bluuebunny/crossref_metadata_2025 huggingface dataset:
Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo
Authors: Xiao Li , Yan Liu , Zhongmei Wen , Chang Li , Huijun Lu , Mingyao Tian , Kuoshi Jin , Lili Sun , Pegn Gao , Encheng Yang , Xiaohong Xu , Shifu Kan , Zhuoyue Wang , Yuhang Wang , Ningyi Jin
Published: January 2010

Background

Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. Here, we generated a conditional replication-competent adenovirus (CRCA), designated Ad-hTERT-E1a-Apoptin, and investigated the effectiveness of the CRCA a gene therapy agent for further clinical trials.

Results

The observation that infection with Ad-hTERT-E1a-Apoptin significantly inhibited growth of the melanoma cells, protecting normal human epidermal melanocytes from growth inhibition confirmed cancer cell selective adenoviral replication, growth inhibition, and apoptosis induction of this therapeutic approach. The in vivo assays performed by using C57BL/6 mice containing established primary or metastatic tumors expanded the in vitro studies. When treated with Ad-hTERT-E1a-Apoptin, the subcutaneous primary tumor volume reduction was not only observed in intratumoral injection group but in systemic delivery mice. In the lung metastasis model, Ad-hTERT-E1a-Apoptin effectively suppressed pulmonary metastatic lesions. Furthermore, treatment of primary and metastatic models with Ad-hTERT-E1a-Apoptin increased mice survival.

Conclusions

These data further reinforce the previously research showing that an adenovirus expressing Apoptin is more effective and advocate the potential applications of Ad-hTERT-E1a-Apoptin in the treatment of neoplastic diseases in future clinical trials.
Can we use biomarkers in combination with self-reports to strengthen the analysis of nutritional epidemiologic studies?
Authors: Freedman Laurence S , Kipnis Victor , Schatzkin Arthur , Tasevska Nataša , Potischman Nancy
Published: January 2010

Identifying diet-disease relationships in nutritional cohort studies is plagued by the measurement error in self-reported intakes.

The authors propose using biomarkers known to be correlated with dietary intake, so as to strengthen analyses of diet-disease hypotheses. The authors consider combining self-reported intakes and biomarker levels using principal components, Howe's method, or a joint statistical test of effects in a bivariate model. They compared the statistical power of these methods with that of conventional univariate analyses of self-reported intake or of biomarker level. They used computer simulation of different disease risk models, with input parameters based on data from the literature on the relationship between lutein intake and age-related macular degeneration.

The results showed that if the dietary effect on disease was fully mediated through the biomarker level, then the univariate analysis of the biomarker was the most powerful approach. However, combination methods, particularly principal components and Howe's method, were not greatly inferior in this situation, and were as good as, or better than, univariate biomarker analysis if mediation was only partial or non-existent. In some circumstances sample size requirements were reduced to 20-50% of those required for conventional analyses of self-reported intake.

The authors conclude that (i) including biomarker data in addition to the usual dietary data in a cohort could greatly strengthen the investigation of diet-disease relationships, and (ii) when the extent of mediation through the biomarker is unknown, use of principal components or Howe's method appears a good strategy.
Seroepidemiological study of Q fever in domestic ruminants in semi-extensive grazing systems
Authors: Ruiz-Fons Francisco , Astobiza Ianire , Barandika Jesús F , Hurtado Ana , Atxaerandio Raquel , Juste Ramón A , García-Pérez Ana L
Published: January 2010

Background

Q fever, a worldwide zoonotic disease caused byCoxiella burnetii, is endemic in northern Spain where it has been reported as responsible for large series of human pneumonia cases and domestic ruminants' reproductive disorders. To investigate pathogen exposure among domestic ruminants in semi-extensive grazing systems in northern Spain, a serosurvey was carried out in 1,379 sheep (42 flocks), 626 beef cattle (46 herds) and 115 goats (11 herds). Serum antibodies were analysed by ELISA and positive samples were retested by Complement Fixation test (CFT) to detect recent infections.

Results

ELISA anti-C. burnetiiantibody prevalence was slightly higher in sheep (11.8 ± 2.0%) than in goats (8.7 ± 5.9%) and beef cattle (6.7 ± 2.0%). Herd prevalence was 74% for ovine, 45% for goat and 43% for bovine. Twenty-one percent of sheep flocks, 27% of goat and 14% of cattle herds had aC. burnetiiseroprevalence ≥ 20%. Only 15 out of 214 ELISA-positive animals reacted positive by CFT. Age-associated seroprevalence differed between ruminant species with a general increasing pattern with age. No evidence of correlation between abortion history and seroprevalence rates was observed despite the known abortifacient nature ofC. burnetiiin domestic ruminants.

Conclusions

Results reported herein showed that sheep had the highest contact rate withC. burnetiiin the region but also that cattle and goats should not be neglected as part of the domestic cycle ofC. burnetii. This work reports basic epidemiologic patterns ofC. burnetiiin semi-extensive grazed domestic ruminants which, together with the relevant role ofC. burnetiias a zoonotic and abortifacient agent, makes these results to concern both Public and Animal Health Authorities.
Bortezomib With or Without Dexamethasone in Primary Systemic (Light Chain) Amyloidosis
Authors: Kastritis Efstathios , Wechalekar Ashutosh D. , Dimopoulos Meletios A. , Merlini Giampaolo , Hawkins Philip N. , Perfetti Vittorio , Gillmore Julian D. , Palladini Giovanni
Published: January 2010

Purpose

To assess the efficacy and tolerability of bortezomib with or without dexamethasone and to define prognostic factors for patients with primary systemic light chain (AL) amyloidosis treated with bortezomib or both.

