bluuebunny/crossref_metadata_2025 huggingface dataset:
A 10‐year prospective study of ITI dental implants placed in the posterior region. I: Clinical and radiographic results
Authors: Blanes Rafael Juan , Bernard Jean Pierre , Blanes Zulema Maria , Belser Urs Christoph
Published: August 2007

Objectives: To evaluate the long‐term fixture success rate, crestal bone loss and peri‐implant soft tissue parameters around ITI dental implants placed in the posterior region of partially edentulous patients.

Material and methods: A total of 192 ITI dental implants were consecutively placed in premolars and molars of 83 partially edentulous patients admitted for treatment at Geneva Dental School. All implants were restored by means of ceramic‐to‐metal fused fixed partial dentures and single crowns. Patients were followed as part of a prospective longitudinal study focusing on implant success. Surgical, radiographic and clinical variables were collected at the 1‐year recall after implant placement and at the most recent clinical evaluation.

Results: The mean observation time was 6 years (range 5–10 years). Four implants failed, yielding a 10‐year cumulative survival rate of 97.9%. The mean annual crestal bone loss was −0.04±0.2 mm. Hollow‐cylinder implants displayed more crestal bone loss (−0.13±0.24 mm) than hollow‐screw implants (−0.02±0.19 mm; P=0.032). Clinical parameters such as age, gender, implant length and bone quality did not affect crestal bone levels. Increase in recession depth (P=0.025) and attachment level (P=0.011) were significantly associated with crestal bone loss.

Conclusions: ITI dental implants placed in the posterior jaw demonstrate excellent long‐term clinical success. Hollow‐cylinder implants seem to display a higher risk for crestal bone loss. Recession depth and attachment levels appear to be good clinical indicators of peri‐implant bone loss.
Vertical ridge augmentation by expanded‐polytetrafluoroethylene membrane and a combination of intraoral autogenous bone graft and deproteinized anorganic bovine bone (Bio Oss)
Authors: Simion Massimo , Fontana Filippo , Rasperini Giulio , Maiorana Carlo
Published: August 2007

Objective: To evaluate, from a histological and histomorphometrical perspective, the efficacy of a 1 : 1 mixture of deproteinized bovine bone mineral (DBBM) and autogenous bone graft associated with an expanded‐polytetrafluoroethylene (e‐PTFE) membrane for vertical ridge augmentation in the human.

Material and methods: Seven patients with 10 surgical sites requiring vertical ridge augmentation of partially edentulous lower jaws were included in the study. The vertical augmentation procedure was performed combining a titanium‐reinforced e‐PTFE Gore‐Tex membrane with a composite graft consisting of a 1 : 1 ratio of DBBM (Bio‐Oss) and autogenous bone. Twenty‐seven Branemark implants have been inserted. Eleven biopsies from the regenerated area were analyzed histologically and histomorphometrically.

Results: The healing period was uneventful in nine surgical sites. In one site the membrane showed an exposure after 3 months. At the abutment connection, all implants appeared stable and submerged by a hard regenerated tissue clinically similar to bone. The histological analysis showed new bone formation and ongoing remodelling of the autogenous bone and the DBBM particles.

Conclusions: The findings from the present clinical and histological study support the use of a 1 : 1 combination of DBBM and autogenous bone chips for vertical ridge augmentation by means of guided bone regeneration techniques. The regenerated bone may lead to proper osseointegration of a dental implant inserted at the time of the regenerative procedure or after a healing period of at least 6 months. DBBM undergoes very slow resorption and substitution with new bone. Furthermore, long‐term clinical studies are needed to confirm the positive effect of DBBM in enhancing the lasting stability of the vertically augmented bone.
Effects of atmospheric temperature and humidity on outbreak of diseases
Authors: Choi Sung Hyuk , Lee Sung Woo , Hong Yun Sik , Kim Su Jin , Kim Nak Hoon
Published: August 2007

Objective:  The present study aimed to determine the plausibility of forecasting the outbreak of diseases based on the weather by analysing the impact of atmospheric temperature and humidity on the occurrence of different diseases.

Methods:  The subjects of the present study were the 30 434 patients who visited the ED in 1 year from 1 February 2005 to 3 February 2006. The present study analysed the correlation between the daily number of patients who suffered from 22 types of traumatic and non‐traumatic diseases and the data on atmospheric temperature and humidity provided by the Korea Meteorological Administration.

Results:  With traumatic disease, the occurrence tended to increase in proportion to the rise in temperature and humidity; whereas with non‐traumatic disease, the occurrence tended to increase according to the rise in temperature, irrespective of humidity changes. The research on the impact of atmospheric temperature and humidity on different diseases revealed a high level of distribution of most diseases in an environment with high temperature and humidity. However, in the case of pulmonary diseases and trauma to multiple body regions, the occurrence increased in environments with low temperature and high humidity for pulmonary diseases, and with low temperature and low humidity for trauma to multiple body regions.

