bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodistribution and expression of targeted fusion anti‐caries DNA vaccine pGJA‐P/VAX in mice
Authors: Liu Chang , Fan Mingwen , Xu Qingan , Li Yuhong
Published: December 2007

Objective

To study the biodistribution and expression of anti‐caries DNA vaccine pGJA‐P/VAX in mice models following intranasal (i.n.) and intramuscular (i.m.) immunization.

Methods

pGJA‐P/VAX and pVAX1 were administrated i.n. and i.m. to mice, respectively. Blood and organs were harvested and then genomic DNA was extracted. mRNA in the original tissues and draining lymph nodes was isolated. The in vivo fate of plasmid DNA in these samples was evaluated with real‐time quantitative polymerase chain reaction (PCR).

Results

The ratio of the area under the curve (AUC) and maximum concentration (Cmax) after i.n. immunization were higher than that after i.m. injection. At 1 day post i.n. immunization, the localization of plasmid to the heart, spleen and lung was notable compared with that to the nasal mucosa. At 2 days, for i.n. immunization, the concentration value of plasmid in the mucosa‐associated lymphoid tissues such as lung, kidney and gastrointestine had increased and was greater than that via i.m. injection. At later time points, the plasmid was primarily in the original tissues and draining lymph nodes. mRNA expression was observed in the topical tissues up to 7 days and in the draining lymph nodes for at least 3 days.

Conclusions

These results indicate that the distribution of pGJA‐P/VAX was widespread in vivo, and the expression was significant in the inoculation tissue and draining lymph nodes after i.n. immunization and i.m. injection. This data provides evidence which supports the long‐term immune responses and the basis of further research on safety issues. Copyright © 2007 John Wiley & Sons, Ltd.
Adenoviral vector‐mediated glucagon‐like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats
Authors: Lee Yongho , Kwon Mi Kyong , Kang Eun Seok , Park Young Mi , Choi Seung Ho , Ahn Chul Woo , Kim Kyung Sub , Park Chul Won , Cha Bong Soo , Kim Sung Wan , Sung Je Kyung , Lee Eun Jig , Lee Hyun Chul
Published: December 2007

Background

Glucagon‐like peptide‐1 (GLP‐1) is a gut‐derived incretin hormone that plays an important role in glucose homeostasis. Its functions include glucose‐stimulated insulin secretion, suppression of glucagon secretion, deceleration of gastric emptying, and reduction in appetite and food intake. Despite the numerous antidiabetic properties of GLP‐1, its therapeutic potential is limited by its short biological half‐life due to rapid enzymatic degradation by dipeptidyl peptidase IV. The present study aimed to demonstrate the therapeutic effects of constitutively expressed GLP‐1 in an overt type 2 diabetic animal model using an adenoviral vector system.

Methods

A novel plasmid (pAAV‐ILGLP‐1) and recombinant adenoviral vector (Ad‐ILGLP‐1) were constructed with the cytomegalovirus promoter and insulin leader sequence followed by GLP‐1(7–37) cDNA.

Results

The results of an enzyme‐linked immunosorbent assay showed significantly elevated levels of GLP‐1(7–37) secreted by human embryonic kidney cells transfected with the construct containing the leader sequence. A single intravenous administration of Ad‐ILGLP‐1 into 12‐week‐old Zucker diabetic fatty (ZDF) rats, which have overt type 2 diabetes mellitus (T2DM), achieved near normoglycemia for 3 weeks and improved utilization of blood glucose in glucose tolerance tests. Circulating plasma levels of GLP‐1 increased in GLP‐1‐treated ZDF rats, but diminished 21 days after treatment. When compared with controls, Ad‐ILGLP‐1‐treated ZDF rats had a lower homeostasis model assessment for insulin resistance score indicating amelioration in insulin resistance. Immunohistochemical staining showed that cells expressing GLP‐1 were found in the livers of GLP‐1‐treated ZDF rats.

Conclusions

These data suggest that GLP‐1 gene therapy can improve glucose homeostasis in fully developed diabetic animal models and may be a promising treatment modality for T2DM in humans. Copyright © 2007 John Wiley & Sons, Ltd.
A reversed superficial peroneal neurocutaneous island flap based on the descending branch of the distal peroneal perforator: Clinical experiences and modifications
Authors: Chai Yimin , Zeng Bingfang , Cai Peihua , Kang Qinlin , Chen Yunfeng , Wang Chunyang
Published: December 2007

The distally based neurocutaneous flaps have been popular for lower leg and foot reconstruction. On the basis of pre‐existing anatomic studies and clinical experiences, we designed a reversed superficial peroneal neurocutaneous island flap with the descending branch of the distal peroneal perforator as the pedicle. The flap is supplied through both axial perforator and longitudinal chain‐linked vascular plexuses. This modified neurocutaneous island flap, measuring around 5 cm × 4 cm to 12 cm × 13 cm in size, was transferred for coverage of foot soft‐tissue defects in 21 cases with a low complication rate. Compared to the original neurocutaneous flap, the rotation point of this flap is more distal and the pedicle is thinner. It could provide good texture and contour matching to the recipient area. In conclusion, the modified neurocutaneous island flap provides a reliable tool for repairing soft‐tissue defects of the ankle and foot. © 2007 Wiley‐Liss, Inc. Microsurgery, 2008.
Proliferation and neurogenesis of neural stem cells enhanced by cerebral microvascular endothelial cells
Authors: Guo Ying , Shi Dejin , Li Wensheng , Liang Chaofeng , Wang Hui , Ye Zhuopeng , Hu Liping , Wang Hua‐Qiao , Li Yan
Published: December 2007