Patients and Methods

Ninety-four patients from three centers were analyzed: 19% received the combination as first-line treatment, 81% had a median of two previous therapies, and 69% had refractory disease, while most patients had symptomatic heart involvement or elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP).

Results

A hematologic response was achieved in 71% within a median of 52 days, including 25% complete responses (CRs). Previously untreated patients had a 47% CR rate. Age 65 years or younger (P = .043) and twice weekly administration of bortezomib (P = .041) were associated with higher response rates. A cardiac response was documented in 29% of patients, in most as sustained improvement of functional class and less often as a decrease in wall thickness. Hematologic responses were associated with a cardiac response and NT-proBNP reduction. After a median follow-up of 12 months, 29% of patients had organ progression and 27% had hematologic progression. Median survival has not been reached and the 1-year survival rate is 76%. Baseline NT-proBNP was independently associated with survival (P = .001), while in a landmark analysis, survival was associated with NT-proBNP reduction of ≥ 30% (P = .006) and achievement of hematologic response (P = .001). Toxicity was manageable and mostly consisted of neuropathy, orthostasis, peripheral edema, and constipation or diarrhea.

Conclusion

Bortezomib with or without dexamethasone is active in AL amyloidosis and induces rapid responses and high rates of hematologic and organ responses. Serial measurement of cardiac biomarkers is a powerful predictor of outcome.
Association of Skeletal Muscle Wasting With Treatment With Sorafenib in Patients With Advanced Renal Cell Carcinoma: Results From a Placebo-Controlled Study
Authors: Antoun Sami , Birdsell Laura , Sawyer Michael B. , Venner Peter , Escudier Bernard , Baracos Vickie E.
Published: January 2010

Purpose

Effects of specific antineoplastic therapies on progression of cancer-associated wasting remain uncharacterized. We selected a targeted therapy, sorafenib, because of its reported association with weight loss.

Patients and Methods

Patients with metastatic renal cell cancer (RCC) who were resistant to standard therapy (N = 80) received sorafenib 400 mg twice daily or placebo in a randomized, double-blinded clinical trial. Computed tomography image analysis, which has high precision and specificity for evaluation of specific muscles and adipose tissues, was used to define change in total skeletal muscle and adipose tissue.

Results

At inclusion, 51% of patients were overweight or obese (ie, body mass index [BMI] > 25 kg/m2). Only 5% were underweight. Advanced muscle wasting (ie, sarcopenia) was present in 72% of patients with BMI less than 25 and in 34% of those with a BMI greater than 25. Patients received placebo for an average of 6 months and received sorafenib for 1 year. Patients in the placebo group had stable body weight during 6 months (0.8 kg ± 0.7 kg), with no significant alteration of muscle or fat. Patients who received sorafenib lost 2.1 kg ± 0.6 kg (P < .01) in 6 months and lost 4.2 kg ± 0.7 kg (P < .01) by 1 year. Sorafenib-treated patients lost skeletal muscle progressively at 6 months (decrease of 4.9%; P < .01) and 12 months (decrease of 8.0%; P < .01).

Conclusion

Sarcopenia is prevalent in patients with metastatic RCC and is an occult condition in patients with normal or high BMI. Muscle loss is specifically exacerbated by sorafenib, consistent with the evidence for a role of kinases in regulating muscle mass. Muscle loss is a sorafenib adverse effect that may relate to asthenia, fatigue, and physical disability.
Long-Term Follow-Up of Autotransplantation Trials for Multiple Myeloma: Update of Protocols Conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences
Authors: Barlogie Bart , Attal Michel , Crowley John , van Rhee Frits , Szymonifka Jackie , Moreau Philippe , Durie Brian G.M. , Harousseau Jean-Luc
Published: January 2010

Purpose

The purpose of this study was to update outcomes of autotransplantation trials for myeloma conducted by the Intergroupe Francophone du Myelome (IFM), the Southwest Oncology Group, and the University of Arkansas for Medical Sciences (Total Therapy [TT]).

Methods

IFM90 (N = 194), IFM04 (N = 402), IFM9902 (N = 692), IFM9904 (N = 197), S9321 (N = 817), TT1 (N = 231), TT2 (N = 668), and TT3 (N = 303) were updated, and results were compared with original reports.

Results

Superior survival with single transplantation versus standard therapy in IFM90 was confirmed (P = .004), and a trend in favor of tandem versus single transplantation was maintained in IFM94 (P = .08). S9321 data were validated, with comparable survival in single transplantation and standard treatment arms (P = .35). A survival benefit from thalidomide maintenance in IFM9902 was not confirmed (P = .39) but emerged for the thalidomide arm of TT2 (P = .04). On multivariate analysis, survival was superior in TT2, TT3, and IFM9902 (all P < .001); tandem transplantations were superior to both single transplantations and standard therapies (P < .001), as were tandem transplantations with added thalidomide versus trials without thalidomide (P < .001). Postrelapse survival (PRS) was superior when initial event-free survival (EFS) exceeded 1280 days and when tandem transplantations had been administered, whereas PRS was shorter when EFS lasted 803 days or less and when trials had included thalidomide and bortezomib.

