bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multiobjective Optimization Approach to a Design Problem of Heat Insulation for Thermal Distribution Piping Network Systems
Authors: Ito K. , Akagi S. , Nishikawa M.
Published: November 2009

A multiobjective optimization method is applied to a design problem of heat insulation for thermal distribution piping network systems. As the system’s multiple design objectives, the following two mutually conflicting and noncommensurable objective functions are considered simultaneously: (a) minimization of the total amount of heat loss from the whole system, and (b) minimization of the total volume of heat insulating material installed into the whole system. First, for a piping system of fundamental network structure, the set of Pareto optimal solutions is derived for the optimal design problem mentioned above by adopting the weighting method and the generalized reduced gradient algorithm. Second, for the purpose of investigating the same problem for piping systems of more complex network structure, a computer-aided interactive planning system is developed based on decomposition and coordination principles in the theory of hierarchical multilevel systems. Lastly, the validity and the effectiveness of the optimal design method proposed here are ascertained through numerical studies for some typical piping network systems.
Optimal Design of Rack-and-Pinion Steering Linkages
Authors: Zarak C. E. , Townsend M. A.
Published: November 2009

A mathematical model is developed for the design synthesis of rack-and-pinion steering linkages. The general objective is to minimize the difference between the steering centers over the full range of steering angle inputs while fitting into a reasonable space. Because there is a substantial amount of design art in these systems and the mathematical representation is not clear, the model, constraints, and objective actually “evolve” to the eventual desired form. The problem has multiple optima, and practical and heuristic considerations are used to choose suboptimal but more realistic solutions, once satisfactory optimal solutions are identified. These involve manipulation of the objective function, constraint set, and intitial guesses. Both leading and trailing link designs are considered, the former being slightly better. Limitations of the model are also presented.
Tooth Profile Analysis of Circular-Cut, Spiral-Bevel Gears
Authors: Huston R. L. , Lin Y. , Coy J. J.
Published: November 2009

An analysis of tooth profile changes in the transverse plane of circular-cut, spiral-bevel crown gears is presented. The analysis assumes a straight-line profile in the midtransverse plane. The profile variation along the centerline is determined by using expressions for the variation of the spiral angle along the tooth centerline, together with the profile description at the midtransverse plane. It is shown that the tooth surface is a hyperboloid and that significant variations in the pressure angle are possible.
An Analytical Method for Computing the Instant Centers, Centrodes, Inflection Circles, and Centers of Curvature of the Centrodes by Successively Grounding Each Link
Authors: Gilmore B. J. , Cipra R. J.
Published: November 2009

An analytical method is presented for determining the instant centers, centrodes, inflection circles, and centers of curvature of the centrodes of a mechanism. The method uses the vector loop and kinematic coefficient concepts and is applicable to any mechanism which can be represented by vector loops. A modified vector loop approach includes the idea of mechanism inversion to obtain relative kinematic coefficients, thus eliminating the need for recalculating them. A computer program was written incorporating the method, and examples are given.
Flexible indium zinc oxide/Ag/indium zinc oxide multilayer electrode grown on polyethersulfone substrate by cost-efficient roll-to-roll sputtering for flexible organic photovoltaics
Authors: Park Yong-Seok , Kim Han-Ki
Published: November 2009

The authors describe the preparation and characteristics of flexible indium zinc oxide (IZO)-Ag-IZO multilayer electrodes grown on flexible polyethersulfone (PES) substrates using a roll-to-roll sputtering system for use in flexible organic photovoltaics. By the continuous roll-to-roll sputtering of the bottom IZO, Ag, and top IZO layers at room temperature, they were able to fabricate a high quality IZO-Ag-IZO multilayer electrode with a sheet resistance of 6.15ε/square, optical transmittance of 87.4%, and figure of merit value of 42.03×10−3Ω−1 on the PES substrate. In addition, the IZO-Ag-IZO multilayer electrode exhibited superior flexibility to the roll-to-roll sputter grown single ITO electrode due to the existence of a ductile Ag layer between the IZO layers and stable amorphous structure of the IZO film. Furthermore, the flexible organic solar cells (OSCs) fabricated on the roll-to-roll sputter grown IZO-Ag-IZO electrode showed higher power efficiency (3.51%) than the OSCs fabricated on the roll-to-roll sputter grown single ITO electrode (2.67%).
University Head Zhu Qingshi Challenges Old Academic Ways
Authors: Stone Richard
Published: November 2009

In an interview with
Science
, Zhu Qingshi, the newly appointed president of China's planned South University of Science and Technology, explained how he intends to shake up China's university system—whether the education ministry likes it or not.
PKM2 Tyrosine Phosphorylation and Glutamine Metabolism Signal a Different View of the Warburg Effect
Authors: Dang Chi V.
Published: November 2009

Aerobic glycolysis in cancer cells is associated with tyrosine phosphorylation of a metabolic enzyme.
Generic and Specific Adaptive Responses ofStreptococcus pneumoniaeto Challenge with Three Distinct Antimicrobial Peptides, Bacitracin, LL-37, and Nisin
Authors: Majchrzykiewicz Joanna A. , Kuipers Oscar P. , Bijlsma Jetta J. E.
Published: November 2009