In adult mammalian brain, vascular cells reside throughout life, close to central nervous system germinal zones, and neural stem cells (NSCs) mainly localize in the dentate gyrus of the hippocampus, subventricular zone, and olfactory bulb. Microvessels appear to produce a special microenvironment that may influence the characteristics of NSCs. To explore this potential correlation, an in vitro model with cocultured cerebral microvascular endothelial cells (CMECs) and NSCs was established in our study by using a transwell coculture system. The expression of nestin and NF in the early stage of coculture, and NF in the late stage, was detected by immunostaining. The results demonstrated that CMECs can stimulate self‐renewal of NSCs and inhibit their differentiation, implying the potential of CMECs in promoting the neural differentiation of NSCs. © 2007 Wiley‐Liss, Inc. Microsurgery, 2008.
The effect of carbonyl group in the asymmetry of 3, 4JCH coupling constants in norbornanones
Authors: dos Santos Francisco P. , Tormena Cláudio F. , Contreras Rubén H. , Rittner Roberto , Magalhães Alvicler
Published: December 2007

A rationalization of the known difference between the 3, 4J and 3, 4J couplings transmitted mainly through the 7‐bridge in norbornanone is presented in terms of the effects of hyperconjugative interactions involving the carbonyl group. Theoretical and experimental studies of 3, 4JCH couplings were carried out in 3‐endo‐ and 3‐exo‐X‐2‐norbornanone derivatives (X = Cl, Br) and in exo‐ and endo‐2‐noborneol compounds. Hyperconjugative interactions were studied with the natural bond orbital (NBO) method. Hyperconjugative interactions involving the carbonyl π* and σ* antibonding orbitals produce a decrease of three‐bond contribution to both 3, 4J and 3, 4J couplings. However, the latter antibonding orbital also undergoes a strong σ → σ* interaction, which defines an additional coupling pathway for 3, 4J but not for 3, 4J. This pathway is similar to that known for homoallylic couplings, the only difference being the nature of the intermediate antibonding orbital; i.e. for 3, 4J it is of σ*‐type, while in homoallylic couplings it is of π*‐type. Copyright © 2007 John Wiley & Sons, Ltd.
Transfer of complex frontline anticancer therapy to a developing country: The St. Jude osteosarcoma experience in Chile
Authors: Rivera Gaston K. , Quintana Juan , Villarroel Milena , Santana Victor M. , Rodriguez‐Galindo Carlos , Neel Michael D. , Velez George , Ribeiro Raul C. , Daw Najat C.
Published: December 2007

Background

A frontline protocol for newly diagnosed osteosarcoma was conducted simultaneously at St. Jude Children's Research Hospital (sponsor) and Calvo Mackenna Hospital (CMH, partner), a public pediatric hospital and national center for the treatment of bone tumors in Santiago, Chile.

Procedure

Of 72 eligible patients, 22 (31%) were enrolled and managed in Santiago, without travel to Memphis. Pathology specimens and imaging material were centrally reviewed at St. Jude. Patients received 12 intensive courses of systemic chemotherapy with hematopoietic growth factor support over 35 weeks, and amputation or limb‐salvage surgery as indicated for local control. The sponsor assisted the partner site to establish a clinical research infrastructure and obtain hematopoietic growth factor. Communication among medical and nursing teams was maintained throughout the study. Patient‐care and protocol issues were discussed frequently between the two centers via scheduled videoconferences and electronic communications. Auditors monitored appropriate study conduct at the international site.

Results

No major discrepancies were identified in histologic findings, staging, or imaging studies. Preliminary results demonstrated similar outcome and treatment tolerance; the 2‐year event‐free survival estimate was 78.5% (95% CI, 51–100%) for patients treated at CMH (median follow‐up, 1.6 years) and 74.3% (95% CI, 62–87%) for patients treated at St. Jude (median follow‐up, 4 years). Overall per‐patient costs were significantly lower in Chile.

Conclusions

Through a twinning mechanism, it is feasible to simultaneously conduct complex front‐line osteosarcoma clinical trials at two institutions in countries with different levels of resources. Pediatr Blood Cancer 2008;50:1143–1146. © 2007 Wiley‐Liss, Inc.
Interferometrie auf dem Küchentisch. Wellenoptik
Authors: Möllmann Klaus‐Peter , Vollmer Michael
Published: December 2007

Bei Interferometrie denkt man an teure optische Aufbauten. Doch für Schulversuche geht es viel einfacher. Auf einem Küchentisch lassen sich mit Laserpointern oder Laserdioden, Glasplättchen, Spiegeln, Linse und Knetgummi in wenigen Minuten komplette Interferometer aufbauen. Wir konnten das mit funktionsfähigen Jamin‐, Michelson‐ und Mach‐Zehnder‐Interferometern demonstrieren. Sie erlauben sogar Versuche mit Proben, zum Beispiel die Bestimmung der Brechzahl von erhitzter Luft.
Von der Erbsenschote zum Nanoreaktor. Innenraum einwandiger Kohlenstoff‐Nanoröhrchen
Authors: Kuzmany Hans , Pfeiffer Rudolf , Simon Ferenc
Published: December 2007

