bluuebunny/crossref_metadata_2025 huggingface dataset:
Failing constitutionalism: From political legalism to defective empowerment
Authors: MAZMANYAN ARMEN
Published: June 2012

The recent wave of popular uprisings in the Middle East and Northern Africa has sparked a renewed attention to democratization across the world. One of many intriguing questions in this context is whether this trend will be spread globally and will flash another wave of democratization among some regions and countries where democratic euphoria has faded away. Another intriguing question is whether this new wave, in the Middle East or elsewhere, will take a constitutional path or will evolve through undemocratic and unconstitutional channels. In this light, it looks perfectly timely to discuss the lessons from and the modern prospects of building constitutional democracies in post-Soviet countries.

This article offers perspectives on challenges facing post-Soviet higher courts in the effort to promote constitutional democracy in their countries. While it argues that there are many such challenges and that their roots are mostly deep in the political culture, selected and discussed are some specific instances which starkly expose the patterns of constitutional perversion and the most relevant limitations facing post-Soviet courts in our days. The solutions to these are seen in the incremental process of institutional learning hence the article suggests some designer strategies which may help moving along this process.

The first section outlines what appears to be a peculiar vision of constitutionalism as embedded in respective societies and assesses this entrenched concept against accepted accounts of Western constitutionalism. The second section discusses some specific challenges to development of constitutionalism in post-Soviet countries, concentrating on inherited mindset and legal culture, as well as corrupt political technologies and flaws in the design of constitutional courts. The third section discusses two illustrative cases before higher tribunals to demonstrate what courts face in the courtroom when confronting the described challenges.
Proportionality and freedom—An essay on method in constitutional law
Authors: PERJU VLAD
Published: June 2012

This article presents a functional explanation of why proportionality has become one of the most successful legal transplants in contemporary constitutional law. It argues that proportionality helps judges mitigate what Robert Cover called the ‘inherent difficulty presented by the violence of the state’s law acting upon the free interpretative process’. More than alternative methods, proportionality calibrates the violence that the justification of state coercion inflicts on private (non-official) jurisgenerative interpretative processes in constitutional cases. The first three sections show, through an analysis of different constitutional styles which I label Doric, Ionic and Corinthian, how proportionality seeks to place a non-deontological conception of rights within a categorical structure of formal legal analysis. This method aims to synthesize fidelity to form and institutional structure (thesis) with ‘fact-sensitivity’ to contexts in which specific controversies arise (antithesis). Proportionality positions judges vis-à-vis the parties and the parties in relation to one another differently from other constitutional methods. The next sections distinguish between constitutional perception and reality. While the normative appeal of proportionality can be traced to the perception of its integrative aims, in reality, judicial technique does not entirely live up to those aims. Proportionality succumbs to pressures from the centrifugal forces of universalism and particularism that it seeks to integrate. The final section draws on the works of Kant and Arendt and discusses the implications of an approach to constitutional method such as that reflected in the advent of proportionality for the project of constitutionalism more generally.
Observational study of relationships between incoming radiation, open water fraction, and ocean‐to‐ice heat flux in the Transpolar Drift: 2002–2010
Authors: Stanton Timothy P. , Shaw William J. , Hutchings Jennifer K.
Published: June 2012

Ocean/ice interface heat fluxes (F0) are calculated from upper ocean measurements obtained from autonomous systems repeatedly deployed in the Arctic Ocean Transpolar Drift between 2002 and 2010. Average F0 values over the nine summer heating season realizations varied between 4.6 and 10.5 W m−2 with an average summer value of 7.6 W m−2. Between 2002 and 2010, summer‐averagedF0passed through a clear minimum, with most inter‐annual variability inF0 dominated by differences in ocean heat content, rather than by differences in surface forcing. We test if Transpolar Drift F0 is supported primarily by local, radiative energy flux entering the upper ocean through areas of open water (Frw). Frwis estimated by combining re‐analysis solar radiation products with satellite‐borne passive microwave ice concentration products and observed divergence of drifting buoys. Inter‐annual variability of summer‐averaged surface insolation is relatively small (0.04 normalized standard deviation, NSTD), so differences in open water fraction (0.30 NSTD) are the most likely sources of the observedF0variability. Ensemble‐averaged over the 2002–2010 summers, the satellite and buoy‐divergenceFrw, are equal to 8.1, and 8.0 W m−2, respectively. Therefore, over the course of the summer season, sufficient energy enters the upper ocean through open water to wholly support the observed F0. Reasonable agreement between the two open water fraction estimates further indicates that mechanical processes, rather than lateral melting, are controlling the amount of radiation entering the upper ocean, implying that ocean ice‐albedo feedbacks were not strong in the Transpolar Drift in the last decade.
Lunar atmospheric helium detections by the LAMP UV spectrograph on the Lunar Reconnaissance Orbiter
Authors: Stern S. A. , Retherford K. D. , Tsang C. C. C. , Feldman P. D. , Pryor W. , Gladstone G. R.
Published: June 2012

