted targeting all 582 final year students from the five medical schools completing their undergraduate studies in the summer of 2005. Format was anonymous questionnaire. Experience of DRE was defined as the student having performed at least one examination on either patient or teaching mannequin.

Results

In total, 396 (68%) of 582 students responded. No experience of DRE was reported in 97 (24%), with mannequin-only experience in a further 78 (20%). Of the remaining 221 (56%) who performed DRE on at least one patient, one third (74) reported no confidence in their ability to interpret their findings properly.

Conclusion

Undergraduate training in DRE is limited. Training in DRE can no longer be reasonably considered part of the core curriculum taught in Irish medical schools.
Carcinoembryonic antigen (CEA) testing in colorectal cancer follow up: what do patients think?
Authors: Steele Nicola , Haigh Rachel , Knowles Gillian , Mackean Melanie
Published: September 2007

The carcinoembryonic antigen (CEA) blood test is included in most colorectal cancer follow up protocols, despite little clear evidence for its cost-effectiveness and survival benefit. In this study, patients' views were sought on the use of the CEA blood test in their follow up. Strong associations were found between the age of a patient's children and their concern about cancer recurrence and between concern about recurrence and anxiety about CEA test results (p<0.0001). Many patients expressed a desire for prognostic information, however uncertain or poor. Patients' views should be sought when designing colorectal cancer follow up protocols to ensure their needs are adequately addressed.
Basal, but not overload-induced, myonuclear addition is attenuated by NG-nitro-l-arginine methyl ester (l-NAME) administration
Authors: Gordon Scott E. , Westerkamp Christopher M. , Savage Kathleen J. , Hickner Robert C. , George Sarah C. , Fick Christopher A. , McCormick Kathleen M.
Published: September 2007

The purpose of this study was to examine the effect of blocking nitric oxide synthase (NOS) activity via NG-nitro-l-arginine methyl ester (l-NAME) on myonuclear addition in skeletal muscle under basal and overloaded conditions. Female Sprague–Dawley rats (approx. 220 g) were placed into 1 of the following 4 groups (n = 7–9/group): 7-day skeletal muscle overload (O), sham operation (S), skeletal muscle overload with l-NAME treatment (OLN), and sham operation with l-NAME treatment (SLN). Plantaris muscles were overloaded via bilateral surgical ablation of the gastrocnemius muscles and l-NAME (0.75 mg/mL) was administered in the animals’ daily drinking water starting 2 days prior to surgery and continued until sacrifice. Myonuclear addition was assessed as subsarcolemmal incorporation of nuclei labeled with 5-bromo-2′-deoxyuridine (approx. 25 mg·(kg body mass)–1·day–1) delivered via osmotic pump during the overload period. As expected, muscle wet mass, total protein content, fiber cross-sectional area, and myonuclear addition were significantly higher (p ≤ 0.05) in O vs. S; however, only the increase in wet mass and total protein content (per body mass) were attenuated by l-NAME administration. Interestingly, l-NAME significantly reduced myonuclear addition by 75% in nonoverloaded muscles (SLN vs. S). Muscle hepatocyte growth factor protein content increased with overload, but was unaffected by l-NAME in either loading state. These data indicate that NOS inhibition in rat plantaris muscle attenuates myonuclear addition under basal, but not overloaded, conditions.
Mechanism and significance of early, rapid shortening in sensitized airway smooth muscleThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.
Authors: Ford Lincoln E. , Gilbert Susan H.
Published: September 2007

It has been reported that sensitization of animals to allergens increases both early shortening velocity and myosin light-chain kinase of their airway smooth muscle without increasing force generated by these muscles. Since early shortening sets muscle length for the duration of a contraction, these responses might be expected to produce greater airway obstruction. Here, it is explained how the more rapid early shortening without increased force production is predicted by the 2-stage process of activation followed by contraction posited by the crossbridge theory of contraction when the rate, but not the extent, of activation is increased. The experimental results are reproduced by a simple model in which activation rate is increased 1.6-fold without any other changes in contractile parameters. These results reinforce suggestions that sensitized animals are a model for reactive airway disease.
Extracellular matrix and airway smooth muscle interactions: a target for modulating airway wall remodelling and hyperresponsiveness?This article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.
Authors: Tran Thai , Halayko Andrew J.
Published: September 2007

