bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Tool Mark Standards with Jewelry Modeling Waxes
Authors: Petraco Nicholas , Petraco Nicholas D.K. , Faber Lisa , Pizzola Peter A.
Published: January 2009

Abstract:  This paper presents how jewelry modeling waxes are used in the preparation of tool mark standards from exemplar tools. We have previously found that jewelry modeling waxes are ideal for preparing test tool marks from exemplar tools. In this study, simple methods and techniques are offered for the replication of accurate, highly detailed tool mark standards with jewelry modeling waxes. The techniques described here demonstrate the conditioning and proper use of jewelry modeling wax in the production of tool mark standards. The application of each test tool’s working surface to a piece of the appropriate wax in a manner consistent with the tool’s design is clearly illustrated. The resulting tool mark standards are exact, highly detailed, 1:1, negative impressions of the exemplar tool’s working surface. These wax models have a long shelf life and are suitable for use in microscopic examination comparison of questioned and known tool marks.
Diagnostic value of zinc protoporphyrin in a screening strategy for α‐thalassemia
Authors: Sardón Estévez Nadia , Herruer Martinus H. , Jansen Ruud , Bergkamp Ferry J. M. , Gorgels Jozef P. M. C.
Published: January 2009

The definitive diagnosis of α‐thalassemia involves detection of a deletion of one or more α‐globin that encode the α‐chains of Hb (hemoglobin). To determine whether DNA analysis is indicated, screening tests such as mean corpuscular volume (MCV) and Hb typing are employed. α‐Thalassemia often correlates with normal or low HbA2 values. Zinc protoporphyrin (ZPP) is usually high in ferropenic anemia or lead‐poisoning and is normal or slightly raised in ß‐thalassemia. Therefore, ZPP is currently used as a marker to discriminate between ferropenic anemia and β‐thalassemia. We investigated the diagnostic potential of ZPP < 150 μmol/mol heme in a screening strategy for α‐thalassemia. We measured ZPP and performed DNA analysis for detecting the seven most prevalent α‐thalassemia deletions, namely, α3.7, SEA, α20.5, α4.2, MED, FIL, and THAI, in the blood samples of 200 patients with MCV < 70 fL and HbA2 ≤ 3.5%. Deletions were detected in 9% subjects in the ZPP ≥ 150 group (n = 175) and 56% subjects in the ZPP < 150 group (n = 29); this difference was statistically significant (chi‐square test, P < 0.001). We conclude that ZPP < 150 μmol/mol heme can be used in a new screening strategy for α‐thalassemia.
Topical pimecrolimus and tacrolimus do not accelerate photocarcinogenesis in hairless mice after UVA or simulated solar radiation
Authors: Lerche Catharina M. , Philipsen Peter A. , Poulsen Thomas , Wulf Hans Christian
Published: January 2009

Abstract:  Pimecrolimus and tacrolimus are topical calcineurin inhibitors developed specifically for the treatment of atopic eczema. Experience with long‐term use of topical calcineurin inhibitors is limited and the risk of rare but serious adverse events remains a concern. We have previously demonstrated the absence of carcinogenic effect of tacrolimus alone and in combination with simulated solar radiation (SSR) on hairless mice. The aim of this study is to determine whether pimecrolimus accelerates photocarcinogenesis in combination with SSR or pimecrolimus and tacrolimus accelerate photocarcinogenesis in combination with UVA. We used 11 groups of 25 hairless female C3.Cg/TifBomTac immunocompetent mice (n = 275). Pimecrolimus cream or tacrolimus ointment was applied on their dorsal skin three times weekly followed by SSR (2, 4, or 6 standard erythema doses, SED) or UVA (25 J/cm2) 3–4 h later. This was done up to 365 days in the SSR‐treated groups and up to 500 days in the UVA‐treated groups. Pimecrolimus did not accelerate the time for development of the first, second or third tumor in any of the groups. Median time to the first tumor was 240 days for the control‐2SED group compared with pimecrolimus‐2SED group (233 days), control‐4SED group (156 days) compared with pimecrolimus‐4SED group (163 days) and control‐6SED group (162 days) compared with pimecrolimus‐6SED group (170 days). Only one mouse in each of the three UVA groups developed a tumor. We conclude that pimecrolimus in combination with SSR and both pimecrolimus and tacrolimus in combination with UVA do not accelerate photocarcinogenesis in hairless mice.
A novel electrophysiologic effect of melatonin on ischemia/reperfusion‐induced arrhythmias in isolated rat hearts
Authors: Diez Emiliano Raúl , Prados Laura Vanina , Carrión Adriana , Ponce Zumino Amira Zulma , Miatello Roberto Miguel
Published: January 2009