The LAMP far ultraviolet spectrograph aboard the NASA Lunar Reconnaissance Orbiter has been used in 2011 to search for helium, the lightest noble gas in the tenuous lunar atmosphere. Based on that search, we report here the first detection of lunar atmospheric He by remote sensing, and point to future observations that can address questions about its source; we also discuss a search for lunar atmospheric argon.
Interdecadal change of the boreal summer circumglobal teleconnection (1958–2010)
Authors: Wang Hong , Wang Bin , Huang Fei , Ding Qingua , Lee June‐Yi
Published: June 2012

The tropical‐extratropical teleconnection during boreal summer is characterized by a circumglobal teleconnection (CGT) pattern in the northern hemisphere (NH). Around the late 1970s, there was an abrupt change in the coupled atmosphere‐ocean system over the NH and global tropics. This study found that the CGT has experienced a significant change since late 1970s. During the recent epoch (1979‐2010), the major CGT centers weakened with pronounced changes over the North Atlantic and Europe. Partial correlation analysis of 200‐hPa geopotential height and the NH summer monsoon heat sources indicates that the change of Indian summer monsoon (ISM) rainfall has a global impact on the CGT, whereas other NH summer monsoons (West African, western North Pacific, and North American) have only a regional modification to the CGT. The weakening of the CGT pattern in the recent epoch is a consequence of weakened coupling between ISM rainfall and midlatitude circulation, which results from the reduced interannual variability of ISM rainfall due to changes in El Niño‐Southern Oscillation properties. The large change of the CGT over the North Atlantic and Europe is attributed to a southward shift of upper‐level westerlies and enhanced coupling to West African monsoon rainfall.
Analysis of Cassini magnetic field observations over the poles of Rhea
Authors: Simon Sven , Kriegel Hendrik , Saur Joachim , Wennmacher Alexandre , Neubauer Fritz M. , Roussos Elias , Motschmann Uwe , Dougherty Michele K.
Published: June 2012

We analyze Cassini magnetic field observations from the only two polar flybys of Saturn's largest icy satellite Rhea (R2 on 02 March 2010 and R3 on 11 January 2011) which are scheduled between Saturn Orbit Insertion and the end of the mission in 2017. For the interpretation of these data, we apply estimations from simple analytical models as well as results from numerical hybrid simulations (kinetic ions, fluid electrons) of Rhea's interaction with the incident magnetospheric plasma. In‐situ observations of exospheric neutral gas and pick‐up ions suggest Rhea to be embedded in a tenuous gas envelope. However, the interaction of this gas with the magnetospheric flow does not make any measurable contributions to the magnetic field perturbations detected above the poles of the moon. Instead, the field perturbations observed in these regions mainly arise from the absorption of magnetospheric particles with large field‐aligned velocities, impinging on the north and south polar surface of Rhea. In addition to numerous interaction features known from preceding Cassini flybys of Saturn's plasma‐absorbing moons, the magnetic field data acquired above Rhea's poles reveal perturbations of the flow‐aligned field component, corresponding to a draping/Alfvén wing pattern. Based on our hybrid simulations, we suggest that these signatures arise from the finite extension of Rhea's wakeside plasma void along the corotational flow direction, yielding a density gradient in corotation direction, and thereby generating a diamagnetic current from the Saturn‐facing into the Saturn‐averted hemisphere of the moon. This transverse current is responsible for generating a weak Alfvén wing pattern at Rhea which has been detected by the Cassini spacecraft during the R2 and R3 flybys. Due to the large gyroradii of the incident magnetospheric ions, this structure features a pronounced asymmetry with respect to the direction of the convective electric field. Results of our simulation, considering only plasma absorption on the moon, are in good agreement with Cassini magnetometer data from both flybys. At Saturn's icy satellites Tethys and Dione, the low value of the magnetospheric plasma beta most likely prevents the formation of similar currents and measurable flow‐aligned magnetic field distortions.
Near‐real‐time global biomass burning emissions product from geostationary satellite constellation
Authors: Zhang Xiaoyang , Kondragunta Shobha , Ram Jessica , Schmidt Christopher , Huang Ho‐Chun
Published: June 2012