Der Innenraum von einwandigen Kohlenstoff‐Nanoröhrchen hat einen Durchmesser von grob einem Nanometer. In axialer Richtung ist er praktisch unbegrenzt lang. Damit bildet er eine ideale Maske zur Herstellung von eindimensionalen Systemen. Seine Befüllung mit Fullerenen führt zu Peapod‐Strukturen (Erbsenschoten). Wenn die Fullerene einen ungepaarten Elektronenspin tragen, lassen sich so lineare Spinketten aufbauen. Der Innenraum funktioniert auch als Nanoreaktor, in dem sich Fullerene in ein sekundäres, weitgehend defektfreies inneres Röhrchen umwandeln. Bestehen diese Fullerene aus 13C‐Atomen, dann entstehen innere Röhrchen aus 13C, die sich hervorragend für NMR‐Spektroskopie eignen. Solche Messungen zeigen zum Beispiel, dass die inneren Röhrchen bei höheren Temperaturen metallische Eigenschaften besitzen.
Heißer Glühwein mit Biss
Authors: Vilgis Thomas
Published: December 2007

Ein Glas heißer Glühwein in der kalten Jahreszeit ist nie verkehrt. Der Wein, versetzt mit Gewürzen und Zucker, kann in dunklen Tagen die Stimmung ein wenig aufhellen. Selbst als Dessert versetzt er uns in Staunen, da er nicht nur heiß, sondern als fester, heißer Würfel die Teller ziert. Hitzestabile Hydrogele sind ein moderner Trend in der molekularen Gastronomie und machen selbst vor der Kinetik bei Phasenübergängen nicht Halt.
Eisbildung durch Laserbeschuss
Authors: Mettin Robert , Lindinger Bernhard
Published: December 2007

In einer unterkühlten Flüssigkeit bilden sich unter bestimmten Bedingungen Eiskristalle, die zur vollständigen Vereisung führen. Die genauen Vorgänge bei dieser Nukleation sind noch nicht vollständig aufgeklärt. Dies gilt insbesondere für verschiedene Arten der dynamischen Nukleation, bei der ein zeitlich variabler Stimulus als Auslöser wirkt. Um Details hiervon zu ergründen, wurde von unserer Gruppe an der Universität Göttingen eine neue Methode eingesetzt: Eisbildung durch Laserbeschuss.
Azithromycin does not improve disease course in hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease: A randomized equivalence trial
Authors: Kneyber Martin C.J. , van Woensel Job B.M. , Uijtendaal Esther , Uiterwaal Cuno S.P.M. , Kimpen Jan L.L. ,   on behalf of the Dutch Antibiotics in RSV Trial (DART) Research Group
Published: December 2007

Background

Nearly half of all hospitalized infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) are treated with (parenteral) antibiotics. The present study was designed to test our hypothesis that the use of antibiotics would not lead to a reduced duration of hospitalization in mild to moderate RSV LRTD.

Methods

Seventy‐one patients ≤24 months of age with a virologically confirmed clinical diagnosis of RSV LRTD were randomized to azithromycin 10 mg/kg/day (n = 32) or placebo (n = 39) in a multicenter, randomized, double‐blind, placebo‐controlled equivalence trial during three RSV seasons (2002–2004 through 2005–2006). Primary endpoint was duration of hospitalization, secondary endpoints included duration of oxygen supplementation and nasogastric tube feeding, course of RSV symptom score, number of PICU referrals and number of patients who received additional antibiotic treatment. Data were analyzed according to the intention‐to‐treat principle using the Mann–Whitney U‐test or χ2 test considering P < 0.05 as statistically significant.

Results

Included patients were comparable with respect to baseline demographics, clinical characteristics, laboratory and roentgenologic investigations. The mean duration of hospitalization was not significantly different between patients treated with azithromycin or placebo (132.0 ± 10.8 vs. 139.6 ± 7.7 hr, P = 0.328). Azithromycin was not associated with a stronger resolution of clinical symptoms represented by the RSV symptom score. Four patients were treated with antibiotics after 72 hr, three of them were assigned to placebo (P = 0.406).

Conclusions

Infants and young children with RSV LRTD do not benefit from routine treatment with antibiotics (ISRCTN number 86554663). Pediatr Pulmonol. 2008; 43:142–149. © 2007 Wiley‐Liss, Inc.
Histamine H3 receptors and their role in basal ganglia physiology and pathophysiology
Authors: Arias‐Montaño José‐Antonio
Published: December 2007

Through interaction with G protein‐coupled receptors, histamine regulates pre‐ and post‐synaptically a number of brain functions such as wakefulness, locomotor activity, autonomic and vestibular functions, feeding, drinking, analgesia and memory. Four such receptors have been cloned to date, and three of them (H1, H2, and H3) are widely distributed in the central nervous system, which contains the great majority of histamine H3 receptors (H3Rs). These receptors are expressed at high densities in the basal ganglia, a group of subcortical neuronal nuclei intimately involved in the regulation of posture and movement. In this review the main characteristics of H3Rs (structure, isoforms, constitutive activity and signaling) are briefly described, to then summarize our own work regarding the H3R‐mediated regulation of synaptic transmission in the basal ganglia. Finally, the possible participation of H3Rs in the pathophysiology of Parkinson's disease is discussed. Based on the information herein reviewed it is concluded that H3Rs play a relevant role in basal ganglia function both in normal and pathological conditions, and that H3R agonists and antagonists may have potential use in the treatment of both Parkinson's disease and the complications of the current pharmacological therapies of the disorder.
ON THE LAW OF THE iTH WAITING TIME IN A BUSY PERIOD OF G/M/c QUEUES
Authors: Baron Opher
Published: December 2007