To investigate the response ofStreptococcus pneumoniaeto three distinct antimicrobial peptides (AMPs), bacitracin, nisin, and LL-37, transcriptome analysis of challenged bacteria was performed. Only a limited number of genes were found to be up- or downregulated in all cases. Several of these common highly induced genes were chosen for further analysis, i.e.,SP0385-SP0387(SP0385-0387herein),SP0912-0913,SP0785-0787,SP1714-1715, and theblpgene cluster. Deletion of these genes in combination with MIC determinations showed that several putative transporters, i.e., SP0785-0787 and SP0912-0913, were indeed involved in resistance to lincomycin and LL-37 and to bacitracin, nisin, and lincomycin, respectively. Mutation of theblpbacteriocin immunity genes resulted in an increased sensitivity to LL-37. Interestingly, a putative ABC transporter (SP1715) protected against bacitracin and Hoechst 33342 but conferred sensitivity to LL-37. A GntR-like regulator, SP1714, was identified as a negative regulator of itself and two of the putative transporters. In conclusion, we show that resistance to three different AMPs inS. pneumoniaeis mediated by several putative ABC transporters, some of which have not been associated with antimicrobial resistance in this organism before. In addition, a GntR-like regulator that regulates two of these transporters was identified. Our findings extend the understanding of defense mechanisms of this important human pathogen against antimicrobial compounds and point toward novel proteins, i.e., putative ABC transporters, which can be used as targets for the development of new antimicrobials.
In Vitro
Potency of CXA-101, a Novel Cephalosporin, against
Pseudomonas aeruginosa
Displaying Various Resistance Phenotypes, Including Multidrug Resistance
Authors: Bulik Catharine C. , Christensen Henry , Nicolau David P.
Published: November 2009

We describe the activity of a novel cephalosporin, CXA-101 (FR26 4205), against a panel of highly resistant
Pseudomonas aeruginosa
isolates collected from U.S. hospitals. CXA-101 demonstrated increased potency against this population of resistant isolates, with activity that is 4- to 10-fold higher than that of comparator agents in each phenotypic category. The addition of tazobactam did not improve its activity. CXA-101 appears to be a promising addition to the category of antipseudomonal β-lactams.
Mutasynthesis of Lincomycin Derivatives with Activity against Drug-Resistant Staphylococci
Authors: Ulanova Dana , Novotná Jitka , Smutná Yvona , Kameník Zdeněk , Gažák Radek , Šulc Miroslav , Sedmera Petr , Kadlčík Stanislav , Plháčková Kamila , Janata Jiří
Published: November 2009

The lincomycin biosynthetic gene
lmbX
was deleted in
Streptomyces lincolnensis
ATCC 25466, and deletion of this gene led to abolition of lincomycin production. The results of complementation experiments proved the blockage in the biosynthesis of lincomycin precursor 4-propyl-
l
-proline. Feeding this mutant strain with precursor derivatives resulted in production of 4′-butyl-4′-depropyllincomycin and 4′-pentyl-4′-depropyllincomycin in high titers and without lincomycin contamination. Moreover, 4′-pentyl-4′-depropyllincomycin was found to be more active than lincomycin against clinical
Staphylococcus
isolates with genes determining low-level lincosamide resistance.
Efficacy of Posaconazole against Three Clinical
Aspergillus fumigatus
Isolates with Mutations in the
cyp51A
Gene
Authors: Mavridou Eleftheria , Brüggemann Roger J. M. , Melchers Willem J. G. , Mouton Johan W. , Verweij Paul E.
Published: November 2009

The
in vivo
efficacy of posaconazole against 4 clinical
Aspergillus fumigatus
isolates with posaconazole MICs ranging from 0.03 to 16 mg/liter, as determined by CLSI method M38A, was assessed in a nonneutropenic murine model of disseminated aspergillosis. The underlying resistance mechanisms of the isolates included substitutions in the
cyp51A
gene at codon 220 (M220I), codon 54 (G54W), and codon 98 (L98H). The latter was combined with a 34-bp tandem repeat in the gene promoter region (TR L98H). The control isolate exhibited a wild-type phenotype without any known resistance mechanism. Oral posaconazole therapy was started 24 h after infection and was given once daily for 14 consecutive days. Mice were treated with four different doses (1 to 64 mg/kg of body weight), and survival was used as the end point. Survival was dependent both on the dose and on the MIC. The Hill equation with a variable slope fitted the relationship between the dose/MIC ratio and 14-day survival well (
R
2
, 0.92), with a 50% effective dose (ED
50
) of 29.0 mg/kg (95% confidence interval [CI], 15.6 to 53.6 mg/kg). This also applied to the relationship between the area under the plasma concentration-time curve (AUC)/MIC ratio and 14-day survival (50% effective pharmacodynamic index [EI
50
], 321.3 [95% CI, 222.7 to 463.4]). Near-maximum survival was reached at an AUC/MIC ratio of nearly 1,000. These results indicate that treatment of infections with
A. fumigatus
strains for which MICs are 0.5 mg/liter requires doses exceeding the present licensed doses. Increasing the standard dosing regimen may have some effect and may be clinically useful if no alternatives are available.
Cellular Pharmacology of the Anti-Hepatitis B Virus Agent β-l-2′,3′-Didehydro-2′,3′-Dideoxy-N4-Hydroxycytidine: Relevance for Activation in HepG2 Cells
Authors: Matthes E. , Bünger H.
Published: November 2009