Abstract:  Reperfusion after a short period of cardiac ischemia triggers ventricular arrhythmias attributable to ionic imbalance and oxidative stress. Melatonin offers some degree of protection, but its effects on the cardiac action potentials are unknown. We evaluated the effects of 5, 10, 20 and 50 μm melatonin in isolated perfused rat hearts subjected to 10 min of regional ischemia. ECG and membrane potentials were synchronously displayed. After 15 min of reperfusion, total antioxidant capacity (TAC) was determined. Melatonin did not change the ischemic depolarization nor the action potential amplitude depression, but at the end of ischemia the action potential duration (APD) decreased in control and 5 μm melatonin‐treated hearts. By contrast, it returned to preischemic levels in hearts given 20 and 50 μm melatonin. Melatonin reduced the incidence of reperfusion arrhythmias from 100% in control to 50% in 5 and 10 μm, to 40% in 20 μm and 30% in 50 μm hearts. TAC values were higher at all melatonin concentrations. We conclude that melatonin reduced the incidence of reperfusion arrhythmias because of its antioxidant effects. In addition, at 20 and 50 μm lengthened APD and promoted an improved protection. This latter effect should be considered when in vivo applications of melatonin are considered.
Microtubules modulate melatonin receptors involved in phase‐shifting circadian activity rhythms: in vitro and in vivo evidence
Authors: Jarzynka Michael J. , Passey Deepshikha K. , Johnson David A. , Konduru Nagarjun V. , Fitz Nicholas F. , Radio Nicholas M. , Rasenick Mark , Benloucif Susan , Melan Melissa A. , Witt‐Enderby Paula A.
Published: January 2009

Abstract: MT1 melatonin receptors expressed in Chinese hamster ovary (CHO) cells remain sensitive to a melatonin re‐challenge even following chronic melatonin exposure when microtubules are depolymerized in the cell, an exposure that normally results in MT1 receptor desensitization. We extended our findings to MT2 melatonin receptors using both in vitro and in vivo approaches. Using CHO cells expressing human MT2 melatonin receptors, microtubule depolymerization prevents the loss in the number of high potency states of the receptor when compared to melatonin‐treated cells. In addition, microtubule depolymerization increases melatonin‐induced PKC activity but not PI hydrolysis via Gi proteins similar to that shown for MT1Rs. Furthermore, microtubule depolymerization in MT2‐CHO cells enhances the exchange of GTP on Gi‐proteins using a photoaffinity analog of GTP. To test whether microtubules are capable of modulating melatonin‐induced phase‐shifts, microtubules are depolymerized specifically within the suprachiasmatic nucleus of the hypothalamus (SCN) of the Long Evans rat and the efficacy of melatonin to phase shift their circadian activity rhythms was assessed and compared to animals with intact SCN microtubules. We find that microtubule depolymerization in the SCN using either Colcemid or nocodazole enhances the efficacy of 10 pmmelatonin to phase‐shift the activity rhythms of the Long Evans rat. No enhancement occurs in the presence of β‐lumicolchicine, the inactive analog of Colcemid. Taken together, these data suggest that microtubule dynamics can modulate melatonin‐induced phase shifts of circadian activity rhythms which may explain, in part, why circadian disturbances occur in individuals afflicted with diseases associated with microtubule disturbances.
Comparing fecundity in parthenogenetic versus sexual populations of the freshwater snail Campeloma limum: is there a two‐fold cost of sex?
Authors: Crummett Lisa T. , Wayne Marta L.
Published: January 2009

Abstract. The predominance of sexuality in eukaryotes remains an evolutionary paradox, given the “two‐fold cost of sex” also known as the “cost of males.” [Correction added after online publication 29 January 2009: in the preceding sentence, extraneous words were deleted.] As it requires two sexual parents to reproduce and only one parthenogenetic parent, parthenogens should have twice the reproductive rate compared with their sexual counterparts and their genes should spread twice as fast, if all else is equal. Yet, parthenogenesis is relatively rare and considered an evolutionary dead‐end, while sexuality is the dominant form of reproduction in multicellular eukaryotes. Many studies have explored short‐term benefits of sex that could outweigh its two‐fold cost, but few have compared fecundity between closely related sexuals and parthenogens to first verify that “all else is equal” reproductively. We compared six fecundity measures between sexual and parthenogenetic populations of the freshwater snail, Campeloma limum, during a brooding cycle (1 year) across two drainages. Drainages were analyzed separately because of a significant drainage effect. In the Savannah drainage, fecundity was not significantly different between sexuals and parthenogens, even though parthenogens had significantly more empty egg capsules per brood. In the Ogeechee drainage, parthenogens had significantly more egg capsules with multiple embryos and more hatched embryos than sexuals. Taken over 1 year, embryo size was not significantly different between parthenogens and sexuals in either drainage. Given these results and the close proximity of sexual and parthenogenetic populations, it is perplexing why parthenogenetic populations have not completely replaced sexual populations in C. limum.
Development of microsatellite markers from loquat, Eriobotrya japonica (Thunb.) Lindl.
Authors: GISBERT A. D. , LOPEZ‐CAPUZ I. , SORIANO J. M. , LLACER G. , ROMERO C. , BADENES M. L.
Published: January 2009

Loquat (Eriobotrya japonica) is a minor fruit which has become an interesting alternative into the European fruit industry. This interest resulted in a loquat germplasm collection established at the Instituto Valenciano de Investigaciones Agrarias, Valencia, Spain. Currently, it is the main reservoir of this species outside Asia. We developed and characterized the first 21 polymorphic microsatellite loci from a CT/AG‐enriched loquat genomic library. The observed heterozygosity ranged between 0.20 and 1.00, expected heterozygosity ranged between 0.17 and 0.81, three markers were multilocus and eight loci departed significantly from Hardy–Weinberg equilibrium. These markers will facilitate diversity and genetic studies into the species.
A new set of universal de novo sequencing primers for extensive coverage of noncoding chloroplast DNA: new opportunities for phylogenetic studies and cpSSR discovery
Authors: EBERT DANIEL , PEAKALL ROD
Published: January 2009