We use induction to derive the distribution of the waiting time of the ith waiting customer in a busy period for a G/M/1 queue with a first come–first serve service. A trivial implication gives the law for the ith waiting time in a busy period for a G/M/c queue. Finally, we use the Lindley recursion to relate our results to the distribution of random walks.
From Spark to Flame: Implementing LawPort
Authors: Mullan James
Published: December 2007

In this article, which is a summary of his presentation at the 38th BIALL Annual Study Conference held in Sheffield in June 2007, James Mullan provides an account of how the Content Team at CMS Cameron McKenna implemented LawPort and the issues they faced from the initial pilot to completion of the project.
Integrated Search Strategies for the Modern Law Firm
Authors: Martin Rob
Published: December 2007

This article by Rob Martin addresses the issue of effectively managing the searching of enterprise information systems in law firms. It discusses the relative merits of federated, enterprise and integrated search and includes a case study of the combined solution adopted by City law firm, Ashurst.
NELLCO International Fellowship – What a Thrill!
Authors: Renner Melinda
Published: December 2007

Melinda Renner, from the University of New Brunswick, writes about her experiences as a New England Law Library Consortium International Fellow who was seconded to the Institute of Advanced Legal Studies in London. She describes the visits she made and her impressions of how academic librarianship in Britain and Canda appear to share many of the same issues and problems.
A temperature‐sensitive expression system based on the Geobacillus stearothermophilus NRS 2004/3a sgsE surface‐layer gene promoter
Authors: Novotny Rene , Berger Harald , Schinko Thorsten , Messner Paul , Schäffer Christina , Strauss Joseph
Published: December 2007

The sgsE gene coding for the S‐layer (surface layer) protein in the thermophilic Gram‐positive bacterium Geobacillus stearothermophilus NRS 2004/3a is strongly induced when the culture is shifted from optimal (55 °C) to maximally tolerable growth temperature (67 °C). Here, we investigated the regulation of the sgsE promoter in G. stearothermophilus and tested the function of this promoter in Bacillus subtilis. We used EGFP (enhanced green fluorescent protein) reporter constructs and found that the sgsE promoter has very low basal activity at 28 °C, but is approx. 20‐fold induced by elevated growth temperatures (37 and 45 °C). The promoter confers high expression levels, as EGFP mRNA levels at 45 °C were approx. 120‐fold more abundant than mRNA levels of the cat (chloramphenicol resistance) gene, which was transcribed from a constitutive promoter on the same plasmid. In fluorescence‐microscopic and Western‐blot analysis, the EGFP protein was barely detectable at 28 °C, whereas intermediate and high levels were detected at 37 and 45 °C respectively. The potential to tune expression levels of genes driven by the sgsE promoter in B. subtilis by simple temperature adjustments presents a considerable potential for its future use as high‐yield protein expression system for B. subtilis.
Cryptic diversity in Engaeus Erichson, Geocharax Clark and Gramastacus Riek (Decapoda : Parastacidae) revealed by mitochondrial 16S rDNA sequences
Authors: Schultz Mark B. , Smith Sarah A. , Richardson Alastair M. M. , Horwitz Pierre , Crandall Keith A. , Austin Christopher M.
Published: December 2007

Nucleotide sequence data from the mitochondrial 16S rDNA region were utilised to investigate phylogenetic relationships and species boundaries among Australian freshwater crayfish belonging to the genera Engaeus Erichson, 1846, Geocharax Clark, 1936 and Gramastacus Riek, 1972. Geocharax and Gramastacus were found to be monophyletic genera but one species currently assigned to Engaeus may belong to another genus. Relationships between the three existing genera were not resolved. Analysis of species boundaries within Geocharax suggests that there are an additional two species in this genus, and our analysis of Gramastacus indicates that undescribed populations from central New South Wales may comprise a second species. The data provide at least one instance of a taxon crossing the Great Dividing Range and provide confirmation of previously proposed hypotheses seeking to explain trans-Bass Strait distributions of species.
An extremes of outcome strategy provides evidence that multiple sclerosis severity is determined by alleles at the
HLA-DRB1
locus
Authors: DeLuca G. C. , Ramagopalan S. V. , Herrera B. M. , Dyment D. A. , Lincoln M. R. , Montpetit A. , Pugliatti M. , Barnardo M. C. N. , Risch N. J. , Sadovnick A. D. , Chao M. , Sotgiu S. , Hudson T. J. , Ebers G. C.
Published: December 2007

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system unsurpassed for variability in disease outcome. A cohort of sporadic MS cases (
n
= 163), taken from opposite extremes of the distribution of long-term outcome, was used to determine the role of the
HLA-DRB1
locus on MS disease severity. Genotyping sets of benign and malignant MS patients showed that
HLA-DRB1
*
01
was significantly underrepresented in malignant compared with benign cases. This allele appears to attenuate the progressive disability that characterizes MS in the long term. The observation was doubly replicated in (
i
) Sardinian benign and malignant patients and (
ii
) a cohort of affected sibling pairs discordant for
HLA-DRB1
*
01
. Among the latter, mean disability progression indices were significantly lower in those carrying the
HLA-DRB1
*
01
allele compared with their disease-concordant siblings who did not. The findings were additionally supported by similar transmission distortion of
HLA-DRB1
*
04
subtypes closely related to
HLA-DRB1
*
01.
The protective effect of
HLA-DRB1
*
01
in sibling pairs may result from a specific epistatic interaction with the susceptibility allele
HLA-DRB1
*
1501
. A high-density (>700) SNP examination of the MHC region in the benign and malignant patients could not identify variants differing significantly between the two groups, suggesting that
HLA-DRB1
may itself be the disease-modifying locus. We conclude that
HLA-DRB1
*
01
, previously implicated in disease resistance, acts as an independent modifier of disease progression. These results closely link susceptibility to long-term outcome in MS, suggesting that shared quantitative MHC-based mechanisms are common to both, emphasizing the central role of this region in pathogenesis.
Genetic structure of Octopus vulgaris around the Iberian Peninsula and Canary Islands as indicated by microsatellite DNA variation
Authors: Cabranes C. , Fernandez-Rueda P. , Martínez J. L.
Published: December 2007

