bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Reactivity of Germ Line Allelic Variants of a Broadly Neutralizing HIV-1 Antibody to a gp41 Fusion Intermediate Conformation
Authors: Alam S. Munir , Liao Hua-Xin , Dennison S. Moses , Jaeger Frederick , Parks Robert , Anasti Kara , Foulger Andrew , Donathan Michele , Lucas Judith , Verkoczy Laurent , Nicely Nathan , Tomaras Georgia D. , Kelsoe Garnett , Chen Bing , Kepler Thomas B. , Haynes Barton F.
Published: September 2011

Genetic factors, as well as antigenic stimuli, can influence antibody repertoire formation. Moreover, the affinity of antigen for unmutated naïve B cell receptors determines the threshold for activation of germinal center antibody responses. The gp41 2F5 broadly neutralizing antibody (bNAb) uses the VH2-5 gene, which has 10 distinct alleles that use either a heavy-chain complementarity-determining region 2 (HCDR2) aspartic acid (DH54) or an HCDR2 asparagine (NH54) residue. The 2F5 HCDR2 DH54residue has been shown to form a salt bridge with gp41665K; the VH2-5 germ line allele variant containing NH54cannot do so and thus should bind less avidly to gp41. Thus, the induction of 2F5 bNAb is dependent on both genetic and structural factors that could affect antigen affinity of unmutated naïve B cell receptors. Here, we studied allelic variants of the VH2-5 inferred germ line forms of the HIV-1 gp41 bNAb 2F5 for their antigen binding affinities to gp41 linear peptide and conformational protein antigens. Both VH2-5 2F5 inferred germ line variants bound to gp41 peptides and protein, including the fusion intermediate protein mimic, although more weakly than the mature 2F5 antibody. As predicted, the affinity of the NH54variant for fusion-intermediate conformation was an order of magnitude lower than that of the DH54VH2-5 germ line antibody, demonstrating that allelic variants of 2F5 germ line antibodies differentially bind to gp41. Thus, these data demonstrate a genetically determined trait that may affect host responses to HIV-1 envelope epitopes recognized by broadly neutralizing antibodies and has implications for unmutated ancestor-based immunogen design.
TRIM5α Does Not Affect Simian Immunodeficiency Virus SIV
mac251
Replication in Vaccinated or Unvaccinated Indian Rhesus Macaques following Intrarectal Challenge Exposure
Authors: Fenizia Claudio , Keele Brandon F. , Nichols David , Cornara Stefano , Binello Nicolò , Vaccari Monica , Pegu Poonam , Robert-Guroff Marjorie , Ma Zhong-Min , Miller Christopher J. , Venzon David , Hirsch Vanessa , Franchini Genoveffa
Published: September 2011

TRIM5α is a natural resistance factor that binds retroviral capsid proteins and restricts virus replication. The B30.2/SPRY domain of TRIM5α is polymorphic in rhesus macaques, and some alleles are associated with reduced simian immunodeficiency virus (SIV) SIV
mac251
and SIV
smE543
replication
in vivo
. We determined the distribution of TRIM5α alleles by PCR and sequence analysis of the B30.2/SPRY domain in a cohort of 82 macaques. Thirty-nine of these macaques were mock vaccinated, 43 were vaccinated with either DNA-SIV/ALVAC-SIV/gp120, ALVAC-SIV/gp120, or gp120 alone, and all were exposed intrarectally to SIV
mac251
at one of three doses. We assessed whether the TRIM5α genotype of the macaques affected the replication of challenge virus by studying the number of SIV variants transmitted, the number of exposures required, the SIV
mac251
viral level in plasma and tissue, and the CD4
+
T-cell counts. Our results demonstrated that TRIM5α alleles, previously identified as restrictive for SIV
mac251
replication
in vivo
following intravenous exposure, did not affect SIV
mac251
replication following mucosal exposure, regardless of prior vaccination, challenge dose, or the presence of the protective major histocompatibility complex alleles (MamuA01
+
, MamuB08
+
, or MamuB017
+
). The TRIM5α genotype had no apparent effect on the number of transmitted variants or the number of challenge exposures necessary to infect the animals. DNA sequencing of the SIV
mac251
Gag gene of the two stocks used in our study revealed SIV
mac239
-like sequences that are predicted to be resistant to TRIM5α restriction. Thus, the TRIM5α genotype does not confound results of mucosal infection of rhesus macaques with SIV
mac251
.
HepG2 Cells Expressing MicroRNA miR-122 Support the Entire Hepatitis C Virus Life Cycle
Authors: Narbus Christopher M. , Israelow Benjamin , Sourisseau Marion , Michta Maria L. , Hopcraft Sharon E. , Zeiner Gusti M. , Evans Matthew J.
Published: September 2011

The liver-specific microRNA miR-122 is required for efficient hepatitis C virus (HCV) RNA replication both in cell culture and
in vivo
. In addition, nonhepatic cells have been rendered more efficient at supporting this stage of the HCV life cycle by miR-122 expression. This study investigated how miR-122 influences HCV replication in the miR-122-deficient HepG2 cell line. Expression of this microRNA in HepG2 cells permitted efficient HCV RNA replication and infectious virion production. When a missing HCV receptor is also expressed, these cells efficiently support viral entry and thus the entire HCV life cycle.
The DBA.2 Mouse Is Susceptible to Disease following Infection with a Broad, but Limited, Range of Influenza A and B Viruses
Authors: Pica Natalie , Iyer Arun , Ramos Irene , Bouvier Nicole M. , Fernandez-Sesma Ana , García-Sastre Adolfo , Lowen Anice C. , Palese Peter , Steel John
Published: September 2011