Near‐real‐time estimates of biomass burning emissions are crucial for air quality monitoring and forecasting. We present here the first near‐real‐time global biomass burning emission product from geostationary satellites (GBBEP‐Geo) produced from satellite‐derived fire radiative power (FRP) for individual fire pixels. Specifically, the FRP is retrieved using WF_ABBA V65 (wildfire automated biomass burning algorithm) from a network of multiple geostationary satellites. The network consists of two Geostationary Operational Environmental Satellites (GOES) which are operated by the National Oceanic and Atmospheric Administration, the Meteosat second‐generation satellites (Meteosat‐09) operated by the European Organisation for the Exploitation of Meteorological Satellites, and the Multifunctional Transport Satellite (MTSAT) operated by the Japan Meteorological Agency. These satellites observe wildfires at an interval of 15–30 min. Because of the impacts from sensor saturation, cloud cover, and background surface, the FRP values are generally not continuously observed. The missing observations are simulated by combining the available instantaneous FRP observations within a day and a set of representative climatological diurnal patterns of FRP for various ecosystems. Finally, the simulated diurnal variation in FRP is applied to quantify biomass combustion and emissions in individual fire pixels with a latency of 1 day. By analyzing global patterns in hourly biomass burning emissions in 2010, we find that peak fire season varied greatly and that annual wildfires burned 1.33 × 1012 kg dry mass, released 1.27 × 1010 kg of PM2.5 (particulate mass for particles with diameter <2.5 μm) and 1.18 × 1011kg of CO globally (excluding most parts of boreal Asia, the Middle East, and India because of no coverage from geostationary satellites). The biomass burning emissions were mostly released from forest and savanna fires in Africa, South America, and North America. Evaluation of emission result reveals that the GBBEP‐Geo estimates are comparable with other FRP‐derived estimates in Africa, while the results are generally smaller than most of the other global products that were derived from burned area and fuel loading. However, the daily emissions estimated from GOES FRP over the United States are generally consistent with those modeled from GOES burned area and MODIS (Moderate Resolution Imaging Spectroradiometer) fuel loading, which produces an overall bias of 5.7% and a correlation slope of 0.97 ± 0.2. It is expected that near‐real‐time hourly emissions from GBBEP‐Geo could provide a crucial component for atmospheric and chemical transport modelers to forecast air quality and weather conditions.
A functional interaction between the MAGUK protein hDlg and the gap junction protein connexin 43 in cervical tumour cells
Authors: MacDonald Alasdair I. , Sun Peng , Hernandez-Lopez Hegel , Aasen Trond , Hodgins Malcolm B. , Edward Michael , Roberts Sally , Massimi Paola , Thomas Miranda , Banks Lawrence , Graham Sheila V.
Published: June 2012

Gap junctions, composed of Cxs (connexins), allow direct intercellular communication. Gap junctions are often lost during the development of malignancy, although the processes behind this are not fully understood. Cx43 is a widely expressed Cx with a long cytoplasmic C-terminal tail that contains several potential protein-interaction domains. Previously, in a model of cervical carcinogenesis, we showed that the loss of gap junctional communication correlated with relocalization of Cx43 to the cytoplasm late in tumorigenesis. In the present study, we demonstrate a similar pattern of altered expression for the hDlg (human discs large) MAGUK (membrane-associated guanylate kinase) family tumour suppressor protein in cervical tumour cells, with partial co-localization of Cx43 and hDlg in an endosomal/lysosomal compartment. Relocalization of these proteins is not due to a general disruption of cell membrane integrity or Cx targeting. Cx43 (via its C-terminus) and hDlg interact directly in vitro and can form a complex in cells. This novel interaction requires the N- and C-termini of hDlg. hDlg is not required for Cx43 internalization in W12GPXY cells. Instead, hDlg appears to have a role in maintaining a cytoplasmic pool of Cx43. These results demonstrate that hDlg is a physiologically relevant regulator of Cx43 in transformed epithelial cells.
A key regulator of cholesterol homoeostasis, SREBP-2, can be targeted in prostate cancer cells with natural products
Authors: Krycer James R. , Phan Lisa , Brown Andrew J.
Published: June 2012

There is growing evidence showing that prostate cancer cells have perturbed cholesterol homoeostasis, accumulating cholesterol to promote cell growth. Consequently, cholesterol-lowering drugs such as statins are being evaluated in prostate cancer treatment. Furthermore, natural products such as betulin (from birch tree bark) and tocotrienol (a minor form of vitamin E) have been shown to lower cholesterol levels. Using these drugs and oxysterols, we have determined which aspects of cholesterol homoeostasis should be targeted in prostate cancer, e.g. cellular cholesterol levels are increased by the transcription factor SREBP-2 (sterol-regulatory-element-binding protein isoform 2), whereas LXR (liver X receptor) promotes cholesterol efflux. Whereas betulin exerted non-specific effects on cell viability, tocotrienols produced a strong direct correlation between SREBP-2 activity and cell viability. Mechanistically, tocotrienols lowered SREBP-2 activity by degrading mature SREBP-2 independently of the proteasome. In contrast, no correlation was seen between LXR activity and cell viability, implying that SREBP-2 is a better target than LXR for prostate cancer treatment. Lastly, androgen-dependent and -independent LNCaP cells were both sensitive to tocotrienols. Overall, this suggests that tocotrienols and other drugs targeting the SREBP-2 pathway are a potential therapeutic option for prostate cancer.
Conformations of the apo-, substrate-bound and phosphate-bound ATP-binding domain of the Cu(II) ATPase CopB illustrate coupling of domain movement to the catalytic cycle
Authors: Jayakanthan Samuel , Roberts Sue A. , Weichsel Andrzej , Argüello José M. , McEvoy Megan M.
Published: June 2012

Heavy metal P1B-type ATPases play a critical role in cell survival by maintaining appropriate intracellular metal concentrations. Archaeoglobus fulgidus CopB is a member of this family that transports Cu(II) from the cytoplasm to the exterior of the cell using ATP as energy source. CopB has a 264 amino acid ATPBD (ATP-binding domain) that is essential for ATP binding and hydrolysis as well as ultimately transducing the energy to the transmembrane metal-binding site for metal occlusion and export. The relevant conformations of this domain during the different steps of the catalytic cycle are still under discussion. Through crystal structures of the apo- and phosphate-bound ATPBDs, with limited proteolysis and fluorescence studies of the apo- and substrate-bound states, we show that the isolated ATPBD of CopB cycles from an open conformation in the apo-state to a closed conformation in the substrate-bound state, then returns to an open conformation suitable for product release. The present work is the first structural report of an ATPBD with its physiologically relevant product (phosphate) bound. The solution studies we have performed help resolve questions on the potential influence of crystal packing on domain conformation. These results explain how phosphate is co-ordinated in ATPase transporters and give an insight into the physiologically relevant conformation of the ATPBD at different steps of the catalytic cycle.
The Association of Intervertebral Disk Degeneration on MRI and Low Back Pain: A Population-Based Study
Authors: Samartzis D. , Karppinen J. , Luk K. , Cheung K.
Published: June 2012

