bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of an in silico predicted specific and immunogenic antigen from the OmcB protein for the serodiagnosis of Chlamydia trachomatis infections
Authors: Frikha-Gargouri Olfa , Gdoura Radhouane , Znazen Abir , Gargouri Boutheina , Gargouri Jalel , Rebai Ahmed , Hammami Adnene
Published: December 2008

Background

The OmcB protein is one of the most immunogenic proteins inC. trachomatisandC. pneumoniaeinfections. This protein is highly conserved leading to serum cross reactivity between the various chlamydial species. Since previous studies based on recombinant proteins failed to identify a species specific immune response against the OmcB protein, this study evaluated anin silicopredicted specific and immunogenic antigen from the OmcB protein for the serodiagnosis ofC. trachomatisinfections.

Results

Using the ClustalW and Antigenic programs, we have selected two predicted specific and immunogenic regions in the OmcB protein: the N-terminal (Nt) region containing three epitopes and the C-terminal (Ct) region containing two epitopes with high scores. These regions were cloned into the PinPoint Xa-1 and pGEX-6P-1 expression vectors, incorporating a biotin purification tag and a glutathione-S-transferase tag, respectively. These regions were then expressed inE. coli. Only the pGEX-6P-1 has been found suitable for serological studies as its tag showed less cross reactivity with human sera and was retained for the evaluation of the selected antigens. Only the Ct region of the protein has been found to be well expressed inE. coliand was evaluated for its ability to be recognized by human sera. 384 sera were tested for the presence of IgG antibodies toC. trachomatisby our in house microimmunofluorescence (MIF) and the developed ELISA test. Using the MIF as the reference method, the developed OmcB Ct ELISA has a high specificity (94.3%) but a low sensitivity (23.9). Our results indicate that the use of the sequence alignment tool might be useful for identifying specific regions in an immunodominant antigen. However, the two epitopes, located in the selected Ct region, of the 24 predicted in the full length OmcB protein account for approximately 25% of the serological response detected by MIF, which limits the use of the developed ELISA test when screeningC. trachomatisinfections.

Conclusion

The developed ELISA test might be used as a confirmatory test to assess the specificity of serological results found by MIF.
Antioxidant and free radical scavenging activity of Spondias pinnata
Authors: Hazra Bibhabasu , Biswas Santanu , Mandal Nripendranath
Published: December 2008

Background

Many diseases are associated with oxidative stress caused by free radicals. Current research is directed towards finding naturally-occurring antioxidants of plant origin. The aim of the present study was to evaluate thein vitroantioxidant activities ofSpondias pinnatastem bark extract.

Methods

A 70% methanol extract ofSpondias pinnatastem bark was studiedin vitrofor total antioxidant activity, for scavenging of hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide, peroxynitrite, singlet oxygen and hypochlorous acid, and for iron chelating capacity, reducing power, and phenolic and flavonoid contents.

Results

The extract showed total antioxidant activity with a trolox equivalent antioxidant concentration (TEAC) value of 0.78 ± 0.02. The IC50values for scavenging of free radicals were 112.18 ± 3.27 μg/ml, 13.46 ± 0.66 μg/ml and 24.48 ± 2.31 μg/ml for hydroxyl, superoxide and nitric oxide, respectively. The IC50for hydrogen peroxide scavenging was 44.74 ± 25.61 mg/ml. For the peroxynitrite, singlet oxygen and hypochlorous acid scavenging activities the IC50values were 716.32 ± 32.25 μg/ml, 58.07 ± 5.36 μg/ml and 127.99 ± 6.26 μg/ml, respectively. The extract was found to be a potent iron chelator with IC50= 66.54 ± 0.84 μg/ml. The reducing power was increased with increasing amounts of extract. The plant extract (100 mg) yielded 91.47 ± 0.004 mg/ml gallic acid-equivalent phenolic content and 350.5 ± 0.004 mg/ml quercetin-equivalent flavonoid content.

Conclusion

The present study provides evidence that a 70% methanol extract ofSpondias pinnatastem bark is a potential source of natural antioxidants.
Identification of recruitment and retention strategies for rehabilitation professionals in Ontario, Canada: results from expert panels
Authors: Tran Diem , Hall Linda McGillis , Davis Aileen , Landry Michel D , Burnett Dawn , Berg Katherine , Jaglal Susan
Published: December 2008

Background

Demand for rehabilitation services is expected to increase due to factors such as an aging population, workforce pressures, rise in chronic and complex multi-system disorders, advances in technology, and changes in interprofessional health service delivery models. However, health human resource (HHR) strategies for Canadian rehabilitation professionals are lagging behind other professional groups such as physicians and nurses. The objectives of this study were: 1) to identify recruitment and retention strategies of rehabilitation professionals including occupational therapists, physical therapists and speech language pathologists from the literature; and 2) to investigate both the importance and feasibility of the identified strategies using expert panels amongst HHR and education experts.

Methods

A review of the literature was conducted to identify recruitment and retention strategies for rehabilitation professionals. Two expert panels, one onRecruitment and Retentionand the other onEducationwere convened to determine the importance and feasibility of the identified strategies. A modified-delphi process was used to gain consensus and to rate the identified strategies along these two dimensions.