We assessed the relative susceptibilities to disease of the DBA.2 and C57BL/6 mouse models upon infection with a range of influenza A and B viruses. DBA.2 mice were more susceptible to disease upon inoculation with human H1N1 influenza A virus strains, several swine influenza viruses, and influenza B viruses but were not overtly susceptible to infection with human seasonal H3N2 strains. Hemagglutination inhibition and immunoglobulin isotype profiling indicated that DBA.2 and C57BL/6 mice generate comparable humoral responses upon equivalent 50% mouse lethal dose (MLD
50
) challenges with influenza virus. Our data demonstrate the utility of DBA.2 mice for the elucidation of influenza virus pathogenicity determinants and the testing of influenza vaccines.
Mutations in the Membrane-Proximal Region of the Influenza A Virus M2 Protein Cytoplasmic Tail Have Modest Effects on Virus Replication
Authors: Stewart Shaun M. , Pekosz Andrew
Published: September 2011

Influenza A virus encodes M2, a proton channel that has been shown to be important during virus entry and assembly. In order to systematically investigate the role of the membrane-proximal residues in the M2 cytoplasmic tail in virus replication, we utilized scanning and directed alanine mutagenesis in combination with transcomplementation assays and recombinant viruses. The membrane-proximal residues 46 to 69 tolerated numerous mutations, with little, if any, effect on virus replication, suggesting that protein structure rather than individual amino acid identity in this region may be critical for M2 protein function.
015 Temporal trends in head injury outcomes from 2003 to 2010 in England and Wales, and the effect of specialist neurosciences care: a Cohort Study
Authors: Fuller G , Lecky F , Woodford M , Bouamra O , Jenks T , Coats T , Hutchinson P
Published: September 2011

Objectives and Backgrounds

Head injury (HI) is the leading cause of death in trauma, and case fatality rates after blunt HI did not improve in England and Wales between 1994 and 2003. Subsequent national guidelines have recommended that all severe HIs should be treated in neuroscience units (NSUs). The aim of this study was to investigate case fatality trends in HI since 2003 and establish the effect of specialist neuroscience care on mortality after severe HI.

Methods

We conducted a cohort study using prospectively recorded data from the TARN trauma registry for adult patients presenting with blunt trauma between 2003 and 2009. Temporal trends in log odds of death adjusted for case mix were examined for patients with and without HI. Rates of transfer and mortality were compared for patients with severe HI treated in NSUs vs non-specialist centres. Propensity score adjusted multivariate logistic regression was then used to calculate case mix adjusted odds of death associated with non-NSU care.

Results

Since 2003 there was an average 12% reduction in case mix adjusted log odds of death per annum in patients with HI (n=15 173), with a similar but smaller trend in non-HI trauma mortality (n=48 681). During the study period the proportion of patients with HI treated entirely in non-NSUs decreased from 31% to 19%, (p<0.01). Severe HI management in non-NSUs was associated with a 11% increase in crude mortality (p<0.01) and a case mix adjusted 1.85 (95% CI 1.57 to 2.19) fold increase in odds of death.

Conclusions

The reduction in log odds of death following HI since 2003 is consistent with increased levels of treatment in NSUs, or better management following the introduction of national HI guidelines. Our data suggests that increasing transfer rates to NSUs represents an important strategy in further improving outcomes in severe HI.
018 One-year prognosis after syncope and the failure of the ROSE decision instrument to predict 1-year adverse events: Abstract 018 Figure 1
Authors: Henderson S S , Reed M J , Newby D E , Gray A J
Published: September 2011

Objectives and Backgrounds

(1) To investigate the incidence of adverse events at 1-year in the cohort of Emergency Department (ED) syncope patients enrolled in the original ROSE study; (2) To investigate the time to adverse event; and (3) To investigate the test performance of the ROSE decision instrument to detect events at 1-year.

Methods

This report details the 1-year follow-up of adult syncope patients presenting to the ED who were enrolled into the ROSE study, a single centre, prospective, observational cohort study. The primary end point was the combination of serious outcome (SO) and all-cause death (ACD) at 1 year. SO encompassed acute myocardial infarction, life-threatening arrhythmia, need for pacemaker/implantable defibrillator, pulmonary embolus, cerebrovascular accident, intracranial or subarachnoid haemorrhage, interventional procedure or haemorrhage requiring blood transfusion. Secondary endpoints were ACD and cardiovascular SO at 1 year.

Results

1043 patients were available for analysis; 162 patients (15.5%) had a primary outcome. 28 (17%) of these were within 24 h, 56 (35%) were within 1 week and 77 (48%) were within 1 month. The remaining 85 (52%) outcomes occurred between months 2 and 12. At 1 year, 71 (6.8%) patients had died and 76 (7.3%) had a cardiovascular SO. The sensitivity and specificity of the ROSE decision instrument for 1-year SO and ACD was 71.6% (63.9–78.3) and 71.1% (67.9–74.0), for 1-year ACD was 76.1% (64.2–85.1) and 67.4% (64.3–70.3) and for 1-year cardiovascular SO was 75.0% (63.5–83.9) and 67.5% (64.5–70.5).