Cabranes, C., Fernandez-Rueda, P., and Martínez, J. L. 2008. Genetic structure of Octopus vulgaris around the Iberian Peninsula and Canary Islands as indicated by microsatellite DNA variation. – ICES Journal of Marine Science, 65: 12–16. Microsatellite DNA markers were used for a genetic study of Octopus vulgaris, a cephalopod species of great commercial interest to Spain and Portugal, and therefore subjected to intensive fishing. Improving the demographic knowledge of marine resources supports more-responsible management and conservation. Genetic variation at five microsatellite loci screened in six samples from NE Atlantic and Mediterranean coasts of the Iberian Peninsula was high [mean number of alleles = 18.3, mean He = 0.874]. Analysis of the microsatellites allowed significant subpopulation structure to be identified, consistent with an isolation-by-distance model for Atlantic populations. Differences between pairs of samples separated by <200 km were not significant. From a fisheries management perspective, the results support coordinated management of neighbouring stocks of O. vulgaris around the Iberian Peninsula.
Molecular analysis of avian H7 influenza viruses circulating in Eurasia in 1999–2005: detection of multiple reassortant virus genotypes
Authors: Campitelli Laura , Di Martino Angela , Spagnolo Domenico , Smith Gavin J. D. , Di Trani Livia , Facchini Marzia , De Marco Maria Alessandra , Foni Emanuela , Chiapponi Chiara , Martin Ana Moreno , Chen Honglin , Guan Yi , Delogu Mauro , Donatelli Isabella
Published: December 2007

Avian influenza infections by high and low pathogenicity H7 influenza viruses have caused several outbreaks in European poultry in recent years, also resulting in human infections. Although in some cases the source of H7 strains from domestic poultry was shown to be the viruses circulating in the wild bird reservoir, a thorough characterization of the entire genome of H7 viruses from both wild and domestic Eurasian birds, and their evolutionary relationships, has not been conducted. In our study, we have analysed low pathogenicity H7 influenza strains isolated from wild and domestic ducks in Italy and southern China and compared them with those from reared terrestrial poultry such as chicken and turkey. Phylogenetic analysis demonstrated that the H7 haemagglutinin genes were all closely related to each other, whereas the remaining genes could be divided into two or more phylogenetic groups. Almost each year different H7 reassortant viruses were identified and in at least two different years more than one H7 genotype co-circulated. A recent precursor in wild waterfowl was identified for most of the gene segments of terrestrial poultry viruses. Our data suggest that reassortment allows avian influenza viruses, in their natural reservoir, to increase their genetic diversity. In turn this might help avian influenza viruses colonize a wider range of hosts, including domestic poultry.
A silkworm–baculovirus model for assessing the therapeutic effects of antiviral compounds: characterization and application to the isolation of antivirals from traditional medicines
Authors: Orihara Yutaka , Hamamoto Hiroshi , Kasuga Hiroshi , Shimada Toru , Kawaguchi Yasushi , Sekimizu Kazuhisa
Published: December 2007

Ganciclovir, foscarnet, vidarabine and ribavirin, which are used to treat viral infections in humans, inhibited the proliferation of a baculovirus (Bombyx morinucleopolyhedrovirus) in BmN4 cells, a cultured silkworm cell line. These antiviral agents inhibited the proliferation of baculovirus in silkworm body fluid and had therapeutic effects. Using the silkworm infection model, the antiviral activity of Kampo medicines was screened and it was found that cinnamon bark, a component of the traditional Japanese medicine Mao-to, had a therapeutic effect. Based on the therapeutic activity, the antiviral substance was purified. Nuclear magnetic resonance analysis of the purified fraction revealed that the antiviral activity was due to cinnzeylanine, which has previously been isolated fromCinnamomum zeylanicum. Cinnzeylanine inhibits the proliferation of herpes simplex virus type 1 in Vero cells. These results suggest that the silkworm–baculovirus infection model is useful for screening antiviral agents that are effective for treating humans infected with DNA viruses.
Immunotherapy of equine sarcoid: dose-escalation trial for the use of chimeric papillomavirus-like particles
Authors: Mattil-Fritz Stephanie , Scharner Doreen , Piuko Konrad , Thönes Nadja , Gissmann Lutz , Müller Hermann , Müller Martin
Published: December 2007

