bluuebunny/crossref_metadata_2025 huggingface dataset:
Piezoelectric vs. conventional implant site preparation: ex vivo implant primary stability
Authors: Baker Justin A. , Vora Shweta , Bairam Latifa , Kim Hyeong‐il , Davis Elaine L. , Andreana Sebastiano
Published: September 2011

Objectives

This study aims to determine differences in primary stability between implants placed in cortical bone following Piezoelectric or conventional site preparation, as assessed by resonance frequency analysis (RFA) and reverse torque testing (RTT).

Material and methods

Four fresh bovine ribs were acquired and surgical guides fabricated with five sites per rib (n = 20), for proper site preparation. Implant sites were prepared via conventional drilling technique as per manufacturer's instruction (Implantium) or via Piezoelectric (Mectron) implant site preparation using the Implant Prep kit. Twenty 10 mm long, 3.6 mm diameter Implantium implants were placed with 35 Ncm torque; 10 implants per preparation method. RFA was assessed via the Osstell Mentor. Five values were taken per implant. All implants where subjected to a reverse torque in increasing increments of 5 until 50 Ncm force was reached.

Results

The five RFA values per site were averaged and plotted by placement technique. A paired t‐test statistical analysis was run. The average RFA values showed no statistical significance between the 10 test (RFA = 69.04 ± 5.11) and 10 control (RFA = 70.94 ± 6.41) sites (P > 0.05). All implants in both groups withstood RTT up to 50 Ncm force without movement and thus showed no statistical differences.

Conclusion

Results of this ex vivo study imply that the Piezoelectric implant site preparation affords similar primary implant stability in comparison to conventional rotary instrumentation in cortical bone.
Oral health status in a group of the elderly population residing at home
Authors: Nazliel Haviye Erverdi , Hersek Nur , Ozbek Murat , Karaagaoglu Ergun
Published: September 2011

doi: 10.1111/j.1741‐2358.2011.00556.x

Oral health status in a group of the elderly population residing at home

Objectives:  To determine the oral health status and treatment needs of subjects aged 65 years and older residing in different districts of Ankara.

Materials and methods:  A total of 1300 patients, 751 females and 549 males, age 65 and over with a mean age of 72.8 ± 6.34 were included in this study. The subjects were visited at home and toothbrushing habits, visiting the dentist, tooth loss, denture needs were questioned and body mass index values were recorded.

Results:  52.5% of the subjects were completely edentulous, 83.3% subjects reported wearing a removable denture. Females had a higher total tooth loss frequency when compared to males (p < 0.05). Total tooth loss between 65 and 69 ages was 47.3%, and increased to 62.4% among those aged 75 and over (p < 0.05). 16.2% of the subjects had not visited a dentist in the last 10 years, and only 3% visited a dentist for control check‐ups; no gender‐based difference was observed as to the frequency of dental visits (P > 0.05). No significant relationship was found between tooth loss and BMI values (P > 0.05). 46.3% of the subjects had chewing problems.

Conclusions:  The subjects included in this study showed high tooth loss frequency and poor oral hygiene habits. Education regarding maintenance of oral hygiene and regular dental check up should be stressed for the elderly.
A Life under Pressure: Circumferential Stress in the Microvascular Wall
Authors: Jacobsen Jens C. B. , Holstein‐Rathlou Niels‐Henrik
Published: September 2011

Abstract:  Microvessels live ‘a life under pressure’ in several ways. In a literal sense, vessels of the microcirculation are exposed to high levels of stress caused primarily by the intravascular pressure head. In a figurative sense, the individual vessel and the microvascular network as a whole must continuously strive to meet the changing demands of the surrounding tissue. The ‘principle of optimal operation’ as formulated by Y. C. Fung states that living tissues adapts structurally through remodelling and growth until a level of tensile and compressive stresses is reached at which tissue performance is optimal. This behaviour is characteristic for the microvascular wall. It is highly plastic by nature and meets sustained changes by structural adaptation so as to maintain functional optimality. Owing to the orientation of the vascular smooth muscle cell in the media, in particular, the circumferential stress component has a huge impact on the state of the vascular wall. It is involved as a unifying factor on vastly different timescales in processes as diverse as acute regulation of vessel diameter, structural vessel remodelling and growth or atrophy of the vascular wall. The aim of this MiniReview was to outline in brief this integrative role of circumferential wall stress in the microcirculation.
Regioselective Synthesis of Novel 3‐Thiazolidine Acetic Acid Derivatives from Glycosido Ureides
Authors: Li Yuxin , Chen Wei , Yang Xiaoping , Yu Guanping , Mao Mingzhen , Zhou Yunyun , Liu Tuanwei , Li Zhengming
Published: September 2011