Conclusions

The proportion of patients with SO and ACD 1 year after syncope is similar to recent international syncope studies. We have defined the proportion of patients with cardiovascular SO at 1-year, and have shown that most events occurred in the first month with decreased frequency of events noted after that time frame especially marked for cardiovascular SO. More than 50% of the outcomes observed however occurred after the first month. The ROSE decision instrument does not perform well at predicting 1-year outcome of ED syncope patients.

Abstract 018 Figure 1

Kaplan–Meier survival curve showing 1-year combined SO and ACD, 1-year ACD, 1-year CVS SO and 1-year combined SO and ACD for ROSE positive and ROSE negative patients.
002 Special delivery: where best to take a head injured patient?
Authors: Pickering A , Cooper K , Harnan S , Sutton A
Published: September 2011

Objectives and Backgrounds

The current focus on development of specialist centres in the UK to improve outcomes is based on evidence from overseas care models. While care in a specialist neurosurgical centre will improve outcomes for head injured patients, does transferring them directly have any clinical benefit compared with delivery to a local hospital for initial stabilisation and subsequent transfer to the specialist centre? We performed a systematic review to identify the clinical effectiveness of bypassing local hospital care in moderate or severely head injured patients.

Methods

Relevant studies were identified by an electronic search of key databases. Papers in English were included if they compared the outcomes of moderate or severely head injured patients (GCS<13, AIS≥3) directly transferred and treated at a specialist centre (SC) vs those who received their initial resuscitation at a local hospital (LH) with some or all patients later transferred to a SC. Outcomes were assessed using available mortality and morbidity data.

Results

We identified 6 studies involving 2580 patients. One further study was found that did not report the number of subjects. Most studies used SC registry data and adjusted their outcomes for age, pupil dilatation and injury severity. No studies included results for, or adjusted for, patients not transferred after delivery to the LH. For mortality, the adjusted OR was taken from three studies. For those taken to their LH first the OR of death was higher than for the direct transfer group (SC). The level of significance was marginal and undergoing formal meta-analysis at the time of submission. The adjustment of data tended to favour direct transfer over local hospital delivery. No significant difference was reported for morbidity outcomes (Glasgow Outcome Scale) in the three studies that looked at these.

Conclusions

The reviewed literature comparing direct transfer of head injured patients to specialist neurosurgical centres vs initial local hospital delivery is sparse. What evidence there is supports direct transfer to improve mortality although, at present, this is only marginally significant.
022 Methoxyflurane: would giving the “Green Whistle” the green light benefit mountain casualties in Snowdonia?
Authors: Burgess S , Dykes L
Published: September 2011

Objectives and Backgrounds

Methoxyflurane, currently licensed only in Australasia, is a convenient, rapidly effective pre-hospital analgesic, although it achieves inferior pain reduction compared to intravenous morphine or intranasal fentanyl. Methoxyflurane in analgesic doses causes only minor, rapidly-reversible initial side effects, but repeated exposure can cause irreversible dose-dependent nephrotoxicity which limits duration of administration. In addition, there are occupational health concerns for personnel working in confined spaces. There are methoxyflurane proponents within the UK mountain medicine community, and we wondered whether methoxyflurane would be suitable for use by Mountain Rescue Team first-aiders treating casualties in Snowdonia if it became available in the UK.

Methods

Our Mountain Medicine database (all casualties brought to Bangor ED following mountain incidents resulting in contact with Mountain Rescue Teams and/or RAF Search & rescue helicopter) was interrogated to determine how many trauma casualties could have been treated with methoxyflurane based upon the current Australasian product license indications/contraindications for the Penthox inhaler.

Results

From 651 mountain casualties (January 2004–December 2010) sufficient data were available in 593 cases to identify 429 trauma casualties, 329 (77%) of which could theoretically have been treated with methoxyflurane. This was almost identical to those eligible to receive Entonox (76%). However, many cases would have required methoxyflurane for longer than the maximum 1-h because of prolonged scene/evacuation times in mountain settings.

Conclusions

The maximum duration of methoxyflurane administration would be insufficient as the primary analgesic in many Snowdonia mountain casualties, however, the use of methoxyflurane as a holding measure while I/N diamorphine is being prepared may be a viable option. Mountain casualties are often treated in tent-like rescue shelters and enclosed helicopter fuselages, which may endanger rescuer health if methoxyflurane were used without adequate ventilation. Further work is required to elucidate how frequently low ambient temperature precludes the use of Entonox.
027 Paediatric emergency department attendances between 2000 and 2009: trends in a large UK Children's Hospital
Authors: Lai J , Mason S , Burke D , Julious S A , Freeman J V
Published: September 2011

Objectives and Background

There has been an increase in UK demand for emergency department services. This may be attributed to changes in public behaviour or the availability of out of hours services. The objective of this study is to investigate whether these changes are reflected in paediatric cases by identifying patterns in paediatric emergency department attendances (ED) from a large UK urban hospital.

Methods

Data relating to admissions and ED contacts were obtained from a large UK Children's hospital from 01 January 2000 to 31 December 2009. Cases were categorised as trauma if the diagnosis text inferred physical (penetrating or blunt) injury. Graphical investigation was undertaken of the mean monthly daily counts of trauma/non-trauma contacts.