The airway smooth muscle from asthmatic airways produces increased amounts and an altered composition of extracellular matrix proteins. The extracellular matrix can in turn influence the phenotype and function of airway smooth muscle cells, affecting the biochemical, geometric, and mechanical properties of the airway wall. This review provides a brief overview of the current understanding of the biology associated with airway smooth muscle interactions with the extracellular matrix. We present future directions needed for the study of cellular and molecular mechanisms that determine the outcomes of extracellular matrix – airway smooth muscle interactions, and discuss their possible importance as determinants of airway function in asthma.
Structural basis for exaggerated airway narrowingThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.
Authors: Paré Peter D. , McParland Brent E. , Seow Chun Y.
Published: September 2007

Airway hyperresponsiveness, particularly the ability of airways to narrow excessively in response to stimuli that normally cause little airway narrowing in nonasthmatic subjects, is a characteristic feature of asthma and the basis of its symptoms. Although airway hyperresponsiveness may be partly the result of alterations in the contractile phenotype of the airway smooth muscle, there is evidence that it may also be caused by structural changes in the airway wall, collectively termed airway remodeling. Airway remodeling is defined as changes in composition, quantity, and (or) organization of cellular and molecular constituents of the airway wall. Airway wall remodeling that occurs in asthma can result in functional alterations because of quantitative changes in airway wall compartments, and (or) because of changes in the biochemical composition or material properties of the various constituents of the airway wall. This brief review summarizes the quantitative changes in the dimensions and organization of the airway wall compartments that have been described and explains how structural alterations may lead to the exaggerated airway narrowing.
Neuroprotective effect of dauricine in cortical neuron culture exposed to hypoxia and hypoglycemia: involvement of correcting perturbed calcium homeostasis
Authors: Li Yan-Hong , Gong Pei-Li
Published: September 2007

We have previously reported that dauricine protects brain tissues from focal cerebral ischemia. To corroborate this effect, neurotoxicity due to hypoxia and hypoglycemia was assessed in primary cultures of rat cortical neurons by using a trypan blue exclusion method. To further clarify the mechanism, the intracellular Ca2+concentration ([Ca2+]i) and mitochondrial membrane potential (ΔΨm) of dissociated rat cortical cells were monitored by fura-2 fluorescence measurements and flow cytometry, respectively. The results showed that 1 and 10 μmol/L dauricine significantly enhanced neuronal survival during 4 h of hypoxia and hypoglycemia. Dauricine inhibited the increase in [Ca2+]iand decrease in ΔΨminduced by 30 min of hypoxia and hypoglycemia. When exploring the pathway, we found that 1 μmol/L dauricine inhibited the [Ca2+]iincrease induced by 7.5 nmol/L thapsigargin in either the presence or absence of extracellular Ca2+and by 1 mmol/L l-glutamate in the presence of extracellular Ca2+. These results suggest that dauricine prevents neuronal loss from ischemia in vitro, which is in accordance with our previous research in vivo. In addition, by inhibiting Ca2+release from the endoplasmic reticulum and Ca2+influx from the extracellular space, dauricine suppressed the increase in [Ca2+]iand, subsequently, the decrease in ΔΨminduced by hypoxia and hypoglycemia. This effect may underlie the mechanism of action of dauricine on cerebral ischemia.
Three paradigms of airway smooth muscle hyperresponsiveness in young guinea pigsThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.
Authors: Chitano Pasquale , Wang Lu , Murphy Thomas M.
Published: September 2007