Conclusion:  Most diseases tend to increase in proportion to the rise in atmospheric temperature whereas being less affected by humidity. However, an increase in humidity in an optimum range of atmospheric temperature (12°C or higher) triggers an increase in the occurrence of diseases.
Family‐focused weight management program for five‐ to nine‐year‐olds incorporating parenting skills training with healthy lifestyle information to support behaviour modification
Authors: GOLLEY Rebecca K. , PERRY Rebecca A. , MAGAREY Anthea , DANIELS Lynne
Published: August 2007

This case study aims to describe how general parenting principles can be used as part of parent‐led, family‐focused child weight management that is in line with current Australian Clinical Practice Guidelines. A parent‐led, family‐focused child weight management program was designed for use by dietitians with parents of young children (five‐ to nine‐year‐olds). The program utilises the cornerstones of overweight treatment: diet, activity, behaviour modification and family support delivered in an age‐appropriate, family‐focused manner. Parents participate in 16 sessions (4 parenting‐focused, 8 lifestyle‐focused and 4 individual telephone support calls) conducted weekly, fortnightly then monthly over six months. This case study illustrates how a family used the program, resulting in reduced degree of overweight and stabilised waist circumference in the child over 12 months. In conclusion, linking parenting skills to healthy family lifestyle education provides an innovative approach to family‐focused child weight management. It addresses key Australian Clinical Practice Guidelines, works at the family level, and provides a means for dietitians to easily adopt age‐appropriate behaviour modification as part of their practice.
Back to basics: Estimating energy requirements for adult hospital patients
Authors: FERRIE Suzie , WARD Meagan
Published: August 2007

Predictive equations are a quick and non‐invasive way to estimate a patient's energy requirements, and can be a useful tool when used appropriately. However, as with any tool, the skill and experience of the user will affect the quality of the result. This paper looks at the origins and limitations of some of the more commonly used equations. Considerations in their use and interpretation, such as the use of injury and activity factors, adjusting weight and non‐protein calories, are also discussed.
Prevalence of malnutrition in adults in Queensland public hospitals and residential aged care facilities
Authors: BANKS Merrilyn , ASH Susan , BAUER Judy , GASKILL Deanne
Published: August 2007

Aim:  To determine the prevalence of malnutrition in Queensland public acute and residential aged care facilities, and explore effects of variables associated with malnutrition in these populations.

Methods:  A multicentre, cross‐sectional audit of a convenience sample of subjects was carried out as part of a larger audit of pressure ulcers in Queensland public acute and residential aged care facilities in 2002 and again in 2003. Dietitians in 20 hospitals and six aged care facilities conducted single‐day nutritional status audits of 2208 acute and 839 aged care subjects using the Subjective Global Assessment, in either or both audits. Subjects excluded were obstetric, same‐day, paediatric and mental health patients. Weighted average proportions of nutritional status categories for acute and residential aged care facilities across the two audits were determined and compared. The effects of gender, age, facility location and medical specialty on malnutrition were determined via logistic regression.

Results:  A mean of 34.7 ± 4.0% and 31.4 ± 9.5% of acute subjects and a median of 50.0% and 49.2% of residents of aged care facilities were found to be malnourished in Audits 1 and 2, respectively. Variables found to be significantly associated with an increased odds risk of malnutrition included: older age groups, male (in residential aged care facilities), metropolitan location of facility and medical specialty, in particular, oncology and critical care.

Conclusion:  Malnutrition is significant in public acute and residential aged care facilities in Queensland. Action must be taken to increase the recognition, prevention and treatment of malnutrition especially in high‐risk groups.
Repair of sinocutaneous fistulae in two horses
Authors: Charman RE , Vasey JR
Published: August 2007

Chronic facial defects extending into the sinuses of two mares were repaired using periosteal flaps. Partial osseous bridging was established over the defects following repair. Previous attempts to close the defects with skin alone had failed. A periosteal flap is a simple surgical technique that provides the foundations for successful repair, despite the chronicity of some fistulae.
Survey of porcine circovirus 2 and postweaning multisystemic wasting syndrome in New South Wales piggeries
Authors: Finlaison D , Kirkland P , Luong R , Ross A
Published: August 2007

Objective  To determine if postweaning multisystemic wasting syndrome (PMWS) is occurring in the New South Wales pig population and to determine the current and past seroprevalence of porcine circovirus 2 (PCV2).

Design  Pig veterinarians were contacted seeking submission of tissues from animals with clinical signs suggestive of PMWS. Samples were also accepted from suspected cases of porcine dermatitis and nephropathy syndrome (PDNS). Serological studies were also undertaken on archival sera and sera submitted during the study.

Procedure  Histopathological examination was undertaken on all tissues submitted. The presence of PCV2 was determined by immunohistochemistry. Sera were tested for PCV2 using a commercial enzyme linked immunosorbent assay kit modified for testing of serum samples.

Results  No cases of PMWS were identified during the study. Four cases of PDNS were identified. PCV2 antibody was detected in 80% of archival sera from 1995 and 75.8% from 2001. Seroprevalence in samples tested during 2002–2003 was 87.8%. PCV2 was isolated from tissues of a case of PDNS.

Conclusion  PCV2 is widespread in the New South Wales pig population and has been since at least 1995. This study describes the first isolation of an Australian PCV2. No cases of PMWS were identified in New South Wales.
ANNOTATED REVIEW OF RECENT RESEARCH
Authors: Mecklenburg Robert
Published: August 2007

Abelson, Philip H., ed. An Electronic Revolution. Science, 195:1085–1240, Mar. 18, 1977. (entire issue)
Guidelines for the antiviral therapy of hepatitis C virus carriers with normal serum aminotransferase based on platelet counts
Authors: Okanoue Takeshi , Itoh Yoshito , Minami Masahito , Hashimoto Hiroaki , Yasui Kohichiro , Yotsuyanagi Hiroshi , Takehara Tetsuo , Kumada Takashi , Tanaka Eiji , Nishiguchi Shuhei , Izumi Namiki , Sata Michio , Onji Morikazu , Yamada Gotaro , Okita Kiwamu , Kumada Hiromitsu
Published: August 2007

Aim:  We aimed to identify the candidates for antiviral therapy, among patients who are hepatitis C virus (HCV) carriers with normal serum aminotransferase (ALT), focused on the inhibition of hepatocellular carcinoma (HCC).