Conclusion

These long-term follow-up data of transplantation trials provide a crucial framework of reference for outcome reporting of novel agent–based trials reportedly exhibiting remarkable short-term efficacy approaching high-dose therapy results.
Vinculin regulates cell-surface E-cadherin expression by binding to β-catenin
Authors: Peng Xiao , Cuff Laura E. , Lawton Cort D. , DeMali Kris A.
Published: January 2010

Vinculin was identified as a component of adherens junctions 30 years ago, yet its function there remains elusive. Deletion studies are consistent with the idea that vinculin is important for the organization of cell-cell junctions. However, this approach removes vinculin from both cell-matrix and cell-cell adhesions, making it impossible to distinguish its contribution at each site. To define the role of vinculin in cell-cell junctions, we established a powerful short hairpin-RNA-based knockdown/substitution model system that perturbs vinculin preferentially at sites of cell-cell adhesion. When this system was applied to epithelial cells, cell morphology was altered, and cadherin-dependent adhesion was reduced. These defects resulted from impaired E-cadherin cell-surface expression. We have investigated the mechanism for the effects of vinculin and found that the reduced surface E-cadherin expression could be rescued by introduction of vinculin, but not of a vinculin A50I substitution mutant that is defective for β-catenin binding. These findings suggest that an interaction between β-catenin and vinculin is crucial for stabilizing E-cadherin at the cell surface. This was confirmed by analyzing a β-catenin mutant that fails to bind vinculin. Thus, our study identifies vinculin as a novel regulator of E-cadherin function and provides important new insight into the dynamic regulation of adherens junctions.
A study of a Dutch online decision aid for parents of children with ADHD
Authors: Ossebaard Hans C , van Gemert-Pijnen Julia E W C , Sorbi Marjolijn J , Seydel Erwin R
Published: January 2010

During a three-month study period, visitors to an online decision aid (DA) for attention deficit hyperactivity disorder (ADHD) were invited to complete an online questionnaire before and after working through the DA. Some 75,000 unique visitors found their way to the page on DAs, although fewer than 1 in 10 visited the DA for ADHD, staying there for about six minutes on average and using 8–9 clicks to navigate. A total of 195 people completed the first questionnaire (a response rate of about 3%). Only 12 of the respondents to the first questionnaire (6%) completed the second questionnaire. There was no significant effect of the DA as measured by three decisional outcome measures. Respondents moderately appreciated the information received. Even though the DA was constructed according to evidence-based guidelines and International Patient Decision Aids Standards wherein expert and patient involvement are assured, these preliminary results suggest that the online DA for ADHD needs further work to support the decision-making process of parents with regard to the most appropriate treatment for their child.
User acceptance of an Internet training aid for migraine self-management
Authors: Sorbi Marjolijn J , van der Vaart Rosalie
Published: January 2010

We have developed an Internet training aid (MyMigraine) for migraine self-management derived from an evidence-based protocol for behavioural attack prevention. Its acceptance was tested in two studies concerning the opinions of new patients ( n = 10), and the opinions of expert patients acquainted with the protocol ( n = 6). The questionnaires employed 5-point scales. In study 1, all lessons were rated positively regarding clarity, instructiveness, importance and easy execution. After training, the patients were positive about user-friendliness and clarity (mean score 3.9), training content (3.5), satisfaction (3.6) and benefits (attack risk detection: 3.7; preventive coping: 3.9). In study 2, the expert patients provided positive ratings for the web application (mean score 4.1), digital support (3.8–4.4) and web adaptation of the protocol (4.1–4.8). The expert patients considered MyMigraine instructive, captivating and fun to work with, but emphasized the necessity of patient-to-patient contact. The training aid was very well accepted by new and experienced patients with chronic migraine.
Use of web services for computerized medical decision support, including infection control and antibiotic management, in the intensive care unit
Authors: Steurbaut Kristof , Van Hoecke Sofie , Colpaert Kirsten , Lamont Kristof , Taveirne Kristof , Depuydt Pieter , Benoit Dominique , Decruyenaere Johan , De Turck Filip
Published: January 2010

The increasing complexity of procedures in the intensive care unit (ICU) requires complex software services, to reduce improper use of antibiotics and inappropriate therapies, and to offer earlier and more accurate detection of infections and antibiotic resistance. We investigated whether web-based software can facilitate the computerization of complex medical processes in the ICU. The COSARA application contains the following modules: Infection overview, Thorax, Microbiology, Antibiotic therapy overview, Admission cause with comorbidity and admission diagnosis, Infection linking and registration, and Feedback. After the implementation and test phase, the COSARA software was installed on a physician's office PC and then on the bedside PCs of the patients. Initial evaluation indicated that the services had been integrated easily into the daily clinical workflow of the medical staff. The use of a service oriented architecture with web service technology for the development of advanced decision support in the ICU offers several advantages over classical software design approaches.
The analysis of classroom talk: Methods and methodologies
Authors: Mercer Neil.
Published: January 2010