Introduction

According to previous studies, the presence of disk degeneration based on MRI and its association with low back pain (LBP) remains questionable. However, such studies were not population-based and/or entailed various methodological limitations, and should be interpreted with caution. Therefore, as part of the largest radiographic and clinical population-based study of the lumbar spine, this study addressed the association of disk degeneration as noted on MRI with the presence and severity of LBP.

Materials and Methods

Sagittal T2-weighted MRIs of the lumbar spine were obtained of 2702 adult Southern Chinese. Radiographic evaluation entailed the presence of disk degeneration based on the Schneiderman et al criteria. An overall degenerative disk disease score (range: 0 to 15) was obtained and represented the global severity of disk degeneration. Additional assessment of spine pathology/abnormalities, LBP, visual analog scale (VAS) pain scores, and subject demographics were performed. Based on various modifiable and nonmodifiable risk factors associated with LBP, a LBP profile was assessed.

Results

There were 1614 females and 1088 males (mean age = 42 years). A low back profile was identified, noting younger individuals, females, and Modic changes to be highly associated with the reporting of LBP and although there was an increasing trend of workload severity associated with LBP it was not a significant factor. Individuals with disk degeneration had a higher prevalence and increased likelihood of LBP than individuals without disk degeneration (OR: 1.45; 95% CI, 1.12–1.87; p2 = 0.95) and LBP (DDD = 0 (ref), adjusted OR = 1.4 at 1 to 2 DDD; OR = 1.7 at 3 to 4 DDD; OR = 2.0 at 5 to 6 DDD; OR = 3.4 at >7 DDD; p). Further subgroup analysis suggested that the association of disk degeneration with LBP may be demographically influenced (e.g., age).

Conclusion

This large-scale study noted that disk degeneration based on MRI is significantly associated with LBP. The “global severity” of disk degeneration was found to increase the risk of having LBP. These findings support that the study of disk degeneration on MRI is clinically relevant. In addition, a LBP profile in a Chinese population was established. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Combination of MRI and 99mTc-NTP 15-5 Scintigraphy for the Assessment of Intervertebral Disk Degeneration and Tissue Engineering
Authors: Colombier P. , Clouet J. , Miot-Noirault E. , Vidal A. , Cachin F. , Vinatier C. , Fusellier M. , Fellah B. H. , Gauthier O. , Chezal J. M. , Grimandi G. , Guicheux J.
Published: June 2012

Introduction

Intervertebral disk degeneration is one of the leading causes of low back pain. The development of regenerative cell-based biotherapies for degenerated IVD has recently been contemplated. To evaluate the preclinical relevance of such therapies, animal models combined with longitudinal imaging methods such as MRI are currently used. However, facing the limitations of MRI and to further decipher the early process of IVD degeneration, innovative radio imaging approaches are considered promising. In this context, we were interested in determining whether a scintigraphic imaging approach using a specific proteoglycan radiotracer (99mTc-NTP 15-5) could be instrumental to assess the biofunctionality of IVD extracellular matrix.

Materials and Methods

New Zealand white rabbits (1-, 6-, 12- and 30-month-old; n = 3 for each age) were used. Early aging of lumbar IVD was determined by MRI and scintigraphic analysis. MRI images were analyzed using T2-weighted signal intensity (T2wsi) and scored according to the Pfirrmann grading. In a first set of experiments, scintigraphic analyses were performed to assess the kinetic distribution in 12-month old rabbits. Ratio IVD on muscle fixation was measured. The distribution of 99 mTc-NTP-15-5 in IVD was evaluated by in vivo scintigraphic imaging (BigSpace Gamma Imager) on three rabbits of each age.

Results

MRI assessments of rabbit IVDs reveal as a function of age, a grading decrease in IVD signal intensity (T2wsi) associated with an increase in Pfirrmann grade. These data indicate the existence of an aging/degeneration process of rabbit IVD. As a function of escalating ages, a differential uptake of 99 mTc-NTP 15-5 in IVD was observed. Uptake was maximal at 1 month of age, and was followed by a dramatic decrease as early as 6 months (approximately 50% of radioactive signal). After 6 months, the intensity of decrease was less pronounced (approximately 10% of radioactive signal).