Evidence for contributions of airway smooth muscle (ASM) to the hyperresponsiveness of newborn and juvenile airways continues to accumulate. In our laboratory, 3 novel paradigms of hyperresponsiveness of newborn and young ASM have recently emerged using a guinea pig model of maturation in 3 age groups: 1 week (newborn), 3 weeks (juvenile), and 2–3 months (adult). The first paradigm includes evidence for a natural decline after newborn and juvenile life of the velocity of ASM shortening associated with a decrease in regulatory myosin light chain phosphorylation and a parallel decline in the content of myosin light chain kinase. Associated with the decrease in ASM shortening with age is an increase in the internal resistance to shortening. Dynamic stiffness is shown to relate inversely to the expression of myosin light chain kinase. This suggests that developmental changes in shortening relate inversely to the stiffness of the ASM early in shortening, suggesting a dynamic role for the cytoskeleton in facilitating and opposing ASM shortening. This relationship can be approximated as (dP/dt)max ≈ (dP/dL)passive × (dL/dt)max(the maximal rate of increase of active stress generation ≈ to the passive stiffness × the maximal shortening velocity). The second paradigm demonstrates that newborn ASM, unlike that in adults, does not relax during prolonged electric field stimulation. The impaired relaxation is related to changes in prostanoid synthesis and acetylcholinesterase function. The third paradigm demonstrates that, whereas oscillatory strain serves to transiently relax adult ASM, in newborns it induces (after the initial relaxation) a sustained potentiation of active stress. This is related to developmental changes in the prostanoid release. Together, these paradigms demonstrate that ASM contributes by multiple mechanisms to the natural hyperresponsiveness of newborn and juvenile airways. Future studies will elaborate the mechanisms and extend these paradigms to ASM hyperresponsiveness following sensitization in early life.
A NEW HEURISTIC ALGORITHM FOR CONSTRAINED RECTANGLE-PACKING PROBLEM
Authors: CHEN DUANBING , HUANG WENQI
Published: September 2007

The constrained rectangle-packing problem is the problem of packing a subset of rectangles into a larger rectangular container, with the objective of maximizing the layout value. It has many industrial applications such as shipping, wood and glass cutting, etc. Many algorithms have been proposed to solve it, for example, simulated annealing, genetic algorithm and other heuristic algorithms. In this paper a new heuristic algorithm is proposed based on two strategies: the rectangle selecting strategy and the rectangle packing strategy. We have applied the algorithm to 21 smaller, 630 larger and other zero-waste instances. The computational results demonstrate that the integrated performance of the algorithm is rather satisfying and the algorithm developed is fairly efficient for solving the constrained rectangle-packing problem.
GALAXY FORMATION: THE FIRST 109 YEARS
Authors: SILK JOSEPH
Published: September 2007

Progress has been made in understanding the origin of spiral galaxies, but elliptical galaxy formation continues to pose many problems. At the centres of ellipticals, one finds supermassive black holes which are occasionally fed by gas accretion from their surroundings and are visible as active galactic nuclei. Negative feedback, due to the outflow from the central black hole during its active phase, terminates the gas supply to the spheroid, thereby resulting in an old stellar population. A contemporaneous phase of positive feedback when the protogalaxy is forming could result in the highly efficient phase of early star formation required by the recent data.
FEATURES IN THE PRIMORDIAL POWER SPECTRUM: A RUNNING SPECTRAL INDEX AND FORMATION OF PRIMORDIAL BLACK HOLES
Authors: KAWASAKI MASAHIRO , TAKAYAMA TSUTOMU , YAMAGUCHI MASAHIDE , YOKOYAMA JUN'ICHI
Published: September 2007

We present an inflation model which realizes density fluctuations with a negative running spectral index large enough as inferred by WMAP observation. In this model two different stages of inflation occur successively in the observable regime. As a result of numerical investigation, we find that the fluctuations generated in the late first inflationary stage are enhanced to the level significant amount of primordial black holes could be produced due to parametric resonance and that it is stretched to a cosmological scale in the second inflation.
LARGE-SCALE MODES OF CLEANED THREE-YEAR WMAP CMB MAP
Authors: PARK CHAN-GYUNG , PARK CHANGBOM , RICHARD GOTT J.
Published: September 2007