We present a new set of universal de novo sequencing primers targeting noncoding chloroplast DNA. The set of 107 polymerase chain reaction (PCR) primers span approximately 86% of the noncoding nucleotides in the large single copy region of Nicotiana tabacum, Oryza sativa and the orchid Phalaenopsis aphrodite. PCR tests confirmed the primers are effective in a wide range of monocots and dicots. More than 19.5 kb of cpDNA sequence was obtained across representative orchid genera with up to 82 chloroplast simple sequence repeats (cpSSRs) detected per genus. This primer set will facilitate both phylogenetic studies and rapid discovery of cpSSRs for plants, such as orchids, where there are limited genomic resources.
Species identification of North American guinea worms (Nematoda: Dracunculus) with DNA barcoding
Authors: ELSASSER SARAH C. , FLOYD ROBIN , HEBERT PAUL D. N. , SCHULTE‐HOSTEDDE ALBRECHT I.
Published: January 2009

Dracunculus insignis is a nematode parasite that infects the subcutaneous tissues of mammals such as raccoon (Procyon lotor), mink (Neovison vison) and fisher (Martes pennanti). D. lutrae, a morphologically similar species, has only been recovered from the otter (Lontra canadensis). Species identification of these two North American guinea worms has only been achieved by morphology of males and host identity. As a result, where only female specimens are present, accurate identifications are not possible. To date, specimens recovered from otter have been assumed to be D. lutrae, while those from all other hosts are assumed to be D. insignis. This study uses DNA barcoding to differentiate between these two North American dracunculoids. Our results show that D. insignis is a ‘true’ generalist, showing little sequence divergence regardless of host association, although our studies did validate its occurrence in a new host — the otter. Interestingly, specimens of the host specialist, D. lutrae, showed some sequence divergence, although it was low. The finding of D. insignis in otter substantiates the need to supplement morphology‐based methods in providing species identifications for certain dracunculoids.
Development of compound microsatellite markers in red‐tide‐causing dinoflagellate Akashiwo sanguinea (Dinophyceae)
Authors: CHO S‐Y. , NAGAI S. , NISHITANI G. , HAN M‐S.
Published: January 2009

We isolated 13 polymorphic microsatellites from the red‐tide causing dinoflagellate Akashiwo sanguinea. These loci were highly variable, with between 2 and 10 alleles per locus, and estimated gene diversity ranging from 0.08 to 0.82. These loci have the potential to reveal genetic structure and estimate gene flow among A. sanguinea populations.
New microsatellite loci for the endangered scalloped hammerhead shark, Sphyrna lewini
Authors: NANCE HOLLY A. , DALY‐ENGEL TOBY S. , MARKO PETER B.
Published: January 2009

We isolated 15 microsatellite markers for the scalloped hammerhead shark, Sphyrna lewini. Loci were tested on 80 specimens of S. lewini from four Eastern Pacific samples. The number of alleles per locus ranged from 6 to 31 (mean = 14). Observed and expected levels of heterozygosity per locus ranged from 0.39 to 0.91 (mean = 0.70) and from 0.54 to 0.90 (mean = 0.76), respectively. No pairs of loci were in gametic disequilibrium after Bonferroni correction of α. One locus showed significantly lower heterozygosity than expected under Hardy–Weinberg proportions in two populations, possibly caused by null alleles.
The Observational Evaluation of Subjective Well‐Being in Patients with Rheumatoid Arthritis
Authors: Hassett Afton L. , Maclean Ross , Peterson Christopher , Stuart Marian R. , Buyske Steven , Park Nansook , Savage Shantal V. , Li Tracy , Seligman Martin E.P.
Published: January 2009

An important aspect of general health is subjective well‐being (SWB), which is defined as happiness and overall satisfaction with life. Herein we examined the reliability and validity of observation‐based ratings of SWB in patients with rheumatoid arthritis (RA). Ten RA patients experiencing a disease flare (period of increased symptoms) completed two semi‐structured interviews (baseline and 4 weeks later) that were digitally recorded. Twelve healthcare professionals watched the 20 brief videos in random order and scored them using the Well‐Being Coding System (WBCS) for observer‐reported SWB. Patient‐reported SWB scores and scores from the Medical Outcomes Study: 36‐Item Short Form Survey (SF‐36) were compared to observer‐reported scores for SWB. We found inter‐rater reliability to be extremely high and a significant relationship between observer SWB composite scores and patient SWB composite scores. Observer SWB composite scores and other scores associated with SWB from the SF‐36 were also related significantly. There was also some evidence supporting the ability of observers to detect change in SWB. Taken together, we found preliminary evidence suggesting that when using information gleaned from brief patient interviews clinicians can make reliable and valid evaluations of patients' SWB.
Repair of large segmental bone defects using bone marrow stromal cells with demineralized bone matrix
Authors: Xu Jian‐zhong , Qin Hui , Wang Xu‐quan , Zhou Qiang , Luo Fei , Hou Tian‐yong , He Qing‐yi
Published: January 2009

Objective:  The aim of the present study was to evaluate the effect of tissue‐engineered constructs on repair of large segmental bone defects in goats.

Methods:  Allogenic demineralized bone matrix (aDBM) was seeded with autologous marrow stromal cells (aMSC) for seven days to construct DBM–MSC grafts prior to implantation. 24 goats were randomly divided into three groups (eight in each). In each group, 3 cm diaphyseal femoral defects were created unilaterally, and subsequently filled with the DBM‐MSC grafts, DBM alone and an untreated control, respectively. Radiological analysis and biomechanical evaluation were performed at 12 and 24 weeks after operation.