Equine sarcoids are fibrosarcoma-like skin tumours with a prevalence of approximately 1–2 %. Strong evidence exists for a causative role of bovine papillomavirus (BPV) type 1 or type 2 in the development of sarcoids. No effective treatment of equine sarcoid is available and after surgical excision relapse of the tumours is very frequent. We developed chimeric virus-like particles (CVLPs) of BPV 1 L1–E7 for the immunotherapy of equine sarcoid. In a phase I clinical trial 12 horses suffering from equine sarcoid with an average number of more than 22 tumours per animal were vaccinated in a dose-escalation setting. The animals were followed-up for 63 days, eight of the twelve horses were followed-up for more than a year and side-effects, humoral immune responses and tumour appearance were recorded. BPV DNA was detected in tumours of 11 cases. CVLPs were well tolerated in all dose groups, a robust anti-L1 antibody response was induced in all but one of the horses. Anti-E7 antibodies were detected in five of the 12 animals at low titres. Two animals showed a clear improvement of the clinical status after treatment, i.e. the number of the tumours per horse was reduced. In another horse regression of five sarcoids was observed; three of them relapsed during the study. Two animals showed tumour regression as well as growth of new sarcoids. In two horses the clinical status remained unchanged, in another two horses growth of existing tumours or growth of additional tumours was observed. The remaining three animals showed simultaneously regression and growth of existing tumours. Neither the humoral immune responses nor the observed effects on the tumours was correlated with the dose group.
Vaccination of sarcoid-bearing donkeys with chimeric virus-like particles of bovine papillomavirus type 1
Authors: Ashrafi G. H. , Piuko K. , Burden F. , Yuan Z. , Gault E. A. , Müller M. , Trawford A. , Reid S. W. J. , Nasir L. , Campo M. S.
Published: December 2007

Equine sarcoids are fibroblastic skin tumours affecting equids worldwide. While the pathogenesis is not entirely understood, infection with bovine papillomavirus (BPV) type 1 (and less commonly type 2) has been implicated as a major factor in the disease process. Sarcoids very seldom regress and in fact often recrudesce following therapy. Nothing is known about the immune response of the equine host to BPV. Given that the viral genes are expressed in sarcoids, it is reasonable to assume that vaccination of animals against the expressed viral proteins would lead to the induction of an immune response against the antigens and possible tumour rejection. To this end we vaccinated sarcoid-bearing donkeys in a placebo-controlled trial using chimeric virus-like particles (CVLPs) comprising BPV-1 L1 and E7 proteins. The results show a tendency towards enhanced tumour regression and reduced progression in the vaccinated group compared to control animals. Although promising, further studies are required with larger animal groups to definitely conclude that vaccination with CVLPs is a potential therapy for the induction of sarcoid regression.
Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats
Authors: Pletneva Lioubov M. , Haller Otto , Porter David D. , Prince Gregory A. , Blanco Jorge C. G.
Published: December 2007

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infectionin vivois demanding, as multiple IFN subtypes with overlapping activities are produced. In contrast, Mx gene expression, which is tightly regulated by type I IFN expression, is easily determined. This study therefore measured Mx expression as a reliable surrogate marker of type I IFN activity during RSV infectionin vivoin a cotton rat model. It was shown that expression of Mx genes was dramatically augmented in the lungs of infected animals in a dose- and virus strain-dependent manner. The expression of Mx genes in the lungs was paralleled by their induction in the nose and spleen, although in spleen no simultaneous virus gene expression was detected. Reinfection of RSV-immune animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx gene expression was triggered in reinfected animals, even though virus could not be isolated from their lungs. Furthermore, it was demonstrated that immunity to RSV wanes with time. Virus replication and Mx gene expression became more prominent with increasing intervals between primary infection and reinfection. These results highlight the role of type I IFN in modulation of the immune response to RSV.
Human Macrophage Inflammatory Protein 3α: Protein and Peptide Nuclear Magnetic Resonance Solution Structures, Dimerization, Dynamics, and Anti-Infective Properties
Authors: Chan David I. , Hunter Howard N. , Tack Brian F. , Vogel Hans J.
Published: December 2007

Human macrophage inflammatory protein 3α (MIP-3α), also known as CCL20, is a 70-amino-acid chemokine which exclusively binds to chemokine receptor 6. In addition, the protein also has direct antimicrobial, antifungal, and antiviral activities. The solution structure of MIP-3α was solved by the use of two-dimensional homonuclear proton nuclear magnetic resonance (NMR). The structure reveals the characteristic chemokine fold, with three antiparallel β strands followed by a C-terminal α helix. In contrast to the crystal structures of MIP-3α, the solution structure was found to be monomeric. Another difference between the NMR and crystal structures lies in the angle of the α helix with respect to the β strands, which measure 69 and ∼56.5° in the two structures, respectively. NMR diffusion and pH titration studies revealed a distinct tendency for MIP-3α to form dimers at neutral pH and monomers at lower pH, dependent on the protonation state of His40. Molecular dynamics simulations of both the monomeric and the dimeric forms of MIP-3α supported the notion that the chemokine undergoes a change in helix angle upon dimerization and also highlighted the important hydrophobic and hydrogen bonding contacts made by His40 in the dimer interface. Moreover, a constrained N terminus and a smaller binding groove were observed in dimeric MIP-3α simulations, which could explain why monomeric MIP-3α may be more adept at receptor binding and activation. The solution structure of a synthetic peptide consisting of the last 20 residues of MIP-3α displayed a highly amphipathic α helix, reminiscent of various antimicrobial peptides. Antimicrobial assays with this peptide revealed strong and moderate bactericidal activities against
Escherichia coli
and
Staphylococcus aureus
, respectively. This confirms that the C-terminal α-helical region of MIP-3α plays a significant part in its broad anti-infective activity.
Systemic Pharmacokinetics of Rifaximin in Volunteers with Shigellosis
Authors: Taylor David N. , McKenzie Robin , Durbin Anna , Carpenter Colleen , Haake Robert , Bourgeois A. Louis
Published: December 2007