Conclusion

These in vivo results highlight the interest of combining 99 mTc-NTP-15-5 scintigraphic imaging of proteoglycans with MRI. Whereas MRI T2wsi reflects the hydration level, 99 mTc-NTP-15-5 scintigraphy allowed the functional assessment of IVD at the proteoglycan level. Such multi-imaging approach could be useful for the longitudinal study of engineered IVD following the intradiscal transplantation of mesenchymal stem cells using an injectable biomaterial. In addition, the use of scintigraphy imaging in human should be paid further attention particularly to detect the early IVD degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
The Effect of Scoliosis Correction on Sexual Function of Women with Adolescent Idiopathic Scoliosis
Authors: Schroeder J. E. , Michaeli T. , Luria M. , Barzilay Y. , Hasharoni A. , Kaplan L.
Published: June 2012

Introduction

In the past decades, there has been an increasing interest in quality of life assessment after treatment of adolescent idiopathic scoliosis. Scoliosis affects young patients many of them women that deal with the scoliosis and surgical treatment for the rest of their life. The effect of scoliosis correction on sexual function has yet to be assessed. The female sexual function index (FSFI) is a validated tool for the assessment of sexual function in women.

Materials and Methods

Women (over the age of 18) under the age of 40, who underwent uncomplicated posterior scoliosis correction for idiopathic adolescent scoliosis, were assessed for sexual function via the FSFI. The scores retained were compared to the general population data in the following five categories: desire, sexual arousal, lubrication, orgasm, and satisfaction and pain.

Results

A total of 22 women responded to the questioner. The average age was 28 (range: 19 to 38). Time from surgery was 8.2 years (range: 2 to 17 years). All patients underwent uncomplicated posterior spine fusion, without the need of secondary interventions. The Cobb angle correction in the surgery was 55 degrees (range: 40 to 70). The average FSFI score was 24.2 (range:17.5 to 29.1) (normal score over 26.5). Patients scored within the normal range in sexual desire, pain during intercourse, and lubrication. A decreased score was noted in sexual arousal, orgasms, and satisfaction, when compared to normal population values.

Conclusion

Female patients, who underwent correction of scoliosis due to AIS, have a decreased sexual function, many years after the surgery when compared to the general population. This is due to a decreased arousal, orgasms, and a decreased sexual satisfaction. A distinction still needs to be made if this is due to the scoliosis or the correction. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Low Back Pain in Time: Risk Factors Associated with Persistence, Recurrence, and Time Till Patients Seek Help in Primary Care
Authors: Melloh M. , Stanton T. R. , Elfering A.
Published: June 2012

Introduction

Time characteristics of early episodes of low back pain (LBP) like duration and recurrence may relate to current risk factors and lack of resources that increase the risk of persistent LBP. In addition, when suffering from a first episode of LBP and individuals decide to seek medical care, time till individuals do should be not too long. Again, delay of presentation may relate to risk factors and lack of resources. Aim of our study was to estimate the relationship between time-related LBP characteristics and prognostic factors for acute/subacute LBP in primary care.

Materials and Methods

Prospective inception cohort study of 315 consecutive patients attending a health practitioner for their first episode of acute/subacute LBP or recurrent LBP. One-tailed correlations conducted between patient characteristics and the three time-related characteristics “subacute LBP”, “recurrent LBP,” and “delayed presentation”.

Results

The pattern of correlation between risk factors and resources against persistent LBP differed between three time-related variables. “Subacute LBP” and “delayed presentation” were positively associated with psychological factors (pain catastrophizing, magnification, and helplessness). Both indicators were negatively correlated with resources (job satisfaction and time control) against development of persistent LBP. Moreover, “delayed presentation” was related positively with occupational stressors (“resigned attitude towards the job”, “uncertainty”, “problem with organization of work tasks”, “work interruptions”). In contrast, “recurrent LBP” was only related to more impaired health-related factors (functional limitation, sensory, and affective pain).

Conclusion

Patients with current LBP waiting longer till seeking help in primary care have a more disadvantageous profile of occupational and psychological risk factors and lower resource levels. A similar but less pronounced pattern occurred in those with subacute LBP compared to those with acute LBP. Implications for clinical practice are twofold; (1) LBP-patients with prolonged symptoms or delayed care-seeking behavior, who are at risk of developing persistent LBP, should be screened for psychological factors such as magnification and helplessness, (2) In these patients, occupational resources like job satisfactionand time control should be addressed and strengthened in primary and secondary prevention, where feasible. Future research should examine time-related variables that influence prognostic factors for LBP in different clinical settings such as predominantly retired or unemployed populations. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Differential Intracellular Signaling Pathways Are Activated by Catabolic and Anabolic Factors in the Ivd, and these Could be Targeted in Selected Therapeutic Approaches
Authors: Daniels J. , Phillips K. L. , Chiverton N. , Le Maitre C. L.
Published: June 2012

Introduction

Intervertebral disk (IVD) degeneration is a major cause of lower back pain. Evidence suggests that inflammatory cytokines produced by chondrocyte-like cells within the IVD during degeneration are integral in the pathogenesis of this disease, with a particular role for IL-1 hypothesized. Targeting intracellular signaling mechanisms of IL-1 could provide a mechanism to inhibit multiple catabolic cytokines simultaneously. Many cytokines share intracellular signaling pathways and thus inhibiting signaling rather than direct receptors could prevent compensatory actions occurring. Here we investigated signaling pathways activated by IL-1 together with an anabolic factor to identify differential pathways.