Methods:  Four hundred and sixty‐four HCV carriers with normal serum ALT and 129 HCV carriers with persistently normal ALT (PNALT) and platelet (PLT) counts ≥150 000/μL who received liver biopsies were enrolled. HCV carriers with normal serum ALT were divided into four groups according to their ALT levels (≤30 U/L or 31–40 U/L) and PLT counts (≥150 000/μL or <150 000/μL).

Results:  In 129 HCV carriers with PNALT, the rate of progression of fibrosis stage was 0.05/year and no HCC was detected during the follow up for 10 years. Approximately 20% of patients with ALT ≤40 U/L and PLT counts ≥150 000/μLwere at stage F2–3; however, approximately 50% of patients with ALT ≤ 40 U/L and PLT counts <150 000/μL were at stage F2–4. An algorithm for the management of HCV carriers with normal serum ALT was advocated based on ALT and PLT counts.

Conclusion:  The combination of ALT and PLT counts is useful for evaluating the fibrosis stage in HCV carriers with normal serum ALT. Most patients with PLT counts <150 000/μL are candidates for antiviral therapy, especially those with ALT levels ≥31 U/L when we focus on the inhibition of the development of HCC.
Evolution of Liquid Meniscus Shape in a Capillary Tube
Authors: Lee Shong-Leih , Lee Hong-Draw
Published: August 2007

There are still many unanswered questions related to the problem of a capillary surface rising in a tube. One of the major questions is the evolution of the liquid meniscus shape. In this paper, a simple geometry method is proposed to solve the force balance equation on the liquid meniscus. Based on a proper model for the macroscopic dynamic contact angle, the evolution of the liquid meniscus, including the moving speed and the shape, is obtained. The wall condition of zero dynamic contact angle is allowed. The resulting slipping velocity at the contact line resolves the stress singularity successfully. Performance of the present method is examined through six well-documented capillary-rise examples. Good agreements between the predictions and the measurements are observable if a reliable model for the dynamic contact angle is available. Although only the capillary-rise problem is demonstrated in this paper, the concept of this method is equally applicable to free surface flow in the vicinity of a contact line where the capillary force dominates the flow.
Influence of Passive Flow-Control Devices on the Pressure Fluctuations at Wing-Body Junction Flows
Authors: Ölçmen Semih M. , Simpson Roger L.
Published: August 2007

The effectiveness of passive flow-control devices in eliminating high surface rms pressure fluctuations at the junction of several idealized wing/body junction flows was studied. Wall-pressure fluctuation measurements were made using microphones along the line of symmetry at the wing/body junction of six different wing shapes. The wings were mounted on the wind tunnel floor at a zero degree angle-of-attack. The six wing shapes tested were: a 3:2 semi-elliptical-nosed NACA 0020 tailed generic body shape (Rood wing), a parallel center-body model, a tear-drop model, a Sandia 1850 model, and NACA 0015 and NACA 0012 airfoil shapes. Eight different fence configurations were tested with the Rood wing. The two double-fence configurations were found to be the most effective in reducing the pressure fluctuations. Two of the single fence types were nearly as effective and were simpler to manufacture and test. For this reason one of these single fence types was selected for testing with all of the other wing models. The best fence flow-control devices were found to reduce rms wall-pressure fluctuations by at least 61% relative to the baseline cases.
Unsteady Flow and Wake Transport in a Low-Speed Axial Fan With Inlet Guide Vanes
Authors: Fernández Oro Jesús Manuel , Argüelles Díaz Katia María , Santolaria Morros Carlos , Blanco Marigorta Eduardo
Published: August 2007

The present study is focused on the analysis of the dynamic and periodic interaction between both fixed and rotating blade rows in a single stage, low-speed axial fan with inlet guide vanes. The main goal is placed on the characterization of the unsteady flow structures involved in an axial flow fan of high reaction degree, relating them to working point variations and axial gap modifications. For that purpose, an experimental open-loop facility has been developed to obtain a physical description of the flow across the turbomachine. Using hot-wire anemometry, measurements of axial and tangential velocities were carried out in two transversal sectors: one between the rows and the other downstream of the rotor, covering the whole span of the stage for a complete stator pitch. Ensemble- and time-averaging techniques were introduced to extract deterministic fluctuations from raw data, both of which are essential to understand flow mechanisms related to the blade passing frequency. An exhaustive analysis of the measured wakes has provided a comprehensive description of the underlying mechanisms in both wake-transport phenomena and stator-rotor interaction. In addition, unmixed stator wakes, observed at the rotor exit, have been treated in terms of dispersion and angular displacement to indicate the influence of the blades loading on the transport of the stator wake fluid. The final aim of the paper is to highlight a complete picture of the unsteady flow patterns inside industrial axial fans.
Mechanism of Na
+
/H
+
Antiporting
Authors: Arkin Isaiah T. , Xu Huafeng , Jensen Morten Ø. , Arbely Eyal , Bennett Estelle R. , Bowers Kevin J. , Chow Edmond , Dror Ron O. , Eastwood Michael P. , Flitman-Tene Ravenna , Gregersen Brent A. , Klepeis John L. , Kolossváry István , Shan Yibing , Shaw David E.
Published: August 2007