Results

A total of 34 strategies were identified by theRecruitment and RetentionandEducationexpert panels as being important and feasible for the development of a HHR plan for recruitment and retention of rehabilitation professionals. Seven were categorized under theQuality of Worklife and Work Environmenttheme, another seven inFinancial Incentives and Marketing, two inWorkload and Skill Mix, thirteen inProfessional Developmentand five inEducation and Training.

Conclusion

Based on the results from the expert panels, the three major areas of focus for HHR planning in the rehabilitation sector should include strategies addressingQuality of Worklife and Work Environment,Financial Incentives and MarketingandProfessional Development.
Fat-to-glucose interconversion by hydrodynamic transfer of two glyoxylate cycle enzyme genes
Authors: Cordero P , Campion J , Milagro FI , Marzo F , Martinez JA
Published: December 2008

The glyoxylate cycle, which is well characterized in higher plants and some microorganisms but not in vertebrates, is able to bypass the citric acid cycle to achieve fat-to-carbohydrate interconversion. In this context, the hydrodynamic transfer of two glyoxylate cycle enzymes, such as isocytrate lyase (ICL) and malate synthase (MS), could accomplish the shift of using fat for the synthesis of glucose. Therefore, 20 mice weighing 23.37 ± 0.96 g were hydrodinamically gene transferred by administering into the tail vein a bolus with ICL and MS. After 36 hours, body weight, plasma glucose, respiratory quotient and energy expenditure were measured. The respiratory quotient was increased by gene transfer, which suggests that a higher carbohydrate/lipid ratio is oxidized in such animals. This application could help, if adequate protocols are designed, to induce fat utilization for glucose synthesis, which might be eventually useful to reduce body fat depots in situations of obesity and diabetes.
Protein expression profiling during chick retinal maturation: a proteomics-based approach
Authors: Finnegan Sorcha , Robson Joanne L , Wylie Mildred , Healy Adrienne , Stitt Alan W , Curry William J
Published: December 2008

Background

The underlying pathways that drive retinal neurogenesis and synaptogenesis are still relatively poorly understood. Protein expression analysis can provide direct insight into these complex developmental processes. The aim of this study was therefore to employ proteomic analysis to study the developing chick retina throughout embryonic (E) development commencing at day 12 through 13, 17, 19 and post-hatch (P) 1 and 33 days.

Results

2D proteomic and mass spectrometric analysis detected an average of 1514 spots per gel with 15 spots demonstrating either modulation or constitutive expression identified via MS. Proteins identified included alpha and beta-tubulin, alpha enolase, B-creatine kinase, gamma-actin, platelet-activating factor (PAF), PREDICTED: similar to TGF-beta interacting protein 1, capping protein (actin filament muscle Z line), nucleophosmin 1 (NPM1), dimethylarginine dimethylaminohydrolase, triosphoaphate isomerase, DJ1, stathmin, fatty acid binding protein 7 (FABP7/B-FABP), beta-synuclein and enhancer of rudimentary homologue.

Conclusion

This study builds upon previous proteomic investigations of retinal development and represents the addition of a unique data set to those previously reported. Based on reported bioactivity some of the identified proteins are most likely to be important to normal retinal development in the chick. Continued analysis of the dynamic protein populations present at the early stages and throughout retinal development will increase our understanding of the molecular events underpinning retinogenesis.
Origins, Actions and Dynamic Expression Patterns of the Neuropeptide VGF in Rat Peripheral and Central Sensory Neurones Following Peripheral Nerve Injury
Authors: Moss Andrew , Ingram Rachel , Koch Stephanie , Theodorou Andria , Low Lucie , Baccei Mark , Hathway Gareth J , Costigan Michael , Salton Stephen R , Fitzgerald Maria
Published: December 2008

Background:

The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated.

Results:

Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5–50 nmol) to naïve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses.

Conclusion:

VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naïve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain.
Parasites of importance for human health in Nigerian dogs: high prevalence and limited knowledge of pet owners
Authors: Ugbomoiko Uade Samuel , Ariza Liana , Heukelbach Jorg
Published: December 2008

Background

Dogs are the most common pet animals worldwide. They may harbour a wide range of parasites with zoonotic potential, thus causing a health risk to humans. In Nigeria, epidemiological knowledge on these parasites is limited.

Methods

In a community-based study, we examined 396 dogs in urban and rural areas of Ilorin (Kwara State, Central Nigeria) for ectoparasites and intestinal helminths. In addition, a questionnaire regarding knowledge and practices was applied to pet owners.

Results

Nine ectoparasite species belonging to four taxa and six intestinal helminth species were identified: fleas (Ctenocephalides canis, Pulex irritans, Tunga penetrans), mites (Demodex canis, Otodectessp.,Sarcoptes scabieivar.canis), ticks (Rhipicephalus sanguineus, Ixodessp.), and lice (Trichodectes canis); andToxocara canis, Ancylostomasp.,Trichuris vulpis, Dipylidium caninum, Taenidae andStrongyloidessp. Overall prevalence of ectoparasites was 60.4% and of intestinal helminths 68.4%. The occurrence ofC. canis, R. sanguineus, T. canis, Ancylostomasp. andT. vulpiswas most common (prevalence 14.4% to 41.7%). Prevalence patterns in helminths were age-dependent, withT. canisshowing a decreasing prevalence with age of host, and a reverse trend in other parasite species. Knowledge regarding zoonoses was very limited and the diseases not considered a major health problem. Treatment with antiparasitic drugs was more frequent in urban areas.