ß-l-2′,3′-Didehydro-2′,3′-dideoxy-N4-hydroxycytidine (l-Hyd4C) was demonstrated to be an effective and highly selective inhibitor of hepatitis B virus (HBV) replication in HepG2.2.15 cells (50% effective dose [ED50] = 0.03 μM; 50% cytotoxic dose [CD50] = 2,500 μM). In the present study, we investigated the intracellular pharmacology of tritiatedl-Hyd4C in HepG2 cells.l-[3H]Hyd4C was shown to be phosphorylated extensively and rapidly to the 5′-mono-, 5′-di-, and 5′-triphosphate derivatives. Other metabolites deriving from a reduction or removal of the NHOH group ofl-Hyd4C could not be detected, although both reactions were described as the primary catabolic pathways of the stereoisomer ß-d-N4-hydroxycytidine in HepG2 cells. Also, the formation of liponucleotide metabolites, such as the 5′-diphosphocholine derivative ofl-Hyd4C, as described for somel-deoxycytidine analogues, seems to be unlikely. After incubation of HepG2 cells with 10 μMl-[3H]Hyd4C for 24 h, the 5′-triphosphate accumulated to 19.4 ± 2.7 pmol/106cells. The predominant peak belonged to 5-diphosphate, with 43.5 ± 4.3 pmol/106cells. The intracellular half-life of the 5′-triphosphate was estimated to be 29.7 h. This extended half-life probably reflects a generally low affinity of 5′-phosphorylatedl-deoxycytidine derivatives for phosphate-degrading enzymes but may additionally be caused by an efficient rephosphorylation of the 5′-diphosphate during a drug-free incubation. The high 5′-triphosphate level and its extended half-life in HepG2 cells are consistent with the potent antiviral activity ofl-Hyd4C.
Novel Insights about Class 2 Integrons from Experimental and Genomic Epidemiology
Authors: Ramírez María Soledad , Piñeiro Silvia , Centrón Daniela
Published: November 2009

In order to contribute to the knowledge of the architecture and epidemiology of class 2 integrons, we performed a class 2 integron molecular survey in which we analyzed 726 isolates in two bacterial populations from environmental and nonepidemiologically related clinical samples, respectively, collected from 1982 to 2007. We recovered the
intI2
gene from 130 of 726 isolates, most of which were clinical isolates, and only 1 (a psychrophilic
Pseudomonas
sp.) was from a water sample. Unlike the widespread distribution of class 1 integrons within Gram-negative bacilli, only
Acinetobacter baumannii
and
Enterobacter cloacae
harbored class 2 integrons at a high frequency in our collection. Class 2 integrons with six novel cassette arrays were documented. Characterization of the transposition module of Tn
7
, the genetic platform in which class 2 integrons have always been reported, showed
tns
modules with a mosaic genetic structure. A bioinformatic analysis performed with the
tns
genes present in sequence databases, the finding of
intI2
not associated with
tns
genes, and the genetic examination of novel
tns
-like genes found in three isolates indicated the possibility of the independent evolution of the two components related to horizontal gene transfer, the class 2 integrons and the Tn
7
transposons.
Helicobacter pyloriStimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4+T Lymphocytes
Authors: Khamri Wafa , Walker Marjorie M. , Clark Peter , Atherton John C. , Thursz Mark R. , Bamford Kathleen B. , Lechler Robert I. , Lombardi Giovanna
Published: November 2009

Helicobacter pyloriis a human gastroduodenal pathogen that leads to active chronic inflammation characterized by T-cell responses biased toward a Th1 phenotype. It has been accepted thatH. pyloriinfection induces a Th17 response. At mucosal sites, dendritic cells (DCs) have the capacity to induce effector T cells. Here, we evaluate the role of DCs in theH. pylori-induced interleukin-17 (IL-17) response. Immunohistochemistry and immunofluorescence were performed on human gastric mucosal biopsy samples and showed that myeloid DCs inH. pylori-infected patients colocalized with IL-23- and that IL-17-producing lymphocytes were present inH. pylori-infected antral biopsy samples. In parallel, human monocyte-derived DCs stimulatedin vitrowith liveH. pyloricells produced significant levels of IL-23 in the absence of IL-12 release. The subsequent incubation ofH. pylori-infected DCs with autologous CD4+T cells led to gamma interferon (IFN-γ) and IL-17 expression. The inhibition of IL-1 and, to a lesser extent, IL-23 inhibited IL-17 production by T cells. Finally, isogenicH. pylorimutant strains not expressing major virulence factors were less effective in inducing IL-1 and IL-23 release by DCs and IL-17 release by T cells than parental strains. Altogether, we can conclude that DCs are potent inducers of IL-23/IL-17 expression followingH. pyloristimulation. IL-1/IL-23 as well asH. pylorivirulence factors seem to play an important role in mediating this response.
Major Secretory Antigens of the Helminth
Fasciola hepatica
Activate a Suppressive Dendritic Cell Phenotype That Attenuates Th17 Cells but Fails To Activate Th2 Immune Responses
Authors: Dowling David J. , Hamilton Clare M. , Donnelly Sheila , La Course James , Brophy Peter M. , Dalton John , O'Neill Sandra M.
Published: November 2009