This article describes methods for analysing classroom talk, comparing their strengths and weaknesses. Both quantitative and qualitative methods are described and assessed for their strengths and weaknesses, with a discussion of the mixed use of such methods. It is acknowledged that particular methods are often embedded in particular methodologies, which are based on specific theories of social action, research paradigms, and disciplines; and so a comparison is made of two contemporary methodologies, linguistic ethnography, and sociocultural research. The article concludes with some comments on the current state of development of this field of research and on ways that it might usefully progress.
The Micro-Architecture of Mitochondria at Active Zones: Electron Tomography Reveals Novel Anchoring Scaffolds and Cristae Structured for High-Rate Metabolism
Authors: Perkins Guy A. , Tjong Jonathan , Brown Joshua M. , Poquiz Patrick H. , Scott Raymond T. , Kolson Douglas R. , Ellisman Mark H. , Spirou George A.
Published: January 2010

Mitochondria are integral elements of many nerve terminals. They must be appropriately positioned to regulate microdomains of Ca2+concentration and metabolic demand, but structures that anchor them in place have not been described. By applying the high resolution of electron tomography (ET) to the study of a central terminal, the calyx of Held, we revealed an elaborate cytoskeletal superstructure that connected a subset of mitochondria to the presynaptic membrane near active zones. This cytoskeletal network extended laterally and was well integrated into the nerve terminal cytoskeleton, which included filamentous linkages among synaptic vesicles. ET revealed novel features of inner membrane for these mitochondria. Crista structure was polarized in that crista junctions, circular openings of the inner membrane under the outer membrane, were aligned with the cytoskeletal superstructure and occurred at higher density in mitochondrial membrane facing the presynaptic membrane. These characteristics represent the first instance where a subcomponent of an organelle is shown to have a specific orientation relative to the polarized structure of a cell. The ratio of cristae to outer membrane surface area is large in these mitochondria relative to other tissues, indicating a high metabolic capacity. These observations suggest general principles for cytoskeletal anchoring of mitochondria in all tissues, reveal potential routes for nonsynaptic communication between presynaptic and postsynaptic partners using this novel cytoskeletal framework, and indicate that crista structure can be specialized for particular functions within cellular microdomains.
TRPV1 Gene Deficiency Attenuates Miniature EPSC Potentiation Induced by Mannitol and Angiotensin II in Supraoptic Magnocellular Neurons
Authors: Yokoyama Toru , Saito Takeshi , Ohbuchi Toyoaki , Hashimoto Hirofumi , Suzuki Hitoshi , Otsubo Hiroki , Fujihara Hiroaki , Nagatomo Toshihisa , Ueta Yoichi
Published: January 2010

The release of arginine vasopressin (AVP) from the magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) is crucial for body fluid homeostasis. The MNC activity is modulated by synaptic inputs and humoral factors. A recent study demonstrated that an N-terminal splice variant of the transient receptor potential vanilloid type 1 (TRPV1) is essential for osmosensory transduction in the SON. In the present study, we examined the effects of mannitol and angiotensin II on miniature EPSCs (mEPSCs) in the supraoptic MNCs using whole-cell patch-clamp recording inin vitroslice preparation. Mannitol (60 mm) and angiotensin II (0.1 μm) increased the frequency of mEPSCs without affecting the amplitude. These effects were attenuated by pre-exposure to a nonspecific TRPV channel blocker, ruthenium red (10 μm) and enhanced by pre-exposure to cannabinoid type1 receptor antagonist, AM251 (2 μm). Mannitol-induced potentiation of mEPSCs was not attenuated by angiotensin II receptor antagonist, losartan (10 μm), indicating independent pathways of mannitol and angiotensin II to the TRPV channels. The potentiation of mEPSCs by mannitol was not mimicked by a TRPV1 agonist, capsaicin, and also not attenuated by TRPV1 blockers, capsazepine (10 μm). PKC was involved in angiotensin II-induced potentiation of mEPSCs. The effects of mannitol and angiotensin II on the supraoptic MNCs intrpv1knock-out mice were significantly attenuated compared with those in wild-type mice counterparts. The results suggest that hyperosmotic stimulation and angiotensin II independently modulate mEPSCs through capsaicin-insensitive TRPV1 channel in the presynaptic terminals of the SON.
Neural Integration of Information Specifying Human Structure from Form, Motion, and Depth
Authors: Jackson Stuart , Blake Randolph
Published: January 2010