Results

There were a total of 455 990 contacts made to ED. Of this figure, 46.9% were categorised as trauma overall. There has been a profound increase in hospital admissions from ED (+47.14%), admissions overall (+40.11%) and total ED attendances (+27.11%) throughout this time period. Observing trends for trauma attendances, there was a slight decrease (−11.72%) while for non-trauma attendances, there was a severe increase (+76.71%) in the annual number of attendances. Trends for the average year indicate that for trauma attendances compared to the annual mean, the largest increase and decrease is observed in December (+21.09%) and August (−27.19%) respectively. For non-trauma attendances, the largest increase and decrease is observed in June (+22.48%) and December (−30.97%) respectively.

Conclusion

There has been an increase in paediatric emergency department attendances from 2000 to 2009. However, the increase is mainly attributed to conditions categorised as non-trauma rather than trauma. Annual patterns exhibit seasonal variation. In addition, admissions rates from ED from have increased by 47%. Further investigation is required to understand reasons for the rising demand in emergency department services and specifically, the increase in non-trauma attendances and admissions.
028 Determining the effect of objective and subjective criteria on a risk assessment tool in a Children's Emergency Department: Abstract 028 Table 1
Authors: Roland D , Davies F , Lewis G
Published: September 2011

Objectives and Background

Children with serious illness can be difficult to spot, especially for non-experienced staff. Although adult “early warning scores” are now commonly used in Emergency Departments (ED), there is no such system for children. The Paediatric Observation Priority Score (POPS) is a physiological and observational scoring system (range 0–16) designed for use by healthcare professionals of varying clinical experience at initial assessment in our ED. The aim is to use POPS to identify sick children, aid healthcare professionals in confidently discharging or re-directing patients and providing a departmental level of acuity to aid resource allocation. A first phase of the validation process examined the utility of the more subjective criteria of POPS (level of alertness, work of breathing, nursing concern and relevant background history) against the physiological criteria (heart rate, breathing rate, saturations and temperature) in determining admission to the children's hospital assessment unit from the ED.

Methods

Convenience sample case note review of attendances to the ED, analysing patient discharge disposition against initial POPS recorded.

Results

942 (injuries not included) presentations from 2009 to 2010 were included in the study with an overall admission rate of 36% (339/942). RR of admission of admission with a POPS of >0 was 2.1 (CI 1.6 to 2.7).

Conclusion

The large range of confounding influences affecting the admission of children to hospital makes an initial point of care assessment predictive model difficult. This work demonstrated interesting variation in performance of the component sections of the POPS score. The use of subjective, user dependant factors, may inhibit the performance of physiological values which have traditionally be used in aiding illness recognition. Further work is ongoing to improve the performance of the tool as an adjunct to risk assessment and resource allocation.

Abstract 028 Table 1Ability to predict admissionSensitivitySpecificityPositive predictive valueNegative predictive valuePOPS>00.820.380.420.79Physiological values only (any score>0)0.740.450.430.75Subjective criteria only (any score>0)0.660.670.530.78Any nursing concern0.590.740.570.76
STABILITY OF INTERCELLULAR EXCHANGE OF BIOCHEMICAL SUBSTANCES AFFECTED BY VARIABILITY OF ENVIRONMENTAL PARAMETERS
Authors: MIHAILOVIĆ DRAGUTIN T. , BUDINČEVIĆ MIRKO , BALAŽ IGOR , MIHAILOVIĆ ANJA
Published: September 2011

Communication between cells is realized by exchange of biochemical substances. Due to internal organization of living systems and variability of external parameters, the exchange is heavily influenced by perturbations of various parameters at almost all stages of the process. Since communication is one of essential processes for functioning of living systems it is of interest to investigate conditions for its stability. Using previously developed simplified model of bacterial communication in a form of coupled difference logistic equations we investigate stability of exchange of signaling molecules under variability of internal and external parameters.
COMPUTATIONAL FLUID DYNAMICS (CFD) APPLIED IN THE DRUG DELIVERY DESIGN PROCESS TO THE NASAL PASSAGES: A REVIEW
Authors: KLEVEN MARIT , MELAAEN MORTEN C. , DJUPESLAND PER G.
Published: September 2011

Computer fluid dynamics (CFD) has for many years now been employed to study and solve fluid problems in the industry and offers an attractive method for accurately describing systems at a reasonable cost. Computer-aided methods are becoming increasingly important in medicine. Due to a combination of increased computer efficiency and advanced numerical techniques, the realism of these simulations has been enhanced in recent years. Over the past decade, computer-aided design has emerged as a method that is both sufficiently rigorous and efficient to be used for studies of the fluid dynamics in complex airway structures like the nasal airway. Physical experiments in vitro and in vivo are often expensive and time-consuming, and CFD has gained increasing attention as a tool in the design process of devices delivering drugs to the respiratory tract. This paper provides a review of the development of CFD in the studies of nasal airway fluid dynamics, particle and filtering properties in health and disease. Special emphasis is given to studies related to CFD studies used in the development of nasal drug delivery devices. The accuracy and value of CFD for the study of drug delivery design to the nose is reviewed in comparison to experimental results with other methods. Some important challenges when dealing with grid generation and flow simulations in these complex geometries with variable multiphase flow patterns in alternate directions are discussed.
INVESTIGATION OF LEAFLET GEOMETRY IN A PERCUTANEOUS AORTIC VALVE WITH THE USE OF FLUID-STRUCTURE INTERACTION SIMULATION
Authors: VAN ASWEGEN K. H. J. , SMUTS A. N. , SCHEFFER C. , WEICH H. S. VH. , DOUBELL A. F.
Published: September 2011