A series of 3‐thiazolidine acetic acid‐2‐(per‐O‐acetylglycosyl)‐1′‐imino‐α‐(substituted)‐4‐oxo ethyl ester derivatives (3a–t) were prepared via the reaction of substituted amino acid‐N‐[(per‐O‐acetylglycosylamino)thioxomethyl]‐ethyl ester with ethyl bromoacetate. The crystal structure of 3‐thiazolidine acetic acid‐2‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐d‐galactoyranosyl)‐1′‐imino‐α‐methyl‐4‐oxo ethyl ester 3g and 1H‐13C HMBC (2D NMR experiments) measurements of 3‐thiazolidine acetic acid‐2‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐d‐galactopyranosyl)‐1′‐imino‐α‐(1‐methylthio)ethyl‐4‐oxo ethyl ester 3j revealed the exclusive regioselectivity during the closure of these rings toward the N‐2 position of the thiourea moiety. Furthermore, the crystal structure of compound 3g showed that the attack of N‐1 was blocked by sugar ring owing to the steric effect. The bioactivity data suggested that compound 2e has mild anticancer activity.
The efficacy of Back School on chronic low back pain of workers of a pharmaceutical company in a Tehran Suburb. COPCORD stage II study
Authors: SADEGHI‐ABDOLLAHI Bahar , ESHAGHI Anita , HOSSEINI Siavash Nejad , GHAHREMANI Mojgan , DAVATCHI Fereydoun
Published: September 2011

Aim:  Low back pain (LBP) is the second most frequent reason for seeking medical advice. Various treatments are proposed from no intervention, to analgesics, rest, exercises, local interventions and surgical procedures. Results and outcomes are differently reported. Back School (BS), a combination of patient education and physical exercises, seems to have good results. The aim of this study was to check the effect of BS in factory workers.

Patients and Methods:  All (70) workers were interviewed and 26 of them (37.1%) had chronic LBP. Secondary causes were excluded. Anatomy, physiology, biomechanics of the spine, correct postures at work and back exercises were taught. Pain on a visual analog scale (VAS) of 0–100, and Short Form (SF)‐36 health survey were applied, before, at the end of BS sessions, and 3 months after BS. Analysis was done by t‐test, Wilcoxon and Pearson’s correlation test.

Results:  The mean VAS on pain before BS was 43.4 ± 22.3, improving to 38.6 ± 17.5 at the end of BS. The difference was not significant (P = 0.19). The mean VAS improved to 27.5 ± 20 at 3 months after BS. The difference was significant compared to before BS (P = 0.001). The quality of life measured by the SF‐36 questionnaire, did not improve significantly, except for two of its eight subgroups (Role Physical, Social Functioning) at the end of BS, and two of its subgroup (Mental Health, Social Functioning) at 3 months after BS.

Conclusion:  Among industrial workers, BS is mainly effective on pain, but is less evident on SF‐36.
Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis B patients treated with nucleoside analog
Authors: Ogawa Eiichi , Furusyo Norihiro , Murata Masayuki , Ohnishi Hachiro , Toyoda Kazuhiro , Taniai Hiroaki , Ihara Takeshi , Ikezaki Hiroaki , Hayashi Takeo , Kainuma Mosaburo , Hayashi Jun
Published: September 2011

Aim:  To evaluate the association between liver stiffness measured by transient elastography (FibroScan) and the efficacy of long‐term nucleoside analog (NA) treatment for patients with chronic hepatitis B.

Methods:  Study 1: Forty‐four chronic HBV patients had liver stiffness measured by FibroScan and underwent liver biopsy. Study 2: Group A: 22 patients started NA treatment at entry and FibroScan was done annually for 3 years. Group B: 23 patients started NA treatment prior to pretreatment FibroScan measurement, and FibroScan was done for from 3 to 5 years after the start of NA treatment.

Results:  Study 1: The FibroScan values were significantly correlated with fibrosis stage (r = 0.672, P < 0.0001). Optimal cutoff of FibroScan values were 6.1 kPa for ≥ F1, 6.3 kPa for ≥ F2, 8.9 kPa for ≥ F3 and 12.0 kPa for F4. Study 2: For Group A, the baseline median FibroScan value was 8.2 kPa. FibroScan values significantly decreased annually for 3 years after the start of NA treatment (6.4 kPa, 5.8 kPa and 5.3 kPa at years 1, 2 and 3, respectively). For Group B, the FibroScan values did not significantly improve over the 3 years after the start of NA treatment.

Conclusions:  Liver stiffness, measured by transient elastography, of chronic hepatitis B patients treated with NA showed a rapid decline in the first 3 years followed by a more steady transition for from 3 to 5 years irrespective of long term virological effect.
Hepatocellular carcinoma in non‐alcoholic steatohepatitis: Growing evidence of an epidemic?
Authors: Hashimoto Etsuko , Tokushige Katsutoshi
Published: September 2011

The incidence of hepatocellular carcinoma in non‐viral‐related chronic liver disease has gradually increased in Japan. Obesity and diabetes mellitus type 2 have been established as a significant risk factor for hepatocellular carcinoma (HCC) by epidemiologic observations and experimental studies. The risks of these factors for HCC are likely conferred by two factors: the increased risk for development of non‐alcoholic steatohepatitis (NASH) and the carcinogenic potential of themselves. Hepatocellular carcinoma in NASH is difficult to evaluate because histological diagnosis is required for diagnosis of NASH, which can lead selection bias. Furthermore, end‐stage NASH is in effect “burned‐out” NASH, for which the diagnosis of NASH cannot be made any more. At all events, previous studies on the etiology of Japanese HCC showed that non‐alcoholic fatty liver disease accounts for 1–5% of all HCC (male predominant, median age 72 years). They have high prevalences of obesity and/or diabetes mellitus type 2 and 10–75% of the HCC arose from non‐cirrhotic livers. HCC in NASH may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important especially in cirrhotic NASH patients and recurrence should be warned. In western and Asian countries, the prevalence of non‐alcoholic fatty liver disease in the general population is increasing dramatically. Therefore, there is an urgent need to elucidate pathogenesis and clinical features of HCC in NASH. In this review we summarize current concepts for HCC in NASH.
A Review of the State-of-the-Art for the Design of Self-Acting Gas-Lubricated Bearings
Authors: Fuller D. D.
Published: September 2011