Materials and Methods

Human nucleus pulposus (NP) cells were extracted via collagenase digestion and expanded in monolayer culture, prior to transfer to alginate bead culture for 2 weeks to enable redifferentiation. Following redifferentiation cells were treated with either IL-1 (10 ng/mL) or CDMP-1 (10 ng/ml) for 30 minutes, protein extracted and R&D proteome array deployed to investigate potential differential signaling molecules. In addition, NFkB activation was investigated using immuno-fluorescence and activation of pERK, pP38 MAPK, and AKT were investigated using BD phosflow techniques. In addition, cells were pretreated with inhibitors of signaling pathways: SB203580 (p38 MAPK) and Helenalin (NFkB) to investigate effects on matrix and matrix degrading enzyme gene expression following stimulation with CDMP and IL-1.

Results

R&D proteome array enabled the investigation of 46 signaling molecules simultaneously following and identified a number of differentially activated pathways, including p38MAPK (Fig. 1). IL-1 induced p38MAPK, NFkB, AKT, and ERK pathways were confirmed using BD phosflow and immunofluorescence techniques. Inhibition of NFkB pathway using helenine reduced the inhibitory effect on aggrecan induced by IL-1, but helenine alone also induced an inhibition of aggrecan induction by CDMP.

Conclusion

The catabolic cytokine IL-1 has been implicated in the pathogenesis of IVD degeneration which leads to low back pain. The identification of differential intracellular signaling pathways between anabolic and catabolic factors could provide new methods for modulating the catabolic response, and preventing further IVD degeneration. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Multiparametric Magnetic Resonance Imaging of Normal and Degenerative Lumbar Intervertebral Disks
Authors: Kim M. , Chan Q. , Anthony M. P. , Samartzis D. , Cheung K. , Khong P.
Published: June 2012

Introduction

Magnetic resonance imaging (MRI) has been shown to improve the diagnosis and management of patients with intervertebral disk (IVD) related disorders. Multiparametric MRI offers the possibility of noninvasively assessing multiple aspects of pathophysiological processes that exist simultaneously, thereby further assisting in patient treatment management. The purpose of this study is to determine the correlation between relaxation parameters (T1-rho and T2), diffusion properties including fractional anisotropy (FA) and mean diffusivity (MD) measured by diffusion tensor imaging (DTI), and degenerative grades in human IVD based on T2-weighted MRI.

Materials and Methods

Total 21 subjects (mean age 41.3 years; age range: 24 to 61 years; gender: 10 females, 11 males) with no prior spine surgery were recruited. Sagittal T2-weighted, T1-rho, T2, FA and MD MRI of the lumbar spine were obtained. All images of the lumbar spine were acquired using a 3T Achieva scanner. High-resolution T2-weighted discs were qualitatively graded by two spine specialists in consensus according to Schneiderman's classification (score range: 0 to 3). T1-rho, T2, FA, and MD maps were quantitatively assessed based on a voxel-by-voxel basis.

Results

By visual inspection, the nucleus pulposus (NP) and annulus fibrosus (AF) in IVDs were distinctively separable on all quantitative maps while some of the discs on T2-weighted images did not show a clear difference between the NP and the AF. The Schneiderman grades and subjects' age significantly correlated with all parameters ( p < 0.001). Univariate analysis demonstrated that T1-rho correlated significantly with MD and FA (r = 0.729 and −0.715, respectively; p < 0.001 for both). Quantitative T2 also correlated significantly with MD and FA (r = 0.805 and −0.811, respectively; p < 0.001 for both). In addition, T1-rho showed significant correlation with quantitative T2 (r = 0.824; p < 0.001).

Conclusion

In this study, we performed quantitative multiparametric MRI to investigate its sensitivity to changes in tissue microstructure of in vivo human lumbar IVDs. Our results suggest that each imaging parameter may attribute different sensitivity to tissue properties. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Histomorphometric and Radiographic Changes after Implantation of Peek-Interspinous Device in the BB.4Sd1 Rat Model
Authors: Melloh M. , Barz T. , Lange J. , Staub L. , Merk H. R. , Klöting I. , Follak N.
Published: June 2012

Introduction

Clinical effectiveness of the PEEK nonfusion interspinous device is well documented. However, there is a lack of evidence on the long-term behavior of this implant in regard to bone in general and especially its influence on structural changes of bone elements of the lumbar spine. Aim of our study was to investigate histomorphometric and radiographic changes in the BB.4Sd1 rat model after implantation of an interspinous PEEK implant.

Materials and Methods

Total 24 male BB.4Sd1 rats 11-week old underwent surgery for implantation of an interspinous PEEK device or for a sham procedure in three groups of eight animals each viz: (1) implantation at level L4-5, (2) implantation at level L5-6, and (3) sham surgery. Total 11 weeks postoperatively osteolyses at the implant-bone interface were measured via X-ray, bone mineral density of vertebral bodies was analyzed using osteodensitometry, and bone mineral content as well as osteolyses of the spinous processes examined by histomorphometry.

Results

Osteolyses of the spinous processes at the site of the interspinous implant were found in all treated segments. There was no significant difference in either bone density of vertebral bodies or histomorphometric structure of the spinous processes.