Fasciola hepatica
is a helminth pathogen that drives Th2/Treg immune responses in its mammalian host. The parasite releases a large number of molecules that are critical to inducing this type of immune response. Here we have selected recombinant forms of two major
F. hepatica
secreted molecules, the protease cathepsin L (rFhCL1) and an antioxidant, sigma class glutathione transferase (rFhGST-si), to examine their interactions with dendritic cells (DCs). Despite enzymatic and functional differences between these molecules, both induced interleukin-6 (IL-6), IL-12p40, and macrophage inflammatory protein 2 (MIP-2) secretion from DCs and enhanced CD40 expression. While this induction was mediated by Toll-like receptor 4 (TLR4), the subsequent intracellular signaling pathways differed; rFhCL1 signaled through p38, and rFhGST-si mediated its effect via c-Jun N-terminal kinase (JNK), p38, p-NF-κBp65, and IRF5. Neither rFhCL1 nor rFhGST-si enhanced DC phagocytosis or induced Th2 immune responses
in vivo
. However, DCs matured in the presence of either enzyme attenuated IL-17 production from OVA peptide-specific T cells
in vivo
. In addition, DCs exposed to either antigen secreted reduced levels of IL-23. Therefore, both
F. hepatica
FhCL1 and FhGST-si modulate host immunity by suppressing responses associated with chronic inflammation—an immune modulatory mechanism that may benefit the parasite's survival within the host.
Aspergillus fumigatus
LaeA-Mediated Phagocytosis Is Associated with a Decreased Hydrophobin Layer
Authors: Dagenais Taylor R. T. , Giles Steve S. , Aimanianda Vishukumar , Latgé Jean-Paul , Hull Christina M. , Keller Nancy P.
Published: November 2009

Aspergillus fumigatus
is the causal agent of the life-threatening disease invasive aspergillosis.
A. fumigatus laeA
deletants, aberrant in toxin biosynthesis and spore development, are decreased in virulence. Among other characteristics, the decreased virulence is associated with increased spore susceptibility to macrophage phagocytosis. Three characteristics, cell wall microbe-associated molecular patterns (MAMPs), secreted metabolites, and rodlet content, thought to be important in macrophage
-Aspergillus
spore interactions were examined. Flow cytometry analysis of wild-type and
ΔlaeA
spores did not reveal any differences in surface-accessible MAMPs, including β-(1,3)-glucan, α-mannose, chitin, and other carbohydrate ligands. Blocking experiments with laminarin and mannan supported the conclusion that differences in cell wall carbohydrates were not responsible for enhanced
ΔlaeA
spore phagocytosis.
Aspergillus
spores have been reported to secrete metabolites affecting phagocytosis. Neither spent culture exchange, transwell, nor coincubation internalization experiments supported a role for secreted metabolites in the differential uptake of wild-type and
ΔlaeA
spores. However, sonication assays implicated a role for surface rodlet protein/hydrophobin (RodAp) in differential spore phagocytosis. A possible role of RodAp in enhanced
ΔlaeA
spore uptake was further assessed by RodAp extraction and quantification, where wild-type spores were found to contain 60% more RodAp than
ΔlaeA
spores. After removal of the surface rodlet layer, wild-type spores were phagocytosed at similar rates as
ΔlaeA
spores. We conclude that increased uptake of
ΔlaeA
resting spores is not associated with changes in secreted metabolite production of this mutant or surface carbohydrate availability but, rather, due to a decrease in the surface RodAp content of
ΔlaeA
spores. We theorize that RodAp acts as an antiphagocytic molecule, possibly via physicochemical means and/or by impeding MAMP recognition by macrophage receptors.
Invasion of Melanoma Cells byMycoplasma hyorhinis: Enhancement by Protease Treatment
Authors: Kornspan Jonathan D. , Tarshis Mark , Rottem Shlomo
Published: November 2009

Mycoplasma hyorhinis(strain MCLD) was recently isolated from a melanoma cell culture. Growth of MCLD was considerably improved by 24 serial passages in a modified Hayflick's mycoplasma medium. Transmission electron microscopy showed that MCLD exhibits a polymorphic appearance, with ovoid or elongated cells frequently harboring an electron-dense core at one of the poles. Adherence ofM. hyorhinisto melanoma cells followed saturation kinetics. Furthermore, althoughM. hyorhinishas been considered to remain attached to the surface of the host cells, we show for the first time, qualitatively by confocal laser scanning microscopy and quantitatively by a gentamicin resistance assay, that MCLD is able to invade melanoma cells. The ingested mycoplasmas were randomly distributed in the cytoplasm, tending to concentrate near the plasma membrane. Both adherence to and invasion of melanoma cells byM. hyorhinisstrain MCLD were dramatically enhanced by mild proteolytic digestion with proteinase K (2.5 μg/mg cell protein for 2.5 min at 37°C) that affected the surface-exposed proteins of this organism, mainly the major 47-kDa lipoprotein. We suggest that the intracellular location ofM. hyorhinisstrain MCLD is a privileged niche, which may explain the survival ofM. hyorhinisin tissue cultures. The enhanced binding to and invasion of melanoma cells by protease treatment may be due to either the activation or the enhanced exposure of an adhesin(s) on the mycoplasmal cell surface.
Efficient Serum Clearance of Botulinum Neurotoxin Achieved Using a Pool of Small Antitoxin Binding Agents
Authors: Sepulveda Jorge , Mukherjee Jean , Tzipori Saul , Simpson Lance L. , Shoemaker Charles B.
Published: November 2009