Prosthetic aortic valves have been used for the replacement of dysfunctional native aortic valves in humans for more than fifty years. Current prosthetic valves have significant limitations and the development of improved aortic valve prostheses remains an important research focus area. This paper investigates one of the newer additions to the family of replacement valves, namely the stented percutaneous valve. An important design aspect of stented percutaneous valves, is the configuration of the leaflet's attachment to the surrounding stent. There are essentially two possible configurations: The first method is attaching the leaflets in a straight configuration, and the second method is to attach the leaflets in a curved configuration. Finite element models of both configurations were created, and the behavior of these configurations was then studied using a fluid-structure interaction (FSI) simulation. The FSI simulation was validated by means of comparing simulation results to actual measurements from a pulse duplicator using prototype valves of both configurations. The FSI results showed no significant difference between the valves' opening and closing behaviors. The von Mises stress distributions proved to be the largest differentiating and decisive factor between the two valves. The FSI simulations did however show that the leaflets that are attached in the straight configuration form folds that resembles that of the curved configuration as well as the native valve, but to a larger scale. The effect that these folds might have on valve tissue fatigue leaves room for future investigation.
HEATING EFFECT OF THERMALLY SIGNIFICANT BLOOD VESSELS IN PERFUSED TUMOR TISSUE DURING CRYOSURGERY
Authors: LIU Z. F. , ZHAO G. , CHENG Y. H. , GAO D. Y.
Published: September 2011

The purpose of this work is to evaluate the heating effect of thermally significant blood vessels (TSBVs) during cryosurgery process. A theoretical model is developed to describe the heat transfer of perfused tissue containing a 6 mm-radius tumor and a countercurrent artery–vein pair in the vicinity of the tumor. The novelty of the model is that both the Pennes bio-heat transfer equation and the energy transport equation are used to govern the heat transfer of perfused tumor tissue and the heat convection and diffusion of the blood flow. The explicit finite different method is used to solve the transient equations with the second boundary condition set for the boundary of both the blood vessels and the tissue. The results indicate that the heating effect of the blood on the tissue surrounding the countercurrent artery–vein pair may cause parts of the tumor to be insufficiently frozen for a pre-designed cryosurgery protocols, and which may lead to regeneration of the tumor cells. A quite important issue has been raised by this study, i.e., the cryosurgery protocols should be carefully designed with full attention being paid to the heating effect of TSBVs in case of a countercurrent artery–vein pair in the vicinity of the tumor.
NUMERICAL SIMULATION OF HUMAN SYSTEMIC ARTERIAL HEMODYNAMICS BASED ON A TRANSMISSION LINE MODEL AND RECURSIVE ALGORITHM
Authors: HE WEI , XIAO HANGUANG , LIU XINGHUA
Published: September 2011

A novel recursive algorithm was proposed to calculate the input impedance of human systemic arterial tree, and to simulate the human systemic arterial hemodynamics with an 55 segment transmission line model. In calculation of input impedance, the structure of the arterial tree was expressed as a single linked list. An infinitesimal constant was used to replace 0 Hz frequency to calculate the DC and AC part of input impedance simultaneously. The input impedance at any point of the arterial tree can obtain easily by the proposed recursive algorithm. The results of input impedance are in accord with experimental data and other models' results. In addition, some comparisons were conducted about the effects of arterial compliance, length, internal radius and wall thickness on the input impedance of ascending aorta. The results showed input impedances of ascending aorta displayed significantly different characteristics for different kinds of parameters. Finally, the blood pressure and flow waveforms of all arterial segments were calculated and displayed in 3D. The arterial elasticity and viscosity were discussed by changing the Young's modulus and the phase difference, respectively. The simulation results showed that the blood pressure and flow waveforms of the arterial tree reflected accurately the main characteristic features of physiopathological changes, which demonstrated the effectiveness of the proposed model.
HOMOTOPY ANALYSIS OF TRANSIENT MAGNETO-BIO-FLUID DYNAMICS OF MICROPOLAR SQUEEZE FILM IN A POROUS MEDIUM: A MODEL FOR MAGNETO-BIO-RHEOLOGICAL LUBRICATION
Authors: BÉG O. ANWAR , RASHIDI M. M. , BÉG T. A. , ASADI M.
Published: September 2011