Conclusion

Parasites of importance for human health were highly prevalent in Nigerian dogs. Interventions should include health education provided to dog owners and the establishment of a program focusing on zoonotic diseases.
Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life
Authors: van Rij CM , Oughlane-Heemsbergen WD , Ackerstaff AH , Lamers EA , Balm AJM , Rasch CRN
Published: December 2008

Background and purpose

To assess the impact of intensity modulated radiotherapy (IMRT) versus conventional radiation on late xerostomia and Quality of Life aspects in head and neck cancer patients.

Patients and nethods

Questionnaires on xerostomia in rest and during meals were sent to all patients treated between January 1999 and December 2003 with a T1-4, N0-2 M0 head and neck cancer, with parotid gland sparing IMRT or conventional bilateral neck irradiation to a dose of at least 60 Gy, who were progression free and had no disseminated disease (n = 192). Overall response was 85% (n = 163); 97% in the IMRT group (n = 75) and 77% in the control group (n = 88) the median follow-up was 2.6 years. The prevalence of complaints was compared between the two groups, correcting for all relevant factors at multivariate ordinal regression analysis.

Results

Patients treated with IMRT reported significantly less difficulty transporting and swallowing their food and needed less water for a dry mouth during day, night and meals. They also experienced fewer problems with speech and eating in public. Laryngeal cancer patients in general had fewer complaints than oropharynx cancer patients but both groups benefited from IMRT. Within the IMRT group the xerostomia scores were better for those patients with a mean parotid dose to the "spared" parotid below 26 Gy.

Conclusion

Parotid gland sparing IMRT for head and neck cancer patients improves xerostomia related quality of life compared to conventional radiation both in rest and during meals. Laryngeal cancer patients had fewer complaints but benefited equally compared to oropharyngeal cancer patients from IMRT.
Intraneural injection of corticosteroids to treat nerve damage in leprosy: a case report and review of literature
Authors: Nashed Sherine G , Rageh Tarek A , Attallah-Wasif Emad S , Abd-Elsayed Alaa A
Published: December 2008

Introduction

Nerve damage in leprosy patients leads to deformities and disabilities. Oral corticosteroids are given early to prevent permanent injury. We present a new approach to treat well-established nerve damage with local injection of corticosteroids.

Case presentation

A 60-year-old leprosy patient presented with right claw hand deformity secondary to right ulnar and median neuropathy. Monthly intraneural injection of corticosteroids resulted in improvement in sensory and motor function of his right hand over a 6-month period. Nerve conduction velocity testing documented the success of our therapy.

Conclusion

We report the first case of successful nerve regeneration in neglected neuropathy secondary to leprosy after local injection of corticosteroids. Intraneural extra-fascicular injection of corticosteroids improved the sensory and motor nerve function in our patient with borderline leprosy regardless of the duration of nerve function loss.
Orthodontic traction of impacted canine using magnet: a case report
Authors: Li Larry CF , Wong Ricky WK , King Nigel M
Published: December 2008

A 15 year and 1 month old Chinese female with palatally impacted upper left canine was successfully treated with an upper removable appliance with a magnet incorporated to provide orthodontic traction force. This case report indicates the possibility of using magnetic force as a safe, effective and comfortable way for orthodontic traction.
All-trans retinoic acid suppresses interleukin-6 expression in interleukin-1-stimulated synovial fibroblasts by inhibition of ERK1/2pathway independently of RAR activation
Authors: Kirchmeyer Mélanie , Koufany Meriem , Sebillaud Sylvie , Netter Patrick , Jouzeau Jean-Yves , Bianchi Arnaud
Published: December 2008

Introduction

Interleukin-6 (IL-6) is thought to play a pathogenic role in rheumatoid arthritis and synovium is a major source of IL-6 release. We investigated the ability of retinoids to suppress IL-6 expression in IL-1-stimulated synovial fibroblasts, with special care to the contribution of retinoic acid receptor (RAR) and retinoid X receptor (RXR) subtypes, and the implication of the mitogen-activated protein kinase (MAPK) pathway.

Methods

RAR-α, -β, and -γ and RXR-α, -β, and -γ levels were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or Western blot in rat synovial fibroblasts stimulated with 10 ng/mL of IL-1β. Stimulated levels of IL-6 were assessed by RT-qPCR or immunoassays in the presence or absence of 1 μM all-transretinoic acid (ATRA) (RAR agonist) or 0.3 μM BMS-649 (RXR agonist). The contribution of RAR subtypes was checked with selective agonists or small interfering RNAs. The effect of ATRA on upstream MAPK (p38 MAPK, c-Jun N-terminal kinase [JNK], and extracellularly regulated kinase 1/2 [ERK1/2]) was assessed by Western blot, and the contribution of the ERK1/2pathway to the activation of pro-inflammatory transcription factors was studied by TransAm™ assays.