Na
+
/H
+
antiporters are central to cellular salt and pH homeostasis. The structure of
Escherichia coli
NhaA was recently determined, but its mechanisms of transport and pH regulation remain elusive. We performed molecular dynamics simulations of NhaA that, with existing experimental data, enabled us to propose an atomically detailed model of antiporter function. Three conserved aspartates are key to our proposed mechanism: Asp
164
(D164) is the Na
+
-binding site, D163 controls the alternating accessibility of this binding site to the cytoplasm or periplasm, and D133 is crucial for pH regulation. Consistent with experimental stoichiometry, two protons are required to transport a single Na
+
ion: D163 protonates to reveal the Na
+
-binding site to the periplasm, and subsequent protonation of D164 releases Na
+
. Additional mutagenesis experiments further validated the model.
Ultrafast Flash Thermal Conductance of Molecular Chains
Authors: Wang Zhaohui , Carter Jeffrey A. , Lagutchev Alexei , Koh Yee Kan , Seong Nak-Hyun , Cahill David G. , Dlott Dana D.
Published: August 2007

At the level of individual molecules, familiar concepts of heat transport no longer apply. When large amounts of heat are transported through a molecule, a crucial process in molecular electronic devices, energy is carried by discrete molecular vibrational excitations. We studied heat transport through self-assembled monolayers of long-chain hydrocarbon molecules anchored to a gold substrate by ultrafast heating of the gold with a femtosecond laser pulse. When the heat reached the methyl groups at the chain ends, a nonlinear coherent vibrational spectroscopy technique detected the resulting thermally induced disorder. The flow of heat into the chains was limited by the interface conductance. The leading edge of the heat burst traveled ballistically along the chains at a velocity of 1 kilometer per second. The molecular conductance per chain was 50 picowatts per kelvin.
Evolution of an International External Quality Assurance Model To Support Laboratory Investigation of
Streptococcus pneumoniae
, Developed for the SIREVA Project in Latin America, from 1993 to 2005
Authors: Lovgren Marguerite , Talbot James A. , Brandileone Maria Cristina , Casagrande Silvana T. , Agudelo Clara Inés , Castañeda Elizabeth , Regueira Mabel , Corso Alejandra , Heitmann Ingrid , Maldonado Aurora , Echániz-Avilés Gabriela , Soto-Noguerón Araceli , Hortal María , Camou Teresa , Gabastou Jean-Marc , Fabio José Luis Di
Published: August 2007

In 1993 the Pan American Health Organization initiated a laboratory-based surveillance system, called the SIREVA project, to learn about
Streptococcus pneumoniae
invasive disease in Latin American children. In 1994, National Laboratories in six countries were trained to perform serotyping and antibiotic susceptibility testing using broth microdilution to determine the MIC for specified antibiotics. An international External Quality Assurance (EQA) program was developed to monitor and support ongoing laboratory performance. The EQA program was coordinated by the National Centre for Streptococcus (NCS), Edmonton, Canada, and included external proficiency testing (EPT) and a validation process requiring regular submission of a sample of isolates from each laboratory to the NCS for verification of the serotype and MIC. In 1999, the EQA program was decentralized to use three of the original laboratories as regional quality control centers to address operational concerns and to accommodate the growth of the laboratory network to more than 20 countries including the Caribbean region. The overall EPT serotyping accuracies for phase I (1993 to 1998) and phase II (1999 to 2005) were 88.0 and 93.8%, respectively; the MIC correlations within ±1 log
2
dilution of the expected result were 83.0 and 91.0% and the interpretive category agreements were 89.1 and 95.3%. Overall, the validation process serotyping accuracies for phases I and II were 81.9 and 88.1%, respectively, 80.4 and 90.5% for MIC agreement, and 85.8 and 94.3% for category agreement. These results indicate a high level of testing accuracy in participating National Laboratories and a sustained increase in EQA participation in Latin America and the Caribbean.
Spontaneous Reactivation of Herpes Simplex Virus Type 1 in Latently Infected Murine Sensory Ganglia
Authors: Margolis Todd P. , Elfman Fred L. , Leib David , Pakpour Nazzy , Apakupakul Kathleen , Imai Yumi , Voytek Cindy
Published: August 2007

Careful studies of mouse trigeminal ganglia (TG) latently infected with herpes simplex virus type 1 (HSV-1) indicate the presence of productive cycle viral gene products and persistent immune response, suggesting ongoing spontaneous viral reactivation in these tissues. In the present study we set out to determine whether infectious virus is present in murine TG latently infected with HSV-1 (KOS). At 37 days after ocular inoculation we found a small amount of infectious virus in ca. 6% of latently infected murine TG. Furthermore, the amount of infectious virus that we detected (PFU per viral antigen-positive neuron) was similar to that detected in acutely infected ganglia. We conclude that spontaneous reactivation of infectious HSV-1 occurs in the mouse TG and is likely the principle cause of viral protein expression in these tissues. We next examined the role of latency-associated transcript (LAT) in spontaneous ganglionic reactivation by examining ganglia latently infected with KOSdlLAT1.8, a LAT deletion virus. Through the use of immunocytochemistry we found that KOSdlLAT1.8 had a rate of spontaneous ganglionic reactivation very similar to that of HSV-1 (KOS). Studying spontaneous ganglionic reactivation of HSV in the mouse TG allows a direct study of viral reactivation from latently infected neurons without the potential confounders and complicating downstream events that accompany the study of viral reactivation by explantation or peripheral viral shedding. Since most cases of human viral shedding and reactivation are not associated with a known trigger, spontaneous ganglionic reactivation of HSV-1 may be a better model of human disease than existing models.
Promoter Complex in the Central Part of the Mouse Mammary Tumor Virus Long Terminal Repeat
Authors: Rouault Francoise , Nejad Asl Shiva Badihi , Rungaldier Stefanie , Fuchs Eva , Salmons Brian , Günzburg Walter H.
Published: August 2007