Recent computational models of biological motion perception operate on ambiguous two-dimensional representations of the body (e.g., snapshots, posture templates) and contain no explicit means for disambiguating the three-dimensional orientation of a perceived human figure. Are there neural mechanisms in the visual system that represent a moving human figure's orientation in three dimensions? To isolate and characterize the neural mechanisms mediating perception of biological motion, we used an adaptation paradigm together with bistable point-light (PL) animations whose perceived direction of heading fluctuates over time. After exposure to a PL walker with a particular stereoscopically defined heading direction, observers experienced a consistent aftereffect: a bistable PL walker, which could be perceived in the adapted orientation or reversed in depth, was perceived predominantly reversed in depth. A phase-scrambled adaptor produced no aftereffect, yet when adapting and test walkers differed in size or appeared on opposite sides of fixation aftereffects did occur. Thus, this heading direction aftereffect cannot be explained by local, disparity-specific motion adaptation, and the properties of scale and position invariance imply higher-level origins of neural adaptation. Nor is disparity essential for producing adaptation: when suspended on top of a stereoscopically defined, rotating globe, a context-disambiguated “globetrotter” was sufficient to bias the bistable walker's direction, as were full-body adaptors. In sum, these results imply that the neural signals supporting biomotion perception integrate information on the form, motion, and three-dimensional depth orientation of the moving human figure. Models of biomotion perception should incorporate mechanisms to disambiguate depth ambiguities in two-dimensional body representations.
Glia-Dependent Switch of Kainate Receptor Presynaptic Action
Authors: Bonfardin Valérie D. J. , Fossat Pascal , Theodosis Dionysia T. , Oliet Stéphane H. R.
Published: January 2010

Presynaptic kainate receptors (KARs) exert a modulatory action on transmitter release. This effect can be switched from facilitation to inhibition by an increased concentration of KAR agonists. We here report that activation of presynaptic GluK1-containing KARs facilitates GABA release on oxytocin and vasopressin neurons in the supraoptic nucleus of the hypothalamus. Increase in ambient levels of glutamate associated with the physiological reduction of astrocytic coverage of oxytocin neurons in lactating rats switches this KAR-mediated facilitation to inhibition of GABAergic transmission. This effect was reproduced in both oxytocin and vasopressin neurons of virgin rats when glutamate transporters were blocked pharmacologically, thereby establishing that enhanced levels of extracellular glutamate induce the switch in KAR-mediated action. The facilitation of GABA release was inhibited with philanthotoxin, a Ca2+-permeable KAR antagonist, suggesting that this effect was associated with an ionotropic mode of action. Conversely, KAR-mediated inhibition was compromised in the presence of U73122, a phospholipase C inhibitor, in agreement with the involvement of a metabotropic pathway. We thus reveal that physiological astrocytic plasticity modifies the mode of action of presynaptic KARs, thereby inversing their coupling with GABA release.
Nitric Oxide Induces Pathological Synapse Loss by a Protein Kinase G-, Rho Kinase-Dependent Mechanism Preceded by Myosin Light Chain Phosphorylation
Authors: Sunico Carmen R. , González-Forero David , Domínguez Germán , García-Verdugo José Manuel , Moreno-López Bernardo
Published: January 2010

The molecular signaling that underpins synapse loss in neuropathological conditions remains unknown. Concomitant upregulation of the neuronal nitric oxide (NO) synthase (nNOS) in neurodegenerative processes places NO at the center of attention. We found thatde novonNOS expression was sufficient to induce synapse loss from motoneurons at adult and neonatal stages. In brainstem slices obtained from neonatal animals, this effect required prolonged activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and RhoA/Rho kinase (ROCK) signaling. Synapse elimination involved paracrine/retrograde action of NO. Furthermore, before bouton detachment, NO increased synapse myosin light chain phosphorylation (p-MLC), which is known to trigger actomyosin contraction and neurite retraction. NO-induced MLC phosphorylation was dependent on cGMP/PKG-ROCK signaling. In adulthood, motor nerve injury induced NO/cGMP-dependent synaptic stripping, strongly affecting ROCK-expressing synapses, and increased the percentage of p-MLC-expressing inputs before synapse destabilization. We propose that this molecular cascade could trigger synapse loss underlying early cognitive/motor deficits in several neuropathological states.
Abnormalities in Metabolic Network Activity Precede the Onset of Motor Symptoms in Parkinson's Disease
Authors: Tang Chris C. , Poston Kathleen L. , Dhawan Vijay , Eidelberg David
Published: January 2010

Imaging studies show that Parkinson's disease (PD) alters the activity of motor- and cognition-related metabolic brain networks. However, it is not known whether the network changes appear at or before symptom onset. In this study, we examined 15 hemiparkinsonian patients who underwent serial metabolic imaging with [18F]-fluorodeoxyglucose (FDG) PET at baseline and again 2.1 ± 0.6 (mean ± SD) and 3.9 ± 0.7 years later. We assessed longitudinal changes in network activity in each cerebral hemisphere, focusing specifically on the “presymptomatic” hemisphere—ipsilateral to the initially involved body side. At the network level, the activity of the PD motor-related pattern (PDRP) increased symmetrically in both hemispheres over time (p< 0.001), with significant bilateral elevations at each of the three time points. Hemispheric expression of the PD cognition-related pattern likewise increased symmetrically (p< 0.001), although significant elevations were not evident on either side until 4 years. At the regional level, putamen metabolism contralateral to the initially affected body side was elevated at all three time points, without longitudinal change. In contrast, in the initially presymptomatic hemisphere, putamen metabolic activity increased steadily over time, reaching abnormal levels only at 4 years. Metabolic activity in the contralateral precuneus fell to subnormal levels by the final time point. These findings suggest that abnormal PDRP activity antecedes the appearance of motor signs by ∼2 years. The timing and laterality of symptom onset relates to focal asymmetric metabolic changes at the putamenal node of this network.
Altered Intracellular Ca2+Homeostasis in Nerve Terminals of Severe Spinal Muscular Atrophy Mice
Authors: Ruiz Rocío , Casañas Juan José , Torres-Benito Laura , Cano Raquel , Tabares Lucía
Published: January 2010