Results:  Obvious increases in radiological scoring and biomechanical strength were found in the DBM‐MSC group when compared to the DBM group. X‐ray examination showed excellent bone healing in the DBM‐MSC group, whereas only partial bone repair was seen in the DBM group, and no healing in untreated controls. Histologically, a tendency to bone regeneration and remodeling was far more obvious for the DBM‐MSC group than the DBM only and untreated controls.

Conclusion:  Our results strongly suggest that transplantation of bone MSC within a DBM could have advantages for the bone repair of large segmental defects.
The clinical features of, and microendoscopic decompression for, extraforaminal entrapment of the L5 spinal nerve
Authors: Zhou Yue , Zheng Wen‐jie , Wang Jian , Chu Tong‐wei , Li Chang‐qing , Zhang Zheng‐feng , Wang Wei‐dong
Published: January 2009

Objective:  To evaluate the clinical results of, and surgical techniques for, microendoscopic (METRx) decompression of extraforaminal entrapment of the L5 spinal nerve at the lumbosacral tunnel.

Methods:  Five patients with extraforaminal entrapment of the L5 spinal nerve in the lumbosacral tunnel were treated in our department, including three men and two women. The average age was 65.6 years. All patients suffered severe leg pain and neurological deficits compatible with L5 radiculopathy. Minimally invasive decompression of the L5 spinal nerve was performed under METRx intertransverse decompression.

Results:  With an average follow‐up of 17.8 months, clinical results were assessed based on Nakai criteria and Visual Analogue scale (VAS). All patients experienced immediate pain relief postoperatively. Clinical outcomes were excellent in three patients and good in two. The average intraoperative blood loss was 59 ml, with an average operative time of 103 min. Average post‐operative stay in bed was 7 days, and average cost was $1860.

Conclusion:  Extraforaminal entrapment of the L5 spinal nerve in the lumbosacral tunnel can cause L5 radiculopathy. METRx partial resection of the L5 transverse processes, sacral ala and osteophytes of L5‐S1 vertebral bodies to relieve extraforaminal entrapment of the L5 spinal nerve is a very effective and minimally invasive surgical option.
Cascadia Tremor Located Near Plate Interface Constrained by
S
Minus
P
Wave Times
Authors: La Rocca Mario , Creager Kenneth C. , Galluzzo Danilo , Malone Steve , Vidale John E. , Sweet Justin R. , Wech Aaron G.
Published: January 2009

Nonvolcanic tremor is difficult to locate because it does not produce impulsive phases identifiable across a seismic network. An alternative approach to identifying specific phases is to measure the lag between the
S
and
P
waves. We cross-correlate vertical and horizontal seismograms to reveal signals common to both, but with the horizontal delayed with respect to the vertical. This lagged correlation represents the time interval between vertical compressional waves and horizontal shear waves. Measurements of this interval, combined with location techniques, resolve the depth of tremor sources within ±2 kilometers. For recent Cascadia tremor, the sources locate near or on the subducting slab interface. Strong correlations and steady
S
-
P
time differences imply that tremor consists of radiation from repeating sources.
Control of Graphene's Properties by Reversible Hydrogenation: Evidence for Graphane
Authors: Elias D. C. , Nair R. R. , Mohiuddin T. M. G. , Morozov S. V. , Blake P. , Halsall M. P. , Ferrari A. C. , Boukhvalov D. W. , Katsnelson M. I. , Geim A. K. , Novoselov K. S.
Published: January 2009

Although graphite is known as one of the most chemically inert materials, we have found that graphene, a single atomic plane of graphite, can react with atomic hydrogen, which transforms this highly conductive zero-overlap semimetal into an insulator. Transmission electron microscopy reveals that the obtained graphene derivative (graphane) is crystalline and retains the hexagonal lattice, but its period becomes markedly shorter than that of graphene. The reaction with hydrogen is reversible, so that the original metallic state, the lattice spacing, and even the quantum Hall effect can be restored by annealing. Our work illustrates the concept of graphene as a robust atomic-scale scaffold on the basis of which new two-dimensional crystals with designed electronic and other properties can be created by attaching other atoms and molecules.
A DNA Vaccine Encoding the Enterohemorragic
Escherichia coli
Shiga-Like Toxin 2 A
2
and B Subunits Confers Protective Immunity to Shiga Toxin Challenge in the Murine Model
Authors: Bentancor Leticia V. , Bilen Marcos , Brando Romina J. Fernández , Ramos María Victoria , Ferreira Luis C. S. , Ghiringhelli Pablo D. , Palermo Marina S.
Published: January 2009

Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic
Escherichia coli
(EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A
1
peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A
2
peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2ΔAB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A
2
sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte-macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2ΔAB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae.
The Region Approximately between Amino Acids 81 and 137 of Proteinase K-Resistant PrP
Sc
Is Critical for the Infectivity of the Chandler Prion Strain
Authors: Shindoh Ryo , Kim Chan-Lan , Song Chang-Hyun , Hasebe Rie , Horiuchi Motohiro
Published: January 2009