The transient squeezing flow of a magneto-micropolar biofluid in a noncompressible porous medium intercalated between two parallel plates in the presence of a uniform strength transverse magnetic field is investigated. The partial differential equations describing the two-dimensional flow regime are transformed into nondimensional, nonlinear coupled ordinary differential equations for linear and angular momentum (micro-inertia). These equations are solved using the robust Homotopy Analysis Method (HAM) and also numerical shooting quadrature. Excellent correlation is achieved. The influence of magnetic field parameter (Ha) , micropolar spin gradient viscosity parameter (Γ) and unsteadiness parameter (S) on linear and angular velocity (micro-rotation) are presented graphically, for specified values of the micropolar vortex viscosity parameter (R), Darcy number (Da i.e. permeability parameter) and medium porosity parameter (ε). Increasing magnetic field (Ha) serves to decelerate both the linear and angular velocity i.e. enhances lubrication. The excellent potential of HAM in bio-lubrication flows is highlighted.
EFFECT OF AN INDUCED MAGNETIC FIELD ON PERISTALTIC FLOW OF NON-NEWTONIAN FLUID IN A CURVED CHANNEL
Authors: HAYAT T. , NOREEN S. , ALSAEDI A.
Published: September 2011

The purpose of this study is to discuss the influence of induced magnetic field on the peristaltic flow of an incompressible third-grade fluid in a curved channel. The problem formulation is presented in a wave frame of reference. The continuity, linear momentum, and induction equations lead to the mathematical development. The relations of stream function, pressure gradient, magnetic force function, induced magnetic field, and current density are developed. The effects of embedded parameters are explained by plots.
PERISTALTIC TRANSPORT OF A COUPLE STRESS FLUID: SOME APPLICATIONS TO HEMODYNAMICS
Authors: MAITI S. , MISRA J. C.
Published: September 2011

The paper deals with a theoretical investigation of the peristaltic transport of a couple stress fluid in a porous channel. The study is motivated toward investigating the physiological flow of blood in the micro-circulatory system, by taking account of the particle size effect. The velocity, pressure gradient, stream function, and frictional force of blood are investigated, when the Reynolds number is small and the wavelength is large, by using appropriate analytical and numerical methods. Effects of different physical parameters reflecting porosity, Darcy number, couple stress parameter, as well as amplitude ratio on velocity profiles, pumping action and frictional force, streamlines pattern, and trapping of blood are studied with particular emphasis. The computational results are presented in graphical form. The results are found to be in good agreement with those reported by Shapiro et al.52 that was carried out for a non-porous channel without consideration of couple stress effect. The present study puts forward an important observation that for peristaltic transport of a couple stress fluid during free pumping, flow reversal can be considerably controlled by suitably adjusting the couple stress effect of the fluid/Darcy permeability of the channel. It is also possible to avoid the occurrence of trapping, by reducing the permeability.
RELATIONSHIP AMONG QRS COMPLEX CHARACTERS IN ELECTROCARDIOGRAM AND ITS APPLICATION TO MYOCARDIAL ISCHEMIA
Authors: SONG JINZHONG , YAN HONG , YU XINMING , YAO YUHUA , CHEN HUA , CHEN WEI
Published: September 2011

Electrocardiogram (ECG) is a noninvasive, economic, and convenient detecting tool in myocardial ischemia (MI), and its clinical appearance is mainly exhibited by ST-T complex changes. Recently, QRS complex characters in detecting MI were proposed by an increasing number of researchers. In this paper, various QRS complex characters were extracted in ECG, and their relationship was analyzed systematically. As a result, these characters were divided into two groups, and there was good correlation among them in each group, while the correlation between the groups was poor. Finally, these QRS complex characters were applied to myocardial ischemia, and five characters had significant differences after 59 normal ECG recordings verification, which were: QRS upward and downward slopes, transient heart rate, angle R and angle Q in a triangle QRS. Experimental results showed it was apparent that the trend changes of these five characters when MI events occurred were consistent with their relationship. The conduction velocity of action potentials in ventricular depolarization is slower in MI states than in normal states.
MECHANICAL HETEROGENIZATION OF LEWIS LUNG CARCINOMA CELLS CAN IMPROVE ANTIMETASTATIC EFFECT OF DENDRITIC CELLS
Authors: KHRANOVSKAYA NATALYA , OREL VALERII , GRINEVICH YURIY , ALEKSEENKO OXANA , ROMANOV ANDRIY , SKACHKOVA OXANA , DZYATKOVSKAYA NATALYA , BURLAKA ANATOLIY , LUKIN SERGEY
Published: September 2011

The effect of mechanically heterogenized (MCH) microparticles of tumor cells (TCs) on antimetastatic action of dendritic cells (DCs) is studied in C57BL/6 mice with Lewis' carcinoma. DCs isolated from mice spleens and loaded with MCH-TCs are analyzed with flow cytometry methods. MCH-TCs are analyzed with optical and/or electron microscopy. The paper describes an original high-precision medical microvibromill with high-acceleration linear induction motor that generates magnetic levitation to produce mechanical heterogenization of TCs. MCH-TCs have a more asymmetric morphology, larger surface and higher internal structure heterogeneity, and higher concentration of free radicals with respect to conventionally treated TCs. The rate of DCs maturity, being affected by pre-incubation with MCH-TCs is found to be higher than its counterpart treated with conventional TCs. DCs loaded with MCH-TCs show a significantly higher ability to induce proliferation of allogeneic lymphocytes in mixed leukocyte reaction. The inhibition index of metastases formation increases from 42% (conventional TCs) to 66% when DCs are treated with MCH-TCs. The present results demonstrate the feasibility of increasing antimetastatic activity of DCs-based vaccines when MCH-TCs is used for their loading. Mathematical model is developed in order to simulate the processes of capture, processing and presentation of tumor antigens by DCs when using conventional TCs or MCH-TCs.
FLUOROSCOPIC ANALYSIS FOR THE ESTIMATION OF IN VIVO ELBOW KINEMATICS: INFLUENCE OF 3D MODEL
Authors: TERSI LUCA , FANTOZZI SILVIA , STAGNI RITA , CAPPELLO ANGELO
Published: September 2011