Results

Synovial fibroblasts expressed all RAR and RXR subtypes except RXR-γ. In IL-1-stimulated cells, ATRA, but not BMS-649, reducedIL-6expression whereas selective RAR agonists were inactive. The inhibitory effect of ATRA onIL-6was not affected by the silencing of RAR subtypes. ATRA also reduced the phosphorylation of ERK1/2, but not of p38 MAPK or of JNK. The suppressive effect of ATRA on the activation of activator protein-1 (AP-1) and nuclear factor-IL-6 (NF-IL-6) was reproduced by the MEK1 (mitogen-activated protein extracellularly regulated kinase kinase 1) inhibitor PD-98059, whereas ATRA and PD-98059 had no effect on NF-κB activation.

Conclusions

Among RAR and RXR agonists, only ATRA inhibited IL-1-induced IL-6 expression in rat synovial fibroblasts by inhibiting ERK1/2pathway and subsequent activation of AP-1 and NF-IL-6 independently of RAR.
Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy
Authors: Nicaise Roland Pascale , Grootenboer Mignot Sabine , Bruns Alessandra , Hurtado Margarita , Palazzo Elisabeth , Hayem Gilles , Dieudé Philippe , Meyer Olivier , Chollet Martin Sylvie
Published: December 2008

Introduction

Antibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA.

Methods

We studied two groups of RA patients, one with (n = 80) and one without (n = 76) anti-CCP antibodies. The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases (51 psoriatic rheumatism, 58 primary Sjögren syndrome, and 49 ankylosis spondylitis). Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6, 12, 18, and 24 months of infliximab treatment. Anti-CCP2 and anti-MCV levels were assayed using a commercial enzyme-linked immunosorbent assay. IgM rheumatoid factor was determined by nephelometry.

Results

In accordance with the cutoff values recommended by the manufacturer, the specificity of anti-MCV antibodies was 90.9%. We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies (94.2%). With this optimal cutoff, anti-MCV antibodies were found in 11.8% (9/76) of RA patients without anti-CCP, and similarly, anti-CCP antibodies were found in 11.2% (9/80) of RA patients without anti-MCV. Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor. Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline (P < 0.01) as a significant decrease of anti-CCP levels occurred only at 24 months (P < 0.04). Moreover, an anti-MCV decrease was significantly associated with DAS28 (disease activity score using 28 joint counts) improvements 12 months into therapy.

Conclusions

Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV. Moreover, anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy.
Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic
Authors: Merouani Mehdi , Guignard Bruno , Vincent François , Borron Stephen W , Karoubi Philippe , Fosse Jean-Philippe , Cohen Yves , Clec'h Christophe , Vicaut Eric , Marbeuf-Gueye Carole , Lapostolle Frederic , Adnet Frederic
Published: December 2008

Introduction

The rate of weaning of vasopressors drugs is usually an empirical choice made by the treating in critically ill patients. We applied fuzzy logic principles to modify intravenous norepinephrine (noradrenaline) infusion rates during norepinephrine infusion in septic patients in order to reduce the duration of shock.

Methods

Septic patients were randomly assigned to norepinephrine infused either at the clinician's discretion (control group) or under closed-loop control based on fuzzy logic (fuzzy group). The infusion rate changed automatically after analysis of mean arterial pressure in the fuzzy group. The primary end-point was time to cessation of norepinephrine. The secondary end-points were 28-day survival, total amount of norepinephine infused and duration of mechanical ventilation.

Results

Nineteen patients were randomly assigned to fuzzy group and 20 to control group. Weaning of norepinephrine was achieved in 18 of the 20 control patients and in all 19 fuzzy group patients. Median (interquartile range) duration of shock was significantly shorter in the fuzzy group than in the control group (28.5 [20.5 to 42] hours versus 57.5 [43.7 to 117.5] hours; P < 0.0001). There was no significant difference in duration of mechanical ventilation or survival at 28 days between the two groups. The median (interquartile range) total amount of norepinephrine infused during shock was significantly lower in the fuzzy group than in the control group (0.6 [0.2 to 1.0] μg/kg versus 1.4 [0.6 to 2.7] μg/kg; P < 0.01).

Conclusions

Our study has shown a reduction in norepinephrine weaning duration in septic patients enrolled in the fuzzy group. We attribute this reduction to fuzzy control of norepinephrine infusion.

Trial registration

Trial registration: Clinicaltrials.gov NCT00763906.
Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients
Authors: de Jonge Evert , Peelen Linda , Keijzers Peter J , Joore Hans , de Lange Dylan , van der Voort Peter HJ , Bosman Robert J , de Waal Ruud AL , Wesselink Ronald , de Keizer Nicolette F
Published: December 2008

Introduction

The aim of this study was to investigate whether in-hospital mortality was associated with the administered fraction of oxygen in inspired air (FiO2) and achieved arterial partial pressure of oxygen (PaO2).

Methods

This was a retrospective, observational study on data from the first 24 h after admission from 36,307 consecutive patients admitted to 50 Dutch intensive care units (ICUs) and treated with mechanical ventilation. Oxygenation data from all admission days were analysed in a subset of 3,322 patients in 5 ICUs.

Results

Mean PaO2 and FiO2 in the first 24 h after ICU admission were 13.2 kPa (standard deviation (SD) 6.5) and 50% (SD 20%) respectively. Mean PaO2 and FiO2 from all admission days were 12.4 kPa (SD 5.5) and 53% (SD 18). Focusing on oxygenation in the first 24 h of admission, in-hospital mortality was shown to be linearly related to FiO2 value and had a U-shaped relationship with PaO2 (both lower and higher PaO2 values were associated with a higher mortality), independent of each other and of Simplified Acute Physiology Score (SAPS) II, age, admission type, reduced Glasgow Coma Scale (GCS) score, and individual ICU. Focusing on the entire ICU stay, in-hospital mortality was independently associated with mean FiO2 during ICU stay and with the lower two quintiles of mean PaO2 value during ICU stay.