This is a review of selected publications over the past eight years, dealing with the analysis and design of self-acting, gas-lubricated bearings. An effort has been made to evaluate the advances made both in the understanding of the basic phenomena involved and in the technical analytical ability to deal with them. Whenever possible, design procedures have been referenced and illustrated.
Experimental Stability Studies of the Herringbone-Grooved Gas-Lubricated Journal Bearing
Authors: Cunningham Robert E. , Fleming David P. , Anderson William J.
Published: September 2011

Experimental studies were conducted on six rotors, 1 1/2 in. dia by 12 1/4 in. long operating in ambient air to high compressibility numbers. Herringbone-groove geometries and clearances were varied to determine their effect on half-frequency whirl (HFW). All rotors were operated vertically and without any applied radial load. Results show that half-frequency-whirl onset is very sensitive to radial clearance. Limited test results indicate that a fully grooved bearing is more stable than a partially grooved one, other parameters being equal. Generally fair agreement between theory and experiment was achieved for predicting HFW onset speeds.
Rolling Friction, II—Cast-Iron Car Wheels
Authors: Hersey Mayo D. , Downes M. S.
Published: September 2011

Tests made on cast-iron car wheels with machined treads, running on steel rails, are reported here. Wheel diameters ranged from 8 to 24 in., load per wheel from about 100 to 1800 lb, speed from 1 to 6 mph. Static or starting tests were also included. The ratio of horizontal resisting force F to the vertical load W is denoted by f and taken as a measure of rolling friction. The friction ratio f was seen to vary almost inversely as the square root of the diameter. It decreased with increasing load, and increased slightly with increasing speed. These results differ considerably from those published in engineering handbooks.
Rolling Friction, III—Review of Later Investigations
Authors: Hersey Mayo D.
Published: September 2011

Modern tests on solid rollers from 1926 to the present are reviewed here, thus providing a foundation for empirical formulas or calculations. The effects of adhesion, elastic hysteresis, microslip, and plasticity were observed under various conditions. Theoretical studies are summarized.
Why, What, and How: Engine Varnish
Authors: Dimitroff E. , Moffitt J. V. , Quillian R. D.
Published: September 2011

Varnish formation, generated in a spark-ignited engine operating under various modes of speed, temperature, compression ratio, spark-advance, and air-fuel ratios, was investigated to establish the interrelationship between fuels, lubricants, additives, and engine operating conditions with respect to their effect and contribution to varnish deposition. The varnish precursors were identified to be primarily fuel aromatic compound. A series of engine tests was then conducted with blends of fuel aromatics and alkylate to determine their varnishing proclivities. Thus it was established that the varnishing characteristics of fuels are dependent not only on the total aromatics but even more so on the individual compounds. It was also determined that finished lubricants act as varnish inhibitors and thus determine to a high degree the engine varnish formation. On the other hand, of all engine variables, only the compression ratio and jacket temperature were found to be also of importance, although their total effect on varnish formation was smaller than that of the fuel or lubricant. Subsequently, the varnish deposits were removed from the engine parts, and a chemical analysis was made using modern instrumental techniques. The results showed the engine varnish composition is mostly alkane in character and contains condensed hydrocarbons, hydroxy-containing organic compounds, as well as ketones and nitro compounds. In addition, it was established that lead salts are also part of varnish but are not a prerequisite to varnish formation. Knowing the chemical composition of the varnish precursors, the composition of the varnish deposits, and the engine conditions under which these deposits were obtained, the chemical mechanism of varnish formation was defined by means of chemical equations. The final analysis of varnish formation is shown in the form of a computer-derived mathematical equation defining the relative importance of all variables affecting engine varnish deposition. Data are provided which show that piston varnish formation is a chemical process which occurs on the piston rubbing surfaces as the blowby travels from the combustion chamber to the engine sump.
Thermal Effects in Face Seals
Authors: Sneck H. J.
Published: September 2011

The laminar and turbulent flow of an incompressible fluid between the rotating parallel surfaces of a face seal is investigated analytically to determine the influence of conduction, convection, and dissipation on the temperature distribution. A method of estimating the general temperature level within the seal is suggested.
The Effect of Pressure on the Non-Newtonian Behavior of Polymer Blended Petroleum Oils
Authors: Novak J. D. , Winer W. O.
Published: September 2011

The shear dependence of polymer containing oils at elevated pressure was observed in a capillary-type viscometer and is reported. Recoverable shear strain was not observed at elevated pressures but was observed at atmospheric pressure in the blends at the same shear stress. The fluids examined included a paraffinic base oil (B), B plus four and eight weight percent methacrylate, B plus four weight percent styrene, a naphthenic base oil (F), and F plus four weight percent methacrylate.
Load Support and Leakage from Microasperity-Lubricated Face Seals
Authors: Anno J. N. , Walowit J. A. , Allen C. M.
Published: September 2011