Low levels of survival motor neuron (SMN) protein result in spinal muscular atrophy (SMA), a severe genetic disease characterized by motor impairment and premature lethality. Although SMN is a ubiquitous protein, motor neurons are much more vulnerable to low levels of SMN than other cells. To gain insight into the pathogenesis of SMA, we have compared synaptic function of motor terminals in wild-type and severe SMA mice at different ages and in two proximal muscles. Our results show that mutant muscle fibers fire normal action potentials and that multi-innervated terminals are functional. By studying the characteristics of the three main components of synaptic transmission in nerve terminals (spontaneous, evoked, and asynchronous release), we found that the kinetics of the postsynaptic potentials are slowed and evoked neurotransmitter release is decreased by ∼55%. In addition, asynchronous release is increased ∼300%, indicating an anomalous augmentation of intraterminal bulk Ca2+during repetitive stimulation. Together, these results show that the reduction of SMN affects synaptic maturation, evoked release, and regulation of intraterminal Ca2+levels.
Feedforward Inhibition Determines the Angular Tuning of Vibrissal Responses in the Principal Trigeminal Nucleus
Authors: Bellavance Marie-Andrée , Demers Maxime , Deschênes Martin
Published: January 2010

Trigeminal neurons that relay vibrissal messages to the thalamus receive input from first-order afferents that are tuned to different directions of whisker motion. This raises the question of how directional tuning is maintained in central relay stations of the whisker system. In the present study we performed a detailed analysis of the angular tuning properties of cells in the principal trigeminal nucleus of the rat. We found that stimulus direction systematically influences response latency, so that the degree of directional tuning and the preferred deflection angle computed with first-spike latency yielded results nearly similar to those obtained with spike counts. Furthermore, we found that inhibition sharpens directional selectivity, and that pharmacological blockade of inhibition markedly decreases the angular tuning of cellular responses. These results indicate that the angular tuning of cells in the first relay station of the vibrissal system is determined by fast feedforward inhibition, which shapes excitatory inputs at the very beginning of synaptic integration.
Case Study of Multistage Isolating Stimulation in High Temperature Deep Carbonate Horizontal Wells
Authors: Li Yongping , Wang Yonghui , Cheng Xingsheng , Che Mingguang , Zhang Fuxiang , Peng Jianxin , Zhu Raoyun
Published: January 2010

TZ-I carbonate reservoir in the Tarim Basin, Western China is deep buried (>5000m), high temperature (>130°C), low-permeability, and severely inhomogeneous, and the natural fractures, vug and huge cavity often densely distributed in it. Because the aquifer energy is poor, horizontal wells can be adopted as recovery method to expose the area of reservoir as much as possible and connect more naturally fractured formation. But the open-hole interval is too long to be effectively stimulated by un-isolated general stimulation, so the multistage isolation fracturing technique should be conducted to exert the advantage of horizontal well and maximize single-well productivity. A novel one-trip open-hole completion and stimulation system was implemented successfully to isolate the long horizontal interval with multistage packers and sliding sleeve. During the process of treatment, the characterization of opening sliding sleeve is clear, moreover, the ISIP and pressure decline after shut-in is different between every stimulation interval, which shows the system is able to effectively isolate and stimulate specified intervals. The wells productivity increased dramatically after the multistage isolation stimulation, and much higher than the vertical well or general acid fractured horizontal well in the same trap. This shows the horizontal isolating stimulation technique can enhance production and reduce rig time significantly.
ESP Application to De-bottleneck Gas Lift System Offshore
Authors: Shnaib Fathi , Nadar Manickam S. , Booth Steve , Otubaga Ademola
Published: January 2010

The Falah field offshore Dubai consists of four satellite platforms and is mostly produced by gas lift. High pressure lift gas is received from the main SWFateh field and the produced fluid and gas after a two-phase separation are returned to SWFateh through long sub-sea pipelines. The system is constrained both on the gas lift supply and surface production networks. The conversion of two of the major gas lift producers to electric submersible pump (ESP) has helped de-bottleneck the Falah system.

The main objectives were to increase drawdown in these wells using ESP and to reduce the load on the gas lift and production systems. Both of these objectives have been successfully achieved. This paper will describe the system constraints, the options considered and the economics associated with each option. The modeling work that helped the justification for the ESP installation will also be described.

The selection of well candidates was an important criterion for success. From a reservoir perspective the goal was to achieve improved oil recovery with increased drawdown. From a facility perspective the wells were selected at the farthest (FB) platform that had the minimum gas lift pressure in the field. Commissioning of the ESPs has reduced the gas load on the system and the production system pressures have decreased as a result. Gas lift operating depths would be deepened in some of the Falah wells, taking advantage of the increased gas lift header pressure now available.