Conclusions

Actually achieved PaO2 values in ICU patients in The Netherlands are higher than generally recommended in the literature. High FiO2, and both low PaO2 and high PaO2 in the first 24 h after admission are independently associated with in-hospital mortality in ICU patients. Future research should study whether this association is causal or merely a reflection of differences in severity of illness insufficiently corrected for in the multivariate analysis.
Approximate fluid substitution for vertical velocities in weakly anisotropic VTI rocks
Authors: Mavko Gary , Bandyopadhyay Kaushik
Published: December 2008

Despite the prevalence of elastic anisotropy in rocks, most models used routinely for wave propagation, imaging, and rock physics assume an isotropic Earth. The main reason for using isotropic approximations is that we seldom measure enough parameters to characterize the stiffness tensor of a rock completely. Fluid substitution is an important example: because of an incomplete knowledge of the stiffness tensor, often we choose isotropic equations over their anisotropic form. Assuming weak anisotropy, we derive an approximate form of the anisotropic fluid-substitution equation for seismic waves propagating along the symmetry axis of a transversely isotropic medium. The approximation takes the form of the usual isotropic calculation, with a simple first-order correction proportional to the Thomsen anisotropic parameter [Formula: see text], thus requiring only three elastic constants. Because [Formula: see text] can be either greater than or less than zero in a VTI medium, we can explain why isotropic fluid substitution sometimes overpredicts or underpredicts the full anisotropic result. Numerical simulations show that the approximate equation is valid for anisotropic medium with absolute value of [Formula: see text] as high as 0.3.
3D seismic traveltime tomography imaging of the shallow subsurface at the C O2 SINK project site, Ketzin, Germany
Authors: Yordkayhun Sawasdee , Tryggvason Ari , Norden Ben , Juhlin Christopher , Bergman Björn
Published: December 2008

A 3D reflection seismic survey was performed in 2005 at the Ketzin carbon dioxide [Formula: see text] pilot geological-storage site (the [Formula: see text] project) near Berlin, Germany, to image the geological structure of the site to depths of about [Formula: see text]. Because of the acquisition geometry, frequency limitations of the source, and artefacts of the data processing, detailed structures shallower than about [Formula: see text] were unclear. To obtain structural images of the shallow subsurface, we applied 3D traveltime tomography to data near the top of the Ketzin anticline, where faulting is present. Understanding the shallow subsurface structure is important for long-term monitoring aspects of the project after [Formula: see text] has been injected into a saline aquifer at about [Formula: see text] depth. We used a 3D traveltime tomography algorithm based on a combination ofsolving for 3D velocity structure and static corrections in the inversion process to account for artefacts in the velocity structure because of smearing effects from the unconsolidated cover. The resulting velocity model shows low velocities of [Formula: see text] in the uppermost shallow subsurface of the study area. The velocity reaches about [Formula: see text] at a depth of [Formula: see text]. This coincides approximately with the boundary between Quaternary units, which contain the near-surface freshwater reservoir and the Tertiary clay aquitard. Correlation of tomographic images with a similarity attribute slice at [Formula: see text] (about [Formula: see text] depth) indicates that at least one east-west striking fault zone observed in the reflection data might extend into the Tertiary unit. The more detailed images of the shallow subsurface from this study provided valuable information on this potentially risky area.
Sediment with porous grains: Rock-physics model and application to marine carbonate and opal
Authors: Ruiz Franklin , Dvorkin Jack
Published: December 2008

We offer an effective-medium model for estimating the elastic properties of high-porosity marine calcareous sediment and diatomite. This model treats sediment as a pack of porous elastic grains. The effective elastic moduli of the porous grains are calculated using the differential effective-medium (DEM) model, whereby the intragranular ellipsoidal inclusions have a fixed aspect ratio and are filled with seawater. Then the elastic moduli of a pack of these spherical grains are calculated using a modified (scaled to the critical porosity) upper Hashin-Shtrikman bound above the critical porosity and modified lower (carbonates) and upper (opal) Hashin-Shtrikman bounds below the critical porosity. The best match between the model-predicted compressional- and shear-wave velocities and Ocean Drilling Program (ODP) data from three wells is achieved when the aspect ratio of intragranular pores is 0.5. This model assigns finite, nonzero values to the shear modulus of high-porosity marine sediment, unlike the suspension model commonly used in such depositional settings. The approach also allows one to obtain a satisfactory match with laboratory diatomite velocity data.
Grain-size to effective pore-size transformation derived from electrokinetic theory
Authors: Glover P. W. , Walker E.
Published: December 2008