Observations of load support from various shapes of microasperities placed on the surface of a rotary-shaft face seal indicate that all are comparable in this respect and generally follow the theory developed previously for cylindrical asperities. Both positive (protrusions) and negative (valleys) asperities produce similar load support, developing stable hydrodynamic lubricant films of the order of 10−5 in. for linear velocity of at least 50 in./sec, lubricant viscosity as low as 1 cp, and loads of the order of 100 pounds or higher. Variations in the film thickness with these parameters is predicted by the theory developed on the basis that an effective small tilt exists on the tops of the asperities. Leakage from microasperity-lubricated seals on the average follows the predictions of Poiseuille flow, with the exception that a significant effect of rotor rotation is observed. For a leakage channel height of 10−4 in., leakage was typically of the order of 0.2 in.3/hr for a pressure drop of 10 psi across the seal.
Dynamic Capacity of Oscillating Rolling Element Bearings
Authors: Rumbarger J. H. , Jones A. B.
Published: September 2011

The results of life tests of 388 caged, needle-roller bearings under combinations of load, speed, and amplitude of oscillation are analyzed with Weibull statistics. The rolling bearing theory of Lundberg and Palmgren is extended to cover oscillating roller bearings and is favorably compared with the life tests. A formula for basic dynamic capacity in oscillation is developed for amplitudes of oscillation which are less than the critical amplitude. Capacity formulas are also presented for both ball and roller bearings for any amplitude of oscillation.
A Bounded Variable Approach to the Optimum Slider Bearing
Authors: Maday C. J.
Published: September 2011

Contemporary methods for treating inequality constraints in the calculus of variations are employed to determine the maximum load-capacity one-dimensional slider bearing using a lubricant with pressure-dependent viscosity. A lower bound on the minimum film thickness is put into equational form to facilitate the use of the Euler-Lagrange equations, the corner conditions, and the Weierstrass E-function. It is found that, for typical lubricants, the slider bearing contains only one step separting two values of the film thickness. It is shown also that there exist cases for which a solution cannot be obtained to describe a real situation.
An Experimental Study of Turbulent Flow in a Spiral-Groove Configuration
Authors: Burton R. A.
Published: September 2011

Pressure and velocity data are reported for measurements in a large-scale experimental apparatus, designed to act as a model of a spiral-groove configuration operating at turbulent Reynolds numbers, and using air as a working fluid. The results predict that inertial effects at the steps in film thickness will exert a dominant influence on flows in machine elements made in geometric similitude to the model. Negative gage pressures were indicated in the thin-film regions, and these would be expected to lead at times to film breakup in elements using a liquid as the working fluid. Furthermore, negative stiffness under displacement of the journal was indicated for some operating conditions. The results, taken together, indicate the role of inertial effects, and dangerous operating conditions as to film breakup and loss of load support.
Spiral Groove Face Seal Concepts; Comparison to Conventional Face Contact Seals in Sealing Liquid Sodium (400 to 1000 Deg F)
Authors: Strom T. N. , Ludwig L. P. , Allen G. P. , Johnson R. L.
Published: September 2011

Conventional face contact seal performance was improved by incorporation of the spiral-groove geometry. Both conventional face contact seals and seals with spiral grooves were used to seal liquid sodium at a pressure of 20 lb per sq in. gage (14.0 N/cm2 gage), and a sliding velocity of 79 fps (24 m/sec). In comparison with conventional face contact seals, seals with spiral grooves had negligible leakage. The wear and contact patterns indicated that the spiral-groove seal operated with separation of the sealing surfaces, which is necessary for long life. Supporting studies (sealing oil) on face contact seals employing the spiral-geometry are discussed. Successful low-leakage operation was not achieved with conventional face contact seals having carbide seal seats and nosepieces (hard on hard). Thermal and pressure distortions caused edge contact, wear, and scoring. Conventional face contact seals having seal seats and nosepieces with wear-in properties (soft on hard) showed more leakage than those with carbide sealing surfaces.
The Present State of Lubrication and Its Relation to Rheology
Authors: Appeldoorn J. K.
Published: September 2011

In thick-film lubrication, Reynolds’ equation is generally satisfactory. However, the assumptions made in deriving this equation cannot be justified for non-Newtonian, viscoelastic liquids. It is concluded that no satisfactory mathematical treatment is yet available for calculating the load-carrying capacity of such liquids. In thin-film lubrication, elastohydrodynamic calculations indicate that the lubricant film may be quite thick even under heavily loaded conditions, but discrepancies exist between calculation and experiment. These can be explained by assuming non-Newtonian behavior, or unusual viscoelastic effects, but the assumptions are largely unfounded. There is virtually a complete absence of data on the behavior of liquids under impact loading. Such data are needed to resolve whether thin-film lubrication is primarily chemical or primarily physical.
The Steady-State and Dynamic Characteristics of a Full Circular Bearing and a Partial Arc Bearing in the Laminar and Turbulent Flow Regimes
Authors: Orcutt F. K. , Arwas E. B.
Published: September 2011

The steady-state and dynamic characteristics of a full circular bearing and a centrally loaded, 100 deg, arc bearing are calculated for a range of eccentricity ratios to 0.95 and of mean Reynolds numbers to 13,300, and presented in design charts. These are compared with the measured performance of these bearings over the same ranges of the operating parameters. There is good correlation between the theoretical and test data, leading to the conclusion that the present turbulent lubrication analysis may be used to obtain general design data for self-acting bearings, operating in the superlaminar flow regime, to supplement that presently existing for laminar flow bearings.
Improved Method for Numerical Solutions of the General Incompressible Fluid Film Lubrication Problem
Authors: Castelli V. , Shapiro W.
Published: September 2011