We have produced a cleaned map of the WMAP three-year data using an improved version of an internal linear combination (ILC) method to subtract the Galactic foreground emission. We divide the whole sky into hundreds of pixel groups with similar foreground spectral indices over a range of WMAP frequencies, apply the ILC for each group, and obtain a CMB map with foreground emission effectively reduced. With the resulting foreground-reduced ILC map, we have investigated the known anomalies in CMB maps at large scales, and confirmed that the quadrupole power is low and the quadrupole and the octopole are strongly aligned and are planar. Although our estimates are consistent with the previous measurements, ILC simulation implies that the observed low quadrupole power and the alignment between the quadrupole and the octopole are marginally statistically significant, and the observed planarity is not statistically significant.
PERTURBATIONS FROM D-TERM INFLATION
Authors: SETO OSAMU , YOKOYAMA JUN'ICHI
Published: September 2007

We investigated a simple D-term inflation with taking account of higher order corrections in the Kähler potential. These terms may solve the cosmic string problem in D-term inflation model. The mass per unit length of cosmic strings formed after inflation can be suppressed enough. In addition, the change of the potential slope leads simultaneously a more tilted scalar spectral index ns ≃ 0.96 – 0.97 than that in the model without these corrections.
QUASI-LOCAL ENERGY FOR COSMOLOGICAL MODELS
Authors: CHEN CHIANG-MEI , LIU JIAN-LIANG , NESTER JAMES M.
Published: September 2007

First we briefly review our covariant Hamiltonian approach to quasi-local energy, noting that the Hamiltonian-boundary-term quasi-local energy expressions depend on the chosen boundary conditions and reference configuration. Then we present the quasi-local energy values resulting from the formalism applied to homogeneous Bianchi cosmologies. Finally we consider the quasi-local energies of the FRW cosmologies. Our results do not agree with certain widely accepted quasi-local criteria.
HOLOGRAPHIC COSMOLOGY IN NON-SUPERSYMMETRIC GRAVITY: THE COSMIC ROLE OF TACHYON IN THE TYPE 0 STRINGS
Authors: WEN WEN-YU
Published: September 2007

We present a new class of time-dependent solution to the ten-dimensional type 0 effective action. Given a generic potential of tachyon field, there exist phases where tachyon is either frozen at local extremals or free to propagate along flat directions. In the latter phase, a cosmology model is proposed where the tachyon plays the role of time.
DYNAMIC SCALAR TORSION AND AN OSCILLATING UNIVERSE
Authors: YO HWEI-JANG , NESTER JAMES M.
Published: September 2007

For the Poincaré gauge theory of gravity we consider the dynamical scalar torsion mode in a cosmological context. We explore in particular the possibility of using dynamical torsion to explain the current state of the accelerating Universe. With certain suitable sets of chosen parameters, this model can give a (qualitatively) proper description of the current universe without a cosmological constant, and the universe described is oscillating with a period of the Hubble time.
SUPERNOVAE, LANDAU LEVELS, AND PULSAR KICKS
Authors: KISSLINGER LEONARD S.
Published: September 2007

We derive the energy asymmetry given the proto-neutron star during the time when the neutrino sphere is near the surface of the proto-neutron star, using the modified URCA process. The electrons produced with the anti-neutrinos are in Landau levels due to the strong magnetic field, and this leads to asymmetry in the neutrino momentum, and a pulsar kick. Our main prediction is that the large pulsar kicks start at about 10 s and last for about 10 s, with the corresponding neutrinos correlated in the direction of the magnetic field.
FERMION PRODUCTION IN STRONG MAGNETIC FIELD AND ITS ASTROPHYSICAL IMPLICATIONS
Authors: LEE HYUN KYU , YOON YONGSUNG
Published: September 2007