Most permeability models use effective grain size or effective pore size as an input parameter. Until now, an efficacious way of converting between the two has not been available. We propose a simple conversion method for effective grain diameter and effective pore radius using a relationship derived by comparing two independent equations for permeability, based on the electrokinetic properties of porous media. The relationship, which we call the theta function, is not dependent upon a particular geometry and implicitly allows for the widely varying style of microstructures exhibited by porous media by using porosity, cementation exponent, formation factor, and a packing constant. The method is validated using 22 glass bead packs, for which the effective grain diameter is known accurately, and a set of 188 samples from a sand-shale sequence in the North Sea. This validation uses measurements of effective grain size from image analysis, pore size from mercury injection capillary pressure (MICP) measurements, and effective pore radius calculated from permeability experiments, all of which are independent. Validation tests agree that the technique accurately converts an effective grain diameter into an effective pore radius. Furthermore, for the clastic data set, there exists a power law relationship in porosity between effective grain size and effective pore size. The theta function also can be used to predict the fluid permeability of a sample, based on effective pore radius. The result is extremely good predictions over seven orders of magnitude.
Relationship between Total and High Molecular Weight Adiponectin Levels and Plasma Nonesterified Fatty Acid Tolerance during Enhanced Intravascular Triacylglycerol Lipolysis in Men
Authors: Lavoie F. , Frisch F. , Brassard P. , Normand-Lauzière F. , Cyr D. , Gagnon R. , Drouin R. , Baillargeon J. -P. , Carpentier A. C.
Published: December 2008

Context: Increased plasma nonesterified fatty acid (NEFA) appearance during enhanced intravascular triacylglycerol (TG) lipolysis is a marker of metabolic adipose tissue dysfunction and may lead to the development of insulin resistance. The relationship between total and high molecular weight (HMW) adiponectin levels, NEFA appearance, and total TG lipolytic capacity has not been previously studied in humans.

Objectives: Our objective was to determine whether total and HMW adiponectin plasma levels are associated with plasma NEFA level and appearance, and with total TG lipolytic rate during enhanced intravascular TG lipolysis in men.

Design: This was a cross-sectional metabolic study.

Setting: The study was performed at an academic clinical research center.

Participants: There were 15 healthy men (mean ± sd body mass index 25.5 ± 4.7 kg/m2) aged 21–50 yr (mean ± sd 31.1 ± 10.2) without first-degree relatives with type 2 diabetes included in the study.

Interventions: Pancreatic clamps and iv infusion of stable isotopic tracers ([1,1,2,3,3-2H5]glycerol and [U-13C]palmitate) were performed, whereas intravascular TG lipolysis was clamped by iv infusion of heparin plus Intralipid at low (fasting) and high insulin levels. Total and HMW adiponectin levels were measured using an ELISA.

Main Outcome Measures: Levels of total and HMW adiponectin, palmitate appearance (plasma palmitate appearance rate), and glycerol appearance (plasma glycerol appearance rate) were calculated.

Results: During heparin plus Intralipid infusion, total and HMW adiponectin was inversely correlated with plasma palmitate appearance rate (r = −0.65; P = 0.01), but this association was lost when expressed per nonlean weight. Adiponectin levels were positively associated with plasma glycerol appearance rate per nonlean weight (r = 0.71 and r = 0.66, respectively; P ≤ 0.01).

Conclusions: Increased adipose tissue mass likely explains the association between low adiponectin and reduced NEFA tolerance. Adiponectin level is a marker of total TG lipolytic rate per adipose tissue mass in men.
Induction of Spermatogenesis and Fertility during Gonadotropin Treatment of Gonadotropin-Deficient Infertile Men: Predictors of Fertility Outcome
Authors: Liu Peter Y. , Baker H. W. Gordon , Jayadev Veena , Zacharin Margaret , Conway Ann J. , Handelsman David J.
Published: December 2008

Background: The induction of spermatogenesis and fertility with gonadotropin therapy in gonadotropin-deficient men varies in rate and extent. Understanding the predictors of response would inform clinical practice but requires multivariate analyses in sufficiently large clinical cohorts that are suitably detailed and frequently assessed.

Design, Setting, and Participants: A total of 75 men, with 72 desiring fertility, was treated at two academic andrology centers for a total of 116 courses of therapy from 1981–2008.

Outcomes: Semen analysis and testicular examination were performed every 3 months.

Results: A total of 38 men became fathers, including five through assisted reproduction. The median time to achieve first sperm was 7.1 months [95% confidence interval (CI) 6.3–10.1]) and for conception was 28.2 months (95% CI 21.6–38.5). The median sperm concentration at conception for unassisted pregnancies was 8.0 m/ml (95% CI 0.2–59.5). Multivariate correlated time-to-event analyses show that larger testis volume, previous treatment with gonadotropins, and no previous androgen use each independently predicts faster induction of spermatogenesis and unassisted pregnancy.

Conclusions: Larger testis volume is a useful prognostic indicator of response. The association of slower responses after prior androgen therapy suggests that faster pregnancy rates might be achieved by substituting gonadotropin for androgen therapy for pubertal induction, although a prospective randomized trial will be required to prove this.
Effect of Dehydroepiandrosterone Replacement on Lipoprotein Profile in Hypoadrenal Women
Authors: Srinivasan Manivannan , Irving Brian A. , Dhatariya Ketan , Klaus Katherine A. , Hartman Stacy J. , McConnell Joseph P. , Nair K. Sreekumaran
Published: December 2008

Context: Levels of dehydroepiandrosterone (DHEA) and its sulfate form (DHEAS) are inversely associated with cardiovascular mortality in men but not women. Very little evidence is available on the impact of DHEA administration on lipoprotein profile in women. DHEAS levels are very low/undetectable in hypoadrenal women.