A numerical analysis for determining performance characteristics of hydrodynamic, hydrostatic, or hybrid bearings with arbitrary clearance distribution is presented. Solution of the Reynolds lubrication equation for incompressible fluids is achieved by formation of coefficient matrices that act upon column vectors of the pressures progressively from one boundary to the other without requiring an iterative scheme. Multiple recesses are handled by component solutions. The external supply system is included and solved for an arbitrary type of individual recess compensation and supply circuit network. Sample results are indicated.
Elastohydrostatic Lubrication of Circular Plate Thrust Bearings
Authors: Dowson D. , Taylor C. M.
Published: September 2011

The subject of elastohydrodynamic lubrication has developed considerably in recent years and in the present paper the influence of elastic distortion upon the performance of a hydrostatic thrust bearing is considered. A circular plate hydrostatic thrust bearing is considered and one of the pads is assumed to be lined by a thin layer of elastic material. A simplified approach to the calculation of elastic displacements is used and an approximate analytical solution of the governing elastohydrostatic equations is presented. Theoretical solutions showing the influence of elastic distortion upon pressure distribution are presented. Experimental measurements of radial pressure distribution are recorded for bearings lined with low modulus nitrile and polyurethane rubber. Difficulties encountered in the measurement of the rubber properties prevented a strict comparison between experimental and theoretical results but the selection of an equivalent modulus enabled qualitative agreement to be demonstrated. Elastohydrostatic behavior is shown to have a beneficial effect upon bearing performance.
Solution for the Pressure and Temperature in an Infinite Slider Bearing of Arbitrary Profile
Authors: Hahn E. J. , Kettleborough C. F.
Published: September 2011

An iterative method of calculating the steady-state pressure and temperature distributions in the fluid film for infinitely wide slider bearings is presented. The bearing profile is assumed to be quite general, rendering the method particularly applicable to problems involving thermal or elastic distortion. The viscosity of the lubricant is regarded as a function of temperature and pressure; the density as a function of temperature only. The inertia terms are retained in the simplified Navier-Stokes equation and the energy equation includes the compression work term. Heat transfer between the bearing surfaces and the fluid film are accounted for. Several numerical examples are evaluated and compared with existing solutions. The solution presented is believed to be the most complete to date. A subsequent paper will deal with the effect of thermal distortions of similar geometrical arrangements described herein.
Joint Level Test Methods for Solder Pad Cratering Investigations
Authors: Roggeman Brian D. , Raghavan Venkatesh , Borgesen Peter
Published: September 2011

The introduction of less compliant lead free solders together with weaker and more brittle laminate materials has led to major concerns with respect to the resistance of the latter to pad cratering. For purposes of laminate selection as well as for the quantification of acceptable handling and use conditions, there is a general interest in the testing for cratering at the joint level, rather than by testing entire assemblies. Joint level testing is cheaper, faster, and offers more quantitative results. Joint level testing also allows the elimination of confounding factors such as PCB and component stiffness. Developing test procedures and testing, it is important to distinguish between wear out under repeated loads and the failure due to a single overstress. Correlations between these two damage scenarios are largely fortuitous. Focusing on strength testing we have compared alternative methods and identified the most relevant approach. Occasions may arise where shear testing is the most appropriate, but most pad cratering scenarios are best represented by so-called Hot Bump Pull at an angle of about 30° to the pad normal. Replacing the solder balls by paste deposits or pulling in a direction normal to the pad may lead to a different ranking of materials and otherwise obscure systematic trends. We also recommend taking loading rate and temperature effects into account.
HIV Under Cover
Authors: Nyendak Melissa
Published: September 2011

HIV replication by cell-to-cell spread enables the virus to evade destruction by antiretroviral drugs without developing drug-resistance mutations.
Eureka!!! Sewing to Moonbeams
Authors: Skelly Christopher L.
Published: September 2011

A thermoreversible nanopolymer enables a new method of creating sutureless vascular-vascular connections without trauma to the tissue.
Neisseria gonorrhoeae NspA Induces Specific Bactericidal and Opsonic Antibodies in Mice
Authors: Li Guocai , Jiao Hongmei , Jiang Guihua , Wang Jing , Zhu Litian , Xie Rushan , Yan Hua , Chen Hongju , Ji Mingchun
Published: September 2011

Neisseria gonorrhoeaesurface protein A (NspA) is a highly conserved gonococcal antigen. To explore the potential of NspA in vaccine development against gonorrhea, BALB/c mice were immunized with pcNspA containing the NspA gene fromN. gonorrhoeaestrain WHO-A via intramuscular (i.m.) injection, intranasal (i.n.) immunization, or intravaginal (i.vag.) immunization. Following the last DNA immunization, mice were boosted with recombinant NspA (rNspA). Enzyme-linked immunosorbent assays (ELISAs) indicated that all immunized mice generated measurable NspA-specific IgG and IgA in serum and secretory IgA (sIgA) in vaginal wash fluids. The antisera had bactericidal and opsonic activities. These data demonstrated that NspA induced antibodies with antigonococcal activity.
Mechanisms of and Risk Factors for Fluoroquinolone Resistance in Clinical Enterococcus faecalis Isolates from Patients with Urinary Tract Infections
Authors: Yasufuku Tomihiko , Shigemura Katsumi , Shirakawa Toshiro , Matsumoto Minori , Nakano Yuzo , Tanaka Kazushi , Arakawa Soichi , Kawabata Masato , Fujisawa Masato
Published: September 2011