Conclusion

Osteolyses of spinous processes as a result of the implant becoming unsecure inhibit the targeted load redistribution through the interspinous PEEK device in the lumbar spinal segment of the rat. This leads to reduced long-term benefits of the implant in the animal model. These results suggest that the interspinous PEEK implants should only be used under strict indication and in consideration of their time-limited effects. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared Holinka J, Krepler P, Matzner M, et al. Stabilising effect of dynamic interspinous spacers in degenerative low-grade lumbar instability. International Orthopaedics 2011;35:395–400
Reconstitution of Nucleus Pulposus Cell Matrix Niche in 3D Configuration for Mesenchymal Stem Cell Differentiation
Authors: Yuan M. , Yeung C. W. , Chan B. P.
Published: June 2012

Introduction

Degenerative disk disease (DDD) is a medical condition whereby the intervertebral discs (IVD) of the human spine degenerates and causes pain which significantly affects the quality of one's life. A highly possible approach to overcome this problem is to produce injectable microspheres of similar composition to the native NP using MSCs to restore both its structural and functional properties. However, there is no systematic study in identifying the optimal conditions and signals for inducing MSCs differentiation toward nucleus pulposus (NP)-like phenotype.

Materials and Methods

In this project, we attempt to study the possibility to construct injectable microspheres with properties highly similar to that of native NP tissue using MSCs. Our approach was to culture NPCs within collagen microspheres whilst maintaining their phenotype and other characteristics, so that they would remodel the matrix microenvironment to one that was conducive for MSCs differentiation into new NPCs when MSCs were introduced upon removal of the original NPCs. Particular attention will be paid to the interaction between the MSCs and NPC-produced ECM to understand the mechanism for MSC differentiation.

Results

We demonstrated that NPCs could maintain survival within the collagen microspheres and produce NP-like ECM such as glycosaminoglycan (GAG) and Type II Collagen. GAG productions of NPCs were also found to positively correlate to the dosage of TGF-βwithin a period of 6 days. An optimized decellularization protocol was established to completely remove the encapsulated NPCs with partial retention of the GAG-rich matrix. The decellularized microspheres were able to be repopulated with hMSCs. With the effects of acellular matrices, these hMSCs were able to produce new NP-like ECM according to the results of histological, biochemical, immunohistological analysis, and real-time PCR.

Conclusion

The NPC derived acellular matrix is able to support growth of hMSC. Ongoing efforts are to assess the potential of the NPC-constituted matrices to induce MSC differentiation into the NPC lineage. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Novel Matrices for Differentiation of Human Mesenchymal Stem Cells into Disk Cells
Authors: Schmiermund A. , Gebauer E. , Fuchsbauer H.-L. , Czermak P. , Salzig D.
Published: June 2012

Introduction

Degeneration of the nucleus pulposus (NP), part of the intervertebral disk (IVD), is a major reason for back pain. Stem cell therapy is one approach for treatment. Therefore, it is necessary to differentiate the human mesenchymal stem cells (hMSC) into NP-cells. Differentiation requires a 3D environment in a biocompatible matrix in which the cells were embedded. Beside biocompatibility, pressure resistance is a necessary requirement on the matrices. In vivo the IVD is exposed to pressures up to 3 MPa (30 bar). With regard to minimal invasive treatment of patients later on, the matrices have to be injectable and solidify after injection. In this work, different compositions of potential matrices for the regeneration of the NP were analyzed. hMSC-TERT (- telomerase reverse transcriptase) have been embedded in gelatin and a “gelatin-porcine nucleus pulposus” matrix. The enzyme transglutaminase was found used for cross-linking of the matrices. The results were compared with work previously done on agarose matrix.

Materials and Methods

Cells were seeded in different matrices at a density of 4 × 106 cells per cm3, equal to the density in the NP. The immobilized cells were cultivated for 21 days in media, containing growth and differentiation factors. Viability of the cells in the different matrices was proofed by using a tetrazolium salt (WST-1). At certain times, RNA isolation was done following the phenol/guanidine isothiocyanate protocol. RNA was transformed into cDNA followed by a RT-PCR. Different primers were used to analyze the differentiation of hMSC-TERT.

Results

Via WST1-test the survival of hMSC-TERT in gelatine was proofed. The differentiation status of hMSC-TERT in the two different matrices (gelatine, NP extract) was analyzed. The PCR analysis showed a differentiation in a chondrogenic type, less with the NP extract. In agarose a differentiation in a NP cell type could be obtained.

Conclusion

The results lead to the conclusion that the influence of matrices on cell differentiation is greater than recently surmised. Therefore, it is necessary to find a “close to nature”- matrix for the need in cell therapy. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Does Cervical Disk Arthroplasty Reduce Adjacent Segment Disease and Other Complications in Comparison to Anterior Cervical Discectomy and Fusion? a Meta-Analysis of Randomized Controlled Trials
Authors: Samartzis D. , Vavken P. , Modi H. , Luk K. , Cheung K.
Published: June 2012

Introduction

To reduce the risk of adjacent segment disease and other procedure-related complications following anterior cervical discectomy and fusion (ACDF), cervical disk arthroplasty (CDA) has been advocated for one-level cervical disk disease. However, it remains unknown whether CDA decreases the occurrence of such complications. As such, the following study addressed a meta-analysis of randomized controlled trials assessing the efficacy of CDA in reducing adjacent segment disease and other complications in comparison to ACDF.