Unique among the retroviruses, mouse mammary tumor virus (MMTV) carries, in addition to the usual long terminal repeat (LTR) promoter, another promoter, P2, which is located in the central part of the proviral U3 sequence, within the LTR open reading frame (ORF). Using an in vitro reporter system based on a sensitive luciferase expression assay, we investigated the regulation of the P2 promoter in the context of the Mtv-2 and Mtv-8 genomes. Irrespective of the genomic source, the activity of the P2 promoter is regulated by a downstream-located enhancer and an upstream-located negative regulatory element (NRE), the activity of which overrides the activator. During this study, we unexpectedly detected another independent neighboring promoter that we called P3. The novel P3 promoter does not seem to be controlled by any NRE but is influenced by the same enhancer that modulates the P2 promoter. The respective transcription starts of the two promoters located in this tight cluster are only 61 bases apart. The transcripts originating from this promoter complex carry the same first intron, which is bound by canonical splice donor and splice acceptor sites located in the LTR. One novel doubly spliced transcript carrying a 459-nucleotide-long ORF was detected in several MMTV-carrying murine cells and could be successfully expressed in murine cells as a His-tagged fusion product. The novel viral protein, the function of which remains to be elucidated, has an apparent molecular mass of 20 kDa.
The Imidazopyrrolopyridine Analogue AG110 Is a Novel, Highly Selective Inhibitor of Pestiviruses That Targets the Viral RNA-Dependent RNA Polymerase at a Hot Spot for Inhibition of Viral Replication
Authors: Paeshuyse Jan , Chezal Jean-Michel , Froeyen Matheus , Leyssen Pieter , Dutartre Hélène , Vrancken Robert , Canard Bruno , Letellier Carine , Li Tong , Mittendorfer Harald , Koenen Frank , Kerkhofs Pierre , De Clercq Erik , Herdewijn Piet , Puerstinger Gerhard , Gueiffier Alain , Chavignon Olivier , Teulade Jean-Claude , Neyts Johan
Published: August 2007

Ethyl 2-methylimidazo[1,2-
a
]pyrrolo[2,3-
c
]pyridin-8-carboxylate (AG110) was identified as a potent inhibitor of pestivirus replication. The 50% effective concentration values for inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic effect, viral RNA synthesis, and production of infectious virus were 1.2 ± 0.5 μM, 5 ± 1 μM, and 2.3 ± 0.3 μM, respectively. AG110 proved inactive against the hepatitis C virus and a flavivirus. AG110 inhibits BVDV replication at a time point that coincides with the onset of intracellular viral RNA synthesis. Drug-resistant mutants carry the E291G mutation in the viral RNA-dependent RNA polymerase (RdRp). AG110-resistant virus is cross-resistant to the cyclic urea compound 1453 which also selects for the E291G drug resistance mutation. Moreover, BVDV that carries the F224S mutation (because of resistance to the imidazopyridine 5-[(4-bromophenyl)methyl]-2-phenyl-5
H
-imidazo[4,5-
c
]pyridine [BPIP]and VP32947) is also resistant to AG110. AG110 did not inhibit the in vitro activity of recombinant BVDV RdRp but inhibited the activity of BVDV replication complexes (RCs). Molecular modeling revealed that E291 is located in a small cavity near the tip of the finger domain of the RdRp about 7 Å away from F224. Docking of AG110 in the crystal structure of the BVDV RdRp revealed several potential contacts including with Y257. The E291G mutation might enable the free rotation of Y257, which might in turn destabilize the backbone of the loop formed by residues 223 to 226, rendering more mobility to F224 and, hence, reducing the affinity for BPIP and VP32947. It is concluded that a single drug-binding pocket exists within the finger domain region of the BVDV RdRp that consists of two separate but potentially overlapping binding sites rather than two distinct drug-binding pockets.
West Nile Virus-Induced Interferon Production Is Mediated by the Double-Stranded RNA-Dependent Protein Kinase PKR
Authors: Gilfoy Felicia D. , Mason Peter W.
Published: August 2007