We examined
Enterococcus faecalis
strains clinically isolated from 100 patients with urinary tract infections (UTIs) for their susceptibility to levofloxacin (LVX) by measuring the MIC and investigated amino acid mutations by direct DNA sequencing, which were then correlated with LVX resistance. Next, we studied risk factors for LVX resistance, such as age, gender, and previous fluoroquinolone use, and investigated the statistical correlation of these risk factors with each amino acid mutation and LVX resistance. Of the 100 isolates tested, 14 isolates showed LVX resistance and all of these isolates had amino acid mutations. We demonstrated that 2 out of 4 mutations (Ser83-to-Ile in
gyrA
and Ser80-to-Ile in
parC
) had a significant correlation with LVX resistance. There was a significant relationship between isolates with 2 or 3 amino acid mutations and LVX resistance. In addition, we found a significant correlation between the previous use of fluoroquinolones and LVX resistance or the presence of mutations and also demonstrated that previous use of other types of antibiotics was significantly related to the presence of mutations by multivariate analysis. In conclusion, we found significant correlation between amino acid mutations in
E. faecalis
, LVX resistance, and risk factors such as previous use of fluoroquinolones.
Novel Pentameric Structure of the Diarrhea-Inducing Region of the Rotavirus Enterotoxigenic Protein NSP4
Authors: Chacko Anita R. , Arifullah Mohammed , Sastri Narayan P. , Jeyakanthan Jeyaraman , Ueno Go , Sekar Kanagaraj , Read Randy J. , Dodson Eleanor J. , Rao Durga C. , Suguna Kaza
Published: September 2011

A novel pentameric structure which differs from the previously reported tetrameric form of the diarrhea-inducing region of the rotavirus enterotoxin NSP4 is reported here. A significant feature of this pentameric form is the absence of the calcium ion located in the core region of the tetrameric structures. The lysis of cells, the crystallization of the region spanning residues 95 to 146 of NSP4 (NSP4
95-146
) of strain ST3 (ST3:NSP4
95-146
) at acidic pH, and comparative studies of the recombinant purified peptide under different conditions by size-exclusion chromatography (SEC) and of the crystal structures suggested pH-, Ca
2+
-, and protein concentration-dependent oligomeric transitions in the peptide. Since the NSP4
95-146
mutant lacks the N-terminal amphipathic domain (AD) and most of the C-terminal flexible region (FR), to demonstrate that the pentameric transition is not a consequence of the lack of the N- and C-terminal regions, glutaraldehyde cross-linking of the ΔN72 and ΔN94 mutant proteins, which contain or lack the AD, respectively, but possess the complete C-terminal FR, was carried out. The results indicate the presence of pentamers in preparations of these longer mutants. Detailed SEC analyses of ΔN94 prepared under different conditions, however, revealed protein concentration-dependent but metal ion- and pH-independent pentamer accumulation at high concentrations which dissociated into tetramers and lower oligomers at low protein concentrations. While calcium appeared to stabilize the tetramer, magnesium in particular stabilized the dimer. ΔN72 existed primarily in the multimeric form under all conditions. These findings of a calcium-free NSP4 pentamer and its concentration-dependent and largely calcium-independent oligomeric transitions open up a new dimension in an understanding of the structural basis of its multitude of functions.
Human T-Cell Lymphotropic Virus Type 3 (HTLV-3)- and HTLV-4-Derived Antisense Transcripts Encode Proteins with Similar Tax-Inhibiting Functions but Distinct Subcellular Localization
Authors: Larocque Émilie , Halin Marilène , Landry Sébastien , Marriott Susan J. , Switzer William M. , Barbeau Benoit
Published: September 2011

The human T-cell lymphotropic virus (HTLV) retrovirus family is composed of the well-known HTLV type 1 (HTLV-1) and HTLV-2 and the most recently discovered HTLV-3 and HTLV-4. Like other retroviruses, HTLV-1 and HTLV-2 gene expression has been thought to be orchestrated through a single transcript. However, recent reports have demonstrated the unique potential of both HTLV-1 and HTLV-2 to produce an antisense transcript. Furthermore, these unexpected and newly identified transcripts lead to the synthesis of viral proteins termed HBZ (HTLV-1 basic leucine zipper) and APH-2 (antisense protein of HTLV-2), respectively. As potential open reading frames are present on the antisense strand of HTLV-3 and HTLV-4, we tested whether
in vitro
antisense transcription occurred in these viruses and whether these transcripts had a coding potential. Using HTLV-3 and HTLV-4 proviral DNA constructs, antisense transcripts were detected by reverse transcriptase PCR. These transcripts are spliced and polyadenylated and initiate at multiple sites from the 3′ long terminal repeat (LTR). The resulting proteins, termed APH-3 and APH-4, are devoid of a typical basic leucine zipper domain but contain basic amino acid-rich regions. Confocal microscopy and Western blotting experiments demonstrated a nucleus-restricted pattern for APH-4, while APH-3 was localized both in the cytoplasm and in the nucleus. Both proteins showed partial colocalization with nucleoli and HBZ-associated structures. Finally, both proteins inhibited Tax1- and Tax3-mediated HTLV-1 and HTLV-3 LTR activation. These results further demonstrate that retroviral antisense transcription is not exclusive to HTLV-1 and HTLV-2 and that APH-3 and APH-4 could impact HTLV-3 and HTLV-4 replication.
The Assembly-Activating Protein Promotes Capsid Assembly of Different Adeno-Associated Virus Serotypes
Authors: Sonntag F. , Köther K. , Schmidt K. , Weghofer M. , Raupp C. , Nieto K. , Kuck A. , Gerlach B. , Böttcher B. , Müller O. J. , Lux K. , Hörer M. , Kleinschmidt J. A.
Published: September 2011