Although the major component of the prion is believed to be the oligomer of PrP
Sc
, little information is available concerning regions on the PrP
Sc
molecule that affect prion infectivity. During the analysis of PrP
Sc
molecules from various prion strains, we found that PrP
Sc
of the Chandler strain showed a unique property in the conformational-stability assay, and this property appeared to be useful for studying the relationship between regions of the PrP
Sc
molecule and prion infectivity. Thus, we analyzed PrP
Sc
of the Chandler strain in detail and analyzed the infectivities of the N-terminally denatured and truncated forms of proteinase K-resistant PrP. The N-terminal region of PrP
Sc
of the Chandler strain showed region-dependent resistance to guanidine hydrochloride (GdnHCl) treatment. The region approximately between amino acids (aa) 81 and 137 began to be denatured by treatment with 1.5 M GdnHCl. Within this stretch, the region comprising approximately aa 81 to 90 was denatured almost completely by 2 M GdnHCl. Furthermore, the region approximately between aa 90 and 137 was denatured completely by 3 M GdnHCl. However, the C-terminal region thereafter was extremely resistant to the GdnHCl treatment. This property was not observed in PrP
Sc
molecules of other prion strains. Denaturation of the region between aa 81 and 137 by 3 M GdnHCl significantly prolonged the incubation periods in mice compared to that for the untreated control. More strikingly, the denaturation and removal of this region nearly abolished the infectivity. This finding suggests that the conformation of the region between aa 81 and 137 of the Chandler strain PrP
Sc
molecule is directly associated with prion infectivity.
Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections
Authors: Stacey Andrea R. , Norris Philip J. , Qin Li , Haygreen Elizabeth A. , Taylor Elizabeth , Heitman John , Lebedeva Mila , DeCamp Allan , Li Dongfeng , Grove Douglas , Self Steven G. , Borrow Persephone
Published: January 2009

Characterization of the immune responses induced in the initial stages of human immunodeficiency virus type 1 (HIV-1) infection is of critical importance for an understanding of early viral pathogenesis and prophylactic vaccine design. Here, we used sequential plasma samples collected during the eclipse and exponential viral expansion phases from subjects acquiring HIV-1 (or, for comparison, hepatitis B virus [HBV]or hepatitis C virus [HCV]) to determine the nature and kinetics of the earliest systemic elevations in cytokine and chemokine levels in each infection. Plasma viremia was quantitated over time, and levels of 30 cytokines and chemokines were measured using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. The increase in plasma viremia in acute HIV-1 infection was found to be associated with elevations in plasma levels of multiple cytokines and chemokines, including rapid and transient elevations in alpha interferon (IFN-α) and interleukin-15 (IL-15) levels; a large increase in inducible protein 10 (IP-10) levels; rapid and more-sustained increases in tumor necrosis factor alpha and monocyte chemotactic protein 1 levels; more slowly initiated elevations in levels of additional proinflammatory factors including IL-6, IL-8, IL-18, and IFN-γ; and a late-peaking increase in levels of the immunoregulatory cytokine IL-10. Notably, there was comparatively little perturbation in plasma cytokine levels during the same phase of HBV infection and a delayed response of more intermediate magnitude in acute HCV infection, indicating that the rapid activation of a striking systemic cytokine cascade is not a prerequisite for viral clearance (which occurs in a majority of HBV-infected individuals). The intense early cytokine storm in acute HIV-1 infection may have immunopathological consequences, promoting immune activation, viral replication, and CD4
+
T-cell loss.
Identification of TRIM23 as a Cofactor Involved in the Regulation of NF-κB by Human Cytomegalovirus
Authors: Poole Emma , Groves Ian , Macdonald Andrew , Pang Yin , Alcami Antonio , Sinclair John
Published: January 2009

Human cytomegalovirus (HCMV) regulates NF-κB during infection by a variety of mechanisms. For example, the HCMV gene product, UL144, is known to activate NF-κB in a tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-dependent manner, causing the upregulation of the chemokine CCL22 (MDC). Viral UL144 is expressed from the UL/b′ region of the HCMV genome at early times postinfection and is a TNFR1-like homologue. Despite this homology to the TNFR1 receptor superfamily, UL144 does not bind to members of the TNF ligand superfamily. We show here that the upregulation of NF-κB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-κB through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. In contrast, TRIM23 is not involved in conventional double-stranded RNA signaling via NF-κB. Therefore, we present a novel role for TRIM23 that is specific to UL144-mediated activation of NF-κB during the course of virus infection.
Organ-Specific Attenuation of Murine Hepatitis Virus Strain A59 by Replacement of Catalytic Residues in the Putative Viral Cyclic Phosphodiesterase ns2
Authors: Roth-Cross Jessica K. , Stokes Helen , Chang Guohui , Chua Ming Ming , Thiel Volker , Weiss Susan R. , Gorbalenya Alexander E. , Siddell Stuart G.
Published: January 2009