The reliable knowledge that model-based three-dimensional (3D) fluoroscopy can provide about in vivo joints kinematics is essential to diagnose orthopedic pathologies, develop new prosthesis, and evaluate clinical procedures. To exploit 3D fluoroscopy for the analysis of elbow kinematics, its use was evaluated considering a single model for the forearm or two different models for the ulna and radius. Active elbow flexion-extension and prono-supination motor tasks of a healthy male subject were acquired by means of fluoroscopy. The 3D bone models were automatically aligned to the relevant projections. The pose estimation algorithm sought the tangency condition of the projection rays with the model surface, minimizing a cost function and exploiting an adaptive distance map. Five iterative guided alignments were performed to avoid the final convergence to a local minimum. The results highlighted the critical alignment of the ulna/radius model, particularly when prono-supination is performed. From the physiological motion patterns and given the values of the cost function, 3D fluoroscopy was proven to be applicable to the analysis of the elbow kinematics when single bone models for the ulna and radius are used.
Pharmacological AMP-kinase activators have compartment-specific effects on cell physiology
Authors: Kodiha Mohamed , Ho-Wo-Cheong Dennis , Stochaj Ursula
Published: September 2011

5′-AMP-activated kinase (AMPK) regulates numerous biological events and is an essential target for the treatment of type 2 diabetes. The objectives of the present study were first to determine the compartment-specific effects of three established AMPK activators on Thr172 phosphorylation of the α-subunit, an indicator of AMPK activation. Second, we examined how cytoplasmic and nuclear processes are modulated by pharmacological AMPK activators. Specifically, the impact of phenformin, resveratrol, and 5-aminoimidazole-4-carboxamide riboside (AICAR) on Thr172 phosphorylation in the cytoplasm and nucleus was quantified by different methods. To analyze how these activators change cell physiology, we measured the inactivation of acetyl-CoA-carboxylase 1, a predominantly cytoplasmic enzyme that is crucial for lipid metabolism. As a criterion for activities associated with the nucleus, de novo RNA synthesis in nucleoli was quantified. Our studies demonstrate that pharmacological activators of AMPK can alter the balance between nuclear and cytoplasmic AMPK pools. Thus, phenformin and resveratrol caused a strong activation of AMPK in the cytoplasm, whereas the effect was less pronounced in nuclei. By contrast, AICAR elicited a comparable rise in Thr172 phosphorylation in both compartments. Notably, these activators differed drastically in their effects on physiological processes that are located in distinct subcellular compartments. All compounds led to a substantial inactivation of acetyl-CoA-carboxylase 1 in the cytoplasm, with only minor changes to the nuclear enzyme. In the nucleolus, transcription was strongly inhibited by resveratrol, while a moderate inhibition was observed with phenformin and AICAR. Taken together, the compartment-specific phosphorylation of AMPK and downstream events are determined by the activator.
Small conductance potassium channels drive ATP-activated chloride secretion in the oviduct
Authors: Keating N. , Quinlan L. R.
Published: September 2011

The molecular mechanisms controlling fluid secretion within the oviduct have yet to be determined. As in other epithelia, both secretory and absorptive pathways are likely to work in tandem to drive appropriate ionic movement to support fluid movement across the oviduct epithelium. This study explored the role of potassium channels in basolateral extracellular ATP (ATPe)-stimulated ion transport in bovine oviduct epithelium using the Ussing chamber short-circuit current ( ISC) technique. Basal ISC in bovine oviduct epithelium comprises both chloride secretion and sodium absorption and was inhibited by treatment with basolateral K+ channel inhibitors tetrapentlyammonium chloride (TPeA) or BaCl2. Similarly, ATP-stimulated chloride secretion was significantly attenuated by pretreatment with BaCl2, tetraethylammonium (TEA), tolbutamide, and TPeA. Basolateral K+ current, isolated using nystatin-perforation technique, was rapidly activated by ATPe, and pretreatment of monolayers with thapsigargin or TPeA abolished this ATP-stimulated K+ current. To further investigate the type of K+ channel involved in the ATP response in the bovine oviduct, a number of specific Ca2+-activated K+ channel inhibitors were tested on the ATP-induced Δ ISC in intact monolayers. Charbydotoxin, (high conductance and intermediate conductance inhibitor), or paxilline, (high conductance inhibitor) did not significantly alter the ATPe response. However, pretreatment with the small conductance inhibitor apamin resulted in a 60% reduction in the response to ATPe. The presence of small conductance family member KCNN3 was confirmed by RT-PCR and immunohistochemistry. Measurements of intracellular calcium using Fura-2 spectrofluorescence imaging revealed the ability of ATPe to increase intracellular calcium in a phospholipase C-inositol 1,4,5-trisphosphate pathway-sensitive manner. In conclusion, these results provide strong evidence that purinergic activation of a calcium-dependent, apamin-sensitive potassium conductance is essential to promote chloride secretion and thus fluid formation in the oviduct.
Pacemaker activity in the insect (T. molitor) heart: role of the sarcoplasmic reticulum
Authors: Feliciano Danielle F. , Bassani Rosana A. , Oliveira Pedro X. , Bassani José W. M.
Published: September 2011