Antitoxins for botulinum neurotoxins (BoNTs) and other toxins are needed that can be produced economically with improved safety and shelf-life properties compared to conventional therapeutics with large-animal antisera. Here we show that protection from BoNT lethality and rapid BoNT clearance through the liver can be elicited in mice by administration of a pool of epitope-tagged small protein binding agents together with a single anti-tag monoclonal antibody (MAb). The protein binding agents used in this study were single-chain Fv domains (scFvs) with high affinity for BoNT serotype A (BoNT/A). The addition of increasing numbers of differently tagged scFvs synergistically increased the level of protection against BoNT/A. It was not necessary that any of the BoNT/A binding agents possess toxin-neutralizing activity. Mice were protected from a dose equivalent to 1,000 to 10,000 50% lethal doses (LD50) of BoNT/A when given three or four different anti-BoNT scFvs, each fused to an E-tag peptide, and an anti-E-tag IgG1 MAb. Toxin protection was enhanced when an scFv contained two copies of the E tag. Pharmacokinetic studies demonstrated that BoNT/A was rapidly cleared from the sera of mice given a pool of anti-BoNT/A scFvs and an anti-tag MAb but not from the sera of mice given scFvs alone or anti-tag MAb alone. The scFv pool and anti-tag MAb protected mice from lethality when administered up to 2 h following exposure of mice to a dose equivalent to 10 LD50of BoNT/A. These results suggest that it will be possible to rapidly and economically develop and produce therapeutic antitoxins consisting of pools of tagged binding agents that are administered with a single, stockpiled anti-tag MAb.
Selective Exploitation of Capelin (Mallotus villosus) Eggs by Winter Flounder (Pseudopleuronectes americanus): Capelin Egg Mortality Rates, and Contribution of Egg Energy to the Annual Growth of Flounder
Authors: Frank K. T. , Leggett W. C.
Published: November 2009

The consequences of winter flounder (Pseudopleuronectes americanus) predation on capelin (Mallotus villosus) eggs, both in terms of the egg mortality and of the contribution of energy ingested to the annual growth of flounder, were investigated at Bryant's Cove, Conception Bay, Newfoundland. Flounder density in the nearshore area adjacent to the capelin spawning beach increased sharply in each of the three study years in response to the presence of spawning capelin and to the density of capelin eggs on the spawning beaches. Capelin eggs were the dominant item inthedietofwinterflounder14–34 cm TL, averaging 59% by weight. Flounder [Formula: see text] fed less heavily on capelin eggs (22% of food consumed by weight) but because of their larger size and ration were an important source of predation. Egg mortality due to flounder predation was estimated to average 5.0, 2.2, and 1.9% in 1978, 1979, and 1980, respectively. Egg mortality due to predation is believed to be significantly greater at deepwater demersal spawning sites and may have a significant impact on recruitment in demersal spawners. The average energy gain to winter flounder resulting from consumption of capelin eggs was estimated to contribute 23% of the annual growth of flounder in the region (approximate 95% confidence interval: 10–40%). Selective exploitation of capelin eggs by postspawning flounder may also contribute significantly to the rapid recovery of body condition following the extensive depletion of tissue resources due to winter fasting, gonad production, and spawning.
THE GRAVITATIONAL FIELD OF A PLANE SLAB
Authors: GAMBOA SARAVÍ RICARDO E.
Published: November 2009

We discuss the exact solution to Einstein's equation corresponding to a static and plane symmetric distribution of matter with constant positive density located below z = 0 matched to vacuum solutions. The internal solution depends essentially on two constants: the density ρ and a parameter κ. We show that these space–times finish down below at an inner singularity at finite depth [Formula: see text]. We show that for κ ≥ 0.3513 ⋯, the dominant energy condition is satisfied all over the space–time.

We match these singular solutions to the vacuum one and compute the external gravitational field in terms of slab's parameters. Depending on the value of κ, these slabs are either attractive, repulsive or neutral. The external solution turns out to be a Rindler's space–time. Repulsive slabs explicitly show how negative, but finite pressure can dominate the attraction of the matter. In this case, the presence of horizons in the vacuum shows that there are null geodesics which never reach the surface of the slab.

We also consider a static and plane symmetric nonsingular distribution of matter with constant positive density ρ and thickness [Formula: see text] surrounded by two external vacuums. We explicitly write down the pressure and the external gravitational fields in terms of ρ and d. The solution turns out to be attractive and remarkably asymmetric: the "upper" solution is Rindler's vacuum, whereas the "lower" one is the singular part of Taub's plane symmetric solution. Inside the slab, the pressure is positive and bounded, presenting a maximum at an asymmetrical position between the boundaries. We show that if [Formula: see text], the dominant energy condition is satisfied all over the space–time. We also show how the mirror symmetry is restored at the Newtonian limit.

We also find thinner repulsive slabs by matching a singular slice of the inner solution to the vacuum.

We also discuss solutions in which an attractive slab and a repulsive one, and two neutral ones are joined. We also discuss how to assemble a "gravitational capacitor" by inserting a slice of vacuum between two such slabs.
GALILEAN COVARIANCE AND THE GRAVITATIONAL FIELD
Authors: ULHOA SÉRGIO C. , KHANNA FAQIR C. , SANTANA ADEMIR E.
Published: November 2009

This paper is concerned with the development of a gravitational field theory having locally a covariant version of the Galilei group. We show that this Galilean gravity can be used to study the advance of perihelion of a planet, following in parallel with the result of the (relativistic) theory of general relativity in the post-Newtonian approximation.
Biomineralization in Humans: Making the Hard Choices in Life
Authors: Kawasaki Kazuhiko , Buchanan Anne V. , Weiss Kenneth M.
Published: November 2009