The use of ESP for de-bottlenecking a gas lifted field is an excellent example of production system optimization. This demonstrates how a different type of artificial lift can be effectively used to improve the productivity of a field that uses one type of artificial lift.
Rapid Assessment of Petroleum Potential of Bantumilli Marginal Oil Field by Using Infrasonic Passive Differential Spectrascopy (IPDS), an Indian Scenario
Authors: Rode E.D.. D. , Das S.R.. R. , Ravindran S.. , Mukherjee M.K.. K. , Bordoloi Amborish , Jinagam Pydiraju
Published: January 2010

Bantumilli oil field is located in the Krishna - Godavari Basin, in the east coast of India. The field is considered marginal. Quantifying potential in marginal fields involves several challenges like heterogeneous reservoir quality, incomplete reservoir data, production and completion practices. Perhaps the most effective way to establish potential is to conduct a detailed integrated reservoir study, which is often time consuming, expensive and applicable to fields with existing flowing wells. Hence, there is a need for rapid turn around methods that characterize and predict actual volume of oil. Infrasonic Passive Differential Spectroscopy (IPDS) is one such technology that quantifies the hydrocarbon content in a field.

The omni present infrasonic passive sound of the earth, transmitted through a reservoir containing differential media i.e., oil, gas and water, produces unique spectral signatures in the frequency range of 0 to 6 Hz. These signatures are used as direct hydrocarbon indicators. Bantumilli field contains hydrocarbons in multiple reservoirs. These reservoirs are thin and sporadic; their petrophysical characters vary conspicuously from one location to the other, do not indicate any specific trend and are not discernible in the seismic sections. IPDS technology was considered the apt solution as it would indicate the presence or absence of hydrocarbon accumulations in the combination traps of structure and stratigraphy. IPDS was executed for delineation of the oil field.

Measurements conducted after calibration of the existing wells, resulted in the identification of prospects. Additionally, IPDS reaffirmed the faults, earlier envisaged from the seismic data. The potential of the field was established through IPDS survey.

Application of the IPDS technology in marginal fields and by-passed oil in brown fields is significant as it eliminates the risk of drilling dry holes.
Practical Application of Flow Assurance and Production Chemistry Test Results
Authors: Robertson C.A. , Liem D.T. , Singh Probjot , Thomason W.H.
Published: January 2010

This paper describes the flow assurance and production chemistry test program implemented during the exploration and appraisal (E&A) phase of a new development area offshore Vietnam. The impact of the program on the facility design is described and program results are compared to operating experience. Fluid samples from several E&A wells were sent to the ConocoPhillips Production Assurance Technology Group in Bartlesville, Oklahoma for analysis. The analytical program consisted of the following groups of tests:

General Properties: API gravity, sulfur content and total acid number (TAN). Separation Properties: Emulsion and foaming characteristics and asphaltene deposition tendencies Flow Assurance: Viscosity, pour point, paraffin content/distribution, wax appearance temperature (WAT), wax deposition rate and gel strength.

The flow assurance test results had several positive impacts on facility and infrastructure design. Coordination between the Project Team, Operations and the Production Assurance Technology group led to significant insights which improved the facility design and operating procedures.
Rheological Properties of Polymer-Based In-Situ Gelled Acids: Experimental and Theoretical Studies
Authors: Gomaa A. M. , Nasr-El-Din H. A.
Published: January 2010

Polymer-based in-situ gelled acids have been used in the field for more than a decade. These acids are typically used for matrix applications at HCl concentrations of 3-5 wt%. Recent lab work and field data indicated that these acids are not fully understood, and that there is a need to better characterize and understand how these acid systems develop viscosity in-situ. This understanding will enhance the way these acids are used in the field. Therefore, the objective of this study is to determine the elastic and viscous properties of these acids as they react with the rock.

Experimental studies were conducted to measure the rheological properties for in-situ gelled acids using an oscillatory rheometer. To the best of our knowledge, this is the first time that the elastic properties were measured for these acid systems. Measuring the elastic modulus (G’) and viscous modulus (G") were done using two techniques: Dynamic sweep and Creep tests.

Based on experimental results obtained, two regimes were identified: a pure viscous behavior and a semisolid elastic behavior. A viscous regime was noted below pH 2 where G" was dominant. Yield stress, Young's modulus, G’, and G" values were relatively small in the viscous regime. A semisolid elastic behavior was observed at pH greater than 2. Yield stress, Young's modulus, G’, and G" significantly increased at pH 2, and reached their maximum values at pH 3.2. G’ increased by 3 orders of magnitude while G" increased only by an order of magnitude during acid reaction with carbonate rock.

Maxwell and Kelvin-Voigt models were able to predict the experimental data for the viscous regime only. However, for the semisolid elastic regime, these models didn't accurately predict experimental results. Three-parameter model was able to predict the semisolid elastic regime only. Therefore, a new model was developed to predict the rheological properties of these acids over a wide range of pH values. Model predictions were in good agreement with experimental results.
An Anisotropy Study: Integrated Interpretation of Shear Wave and Resistivity Anisotropy in an Offshore Field in India
Authors: Manescu A. , Tang X. , O'Sullivan T. , Pandian S. S.
Published: January 2010

Efficient development and production of hydrocarbon reservoirs depends on the accuracy of the geological and petrophysical models. Historically, these were all basic isotropic models where formation properties do not change with direction. With the recent advancement of measurement technology and processing technqiques, the models started incorporating and integrating variations of petrophysical properties with orientation: anisotropy. Anisotropic petrophysical properties include permeability, acoustic slowness, resistivity, etc. Complex models incorporating variations of petrophysical properties with orientation (anisotropy) are useful for well design and well placement for optimum reservoir drainage, borehole instability and sand production prediction, hydraulic fracturing, surface seismic migration or amplitude-versus-offset studies.