We calculate the effective potential of a strong magnetic field induced by fermions with anomalous magnetic moments which couple to the electromagnetic field in the form of the Pauli interaction. For a uniform magnetic field, we find the explicit form of the effective potential. It is found that the non-vanishing imaginary part develops for a magnetic field stronger than a critical field and has a quartic form which is quite different from the exponential form of the Schwinger process. We also consider a linear magnetic field configuration as an example of inhomogeneous magnetic fields. We find that the imaginary part of the effective potential is nonzero even below the critical field and shows an exponentially decreasing behavior with respect to the inverse of the magnetic field gradient, which is the non-perturbative characteristics analogous to the Schwinger process. These results imply the instability of the strong magnetic field to produce fermion pairs as a purely magnetic effect. The possible applications to the astrophysical phenomena with strong magnetic field are also discussed.
PROBING FOR DYNAMICS OF DARK-ENERGY IN MASS VARYING NEUTRINOS: COSMIC MICROWAVE BACKGROUND RADIATION AND LARGE SCALE STRUCTURE
Authors: KEUM YONG-YEON
Published: September 2007

We present cosmological perturbation theory in neutrino probe interacting dark-energy models, and calculate cosmic microwave background anisotropies and matter power spectrum. In these models, the evolution of the mass of neutrinos is determined by the quintessence scalar field, which is responsible for the cosmic acceleration today. We consider several types of scalar field potentials and put constraints on the coupling parameter between neutrinos and dark energy. Assuming the flatness of the universe, the constraint we can derive from the current observation is Σ mν < 0.87eV at the 95 % confidence level for the sum over three species of neutrinos.
FOURIER ANALYSIS OVER HYPERBOLIC ALGEBRA, PSEUDO-DIFFERENTIAL OPERATORS, AND HYPERBOLIC DEFORMATION OF CLASSICAL MECHANICS
Authors: KHRENNIKOV ANDREI
Published: September 2007

We develop Fourier analysis over hyperbolic algebra (the two-dimensional commutative algebra with the basis e1 = 1, e2 = j, where j2 = 1). We demonstrated that classical mechanics has, besides the well-known quantum deformation over complex numbers, another deformation — so-called hyperbolic quantum mechanics. The classical Poisson bracket can be obtained as the limit h → 0 not only of the ordinary Moyal bracket, but also a hyperbolic analogue of the Moyal bracket.
INTEGRAL REPRESENTATIONS OF CYLINDRICAL LOCAL MARTINGALES IN EVERY SEPARABLE BANACH SPACE
Authors: ONDREJÁT MARTIN
Published: September 2007

A general sufficient condition for a continuous cylindrical local martingale on a separable Banach space to be a stochastic integral with respect to a Wiener process is proven.
NEW SCHEME OF QUANTUM TELEPORTATION
Authors: KOSSAKOWSKI A. , OHYA M.
Published: September 2007

A new scheme for quantum teleportation is presented, in which teleportation channel from Alice to Bob is always linear and complete (total) teleportation can occur even when an entangled state between Alice and Bob is not maximal.
Evolutionary Biology of Insect Learning
Authors: Dukas Reuven
Published: September 2007

Learning and memory, defined as the acquisition and retention of neuronal representations of new information, are ubiquitous among insects. Recent research indicates that a variety of insects rely extensively on learning for all major life activities including feeding, predator avoidance, aggression, social interactions, and sexual behavior. There is good evidence that individuals within an insect species exhibit genetically based variation in learning abilities and indirect evidence linking insect learning to fitness. Although insects rely on innate behavior to successfully manage many types of variation and unpredictability, learning may be superior to innate behavior when dealing with features unique to time, place, or individuals. Among insects, social learning , which can promote the rapid spread of novel behaviors, is currently known only from a few well-studied examples in social Hymenoptera. The prevalence and importance of social learning in insects are still unknown. Similarly, we know little about ecological factors that may have promoted enhanced learning abilities in insects, and whether learning has significantly contributed to speciation in insects.
Inhibition of L-type Ca2+ channel current and negative inotropy induced by arachidonic acid in adult rat ventricular myocytes
Authors: Liu Shi J.
Published: September 2007