Cells carry a variety of molecules, referred to as pathogen recognition receptors (PRRs), which are able to sense invading pathogens. Interaction of PRRs with viral compounds instigates a signaling pathway(s), resulting in the activation of genes, including those for type I interferon (IFN), which are critical for an effective antiviral response. Here we demonstrate that the double-stranded RNA (dsRNA)-dependent protein kinase PKR, which has been shown to function as a PRR in cells treated with the dsRNA mimetic poly(I:C), serves as a PRR in West Nile virus (WNV)-infected cells. Evidence for PKR's role as a PRR was obtained from both human and murine cells. Using mouse embryonic fibroblasts (MEFs), we demonstrated that PKR gene knockout, posttranscriptional gene silencing of PKR mRNA using small interfering RNA (siRNA), and chemical inhibition of PKR function all interfered with IFN synthesis following WNV infection. In three different human cell lines, siRNA knockdown and chemical inhibition of PKR blocked WNV-induced IFN synthesis. Using the same approaches, we demonstrated that PKR was not necessary for Sendai virus-induced IFN synthesis, suggesting that PKR is particularly important for recognition of WNV infection. Taken together, our data suggest that PKR could serve as a PRR for recognition of WNV infection.
No Evidence for Consistent Virus-Specific Immunity in Simian Immunodeficiency Virus-Exposed, Uninfected Rhesus Monkeys
Authors: Letvin Norman L. , Rao Srini S. , Dang Vi , Buzby Adam P. , Korioth-Schmitz Birgit , Dombagoda Dilani , Parvani Jenny G. , Clarke Ryon H. , Bar Liat , Carlson Kevin R. , Kozlowski Pamela A. , Hirsch Vanessa M. , Mascola John R. , Nabel Gary J.
Published: August 2007

Defining the immune correlates of the protection against human immunodeficiency virus type 1 (HIV-1) acquisition in individuals who are exposed to HIV-1 but do not become infected may provide important direction for the creation of an HIV-1 vaccine. We have employed the simian immunodeficiency virus (SIV)/rhesus monkey model to determine whether monkeys can be repeatedly exposed to a primate lentivirus by a mucosal route and escape infection and whether virus-specific immune correlates of protection from infection can be identified in uninfected monkeys. Five of 18 rhesus monkeys exposed 18 times by intrarectal inoculation to SIVmac251 or SIVsmE660 were resistant to infection, indicating that the exposed/uninfected phenotype can be reproduced in a nonhuman primate AIDS model. However, routine peripheral blood lymphocyte gamma interferon enzyme-linked immunospot (ELISPOT), tetramer, and intracellular cytokine staining assays, as well as cytokine-augmented ELISPOT and peptide-stimulated tetramer assays, failed to define a systemic antigen-specific cellular immune correlate to this protection. Further, local cell-mediated immunity could not be demonstrated by tetramer assays of these protected monkeys, and local humoral immunity was not associated with protection against acquisition of virus in another cohort of mucosally exposed monkeys. Therefore, resistance to mucosal infection in these monkeys may not be mediated by adaptive virus-specific immune mechanisms. Rather, innate immune mechanisms or an intact epithelial barrier may be responsible for protection against mucosal infection in this population of monkeys.
The Role of DNA-PKcs and Artemis in Opening Viral DNA Hairpin Termini in Various Tissues in Mice
Authors: Inagaki Katsuya , Ma Congrong , Storm Theresa A. , Kay Mark A. , Nakai Hiroyuki
Published: August 2007

A subset of cellular DNA hairpins at double-strand breaks is processed by DNA-dependent protein kinase catalytic subunit (DNA-PKcs)- and Artemis-associated endonuclease. DNA hairpin termini of adeno-associated virus (AAV) are processed by DNA repair machinery; however, how and what cellular factors are involved in the process remain elusive. Here, we show that DNA-PKcs and Artemis open AAV inverted terminal repeat (ITR) hairpin loops in a tissue-dependent manner. We investigated recombinant AAV (rAAV) genome metabolism in various tissues of DNA-PKcs- or Artemis-proficient or -deficient mice. In the absence of either factor, ITR hairpin opening was impaired, resulting in accumulation of double-stranded linear rAAV genomes capped with covalently closed hairpins at termini. The 5′ end of 3-base hairpin loops of the ITR was the primary target for DNA-PKcs- and Artemis-mediated cleavage. In the muscle, heart, and kidney, DNA-PKcs- and Artemis-dependent hairpin opening constituted a significant pathway, while in the liver, undefined alternative pathways effectively processed hairpins. In addition, our study revealed a Holliday junction resolvase-like activity in the liver that cleaved T-shaped ITR hairpin shoulders by making nicks at diametrically opposed sites. Thus, our approach furthers our understanding of not only rAAV biology but also fundamental DNA repair systems in various tissues of living animals.
Identification and Characterization of Interferon-Induced Proteins That Inhibit Alphavirus Replication
Authors: Zhang Yugen , Burke Crystal W. , Ryman Kate D. , Klimstra William B.
Published: August 2007