Materials and Methods

Three reviewers performed a literature search for randomized controlled trials comparing CDA to ACDF for radiculopathy and/or myelopathy for one-level cervical disk disease. Studies with 2 years or greater follow-up were selected. Adjacent segment disease, secondary surgery (i.e., revision, reoperation, instrumentation/graft removal), and adverse events were assessed and pooled for analyses.

Results

Eight studies were included for review. Due to limitations with study design, studies presented with Level II evidence. CDA exhibited a decrease risk for reoperation attributed to adjacent segment disease, but was not statistically significant ( p > 0.05). Additional procedure-related complications did not statistically differ between groups ( p > 0.05).

Conclusion

Up to 4-year follow-up, CDA does not significantly reduce the risk of adjacent segment disease and other complications in comparison to ACDF. Due to the lack of blinding, variation in surgical management and relatively high withdrawal/drop-out rates among studies at 2 and 4 year follow-up, robust conclusions supporting the advocacy of CDA over ACDF cannot be made at this stage. High-quality studies are needed to properly assess the true efficacy of such interventions. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared
Nonlocal elasticity based magnetic field affected vibration response of double single-walled carbon nanotube systems
Authors: Murmu T. , McCarthy M. A. , Adhikari S.
Published: June 2012

The behaviour of carbon nanotubes in a magnetic field has attracted considerable attention in the scientific community. This paper reports the effects of a longitudinal magnetic field on the vibration of a magnetically sensitive double single-walled carbon nanotube system (DSWNTS). The two nanotubes of the DSWNTS are coupled by an elastic medium. The dynamical equations of the DSWNTS are derived using nonlocal elasticity theory. The two nanotubes are defined as an equivalent nonlocal double-Euler-Bernoulli beam system. Governing equations for nonlocal bending-vibration of the DSWNTS under a longitudinal magnetic field are derived considering the Lorentz magnetic force obtained from Maxwell’s relation. An analytical method is proposed to obtain nonlocal natural frequencies of the DSWNTS. The influence of (i) nanoscale effects and (ii) strength of longitudinal magnetic field on the synchronous and asynchronous vibration phase of the DSWNTS is examined. Nonlocal effects with and without the effect of magnetic field are illustrated. Results reveal the difference (quantitatively) by which the longitudinal magnetic field affects the nonlocal frequency in the synchronous and asynchronous vibration modes of a DSWNTS.
Evidence for electric-field-driven migration and diffusion of oxygen vacancies in Pr0.7Ca0.3MnO3
Authors: Liao Zhaoliang , Gao Peng , Bai Xuedong , Chen Dongmin , Zhang Jiandi
Published: June 2012

Combined in situ scanning probe microscopy with transmission electron microscope (TEM) has been used to study the field-induced migration of oxygen vacancies in the thin films of Pr0.7Ca0.3MnO3. Local structural stripes which are associated with the existing oxygen vacancies in the material have been imaged in situ in real time with TEM and are found to migrate under external electric field. The stripes can also be induced by an electric field and relax as the field is dismissed. The characteristic decay time of field-induced stripes are found to be in the similar order of magnitude as the measured resistance relaxation time in the materials. These results confirm microscopically that oxygen migration plays a key role in the bipolar resistance switching behaviors in this class of oxide materials.
Enhancement of optical absorption by modulation of the oxygen flow of TiO2 films deposited by reactive sputtering
Authors: Pereira André L. J. , Lisboa Filho Paulo N. , Acuña Javier , Brandt Iuri S. , Pasa André A. , Zanatta Antonio R. , Vilcarromero Johnny , Beltrán Armando , Dias da Silva José H.
Published: June 2012

Oxygen-deficient TiO2 films with enhanced visible and near-infrared optical absorption have been deposited by reactive sputtering using a planar diode radio frequency magnetron configuration. It is observed that the increase in the absorption coefficient is more effective when the O2 gas supply is periodically interrupted rather than by a decrease of the partial O2 gas pressure in the deposition plasma. The optical absorption coefficient at 1.5 eV increases from about 1 × 102 cm−1 to more than 4 × 103 cm−1 as a result of the gas flow discontinuity. A red-shift of ∼0.24 eV in the optical absorption edge is also observed. High resolution transmission electron microscopy with composition analysis shows that the films present a dense columnar morphology, with estimated mean column width of 40 nm. Moreover, the interruptions of the O2 gas flow do not produce detectable variations in the film composition along its growing direction. X-ray diffraction and micro-Raman experiments indicate the presence of the TiO2 anatase, rutile, and brookite phases. The anatase phase is dominant, with a slight increment of the rutile and brookite phases in films deposited under discontinued O2 gas flow. The increase of optical absorption in the visible and near-infrared regions has been attributed to a high density of defects in the TiO2 films, which is consistent with density functional theory calculations that place oxygen-related vacancy states in the upper third of the optical bandgap. The electronic structure calculation results, along with the adopted deposition method and experimental data, have been used to propose a mechanism to explain the formation of the observed oxygen-related defects in TiO2 thin films. The observed increase in sub-bandgap absorption and the modeling of the corresponding changes in the electronic structure are potentially useful concerning the optimization of efficiency of the photocatalytic activity and the magnetic doping of TiO2 films.