We have previously shown an increase in arachidonic acid (AA) release in response to proinflammatory cytokines in adult rat ventricular myocytes (ARVM). AA is known to alter channel activities; however, its effects on cardiac L-type Ca2+ channel current ( ICa,L) and excitation-contraction coupling remain unclear. The present study examined effects of AA on ICa,L, using the whole cell patch-clamp technique, and on cell shortening (CS) and the Ca2+ transient of ARVM. ICa,L was monitored in myocytes held at −70 mV and internally equilibrated and externally perfused with Na+- and K+-free solutions. Exposure to AA caused a voltage-dependent block of ICa,L concentration dependently (IC50 8.5 μM). The AA-induced inhibition of ICa,L is consistent with its hyperpolarizing shift in the voltage-dependent properties and reduction in maximum slope conductance. In the presence of AA, BSA completely blocked the AA-induced suppression of ICa,L and CS. Intracellular load with AA had no effect on the current density but caused a small depolarizing shift in the ICa,L activation curve, suggesting a site-specific action of AA. Moreover, intracellular AA had no effect on the extracellular AA-induced decrease in ICa,L. Pretreatment with indomethacin, an inhibitor of cyclooxygenase, or addition of nordihydroguaiaretic acid, an inhibitor of lipoxygenase, had no effect on AA-induced changes in ICa,L. Furthermore, AA suppressed CS and Ca2+ transients of intact ARVM with no significant effect on SR function and myofilament Ca2+ sensitivity. Therefore, these results suggest that AA inhibits contractile function of ARVM, primarily due to its direct inhibition of ICa,L at an extracellular site.
Rac1 is required for reorientation of polarity and lumen formation through a PI 3-kinase-dependent pathway
Authors: Liu Kathleen D. , Datta Anirban , Yu Wei , Brakeman Paul R. , Jou Tzuu-Shuh , Matthay Michael A. , Mostov Keith E.
Published: September 2007

Epithelial cells are characterized by the ability to form sheets of cells that surround fluid-filled lumens. Cells in these sheets exhibit a characteristic subcellular polarity, with an apical pole that faces the lumen and a basolateral pole that is in contact with other cells and the extracellular matrix (ECM). To investigate the signaling events required for polarization and lumen formation, we have taken advantage of the ability of Madin-Darby canine kidney (MDCK) cells to dynamically remodel their polarity in response to changes in ECM cues. When MDCK cells are grown in suspension culture, they form multicellular “inside-out” cysts with apical proteins found on the peripheral surface and basolateral markers on the interior surface. When these inside-out cysts are embedded in ECM, they rapidly reorient their polarity: apical proteins become localized to the inside surface, and basolateral proteins are found on the surface that contacts ECM. Here we have characterized the signaling requirements for these early molecular reorientation events. Specifically, expression of a dominant-negative form of Rac1 (DN-Rac1) blocks the reorientation of polarity. Phosphoinositide 3′-kinase is required for apical membrane protein remodeling from the initial apical membrane surface. Cells expressing DN-Rac1 fail to detectably activate the PI 3-kinase/protein kinase B pathway. Last, we found that atypical protein kinase C (aPKC) is also required for reorientation of polarity, since an inhibitor of atypical PKC blocks reorientation. This effect cannot be overcome by constitutively active Rac1, demonstrating that both Rac1 and atypical PKC are required for reorientation of cellular polarity.
Evidence for restriction of fluid and solute movement across the glomerular capillary wall by the subpodocyte space
Authors: Salmon Andrew H. J. , Toma Ildikó , Sipos Arnold , Muston P. Robert , Harper Steven J. , Bates David O. , Neal Christopher R. , Peti-Peterdi János
Published: September 2007