Adeno-associated virus type 2 (AAV2) capsid assembly requires the expression of a virally encoded assembly-activating protein (AAP). By providing AAP together with the capsid protein VP3, capsids are formed that are composed of VP3 only. Electron cryomicroscopy analysis of assembled VP3-only capsids revealed all characteristics of the wild-type AAV2 capsids. However, in contrast to capsids assembled from VP1, VP2, and VP3, the pores of VP3-only capsids were more restricted at the inside of the 5-fold symmetry axes, and globules could not be detected below the 2-fold symmetry axes. By comparing the capsid assembly of several AAV serotypes with AAP protein from AAV2 (AAP-2), we show that AAP-2 is able to efficiently stimulate capsid formation of VP3 derived from several serotypes, as demonstrated for AAV1, AAV2, AAV8, and AAV9. Capsid formation, by coexpressing AAV1-, AAV2-, or AAV5-VP3 with AAP-1, AAP-2, or AAP-5 revealed the ability of AAP-1 and AAP-2 to complement each other in AAV1 and AAV2 assembly, whereas for AAV5 assembly more specific conditions are required. Sequence alignment of predicted AAP proteins from the known AAV serotypes indicates a high degree of homology of all serotypes to AAP-2 with some divergence for AAP-4, AAP-5, AAP-11, and AAP-12. Immunolocalization of assembled capsids from different serotypes confirmed the preferred nucleolar localization of capsids, as observed for AAV2; however, AAV8 and AAV9 capsids could also be detected throughout the nucleus. Taken together, the data show that AAV capsid assembly of different AAV serotypes also requires the assistance of AAP proteins.
Fixation of Oligosaccharides to a Surface May Increase the Susceptibility to Human Parainfluenza Virus 1, 2, or 3 Hemagglutinin-Neuraminidase
Authors: Tappert Mary M. , Smith David F. , Air Gillian M.
Published: September 2011

The hemagglutinin-neuraminidase (HN) protein of human parainfluenza viruses (hPIVs) both binds (H) and cleaves (N) oligosaccharides that contain
N
-acetylneuraminic acid (Neu5Ac). H is thought to correspond to receptor binding and N to receptor-destroying activity. At present, N′s role in infection remains unclear: does it destroy only receptors, or are there other targets? We previously demonstrated that hPIV1 and 3 HNs bind to oligosaccharides containing the motif Neu5Acα2-3Galβ1-4GlcNAc (M. Amonsen, D. F. Smith, R. D. Cummings, and G. M. Air, J. Virol. 81:8341–8345, 2007). In the present study, we tested the binding specificity of hPIV2 on the Consortium for Functional Glycomics' glycan array and found that hPIV2 binds to oligosaccharides containing the same motif. We determined the specificities of N on red blood cells, soluble small-molecule and glycoprotein substrates, and the glycan array and compared them to the specificities of H. hPIV2 and -3, but not hPIV1, cleaved their ligands on red blood cells. hPIV1, -2, and -3 cleaved their NeuAcα2-3 ligands on the glycan array; hPIV2 and -3 also cleaved NeuAcα2-6 ligands bound by influenza A virus. While all three HNs exhibited similar affinities for all cleavable soluble substrates, their activities were 5- to 10-fold higher on small molecules than on glycoproteins. In addition, some soluble glycoproteins were not cleaved, despite containing oligosaccharides that were cleaved on the glycan array. We conclude that the susceptibility of an oligosaccharide substrate to N increases when the substrate is fixed to a surface. These findings suggest that HN may undergo a conformational change that activates N upon receptor binding at a cell surface.
Evidence for an Increased Risk of Transmission of Simian Immunodeficiency Virus and Malaria in a Rhesus Macaque Coinfection Model
Authors: Trott Kristin A. , Chau Jennifer Y. , Hudgens Michael G. , Fine Jason , Mfalila Chelu K. , Tarara Ross P. , Collins William E. , Sullivan JoAnn , Luckhart Shirley , Abel Kristina
Published: September 2011

In sub-Saharan Africa, HIV-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly,
Mycobacterium tuberculosis
and malaria parasites. The consequences are often devastating, resulting in enhanced morbidity and mortality. Due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (SIV)-malaria coinfection. In sub-Saharan Africa,
Plasmodium falciparum
is the most common malaria parasite and is responsible for most malaria-induced deaths. The simian malaria parasite
Plasmodium fragile
can induce clinical symptoms, including cerebral malaria in rhesus macaques, that resemble those of
P. falciparum
infection in humans. Thus, based on the well-characterized rhesus macaque model of SIV infection, this study reports the development of a novel rhesus macaque SIV-
P. fragile
coinfection model to study human HIV-
P. falciparum
coinfection. Using this model, we show that coinfection is associated with an increased, although transient, risk of both HIV and malaria transmission. Specifically, SIV-
P. fragile
coinfected macaques experienced an increase in SIV viremia that was temporarily associated with an increase in potential SIV target cells and systemic immune activation during acute parasitemia. Conversely, primary parasitemia in SIV-
P. fragile
coinfected animals resulted in higher gametocytemia that subsequently translated into higher oocyst development in mosquitoes. To our knowledge, this is the first animal model able to recapitulate the increased transmission risk of both HIV and malaria in coinfected humans. Therefore, this model could serve as an essential tool to elucidate distinct immunological, virological, and/or parasitological parameters underlying disease exacerbation in HIV-malaria coinfected people.
Vesicular Stomatitis Virus Oncolytic Treatment Interferes with Tumor-Associated Dendritic Cell Functions and Abrogates Tumor Antigen Presentation
Authors: Leveille Simon , Goulet Marie-Line , Lichty Brian D. , Hiscott John
Published: September 2011