TheMurine hepatitis virus(MHV) strain A59 ns2 protein is a 30-kDa nonstructural protein that is expressed from a subgenomic mRNA in the cytoplasm of virus-infected cells. Its homologs are also encoded in other closely related group 2a coronaviruses and more distantly related toroviruses. Together, these proteins comprise a subset of a large superfamily of 2H phosphoesterase proteins that are distinguished by a pair of conserved His-x-Thr/Ser motifs encompassing catalytically important residues. We have used a vaccinia virus-based reverse genetic system to produce recombinant viruses encoding ns2 proteins with single-amino-acid substitutions in, or adjacent to, these conserved motifs, namely, inf-ns2 H46A, inf-ns2 S48A, inf-ns2-S120A, and inf-ns2-H126R. All of the mutant viruses replicate in mouse 17 clone 1 fibroblast cells and mouse embryonic cells to the same extent as the parental wild-type recombinant virus, inf-MHV-A59. However, compared to inf-MHV-A59, the inf-ns2 H46A and inf-ns2-H126R mutants are highly attenuated for replication in mouse liver following intrahepatic inoculation. Interestingly, none of the mutant viruses were attenuated for replication in mouse brain following intracranial inoculation. These results show that the ns2 protein of MHV-A59 has an important role in virus pathogenicity and that a substitution of the histidine residues of the MHV-A59 ns2 His-x-Thr/Ser motifs is critical for virus virulence in the liver but not in the brain. This novel phenotype suggests a strategy to investigate the function of the MHV-A59 ns2 protein involving the search for organ-specific proteins or RNAs that react differentially to wild-type and mutant ns2 proteins.
Transcriptional Coactivators Are Not Required for Herpes Simplex Virus Type 1 Immediate-Early Gene Expression In Vitro
Authors: Kutluay Sebla B. , DeVos Sarah L. , Klomp Jennifer E. , Triezenberg Steven J.
Published: January 2009

Virion protein 16 (VP16) of herpes simplex virus type 1 (HSV-1) is a potent transcriptional activator of viral immediate-early (IE) genes. The VP16 activation domain can recruit various transcriptional coactivators to target gene promoters. However, the role of transcriptional coactivators in HSV-1 IE gene expression during lytic infection had not been fully defined. We showed previously that transcriptional coactivators such as the p300 and CBP histone acetyltransferases and the BRM and Brg-1 chromatin remodeling complexes are recruited to viral IE gene promoters in a manner dependent mostly on the presence of the activation domain of VP16. In this study, we tested the hypothesis that these transcriptional coactivators are required for viral IE gene expression during infection of cultured cells. The disrupted expression of the histone acetyltransferases p300, CBP, PCAF, and GCN5 or the BRM and Brg-1 chromatin remodeling complexes did not diminish IE gene expression. Furthermore, IE gene expression was not impaired in cell lines that lack functional p300, or BRM and Brg-1. We also tested whether these coactivators are required for the VP16-dependent induction of IE gene expression from transcriptionally inactive viral genomes associated with high levels of histones in cultured cells. We found that the disruption of coactivators also did not affect IE gene expression in this context. Thus, we conclude that the transcriptional coactivators that can be recruited by VP16 do not contribute significantly to IE gene expression during lytic infection or the induction of IE gene expression from nucleosomal templates in vitro.
The Infected Cell Protein 0 Encoded by Bovine Herpesvirus 1 (bICP0) Associates with Interferon Regulatory Factor 7 and Consequently Inhibits Beta Interferon Promoter Activity
Authors: Saira Kazima , Zhou You , Jones Clinton
Published: January 2009

The bICP0 protein encoded by bovine herpesvirus 1 stimulates productive infection and viral gene expression but inhibits interferon (IFN)-dependent transcription. bICP0 inhibits beta IFN (IFN-β) promoter activity and induces degradation of IFN regulatory factor 3 (IRF3). Although bICP0 inhibits the
trans
-activation activity of IRF7, IRF7 protein levels are not reduced. In this study, we demonstrate that bICP0 is associated with IRF7. Furthermore, bICP0 inhibits the ability of IRF7 to
trans
-activate the IFN-β promoter in the absence of IRF3 expression. The interaction between bICP0 and IRF7 correlates with reduced
trans
-activation of the IFN-β promoter by IRF7.
Functional Replacement of a Domain in the Rubella Virus P150 Replicase Protein by the Virus Capsid Protein
Authors: Tzeng Wen-Pin , Frey Teryl K.
Published: January 2009

The rubella virus (RUBV) capsid (C) protein rescues mutants with a lethal deletion between two in-frame NotI sites in the P150 replicase gene, a deletion encompassing nucleotides 1685 to 2192 of the RUBV genome and amino acids (aa) 548 to 717 of P150 (which has a total length of 1,301 aa). The complete domain rescuable by the C protein was mapped to aa 497 to 803 of P150. Introduction of aa 1 to 277 of the C protein (lacking the C-terminal E2 signal sequence) between the NotI sites in the P150 gene in a replicon construct yielded a viable construct that synthesized viral RNA with wild-type kinetics, indicating that C and this region of P150 share a common function. Further genetic analysis revealed that an arginine-rich motif between aa 60 and 68 of the C protein was necessary for the rescue of ΔNotI deletion mutants and substituted for an arginine-rich motif between aa 731 and 735 of the P150 protein when the C protein was introduced into P150. Possible common functions shared by these arginine-rich motifs include RNA binding and interaction with cell proteins.
Adenovirus Serotype 5 L4-22K and L4-33K Proteins Have Distinct Functions in Regulating Late Gene Expression
Authors: Morris Susan J. , Leppard Keith N.
Published: January 2009