Alpha/beta interferon (IFN-α/β) produces antiviral effects through upregulation of many interferon-stimulated genes (ISGs) whose protein products are effectors of the antiviral state. Previous data from our laboratory have shown that IFN-α/β can limit Sindbis virus (SB) replication through protein kinase R (PKR)-dependent and PKR-independent mechanisms and that one PKR-independent mechanism inhibits translation of the infecting virus genome (K. D. Ryman et al., J. Virol. 79:1487-1499, 2005). Further, using Affymetrix microarray technology, we identified 44 genes as candidates for PKR/RNase L-independent IFN-induced antiviral activities. In the current studies, we have begun analyzing these gene products for antialphavirus activity using three techniques: (i) overexpression of the protein from SB vectors and assessment of virulence attenuation in mice; (ii) overexpression of the proteins in a stable tetracycline-inducible murine fibroblast culture system and assessment of effects upon SB replication; and (iii) small interfering RNA-mediated knockdown of gene mRNA in fibroblast cultures followed by SB replication assessment as above. Tested proteins included those we hypothesized had potential to affect virus genome translation and included murine ISG20, ISG15, the zinc finger antiviral protein (ZAP), viperin, p56, p54, and p49. Interestingly, the pattern of antiviral activity for some gene products was different between in vitro and in vivo assays. Viperin and ZAP attenuated virulence most profoundly in mice. However, ISG20 and ZAP potently inhibited SB replication in vitro, whereas and viperin, p56, and ISG15 exhibited modest replication inhibition in vitro. In contrast, p54 and p49 had little to no effect in any assay.
Adjunctive Passive Immunotherapy in Human Immunodeficiency Virus Type 1-Infected Individuals Treated with Antiviral Therapy during Acute and Early Infection
Authors: Mehandru Saurabh , Vcelar Brigitta , Wrin Terri , Stiegler Gabriela , Joos Beda , Mohri Hiroshi , Boden Daniel , Galovich Justin , Tenner-Racz Klara , Racz Paul , Carrington Mary , Petropoulos Christos , Katinger Hermann , Markowitz Martin
Published: August 2007

Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type 1-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2F5 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4
+
T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities.
Intracellular Trafficking and Maturation of Herpes Simplex Virus Type 1 gB and Virus Egress Require Functional Biogenesis of Multivesicular Bodies
Authors: Calistri Arianna , Sette Paola , Salata Cristiano , Cancellotti Enrico , Forghieri Cristina , Comin Alessandra , Göttlinger Heinrich , Campadelli-Fiume Gabriella , Palù Giorgio , Parolin Cristina
Published: August 2007

The biogenesis of multivesicular bodies (MVBs) is topologically equivalent to virion budding. Hence, a number of viruses exploit the MVB pathway to build their envelope and exit from the cell. By expression of dominant negative forms of Vps4 and Vps24, two components of the MVB pathway, we observed an impairment in infectious herpes simplex virus (HSV) assembly/egress, in agreement with a recent report showing the involvement in HSV envelopment of Vps4, the MVB-specific ATPase (C. M. Crump, C. Yates, and T. Minson, J. Virol. 81:7380-7387). Furthermore, HSV infection resulted in morphological changes to MVBs. Glycoprotein B (gB), one of the most highly conserved glycoproteins across theHerpesviridaefamily, was sorted to MVB membranes. In cells expressing the dominant negative form of Vps4, the site of intracellular gB accumulation was altered; part of gB accumulated as an endoglycosidase H-sensitive immature form at a calreticulin-positive compartment, indicating that gB traffic was dependent on a functional MVB pathway. gB was ubiquitinated in both infected and transfected cells. Ubiquitination was in part dependent on ubiquitin lysine 63, a signal for cargo sorting to MVBs. Partial deletion of the gB cytoplasmic tail resulted in a dramatic reduction of ubiquitination, as well as of progeny virus assembly and release to the extracellular compartment. Thus, HSV envelopment/egress and gB intracellular trafficking are dependent on functional MVB biogenesis. Our data support the view that the sorting of gB to MVB membranes may represent a critical step in HSV envelopment and egress and that modified MVB membranes constitute a platform for HSV cytoplasmic envelopment or that MVB components are recruited to the site(s) of envelopment.
Proteolytic Processing of
Turnip Yellow Mosaic Virus
Replication Proteins and Functional Impact on Infectivity
Authors: Jakubiec Anna , Drugeon Gabrièle , Camborde Laurent , Jupin Isabelle
Published: August 2007

Turnip yellow mosaic virus
(TYMV), a positive-strand RNA virus belonging to the alphavirus-like supergroup, encodes its nonstructural replication proteins as a 206K precursor with domains indicative of methyltransferase (MT), proteinase (PRO), NTPase/helicase (HEL), and polymerase (POL) activities. Subsequent processing of 206K generates a 66K protein encompassing the POL domain and uncharacterized 115K and 85K proteins. Here, we demonstrate that TYMV proteinase mediates an additional cleavage between the PRO and HEL domains of the polyprotein, generating the 115K protein and a 42K protein encompassing the HEL domain that can be detected in plant cells using a specific antiserum. Deletion and substitution mutagenesis experiments and sequence comparisons indicate that the scissile bond is located between residues Ser879 and Gln880. The 85K protein is generated by a host proteinase and is likely to result from nonspecific proteolytic degradation occurring during protein sample extraction or analysis. We also report that TYMV proteinase has the ability to process substrates in
trans
in vivo. Finally, we examined the processing of the 206K protein containing native, mutated, or shuffled cleavage sites and analyzed the effects of cleavage mutations on viral infectivity and RNA synthesis by performing reverse-genetics experiments. We present evidence that PRO/HEL cleavage is critical for productive virus infection and that the impaired infectivity of PRO/HEL cleavage mutants is due mainly to defective synthesis of positive-strand RNA.
CONSTRUCTING AREA VORONOI DIAGRAM BASED ON DIRECT CALCULATION OF THE FREEMAN CODE OF EXPANDED CONTOURS
Authors: LU YUE , XIAO CHUNYUN , TAN CHEW LIM
Published: August 2007