Oncolytic virotherapy is a promising biological approach to cancer treatment that contributes to tumor eradication via immune- and non-immune-mediated mechanisms. One of the remaining challenges for these experimental therapies is the necessity to develop a durable adaptive immune response against the tumor. Vesicular stomatitis virus (VSV) is a prototypical oncolytic virus (OV) that exemplifies the multiple mechanisms of oncolysis, including direct cell lysis, cellular hypoxia resulting from the shutdown of tumor vasculature, and inflammatory cytokine release. Despite these properties, the generation of sustained antitumor immunity is observed only when VSV is engineered to express a tumor antigen directly. In the present study, we sought to increase the number of tumor-associated dendritic cells (DC)in vivoand tumor antigen presentation by combining VSV treatment with recombinant Fms-like tyrosine kinase 3 ligand (rFlt3L), a growth factor promoting the differentiation and proliferation of DC. The combination of VSV oncolysis and rFLt3L improved animal survival in two different tumor models, i.e., VSV-resistant B16 melanoma and VSV-sensitive E.G7 T lymphoma; however, increased survival was independent of the adaptive CD8 T cell response. Tumor-associated DC were actively infected by VSVin vivo, which reduced their viability and prevented their migration to the draining lymph nodes to prime a tumor-specific CD8 T cell response. These results demonstrate that VSV interferes with tumor DC functions and blocks tumor antigen presentation.
Poorly Neutralizing Cross-Reactive Antibodies against the Fusion Loop of West Nile Virus Envelope Protein ProtectIn Vivovia Fcγ Receptor and Complement-Dependent Effector Mechanisms
Authors: Vogt Matthew R. , Dowd Kimberly A. , Engle Michael , Tesh Robert B. , Johnson Syd , Pierson Theodore C. , Diamond Michael S.
Published: September 2011

The human antibody response to flavivirus infection is dominantly directed against a cross-reactive epitope on the fusion loop of domain II (DII-FL) of the envelope (E) protein. Although antibodies against this epitope fail to recognize fully mature West Nile virus (WNV) virions and accordingly neutralize infection poorlyin vitro, their functional propertiesin vivoremain less well understood. Here, we show that while passive transfer of poorly neutralizing monoclonal antibodies (MAb) and polyclonal antibodies against the DII-FL epitope protect against lethal WNV infection in wild-type mice, they fail to protect mice lacking activating Fcγ receptors (FcγR) and the complement opsonin C1q. Consistent with this, an aglycosyl chimeric mouse-human DII-FL MAb (E28) variant that lacks the ability to engage FcγR and C1q also did not protect against WNV infection in wild-type mice. Using a series of immunodeficient mice and antibody depletions of individual immune cell populations, we demonstrate that the nonneutralizing DII-FL MAb E28 does not require T, B, or NK cells, inflammatory monocytes, or neutrophils for protection. Rather, E28 treatment decreased viral load in the serum early in the course of infection, which resulted in blunted dissemination to the brain, an effect that required phagocytic cells, C1q, and FcγRIII (CD16). Overall, these studies enhance our understanding of the functional significance of immunodominant, poorly neutralizing antibodies in the polyclonal human anti-flavivirus response and highlight the limitations of currentin vitrosurrogate markers of protection, such as cell-based neutralization assays, which cannot account for the beneficial effects conferred by these antibodies.
METHOD TO ANALYZE THE FATIGUE CRACKS IN ACRYLIC BONE CEMENT
Authors: BIALOBLOCKA-JUSZCZYK EWA , CRISTOFOLINI LUCA , ERANI PAOLO , VICECONTI MARCO
Published: September 2011

Acrylic bone cement is a poly(methyl methacrylate)-based material that ensures short-term stability of orthopedic implants after surgery. Its long-term performance can be affected by many factors (e.g., composition, cement mixing and delivery method, temperature, humidity). Furthermore, patient activities produce a spectrum of cyclic loads that generate microdamage within the acrylic bone cement mantle. Therefore, pre-clinical studies on fatigue damage of acrylic bone cements are essential for predicting the long-term stability of cemented implants. There are several methods for analyzing damage of acrylic bone cement. However, they present a number of limitations. The aim of this study was to validate the use of a high-resolution scanner to analyze the presence of microcracks in acrylic bone cement. The proposed method met predetermined criteria to overcome limitations of previous methods, ensuring approximate spatial resolution of 5 microns, reduction of image acquisition time, and reduction of artifacts due to operator and/or environment during image acquisition. Additionally, the described method was applied to three types of acrylic bone cement specimens that previously were subjected to a fatigue test. The presented method enables the accurate assessment of fatigue damage induced during cycling loading, including quantification of the number, length, type and position of cement cracks.