Cairn Energy India Pty. Ltd. recorded acoustic and resistivity anisotropy measurements in several of their offshore wells. Acoustic data was processed for azimuthal anisotropy estimation and resistivity data was processed for formation dip, azimuth, horizontal and vertical resistivity.

Whilst resistivity information has been used for accurate hydrocarbon saturation computation, the continuous dip and azimuth results provided a geological framework that was used for interpretation of acoustic azimuthal anisotropy results.

Integrating both datasets resolved potentially ambiguous interpretation of the azimuthal acoustic anisotropy source. We were able to determine the anisotropy cause (unbalanced stresses in the formation, dipping fracture/faults, highly dipping beds, and shale transverse isotropy with a vertical axis of symmetry [TIV] anisotropy).

This presentation shows how an integration of acoustic anisotropy results with resistivity anisotropy results can provide essential information for interpreting and resolving ambiguous causes of acoustic azimuthal anisotropy. This information could be used for avoiding mistakes in well placement and design, reducing sand production and avoiding borehole instability, for well completion planning and several other applications during the life of the field.
Horizontal Underbalanced Drilling Technology Successfully Applied in Sarir C- Main Field - Libya: Case Study
Authors: Qutob Hani , Ben Shatwan Mohamed , Vieira Paco
Published: January 2010

Recently, underbalanced drilling (UBD) has been used with increasing frequency to minimize problems associated with invasive formation damage which often greatly reduces the productivity of oil and gas reservoirs. When properly designed and executed, the benefits of underbalanced drilling (UBD) are well recognized by the industry and there is increasing raise in interest in this technology. The benefits from UBD generally fall into two categories:

Cost reduction- including mitigation of conventional drilling problems such as lost circulation, differential sticking, reduction in stimulation and cleanup costs, etc.

Value adding- including productivity improvement, increase in ultimate recovery, and real-time reservoir characterization while drilling.

Arabian Gulf oil Company (AGOCO), a major energy player in the Libyan oil industry, decided to pioneer the introduction of the new technology by embarking on a pilot project to drill 6 underbalanced horizontal wells in the Sarir C-Main field. Sarir C-Main Field is located in the Libyan Desert on the south east of Sirte basin. The reservoir consists of sandstone from the Early Cretaceous age. The field was first put on production in 1967. Since 1991 ESP pumps have been used for the production. The target reservoir, Member 5AC, is partly depleted oil bearing reservoir from the initial reservoir pressure of 3995 psi to about 2400 psi (5.3 ppg EMW). 3 out of the 6 well UBD campaign in the Sarir C have been drilled so far. The first two wells identified the technology as an effective method to improve penetration and production rates. The third well built on the experience of the previous wells by emphasizing on minimizing formation damage and maximizing the production of the well. Another objective was the evaluation of production while the well is being drilled, eliminating the need for expensive post drilling production testing.

This paper discusses the objectives, planning, problems encountered and lessons learned during the first application of UBD in the Sarir C Main Field for AGOCO Libya.
New Correlation for Z-Factor using Genetic Programming Technique
Authors: Al-Anazi B. D. , AlQuraishi A. A.
Published: January 2010

Compressibility factor is a measure of the deviation of a real gas from ideal behavior. Accurate information of z-factor values is necessary in engineering applications such as gas metering, pipeline design, reserves estimation, gas flow rate, and material balance calculations. In addition, z-factor is important in calculating gas properties such as gas formation volume factor, gas isothermal compressibility, viscosity, and density. The most common sources of z-factor values are experimental measurement, but if unavailable, equations of state and empirical correlations are utilized for the gas composition, and pressure and temperature conditions.

This paper presents a new model that allow accurate determination of z-factor values both for pure components and gas mixtures including significant amounts of non-hydrocarbon components and rich gas condensates at wide ranges of pressures and temperatures. Large database of experimental z-factor measurement are used. It includes more than 977 samples of worldwide sour and sweet gases. The database consists of gas composition, and z-factor experimental measurements at different pseudo-reduced properties of pressures and temperatures. The new model was developed and tested using linear genetic programming (GP) technique. The proposed model efficiency was compared to four commonly used equations of state (Van der-Walls, Redlech kwong, Peng-Robinson and Lawel-Lake-silberberg) in addition to six empirical correlations (Dranchuk-Purvis-Robinson, Dranchuk-Abu-Kassem, Hall-Yarborough, and Beggs and Brill). Several criteria are used to evaluate the proposed model including the average relative error (ARE), average absolute relative error (AARE), standard deviation (SD), and cross plots. The output of this work indicates the strength of the linear genetic programming technique and the good accuracy and simplicity of the developed model in comparison to the tested commonly utilized models.