Objective: The objective of the study was to determine the impact of DHEA replacement on lipoprotein profile in hypoadrenal women.

Design and Setting: A double-blind, randomized, placebo-controlled, cross-over design study was conducted at the Mayo Clinic.

Participants: Thirty-three hypoadrenal Caucasian women (mean ± sd; age 50.3 ± 15.2 yr, body mass index 26.6 ± 4.4 kg/m2) took part in the study.

Intervention: Study participants were assigned to receive either a placebo or 50 mg/d of DHEA for 3 months each. Lipid levels and lipoprotein profile were analyzed using the Lipo Science Lipoprotein nuclear magnetic resonance system.

Main Outcome Measures: Changes in various lipoprotein sizes and levels were measured.

Results: The DHEA period had higher plasma DHEAS levels than during placebo (<0.3 ± 0.0 vs. 3.5 ± 1.3 nmol/liter, P < 0.001). DHEA replacement significantly reduced total cholesterol (20.0 vs. −22, P = 0.02) and high-density lipoprotein (HDL) levels (2.0 vs. −6.0, P = 0.006) and tends to reduce triglyceride and total low-density lipoprotein levels. Although, DHEA replacement had no effect on low-density lipoprotein particle size, it significantly reduced larger HDL particles and to modest extent small HDL particles.

Conclusions: Our study findings showed that oral DHEA administration in hypoadrenal women results in an unfavorable lipoprotein profile. The results warrant long-term studies to determine the impact of DHEA replacement on cardiovascular risk.
Mild mitochondrial uncoupling induces 3T3-L1 adipocyte de-differentiation by a PPARγ-independent mechanism, whereas TNFα-induced de-differentiation is PPARγ dependent
Authors: Tejerina Silvia , De Pauw Aurélia , Vankoningsloo Sébastien , Houbion Andrée , Renard Patricia , De Longueville Françoise , Raes Martine , Arnould Thierry
Published: December 2008

Impairment of mitochondrial activity affects lipid-metabolizing tissues and mild mitochondrial uncoupling has been proposed as a possible strategy to fight obesity and associated diseases. In this report, we characterized the 3T3-L1-adipocyte `de-differentiation' induced by carbonyl cyanide (p-trifluoromethoxy)-phenylhydrazone (FCCP), a mitochondrial uncoupler. We found a decrease in triglyceride (TG) content in adipocytes incubated with this molecule. We next analyzed the expression of genes encoding adipogenic markers and effectors and compared the differentially expressed genes in adipocytes treated with FCCP or TNFα (a cytokine known to induce adipocyte de-differentiation). Furthermore, a significant decrease in the transcriptional activity of PPARγ and C/EBPα transcription factors was found in adipocytes with impaired mitochondrial activity. However, although these modifications were also found in TNFα-treated adipocytes, rosiglitazone and 9-cis retinoic acid (PPARγ and RXR ligands) were unable to prevent triglyceride loss in FCCP-treated cells. Metabolic assays also revealed that TG reduction could be mediated by a downregulation of lipid synthesis rather than an upregulation of fatty acid oxidation. Finally, lipolysis stimulated by the uncoupler also seems to contribute to the TG reduction, a process associated with perilipin A downregulation. These results highlight some new mechanisms that might potentially be involved in adipocyte de-differentiation initiated by a mitochondrial uncoupling.
Activation of P2X7 receptors causes isoform-specific translocation of protein kinase C in osteoclasts
Authors: Armstrong Souzan , Pereverzev Alexey , Dixon S. Jeffrey , Sims Stephen M.
Published: December 2008

Nucleotides, released in response to mechanical or inflammatory stimuli, signal through P2 nucleotide receptors in many cell types. Osteoclasts express P2X7 receptors (encoded by P2rx7) – Ca2+-permeable channels that are activated by high concentrations of extracellular ATP. Genetic disruption of P2rx7 leads to increased resorption and reduced skeletal response to mechanical stimuli. To investigate whether P2X7 receptors couple to activation of protein kinase C (PKC), RAW 264.7 cells were differentiated into multinucleated osteoclast-like cells and live-cell confocal imaging was used to localize enhanced green fluorescent protein (EGFP)-tagged PKC. Benzoylbenzoyl-ATP (BzATP; a P2X7 agonist) induced transient translocation of PKCα to the basolateral membrane. UTP or ATP (10 μM), which activate P2 receptors other than P2X7, failed to induce translocation. Moreover, BzATP failed to induce PKC translocation in osteoclasts derived from the bone marrow of P2rx7–/– mice, demonstrating specificity for P2X7. BzATP induced a transient rise of cytosolic Ca2+, and removal of extracellular Ca2+ abolished the translocation of PKCα that was induced by BzATP (but not by phorbol ester). We examined the isoform specificity of this response, and observed translocation of the Ca2+-dependent isoforms PKCα and PKCβI, but not the Ca2+-independent isoform PKCδ. Thus, activation of P2X7 receptors specifically induces Ca2+-dependent translocation of PKC to the basolateral membrane domain of osteoclasts, an aspect of spatiotemporal signaling not previously recognized.
Rolling blackout is required for bulk endocytosis in non-neuronal cells and neuronal synapses
Authors: Vijayakrishnan Niranjana , Woodruff Elvin A. , Broadie Kendal
Published: December 2008