Rifaximin is an oral antibiotic indicated for treatment of traveler's diarrhea. Rifaximin pharmacokinetics were evaluated in individuals challenged with
Shigella flexneri
. Peak plasma rifaximin concentrations were low after nine consecutive doses, and no accumulation was observed. Rifaximin serum levels were minimal and similar to those previously reported in studies of healthy volunteers.
Induction of
erm
(C) Expression by Noninducing Antibiotics
Authors: Bailey Marne , Chettiath Tobin , Mankin Alexander S.
Published: December 2007

Ketolides, which represent the newest macrolide antibiotics, are generally perceived to be noninducers of inducible
erm
genes. In the study described in this paper we investigated the effects of several macrolide and ketolide compounds on the expression of the inducible
erm
(C) gene by
Escherichia coli
cells. Exposure to 14-member-ring macrolide drugs and to azithromycin led to a rapid and pronounced increase in the extent of dimethylation of Erm(C) target residue A2058 in 23S rRNA. When cells were incubated with subinhibitory concentrations of ketolides, the extent of A2058 dimethylation was also increased, albeit to a lower level and with kinetics slower than those observed with macrolides. The induction of
erm
(C) expression by ketolides was further confirmed by using a reporter construct which allows the colorimetric detection of induction in a disc diffusion assay. Most of the ketolides tested, including the clinically relevant compounds telithromycin and cethromycin, were able to induce the reporter expression, even though the induction occurred within a more narrow range of concentrations compared to the concentration range at which induction was achieved with the inducing macrolide antibiotics. No induction of the reporter expression was observed with 16-member-ring macrolide antibiotics or with a control drug, chloramphenicol. The deletion of three codons of the
erm
(C) leader peptide eliminated macrolide-dependent induction but left ketolide-dependent induction unchanged. We conclude that ketolides are generally capable of inducing
erm
genes. The narrow range of ketolide inducing concentrations, coupled with the slow rate of induction and the lower steady-state level of ribosome methylation, may mask this effect in MIC assays.
Participation of the Serine-RichEntamoeba histolyticaProtein in Amebic Phagocytosis of Apoptotic Host Cells
Authors: Teixeira Jose E. , Huston Christopher D.
Published: December 2007

Entamoeba histolyticais an intestinal ameba that causes dysentery and liver abscesses. Cytotoxicity and phagocytosis of host cells characterize invasiveE. histolyticainfection. Prior to phagocytosis of host cells,E. histolyticainduces apoptotic host cell death, using a mechanism that requires contact via an amebic galactose-specific lectin. However, lectin inhibition only partially blocks phagocytosis of already dead cells, implicating at least one additional receptor in phagocytosis. To identify receptors for engulfment of apoptotic cells, monoclonal antibodies againstE. histolyticamembrane antigens were screened for inhibition of phagocytosis. Of 43 antibodies screened, one blocked lectin-independent uptake of apoptotic cells, with >90% inhibition at a dose of 20 μg/ml (P< 0.0003 versus control). The same antibody also inhibited adherence to apoptotic lymphocytes and, to a lesser extent, adherence to and killing of viable lymphocytes. The antigen recognized by the inhibitory antibody was purified by affinity chromatography and identified by liquid chromatography-mass spectrometry as the serine-richE. histolyticaprotein (SREHP). Consistent with this, the inhibitory antibody bound to recombinant SREHP present in bacterial lysates on immunoblots. The SREHP is an abundant immunogenic surface protein of unclear function. The results of this unbiased antibody screen strongly implicate the SREHP as a participant inE. histolyticaphagocytosis and suggest that it may play an important role in adherence to apoptotic cells.
A QUESTION CONCERNING THE FACTORIZATION OF CYCLIC GROUPS
Authors: SANDS A. D.
Published: December 2007

In a paper concerning the relationship between coding theory and factorization theory Restivo, Salemi, and Sportelli made a conjecture that if subsets possess certain properties then they cannot form a factorization of a finite cyclic group. In this note it is shown that in fact such factorizations do exist.
COMPUTATIONALLY AND ALGEBRAICALLY COMPLEX FINITE ALGEBRA MEMBERSHIP PROBLEMS
Authors: KOZIK MARCIN
Published: December 2007

In this paper we produce a finite algebra which generates a variety with a PSPACE-complete membership problem. We produce another finite algebra with a γ function that grows exponentially. The results are obtained via a modification of a construction of the algebra A(T) that was introduced by McKenzie in 1996.
JULIA SETS OF GENERALIZED NEWTON'S METHOD
Authors: WANG XINGYUAN , WANG TINGTING
Published: December 2007

The Julia sets theory of generalized Newton's method is analyzed and the Julia sets of generalized Newton's method are constructed using the iteration method. From the research we find that: (1) the basins of attraction of the Julia sets of generalized Newton's method depend on the roots of the equation and their orders and also the existence of the extraneous fixed points; (2) the Steffensen method is an exception to the law given in (1); and (3) if the order of the root is decimal, then the different choice of the range of the principal value of the phase angle will cause a different evolvement of the Julia sets.
Predicting natural cavities in chalk
Authors: Edmonds C. N.
Published: December 2007

Introduction

Chalk is a soluble carbonate rock with extensive karst development. Natural cavity occurrence initially appears to be random. In an area where the degree of influence of all cavity formational factors is similar, but dissolution is focused on one set of joints rather than another, then solution feature occurrence is perhaps random. This might be termed the ‘microscale’ view, measured at a scale of metres. However, if the pattern of natural cavity occurrence is considered at a ‘macroscale’ level, say measured in hundreds of metres or kilometres, then spatial patterns emerge suggesting dissolution is not as random as it might first appear.