The skeleton, teeth, and otoconia are normally the only mineralized tissues or organs in the human body. We describe physiological biomineralization in collagenous matrices as well as a more derived noncollagenous matrix. The origin of the collagenous matrices used in mineralized skeletal tissues can be traced to a soft tissue in early Metazoa. In early vertebrates, a genetic system coding for ancient soft collagenous tissue was co-opted for biomineralization using redundant genes resulting from whole genome duplication. However, genes more specific to mineralized tissues arose subsequent to the genome duplication by genomically local tandem duplication. These new genes are the basis for a novel genetic system for various mineralized tissues in skeleton and teeth. In addition, any tissue can be abnormally mineralized, and many pathologies of mineralization in humans are known.
Multiple Roles for Heterochromatin Protein 1 Genes inDrosophila
Authors: Vermaak Danielle , Malik Harmit S.
Published: November 2009

Heterochromatin is the gene-poor, transposon-rich, late-replicating chromatin compartment that was first cytologically defined more than 70 years ago. The identification of heterochromatin protein 1 (HP1) paved the way for a molecular dissection of this important component of complex eukaryotic genomes. Although initial studies revealed HP1's key role in heterochromatin maintenance and function, more recent studies have discovered a role for HP1 in numerous processes including, surprisingly, euchromatic gene expression. Drosophila genomes possess at least five HP1 paralogs that have significantly different roles, ranging from canonical heterochromatic function at pericentric and telomeric regions to exclusive localization and regulation of euchromatic genes. They also possess paralogs exclusively involved in defending the germline against mobile elements. Pursuing a survey of recent genetic and evolutionary findings, we highlight how Drosophila genomes represent the best opportunity to dissect the diversity and incredible versatility of HP1 proteins in organizing and protecting eukaryotic genomes.
The Role of Mitochondria in Apoptosis
Authors: Wang Chunxin , Youle Richard J.
Published: November 2009

Mitochondria play key roles in activating apoptosis in mammalian cells. Bcl-2 family members regulate the release of proteins from the space between the mitochondrial inner and outer membrane that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient phagocytosis of cell corpses. Here we review the extensive literature on proteins released from the intermembrane space and consider genetic evidence for and against their roles in apoptosis activation. We also compare and contrast apoptosis pathways in Caenorhabditis elegans, Drosophila melanogaster, and mammals that indicate major mysteries remaining to be solved.
GLP-2 potentiates L-type Ca2+ channel activity associated with stimulated glucose uptake in hippocampal neurons
Authors: Wang Yi , Guan Xinfu
Published: November 2009

Glucagon-like peptide-2 (GLP-2) is a neuropeptide secreted from endocrine cells in the gut and neurons in the brain. GLP-2 stimulates intestinal crypt cell proliferation and mucosal blood flow while decreasing gastric emptying and gut motility. However, a GLP-2-mediated signaling network has not been fully established in primary cells. Since the GLP-2 receptor mRNA and protein were highly expressed in the mouse hippocampus, we further characterized that human 125I-labeled GLP-21–33 specifically bound to cultured hippocampal neurons with Kd = 0.48 nM, and GLP-2 acutely induced subcellular translocalization of the early gene c-Fos. Using the whole cell patch clamp, we recorded barium currents ( IBa) flowing through voltage-gated Ca2+ channels (VGCC) in those neurons in the presence of GLP-2 with and without inhibitors. We showed that GLP-2 (20 nM) enhanced the whole cell IBa mediated by L-type VGCC that was defined using an L-type Ca2+ channel blocker (nifedipine, 10 μM). Moreover, GLP-2-potentiation of L-type VGCC was abolished in neurons pretreated with a PKA inhibitor (PKI14–22, 1 μM). Finally, using a fluorescent nonmetabolized glucose analog (6-NBDG) tracing imaging, we showed that glucose was taken up directly by cultured neurons. GLP-2 increased 2-deoxy-d-[3H]glucose uptake that was dependent upon dosage, activation of PKA, and potentiation of L-type VGCC. We conclude that GLP-2 potentiates L-type VGCC activity through activating PKA signaling, partially stimulating glucose uptake by primary cultured hippocampal neurons. The potentiation of L-type VGCC may be physiologically relevant to GLP-2-induced neuroendocrine modulation of neurotransmitter release and hormone secretion.
Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo
Authors: Pires-Oliveira Marcelo , Maragno Ana Leticia G. C. , Parreiras-e-Silva Lucas T. , Chiavegatti Tiago , Gomes Marcelo D. , Godinho Rosely O.
Published: November 2009

Skeletal muscle atrophy induced by denervation and metabolic diseases has been associated with increased ubiquitin ligase expression. In the present study, we evaluate the influence of androgens on muscle ubiquitin ligases atrogin-1/MAFbx/FBXO32 and Murf-1/Trim63 expression and its correlation with maintenance of muscle mass by using the testosterone-dependent fast-twitch levator ani muscle (LA) from normal or castrated adult male Wistar rats. Gene expression was determined by qRT-PCR and/or immunoblotting. Castration induced progressive loss of LA mass (30% of control, 90 days) and an exponential decrease of LA cytoplasm-to-nucleus ratio (nuclear domain; 22% of control after 60 days). Testosterone deprivation induced a 31-fold increase in LA atrogin-1 mRNA and an 18-fold increase in Murf-1 mRNA detected after 2 and 7 days of castration, respectively. Acute (24 h) testosterone administration fully repressed atrogin-1 and Murf-1 mRNA expression to control levels. Atrogin-1 protein was also increased by castration up to 170% after 30 days. Testosterone administration for 7 days restored atrogin-1 protein to control levels. In addition to the well known stimulus of protein synthesis, our results show that testosterone maintains muscle mass by repressing ubiquitin ligases, indicating that inhibition of ubiquitin-proteasome catabolic system is critical for trophic action of androgens in skeletal muscle. Besides, since neither castration nor androgen treatment had any effect on weight or ubiquitin ligases mRNA levels of extensor digitorum longus muscle, a fast-twitch muscle with low androgen sensitivity, our study shows that perineal muscle LA is a suitable in vivo model to evaluate regulation of muscle proteolysis, closely resembling human muscle responsiveness to androgens.
Biomarkers: A Definite Plus in Pneumonia
Authors: Summah Hanssa , Qu Jie-Ming
Published: November 2009