A Voronoi diagram of image elements provides an intuitive and appealing definition of proximity, which has been suggested as an effective tool for the description of relations among the neighboring objects in a digital image. In this paper, an implementation algorithm based on direct calculation of the Freeman code of expanded contours is proposed for generating area Voronoi diagram of connected components. A closed convex polygon is utilized to bound each connected component, as an approximate representation, and the contour is represented using Freeman chain coding, from which we can compute the corresponding Freeman chain coding of its expanded contour directly, without recourse to the operation on pixels. While the contours iteratively expand outwards, the Voronoi diagram is constructed by the intersections of the expanded contours from different connected components. The experimental results show that our proposed approach significantly improves the speed of constructing area Voronoi diagram in digital images.
DYNAMICS OF SEIS EPIDEMIC MODELS WITH VARYING POPULATION SIZE
Authors: HUI JING , ZHU DE-MING
Published: August 2007

In this paper, SEIS epidemic models with varying population size are considered. Firstly, we consider the case when births of population are throughout the year. A threshold σ is identified, which determines the outcome of disease, that is, when σ < 1, the disease dies out; whereas when σ > 1, the disease persists and the unique endemic equilibrium is globally asymptotically stable; when σ = 1, bifurcation occurs and leads to "the change of stability". Two other thresholds σ′ and [Formula: see text] are also identified, which determine the dynamics of epidemic model with varying population size, when the disease dies out or it is endemic. Secondly, we consider the other case, birth pulse. The population density is increased by an amount B(N)N at the discrete time nτ, where n is any non-negative integer and τ is a positive constant, B(N) is density-dependent birth rate. By applying the corresponding stroboscopic map, we obtain the existence of infection-free periodic solution with period τ. Lastly, through numerical simulations, we show the dynamic complexities of SEIS epidemic models with varying population size, there is a sequence of bifurcations, leading to chaotic strange attractors. Non-unique attractors also appear, which implies that the dynamics of SEIS epidemic models with varying population size can be very complex.
THE ECM-BACKBONE OF THE LANG–KOBAYASHI EQUATIONS: A GEOMETRIC PICTURE
Authors: ROTTSCHÄFER VIVI , KRAUSKOPF BERND
Published: August 2007

We perform an analytical study of the external cavity modes of a semiconductor laser subject to conventional optical feedback as modeled by the well-known Lang–Kobayashi equations. Specifically, the bifurcation set is derived in the three-dimensional parameter space of feedback phase, feedback strength and pump current of the laser. Different open regions in this space correspond to different numbers of physically relevant external cavity modes of the laser. Some of their stability properties are determined from the characteristic equation.
COMPLEXITY IN FARADAY EXPERIMENT WITH VISCOELASTIC FLUID
Authors: CABEZA C. , ROSEN M.
Published: August 2007

A systematic experimental study of the Faraday instability in viscoelastic fluid is presented. We have used a shear thinning polymer solution in which the elastic effects are predominant within our work range. We have analyzed the dependence of the threshold instability as a function of the depth in layer. Depending on the fluid layer depth and the driving frequency, harmonic or subharmonic regimes are developed. We have focused our work on the subharmonic region and temporal and spatial behaviors were analyzed. In addition, we have used the onset acceleration to estimate the rheological properties of the fluid. These predictions are supported by experimental measurements.
DYNAMICAL BEHAVIOR OF THE ALMOST-PERIODIC DISCRETE FITZHUGH–NAGUMO SYSTEMS
Authors: WANG BIXIANG
Published: August 2007

In this paper, we study the dynamical behavior of nonautonomous, almost-periodic discrete FitzHugh–Nagumo system defined on infinite lattices. We prove that the nonautonomous infinite-dimensional system has a uniform attractor which attracts all solutions uniformly with respect to the translations of external terms. We also establish the upper semicontinuity of uniform attractors when the infinite-dimensional system is approached by a family of finite-dimensional systems. This paper is based on a uniform tail method, which shows that, for large time, the tails of solutions are uniformly small with respect to bounded initial data as well as the translations of external terms. The uniform tail estimates play a crucial role for proving the uniform asymptotic compactness of the system and the upper semicontinuity of attractors.
STRESS DRIVEN INTERFACE DYNAMICS: THE EFFECTS OF SURFACE STRESS
Authors: BARRA FELIPE
Published: August 2007

We study the effects of surface stress on the dynamics of a solid interface which evolves by surface diffusion. In the absence of surface stress, it is known that a flat interface is unstable for long wavelength perturbations and that in the nonlinear regime this instability develops into the formation of a sharp cusp. We compute the stability spectrum for a circular pore and for a flat interface considering the surface stress contribution, and analyze its effect on the process of formation of the cusp. Analyzing the length scales involved in the problem, we show that, within the context of continuum elasticity theory, surface stress does not suppress the singularity formation.
IMPROVED PARAMETER ESTIMATION FROM NOISY TIME SERIES FOR NONLINEAR DYNAMICAL SYSTEMS
Authors: NAKAMURA TOMOMICHI , HIRATA YOSHITO , JUDD KEVIN , KILMINSTER DEVIN , SMALL MICHAEL
Published: August 2007

In this paper we consider the problem of estimating the parameters of a nonlinear dynamical system given a finite time series of observations that are contaminated by observational noise. The least squares method is a standard method for parameter estimation, but for nonlinear dynamical systems it is well known that the least squares method can result in biased estimates, especially when the noise is significant relative to the nonlinearity. In this paper, it is demonstrated that by combining nonlinear noise reduction and least squares parameter fitting it is possible to obtain more accurate parameter estimates.