The glomerular filtration barrier (GFB) is generally considered to consist of three layers: fenestrated glomerular endothelium, glomerular basement membrane, and filtration slits between adjacent podocyte foot processes. Detailed anatomic examination of the GFB has revealed a novel abluminal structure, the subpodocyte space (SPS), identified as the labyrinthine space between the underside of podocyte cell body/primary processes and the foot processes. The SPS covers 50–65% of the filtration surface of the GFB, indicating that SPS may influence glomerular permeability. We have examined the contribution of the SPS to the permeability characteristics of the GFB using multiphoton microscopy techniques in isolated, perfused glomeruli and in the intact kidney in vivo. SPS were identified using this technique, with comparable dimensions to SPS examined with electron microscopy. The passage of the intermediate-weight molecule rhodamine-conjugated 10-kDa dextran, but not the low-weight molecule lucifer yellow (≈450 Da), accumulated in SPS-covered regions of the GFB, compared with GFB regions not covered by SPS (“naked regions”). Net lucifer yellow flux (taken to indicate fluid flux) through identifiable SPS regions was calculated to be 66–75% of that occurring through naked regions. These observations indicate both ultrafiltration and hydraulic resistance imparted by the SPS, demonstrating the potential physiological contribution of the SPS to glomerular permeability.
Genetic analysis of albuminuria in a cross between C57BL/6J and DBA/2J mice
Authors: Sheehan Susan , Tsaih Shirng-Wern , King Benjamin L. , Stanton Caitlin , Churchill Gary A. , Paigen Beverly , DiPetrillo Keith
Published: September 2007

Chronic kidney disease (CKD) is a growing medical problem and a significant risk factor for the development of end-stage renal disease, cardiovascular disease, and cardiovascular mortality. The genetic basis of CKD is recognized, but knowledge of the specific genes that contribute to the onset and progression of kidney disease is limited, mainly because of the difficulty and expense of identifying genes underlying CKD in humans. Results from genetic studies of CKD in rodents often correspond to findings in humans; therefore, we used quantitative trait locus (QTL) analysis to detect genomic regions affecting albuminuria in a cross between C57BL/6J and DBA/2J mice, strains resistant and susceptible to CKD, respectively. We identified several independent and interacting loci affecting albuminuria, including one QTL on mouse chromosome (Chr) 2 that is concordant with QTL influencing urinary albumin excretion on rat Chr 3 and diabetic nephropathy on human Chr 20p. Because this QTL was identified in multiple mouse crosses, as well as in rats and in humans, we used comparative genomics, haplotype analysis, and expression profiling to narrow the initial QTL interval from 386 genes to 10 genes with known coding sequence polymorphisms or expression differences between the strains. These results support the continued use of multiple cross-mapping and cross-species comparisons to further our understanding of the genetic basis of kidney disease.
Interference with TGF-β signaling by Smad3-knockout in mice limits diabetic glomerulosclerosis without affecting albuminuria
Authors: Wang Amy , Ziyadeh Fuad N. , Lee Eun Young , Pyagay Petr E. , Sung Sun Hee , Sheardown Steven A. , Laping Nicholas J. , Chen Sheldon
Published: September 2007

Transforming growth factor (TGF)-β plays a critical role in diabetic nephropathy. To isolate the contribution of one of the signaling pathways of TGF-β, the Smad3 gene in the mouse was knocked out at exons 2 and 3, and the effect was studied in streptozotocin (STZ)-induced diabetes over a period of 6 wk. TGF-β activity was increased in the diabetic mice but was not able to signal via Smad3 in the knockout (KO) mice. As expected in the wild type, the kidneys of the STZ-diabetic mice showed both structural and functional defects that are characteristic of diabetic renal involvement. In the Smad3-KO mice, however, the defects that were improved were renal hypertrophy, mesangial matrix expansion, fibronectin overproduction, glomerular basement membrane thickening, plasma creatinine, and the blood urea nitrogen. The parameters not significantly altered by the Smad3-KO were albuminuria, reduction in podocyte slit pore density, and the increase in vascular endothelial growth factor abundance and activity. It seems that the absence of Smad3 modifies the natural course of murine diabetic nephropathy, providing renal functional protection and preventing structural lesions relating to kidney hypertrophy and matrix accumulation, even though albuminuria and changes in podocyte morphology persist. In conclusion, the effects of the Smad3-KO mirror the effects of anti-TGF-β therapy in diabetes, suggesting that the chief component of TGF-β signaling that is relevant to kidney disease is the Smad3 pathway.