Adenoviruses express up to 20 distinct mRNAs from five major late transcription unit (MLTU) regions, L1 to L5, by differential splicing and polyadenylation of the primary transcript. MLTU expression is regulated at transcriptional and posttranscriptional levels. The L4-33K protein acts as a splicing factor to upregulate several MLTU splice acceptor sites as the late phase progresses. The L4 region also expresses a 22K protein whose sequence is related to the sequence of L4-33K. L4-22K is shown here also to have an important role in regulating the pattern of MLTU gene expression. An adenovirus genome containing a stop codon in the L4-22K open reading frame expressed low levels of both structural and nonstructural late proteins compared to the wild-type (wt) adenovirus genome; a decrease in intermediate proteins, IVa2 and IX, was also observed. However, early protein synthesis and replication were unaffected by the absence of L4-22K. Intermediate and late protein expression was restored to wt levels by L4-22K expressed in
trans
but not by L4-33K. Increased MLTU promoter activity, resulting from stabilization of the transcriptional activator IVa2 by L4-22K, made a small contribution to this restoration of late gene expression. However, the principal effect of L4-22K was on the processing of MLTU RNA into specific cytoplasmic mRNA. L4-22K selectively increased expression of penton mRNA and protein, whereas splicing to create penton mRNA is known not to be increased by L4-33K. These results indicate that L4-22K plays a key role in the early-late switch in MLTU expression, additional to and distinct from the role of L4-33K.
The close relation between cyclic delocalization, energy effects of cycles and aromaticity
Authors: Ponec Robert , Fias Stijn , Van Damme Sofie , Bultinck Patrick , Gutman Ivan , Stanković Sonja
Published: January 2009

New evidence questioning the multidimensionality of the aromaticity phenomenon exemplified in what is called orthogonality between the classical (structural and energetic) and magnetic aromaticity indices and measures is reported. For this purpose, the recently proposed methodologies for the quantitative characterization of the energy benefits associated with the cyclic arrangement of mobile π-electrons in polycyclic aromatic hydrocarbons are compared with the indices characterizing the extent of cyclic delocalization in the corresponding conjugated circuits. The reported close correlation between both types of indices implies that no discrepancies between classical and magnetic aromaticity measures exist provided the comparison is based on the indices of inherently local nature and/or the interfering contributions of contaminating conjugated circuits is properly taken into account in the description of aromaticity measures like topological resonance energy (TRE) or nucleus independent chemical shift (NICS).
Experimental and computed dipole moments in donor–bridge–acceptor systems with p-phenylene and p-carboranediyl bridges
Authors: Drož Ladislav , Fox Mark A. , Hnyk Drahomír , Low Paul J. , MacBride J. A. Hugh , Všetečka Václav
Published: January 2009

Dipole moments were measured for a series of substituted benzenes, biphenyls, terphenyls, C-monoaryl- and C,C′-diaryl-p-carboranes. For the donor–bridge–acceptor systems, Me2N–X–NO2, where X is 1,4-phenylene, biphenyl-4,4′-diyl, terphenyl and 1,4-C6H4-p-CB10H10C-1,4-C6H4, the measured interaction dipole moments are 1.36, 0.74, 0.51 and 0.00 D, respectively. The magnitude of the dipole moment reflects the ability of the bridge to transmit electronic effects between donor and acceptor groups. Thus, whilst the 1,4-phenylene bridges allow moderate electronic interactions between the remote groups, the p-carboranediyl unit is less efficient as a conduit for electronic effects. Averaged dipole moments computed at the DFT (B3LYP/6-31G*) level of theory from two distinct molecular conformers are in good agreement with the experimental values. Examination of the calculated electronic structures provides insight into the nature of the interactions between the donor and acceptor moieties through these 2D and 3D aromatic bridges. The most significant cooperative effect of the bridge on the dipole moment occurs in systems where there is some overlap between the HOMO and LUMO orbitals. This orbital overlap criterion may help to define the difference between “push-pull” systems in which electronic effects are mediated by the bridging moiety, and simpler systems in which the bridge acts as an electronically innocent spacer unit and through-space charge transfer/separation is dominant.
Acyclic versus cyclic π-electron delocalization. How is the substituent effect related to π-electron delocalization?
Authors: Dobrowolski Michał A. , Kaniewski Jędrzej , Krygowski Tadeusz M. , Cyrański Michał K.
Published: January 2009

Substituent effect stabilization energies were estimated for sets of 27 para-substituted phenol derivatives, meta- and para-homodisubstituted benzene derivatives, trans-substituted ethenes, 4-substituted 1-hydroxy-1,3-cyclohexadienes and 1,4-homodisubstituted 1,3-cyclohexadienes based on the optimizations at the B3LYP/6-311+G** DFT level of theory. The following substituents were taken into account: C≡CH, C(CN)3, CF3, CH2NH2, CH3, CH=CH2, CHO, Cl, CN, COCH3, COCl, CONH2, COOCH3, COOH, F, NH2, NHCH3, N(CH3)2, NHOH, NO, NO2, OCH3, OH, Ph, H, SH, SO2CN. For hydroxyethenes and phenol derivatives the electron-acceptor substituents stabilize the systems, whereas the electron-donors lead to their destabilization. Both electron-acceptor and electron-donor substituents destabilize homodisubstituted ethene and meta- and para-homodisubstituted benzene species. The strongest destabilization is observed for derivatives of ethene, a weaker one for derivatives of cyclohexadiene and the weakest for benzene derivatives.
SystemCoDesigner—an automatic ESL synthesis approach by design space exploration and behavioral synthesis for streaming applications
Authors: Keinert Joachim , Streubūhr Martin , Schlichter Thomas , Falk Joachim , Gladigau Jens , Haubelt Christian , Teich Jūrgen , Meredith Michael
Published: January 2009