Rolling blackout (RBO) is a Drosophila EFR3 integral membrane lipase. A conditional temperature-sensitive (TS) mutant (rbots) displays paralysis within minutes following a temperature shift from 25°C to 37°C, an impairment previously attributed solely to blocked synaptic-vesicle exocytosis. However, we found that rbots displays a strong synergistic interaction with the Syntaxin-1A TS allele syx3-69, recently shown to be a dominant positive mutant that increases Syntaxin-1A function. At neuromuscular synapses, rbots showed a strong defect in styryl-FM-dye (FM) endocytosis, and rbots;syx3-69 double mutants displayed a synergistic, more severe, endocytosis impairment. Similarly, central rbots synapses in primary brain culture showed severely defective FM endocytosis. Non-neuronal nephrocyte Garland cells showed the same endocytosis defect in tracer-uptake assays. Ultrastructurally, rbots displayed a specific defect in tracer uptake into endosomes in both neuronal and non-neuronal cells. At the rbots synapse, there was a total blockade of endosome formation via activity-dependent bulk endocytosis. Clathrin-mediated endocytosis was not affected; indeed, there was a significant increase in direct vesicle formation. Together, these results demonstrate that RBO is required for constitutive and/or bulk endocytosis and/or macropinocytosis in both neuronal and non-neuronal cells, and that, at the synapse, this mechanism is responsive to the rate of Syntaxin-1A-dependent exocytosis.
How Does Outsourcing Affect Performance Dynamics? Evidence from the Automobile Industry
Authors: Novak Sharon , Stern Scott
Published: December 2008

This paper examines the impact of vertical integration on the dynamics of performance over the automobile product development life cycle. Building on recent work in organizational economics and strategy, we evaluate the relationship between vertical integration and different dimensions of product performance. Outsourcing facilitates access to cutting-edge technology and the use of high-powered performance contracts. Vertical integration allows firms to adapt to unforeseen contingencies and customer feedback, maintain balanced incentives over the life cycle, and develop firm-specific capabilities over time. Together, these effects highlight a crucial trade-off: while outsourcing is associated with higher levels of initial performance, vertical integration will be associated with performance improvement over the product life cycle. We test these ideas using detailed data from the luxury automobile segment, establishing three key results. First, initial performance is declining in the level of vertical integration. Second, the level of performance improvement is significantly increasing in the level of vertical integration. Finally, the impact of vertical integration is mediated by the level of preexisting capabilities, by the salience of opportunities to access external technology leaders, and by the scope for learning over the product life cycle. Together, the findings highlight a strategic governance trade-off between short-term performance and the evolution of firm capabilities.
Technical Note—Price Promotions in Asymmetric Duopolies with Heterogeneous Consumers
Authors: Sinitsyn Maxim
Published: December 2008

In this note I investigate the outcome of a static price competition between a strong firm (a firm with an established loyal consumer base) and a weak firm (a firm without loyal consumers). The consumers are divided into the strong firm's loyal segment and the switching segment, members of which have heterogeneous tastes for the firms' products. In the presence of loyal consumers, for a large set of the parameters of the demand function, the firms use mixed strategies over a finite number of prices. These strategies can be interpreted as occurrences of sales. The most common case is that of the strong firm's using two prices and the weak firm's using one price. However, when both firms use sales, the weak firm promotes more often than the strong firm.
Body Mass Index and Serum Lipid Changes During Treatment with Valproic Acid in Children with Epilepsy
Authors: Grosso Salvatore , Mostardini Rosa , Piccini Barbara , Balestri Paolo
Published: December 2008

BACKGROUND

Valproic acid is the drug of choice for a wide variety of epileptic seizures and syndromes because of its broad spectrum of activity and because, in most patients, it is well tolerated. Although weight gain is a well-known adverse effect of valproic acid therapy, only a few studies have addressed weight gain associated with it in children aged 2–8 years.

OBJECTIVE

To evaluate valproic acid–associated changes in the body mass index (BMI) z-scores and to assess changes in serum triglyceride, cholesterol, and fasting glucose levels in young children receiving valproic acid treatment.

METHODS

Eighty-seven patients (39 females, 48 males) receiving valproic acid therapy for at least 3 months were included in the retrospective longitudinal study. Mean ± SD age at initiation of therapy was 4.8 ± 0.8 years. Changes in BMI z-scores as well as serum triglyceride, total cholesterol, and fasting glucose levels were evaluated as continuous variables and analyzed by longitudinal methods for all patients.

RESULTS

The average change from baseline in BMI z-scores was 0.80 (p = 0.001) at 3.1 years of follow-up. No significant change in triglyceride, cholesterol, and serum fasting glucose levels was observed over the same period. The percentage of overweight children at baseline was 6.9% and rose to 16% by the final visit (p = 0.081).

CONCLUSIONS

Valproic acid–associated weight gain may occur in young children. However, only 16% of patients were categorized as overweight at the end of the study; this percentage overlaps the percentage of overweight healthy young Italian children. The BMI z-scores significantly increased during the first 16 months of therapy, then appeared to level off. These observations may influence clinical practice and decision-making regarding suspending the drug due to weight gain in children in whom seizure control has been achieved. A For Our Patients summary of this article is available at www.ForOurPatients.info