During the past few years, biomarkers have emerged as an indispensible tool in the diagnosis of pneumonia. To find an ideal diagnostic biomarker for pneumonia is not an easy task. Not only should it allow an early diagnosis of the condition, but it should also allow differential diagnosis from other noninfectious conditions. Ongoing research is being done in this field so as to put an array of biomarkers at the disposal of doctors to improve the diagnosis of pneumonia when patients present to them with cough or nonspecific symptoms which could easily be misinterpreted as symptoms of other conditions. Procalcitonin and soluble triggering receptor expressed on myeloid cells-1 have emerged as reliable diagnostic markers in pneumonia, and are better when compared to other markers, namely, C-reactive protein, leukocyte count, and proinflammatory cytokines. Many other biomarkers are being studied for their probable use in diagnosing pneumonia but have yet to prove their benefit.
On "Equation missing" -Stability of Picard Iteration in Cone Metric Spaces
Authors: Asadi M. , Soleimani H. , Vaezpour S. M. , Rhoades B. E.
Published: November 2009

The aim of this work is to investigate the "Equation missing"-stability of Picard's iteration procedures in cone metric spaces and give an application.
Answer Set versus Integer Linear Programming for Automatic Synthesis of Multiprocessor Systems from Real‐Time Parallel Programs
Authors: Ishebabi Harold , Mahr Philipp , Bobda Christophe , Gebser Martin , Schaub Torsten
Published: November 2009

An automated design approach for multiprocessor systems on FPGAs is presented which customizes architectures for parallel programs by simultaneously solving the problems of task mapping, resource allocation, and scheduling. The latter considers effects of fixed‐priority preemptive scheduling in order to guarantee real‐time requirements, hence covering a broad spectrum of embedded applications. Being inherently a combinatorial optimization problem, the design space is modeled using linear equations that capture high‐level design parameters. A comparison of two methods for solving resulting problem instances is then given. The intent is to study how well recent advances in propositional satisfiability (SAT) and thus Answer Set Programming (ASP) can be exploited to automate the design of flexible multiprocessor systems. Integer Linear Programming (ILP) is taken as a baseline, where architectures for IEEE 802.11g and WCDMA baseband signal processing are synthesized. ASP‐based synthesis used a few seconds in the solver, faster by three orders of magnitude compared to ILP‐based synthesis, thereby showing a great potential for solving difficult instances of the automated synthesis problem.
Effects of Glycyrrhizic Acid on Peroxisome Proliferator-Activated Receptor Gamma (PPARγ), Lipoprotein Lipase (LPL), Serum Lipid and HOMA-IR in Rats
Authors: Yoke Yin Chia , So Ha Ton , Abdul Kadir Khalid
Published: November 2009

Studies on ligand binding potential of glycyrrhizic acid, a potential agonist to PPARγ, displayed encouraging results in amelioration of metabolic syndrome. The regulation of gene cassettes by PPARγaffects glucose homeostasis, lipid, lipoprotein metabolism and adipogenesis. This study was performed to determine the effects of GA on total PPARγand LPL expression levels, lipid parameters and HOMA-IR. Oral administration of 100 mg/kg GA for 24 hours resulted in an increase in insulin sensitivity with decreases in blood glucose, serum insulin and HOMA-IR. Improvement in serum lipid parameters was also observed with a decrease in triacylglycerol, total cholesterol and LDL-cholesterol and an elevation in HDL-cholesterol. GA administration also resulted in up-regulation of total PPARγand LPL expression levels in the visceral and subcutaneous adipose tissues, abdominal and quadriceps femoris muscles, as well as liver and kidney, with a significant up-regulation only in the visceral adipose tissue, abdominal and quadriceps femoris muscles. Thus, oral administration of 100 mg/kg GA for 24 hours improved insulin sensitivity and lipid profiles and induced upregulation of total PPARγand LPL expression levels in all studied tissues.
Leukocyte urokinase plasminogen activator receptor and PSGL1 play a role in endogenous arterial fibrinolysis
Authors: Bai Xufang , Weitz Jeffrey , Gross Peter
Published: November 2009

Fibrin is an integral component of arterial thrombi. Using a mouse model of arteriolar thrombosis, high-speed fluorescence microscopy reveals that, within minutes, the fibrin content of thrombi rapidly increases and then decreases.The decrease in fibrin coincides with leukocyte binding to the thrombi, a process mediated by the interaction of leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin on the surface of activated platelets. Because leukocytes possess urokinase-type plasminogen activator (uPA) activity,we used mice deficient in uPA or the uPA receptor (uPAR) to explore the contribution of leukocyte associated uPA to the loss of fibrin from these thrombi. Fibrin loss in both uPA-deficient mice and uPAR-deficient mice was reduced compared with that in wild-type controls.Transfusion of leukocytes from wild-type mice into uPAR-deficient mice restored fibrin loss to levels similar to that in wild-type mice. In contrast, transfusion of leukocytes from mice deficient in uPAR or PSGL-1 did not enhance fibrin loss. Thus, fibrin loss from microarteriolar thrombi is mediated, at least in part, by leukocyte-associated uPA in a process that requires leukocyte uPAR and PSGL-1.
Effect of antiplatelet therapy on inflammatory markers in atherothrombotic patients
Authors: Muhlestein Joseph
Published: November 2009