With increasing design complexity, the gap from ESL (Electronic System Level) design to RTL synthesis becomes more and more crucial to many industrial projects. Although several behavioral synthesis tools exist to automatically generate synthesizable RTL code from C/C++/SystemC-based input descriptions and software generation for embedded processors is automated as well, an efficient ESL synthesis methodology combining both is still missing. This article presents SystemCoDesigner, a novel SystemC-based ESL tool to automatically optimize a hardware/software SoC (System on Chip) implementation with respect to several objectives. Starting from a SystemC behavioral model, SystemCoDesigner automatically extracts the mathematical model, performs a behavioral synthesis step, and explores the multiobjective design space using state-of-the-art multiobjective optimization algorithms. During design space exploration, a single design point is evaluated by simulating highly accurate performance models, which are automatically generated from the SystemC behavioral model and the behavioral synthesis results. Moreover, SystemCoDesigner permits the automatic generation of bit streams for FPGA targets from any previously optimized SoC implementation. Thus SystemCoDesigner is the first fully automated ESL synthesis tool providing a correct-by-construction generation of hardware/software SoC implementations. As a case study, a model of a Motion-JPEG decoder was automatically optimized and implemented using SystemCoDesigner. Several synthesized SoC variants based on this model show different tradeoffs between required hardware costs and achieved system throughput, ranging from software-only solutions to pure hardware implementations that reach real-time performance for QCIF streams on a 50MHz FPGA.
A gateway node with duty-cycled radio and processing subsystems for wireless sensor networks
Authors: Jin Zhong-Yi , Schurgers Curt , Gupta Rajesh K.
Published: January 2009

Wireless sensor nodes are increasingly being tasked with computation and communication intensive functions while still subject to constraints related to energy availability. On these embedded platforms, once all low power design techniques have been explored, duty-cycling the various subsystems remains the primary option to meet the energy and power constraints. This requires the ability to provide spurts of high MIPS and high bandwidth connections. However, due to the large overheads associated with duty-cycling the computation and communication subsystems, existing high performance sensor platforms are not efficient in supporting such an option. In this article, we present the design and optimizations taken in a wireless gateway node (WGN) that bridges data from wireless sensor networks to Wi-Fi networks in an on-demand basis. We discuss our strategies to reduce duty-cycling related costs by partitioning the system and by reducing the amount of time required to activate or deactivate the high-powered components. We compare the design choices and performance parameters with those made in the Intel
Stargate
platform to show the effectiveness of duty-cycling on our platform. We have built a working prototype, and the experimental results with two different power management schemes show significant reductions in latency and average power consumption compared to the
Stargate
. The WGN running our power-gating scheme performs about six times better in terms of average system power consumption than the
Stargate
running the suspend-system scheme for large working-periods where the active power dominates. For short working-periods where the transition (enable/disable) power becomes dominant, we perform up to seven times better. The comparative performance of our system is even greater when the sleep power dominates.
A 252Kgates/4.9Kbytes SRAM/71mW multistandard video decoder for high definition video applications
Authors: Chien Chih-Da , Chien Cheng-An , Chu Jui-Chin , Guo Jiun-In , Cheng Ching-Hwa
Published: January 2009

This article proposes a low-cost, low-power multistandard video decoder for high definition (HD) video applications. The proposed design supports multiple-standard (JPEG baseline, MPEG-1/2/4 Simple Profile (SP), and H.264 Baseline Profile (BP)) video decoding through interactive parsing control and common parameter bus interface. In order to reduce hardware cost, the shared adder-based structure and reusable data management are proposed to achieve hardware sharing and reduce internal memory size, respectively. In addition, the proposed design is optimized through reducing memory bandwidth by increasing both data reuse amount and burst length of memory access as well as eliminating cycle overhead in data access for supporting HD video decoding with single AHB-based SDR memory. The proposed 252Kgates/4.9kB/71mW/0.13μm multi-standard video decoder reduces 72% in gate count and 87% in power consumption as compared to the state-of-the-art design, when operating at 120MHz for real-time HD1080 video decoding with single AHB-based SDR memory.
New results on rewrite-based satisfiability procedures
Authors: Armando Alessandro , Bonacina Maria Paola , Ranise Silvio , Schulz Stephan
Published: January 2009

Program analysis and verification require decision procedures to reason on theories of data structures. Many problems can be reduced to the
satisfiability
of sets of
ground literals
in theory
T
. If a sound and complete inference system for first-order logic is guaranteed to
terminate
on
T-satisfiability problems
, any theorem-proving strategy with that system and a fair search plan is a
T-satisfiability procedure
. We prove termination of a rewrite-based first-order engine on the theories of
records
,
integer offsets
,
integer offsets modulo
and
lists
. We give a
modularity theorem
stating sufficient conditions for termination on a
combination of theories
, given termination on each. The above theories, as well as others, satisfy these conditions. We introduce several sets of benchmarks on these theories and their combinations, including both
parametric
synthetic benchmarks to test
scalability
, and real-world problems to test performances on huge sets of literals. We compare the rewrite-based theorem prover E with the validity checkers CVC and CVC Lite. Contrary to the folklore that a general-purpose prover cannot compete with reasoners with built-in theories, the experiments are overall favorable to the theorem prover, showing that not only the rewriting approach is elegant and conceptually simple, but has important practical implications.