Spatial characteristics of natural cavity occurrence on the Chalk

In order to analyse the spatial characteristics of natural cavity occurrence it was first necessary to collect as many records of solution feature occurrence as possible from published and unpublished sources including local authorities, Construction Industry Research and Information Association (CIRIA), Transport Research Laboratory (TRL), Building Research Establishment (BRE), National House Building Council (NHBC), the Environment Agency, water companies, and site investigation reports. Particular emphasis was placed on fieldwork to record new features revealed in a wide range of engineering works, road and motorway construction, and on visits to large numbers of working/disused chalk quarries and aggregate workings. A database of 2226 natural cavities was compiled, composed mainly of solution pipes, sinkholes (dolines) and swallow holes.

The spatially related database (each cavity location being recorded by National Grid Reference) was carefully scrutinized to determine
Engineering geological mapping
Authors: Griffiths J. S.
Published: December 2007

Introduction

The development, scope and examples of best practice in the preparation of geological maps and plans for engineering practice are discussed in detail in Dearman (1991), and this remains the definitive British text on the subject. In the UK engineering geological maps were recognized as forming a significant component of site investigations with the publication of the Geological Society Working Party Report on maps and plans (Anon. 1972). In many parts of the world the practice is also long established (e.g. Peter 1966; Popov
et al.
1950), and in 1976 UNESCO produced a guide for the preparation of engineering geological maps (Anon. 1976). Many examples of international studies were reported at the 1979 IAEG Newcastle Symposium on Engineering Geological Mapping. In contrast, in the United Kingdom, BS5930, the
Code of Practice for Site Investigations
, which was first published in 1981 and has guided the scope and content of site investigations in the UK for the past two decades, makes scant reference to geological or engineering geological mapping (Griffiths & Marsh 1986). As noted in Griffiths & Edwards (2001), this situation has not been corrected in the revision of BS5930 published in 1999. Fookes (1997), in the first Glossop lecture, states ‘that engineering geological mapping, even sketch mapping, is particularly under used in British practice’, and this is despite its longstanding and successful track record (Dearman & Fookes 1974). As with many facets of land surface evaluation, this situation needs to be addressed.

The distinction between engineering geological maps and plans
Geomorphological mapping
Authors: Lee E. M.
Published: December 2007

There has been a long tradition of geomorphological mapping to support land use planning, especially in Poland (e.g. Klimaszewski 1956, 1961; Galon 1962) and France (e.g. Tricart 1965; for a history of geomorphological mapping in Europe, see Verstappen 1983). The Geological Society Working Party Report on maps and plans (Anon. 1972) identified examples of geomorphological mapping that could be of use to engineers. However, the value of the technique was best highlighted by its application to road projects in unstable terrain in Nepal and South Wales during the early 1970s (e.g. Brunsden et al. 1975a, b; Doornkamp et al. 1979; Jones et al. 1983). The techniques have also been successfully applied to dryland problems (e.g. Brunsden et al. 1979; Bush et al. 1980, Doornkamp et al 1980; Cooke et al. 1982, 1985; Jones et al. 1986), soil erosion (e.g. Morgan 1995) and river management (e.g. Doornkamp 1982; Richards et al. 1987). Despite these applications, BS5930, Code of Practice for Site Investigations (British Standards Institution 1981), contains little reference to geomorphological maps (Griffiths & Marsh 1986) and the technique remains a marginal skill practised by a few experienced engineering geomorphologists. Examples of good mapping practice can be found within the references cited in this paper.

The style and format of a geomorphological map needs to reflect the nature of the environment and the problems that need to be addressed. The following are some of the more common types of map.
The design of remedial works to the Dharan-Dhankuta Road, East Nepal
Authors: Martin R. P.
Published: December 2007

Purpose of mapping

Parts of the Dharan-Dhankuta Road in East Nepal were seriously damaged by the Nepal earthquake of 21 August 1988 and subsequently by a locally intense monsoon storm on 12 September 1988. Detailed field mapping was carried out at several of the worst-affected hill sections of the road. The purpose of the mapping was to establish the nature and local extent of earthquake, and subsequent landslide, rockfall and erosion damage as a prerequisite for the design of road remedial works. A full account of the work is given by Roughton & Partners (1988). This is an example of post-construction stage land surface evaluation using the five-stage classification of mountain road projects proposed by Fookes
et al
(1985).

The site

The Dharan-Dhankuta Road is a 50 km long mountain road traversing the first two ranges of the Low Himalaya of East Nepal (Fig. 1). It was built between 1977 and 1982 under the UK Government’s overseas aid programme to the Kingdom of Nepal (Cross 1982).

The epicentre of the earthquake on 21 August 1988 was in the Udayapur District, about 65 km to the west of Dharan (Fig. 1). The focal depth was
c.
60 km and the surface wave magnitude (Ms) was 6.6 (Dikshit 1991). Three weeks after the earthquake, heavy rain fell over part of the site during monsoon thunderstorms. The 24 hour rainfall recorded in Dharan was
c.
160 mm, most of which fell within a few hours.