Inflammation is central to the pathogenesis and progression of atherosclerosis and thrombosis, the underlying cause of major cardiovascular disease. Platelets, in addition to their role in haemostasis, play a key role in both thrombus formation and inflammation following vascular injury, especially atherosclerotic lesions. An increasing body of evidence suggests that inhibition of platelet function can modulate inflammatory markers, particularly those associated with activated platelets, such as CD40 ligand, P-selectin, and C-reactive protein. The currently available antiplatelet agents aspirin, clopidogrel, prasugrel, abciximab, and eptifibatide have shown varying effects on inflammatory markers. These effects seem to be mostly indirect, i.e. mediated primarily through reduced platelet activation that results in reduced inflammatory marker expression. However, there is some evidence that suggests direct effects (i.e. those independent of platelets) may also play a role in modulating inflammatory markers. Evidence linking inflammation and thrombosis supports the hypothesis that agents with both anti-inflammatory and antiplatelet effects may reduce vascular inflammation and limit acute and long-term thrombotic events. An assessment of the involvement of inflammatory mediators in atherosclerosis may provide further insight into important predictive markers of cardiovascular outcomes that may also serve as potential therapeutic targets. This review examines the evidence for and potential clinical relevance of the effects of antiplatelet therapy on inflammatory markers.
Long- and short-term in vitro D-dimer stability measured with INNOVANCE D-Dimer
Authors: Böhm-Weigert Martina , Wissel Thomas , Muth Heidrun , Kemkes-Matthes Bettina , Peetz Dirk
Published: November 2009

In vitro D-dimer stability in plasma is widely assumed, but has not yet been documented by systematic studies using samples covering a wide range of D-dimer. We investigated the short- and long-term stability of D-dimer in clinical citrated plasma samples with normal and pathological levels. The short-term stability was analysed by measuring D-dimer fresh, after storage of plasma for 4 hours at room temperature (RT) and after an additional 24 h storage at +2 to +8°C (n=40). Long-term stability samples (n=40) were measured fresh and after storage for 19, 25 and 36 months at ≤-60°C. The effect of repeated freezing was analysed by measuring samples (n=50) fresh and after four consecutive freeze-thaw cycles. D-dimer was measured on the BCS System using the INNOVANCE D-Dimer assay (Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany). D-dimer values at baseline ranged from 0.23–22.2 mg/l FEU. The mean percentage change after storage for 4 hours at RT and additional 24 hours at +2 to +8°C was +3.8% and +2.7%, respectively. The mean percentage change after frozen storage for 19, 25 and 36 months at ≤-60°C was –11.7%, –4.8% and –9.3%, respectively. The small decrease of D-dimer values after frozen storage was not time-dependent. Repeated freezing did not significantly alter D-dimer values (mean change ≤5%). The data demonstrate stability of D-dimer in plasma prior to freezing for up to 4 hours at RT and for up to 24 hours at +2 to +8°C as well as in plasma stored for up to three years at ≤-60°C.
Coagulation disorders and the risk of retinal vein occlusion
Authors: Scharrer Inge , Lüchtenberg Marc , Hattenbach Lars-Olof , Kuhli-Hattenbach Claudia
Published: November 2009

Over the past years, there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, to date, there are no large, prospective studies to assess an optimal, cost-effective approach with regard to screening and case finding for thrombophilic risk factors in patients presenting with retinal vessel occlusion. Two hundred twenty-eight patients with retinal vein occlusion (RVO) and 130 age-matched healthy controls were prospectively screened for thrombophilic risk factors. Both cohorts were divided into three subgroups, depending on the patients‘ age at the time of the RVO or a previous thromboembolic event. Patient age ≤45 years was associated with a high prevalence of coagulation disorders (p<0.0001). Among patients ≤45 years and >45 to ≤60 years, a family history of thromboembolism was strongly associated with the presence of thrombophilic disorders. The absence of cardiovascular risk factors was found to be a strong predictor for the presence of coagulation disorders in all patient groups (≤45 years, p=0.003; >45 to ≤60 years, p=0.0008; >60 years, p=0.001). Multivariate analysis revealed the presence of resistance to activated protein C (p=0.014), antiphospholipid antibodies (p=0.022), and deficiency of the anticoagulant proteins (p=0.05) as independent risk factors for the development of RVO among patients ≤45 years. Our results indicate that thrombophilic disorders are associated with the development of retinal vein occlusion in patients ≤45 years by the time of the RVO or a previous thromboembolic event, in patients with a family history of thromboembolism, or in patients without cardiovascular risk factors.
Application of platelet function testing to the bedside
Authors: Cherala Ganesh , Serebruany Victor , Williams Craig
Published: November 2009

The ability to test platelet reactivity in clinical practice could help in making informed decisions on both initiation and titration of anti-platelet drug therapies. However, many barriers still remain to the effective implementation of such techniques. Many tests used in the research literature are not yet available for practical, clinical use. Platelet aggregometry, while informative and currently available for bedside use, needs additional research before routine clinical use can be recommended. This review will highlight and update contemporary issues of bedside platelet testing for the clinician and comment on future areas of clinical research.