The electrophysiological properties of the myogenic cardiac cells of insects have been analyzed, but the mechanisms that regulate the pacemaker activity have not been elucidated yet. In mammalian pacemaker cells, different types of membrane ion channels seem to be sequentially activated, perhaps in a cooperative fashion with the current generated by Ca2+extrusion mediated by the electrogenic Na+/Ca2+exchanger, which is sustained by the diastolic sarcoplasmic reticulum (SR) Ca2+release. The objective of the present work was to investigate the role of the SR function on the basal beating rate (BR), and BR modulation by extracellular Ca2+concentration ([Ca2+]o) and neurotransmitters in the in situ dorsal vessel (heart) of the mealworm beetle Tenebrio molitor . The main observations were as follows: 1) basal BR was reduced by 50% by inhibition of SR function, but not affected by perfusion with CsCl or ZD7288; 2) spontaneous activity was abolished by Cd2+; 3) a robust positive chronotropic response could be elicited to serotonin (5-HT), but not to norepinephrine or carbamylcholine; 4) SR inhibition abolished the sustained chronotropic stimulation by [Ca2+]oelevation and by 5-HT, while the latter was unaffected by CsCl. It is concluded that, in T. molitor heart, BR is markedly, but not exclusively, dependent on the SR function, and that BR control and modulation by both [Ca2+]oand 5-HT requires a functional SR.
Time-dependent mediators of HPA axis activation following live Escherichia coli
Authors: Zimomra Z. R. , Porterfield V. M. , Camp R. M. , Johnson J. D.
Published: September 2011

The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 × 107CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE2was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE2correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 × 108CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points.
Endocannabinoids and prostaglandins both contribute to GnRH neuron-GABAergic afferent local feedback circuits
Authors: Glanowska Katarzyna M. , Moenter Suzanne M.
Published: September 2011

Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for central control of fertility. Regulation of GnRH neurons by long-loop gonadal steroid feedback through steroid receptor-expressing afferents such as GABAergic neurons is well studied. Recently, local central feedback circuits regulating GnRH neurons were identified. GnRH neuronal depolarization induces short-term inhibition of their GABAergic afferents via a mechanism dependent on metabotropic glutamate receptor (mGluR) activation. GnRH neurons are enveloped in astrocytes, which express mGluRs. GnRH neurons also produce endocannabinoids, which can be induced by mGluR activation. We hypothesized the local GnRH-GABA circuit utilizes glia-derived and/or cannabinoid mechanisms and is altered by steroid milieu. Whole cell voltage-clamp was used to record GABAergic postsynaptic currents (PSCs) from GnRH neurons before and after action potential-like depolarizations were mimicked. In GnRH neurons from ovariectomized (OVX) mice, this depolarization reduced PSC frequency. This suppression was blocked by inhibition of prostaglandin synthesis with indomethacin, by a prostaglandin receptor antagonist, or by a specific glial metabolic poison, together suggesting the postulate that prostaglandins, potentially glia-derived, play a role in this circuit. This circuit was also inhibited by a CB1 receptor antagonist or by blockade of endocannabinoid synthesis in GnRH neurons, suggesting an endocannabinoid element, as well. In females, local circuit inhibition persisted in androgen-treated mice but not in estradiol-treated mice or young ovary-intact mice. In contrast, local circuit inhibition was present in gonad-intact males. These data suggest GnRH neurons interact with their afferent neurons using multiple mechanisms and that these local circuits can be modified by both sex and steroid feedback.
Generalized vs. stimulus-specific learned fear differentially modifies stimulus encoding in primary sensory cortex of awake rats
Authors: Chen Chien-Fu F. , Barnes Dylan C. , Wilson Donald A.
Published: September 2011

Experience shapes both central olfactory system function and odor perception. In piriform cortex, odor experience appears critical for synthetic processing of odor mixtures, which contributes to perceptual learning and perceptual acuity, as well as contributing to memory for events and/or rewards associated with odors. Here, we examined the effect of odor fear conditioning on piriform cortical single-unit responses to the learned aversive odor, as well as its effects on similar (overlapping mixtures) in freely moving rats. We found that odor-evoked fear responses were training paradigm dependent. Simple association of a condition stimulus positive (CS+) odor with foot shock (unconditioned stimulus) led to generalized fear (cue-evoked freezing) to similar odors. However, after differential conditioning, which included trials where a CS− odor (a mixture overlapping with the CS+) was not paired with shock, freezing responses were CS+ odor specific and less generalized. Pseudoconditioning led to no odor-evoked freezing. These differential levels of stimulus control over freezing were associated with different training-induced changes in single-unit odor responses in anterior piriform cortex (aPCX). Both simple and differential conditioning induced a significant decrease in aPCX single-unit spontaneous activity compared with pretraining levels while pseudoconditioning did not. Simple conditioning enhanced mean receptive field size (breadth of tuning) of the aPCX units, while differential conditioning reduced mean receptive field size. These results suggest that generalized fear is associated with an impairment of olfactory cortical discrimination. Furthermore, changes in sensory processing are dependent on the nature of training and can predict the stimulus-controlled behavioral outcome of the training.