bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen
Authors: Gomez Bianca P , Wang Connie , Viscidi Raphael P , Peng Shiwen , He Liangmei , Wu T-C , Hung Chien-Fu 
Published: October 2012

AbstractBackgroundMerkel cell carcinoma (MCC) is a relatively new addition to the expanding category of oncovirus-induced cancers. Although still comparably rare, the number of cases has risen dramatically in recent years. Further complicating this trend is that MCC is an extremely aggressive neoplasm with poor patient prognosis and limited treatment options for advanced disease. The causative agent of MCC has been identified as the merkel cell polyomavirus (MCPyV). The MCPyV-encoded large T (LT) antigen is an oncoprotein that is theorized to be essential for virus-mediated tumorigenesis and is therefore, an excellent MCC antigen for the generation of antitumor immune responses. As a foreign antigen, the LT oncoprotein avoids the obstacle of immune tolerance, which normally impedes the development of antitumor immunity. Ergo, it is an excellent target for anti-MCC immunotherapy. Since tumor-specific CD8+ T cells lead to better prognosis for MCC and numerous other cancers, we have generated a DNA vaccine that is capable of eliciting LT-specific CD8+ T cells. The DNA vaccine (pcDNA3-CRT/LT) encodes the LT antigen linked to a damage-associated molecular pattern, calreticulin (CRT), as it has been demonstrated that the linkage of CRT to antigens promotes the induction of antigen-specific CD8+ T cells.ResultsThe present study shows that DNA vaccine-induced generation of LT-specific CD8+ T cells is augmented by linking CRT to the LT antigen. This is relevant since the therapeutic effects of the pcDNA3-CRT/LT DNA vaccine is mediated by LT-specific CD8+ T cells. Mice vaccinated with the DNA vaccine produced demonstrably more LT-specific CD8+ T cells. The DNA vaccine was also able to confer LT-specific CD8+ T cell-mediated protective and therapeutic effects to prolong the survival of mice with LT-expressing tumors. In the interest of determining the LT epitope which most MCC-specific CD8+ T cells recognize, we identified the amino acid sequence of the immunodominant LT epitope as aa19-27 (IAPNCYGNI) and found that it is H-2kb-restricted.ConclusionThe results of this study can facilitate the development of other modes of MCC treatment such as peptide-based vaccines and adoptive transfer of LT-specific CD8+ T cells. Likewise, the MCC DNA vaccine has great potential for clinical translation as the immunologic specificity is high and the treatment strategy can be exported to address other virus-induced tumors.
Counteracting ring formation in rotary kilns
Authors: Pisaroni M , Sadi R , Lahaye D 
Published: October 2012

Abstract
Avoiding the formation of rings in rotary kilns is an issue of primary concern to the cement production industry. We developed a numerical combustion model that revealed that in our case study rings are typically formed in zones of maximal radiative heat transfer. This local overheating causes an overproduction of the liquid phase of the granular material, which tends to stick to the oven’s wall and to form rings. To counteract for this phenomenon, we propose to increase the amount of secondary air injected to cool the oven. Experimental validation at the plant has confirmed that our solution is indeed effective. For the first time in years, the kiln has been operating without unscheduled shut-downs, resulting in hugely important cost savings.
An approach to predict the risk of glaucoma development by integrating different attribute data
Authors: Tokuda Yuichi , Yagi Tomohito , Yoshii Kengo , Ikeda Yoko , Fuwa Masahiro , Ueno Morio , Nakano Masakazu , Omi Natsue , Tanaka Masami , Mori Kazuhiko , Kageyama Masaaki , Nagasaki Ikumitsu , Yagi Katsumi , Kinoshita Shigeru , Tashiro Kei 
Published: October 2012

Abstract
Primary open-angle glaucoma (POAG) is one of the major causes of blindness worldwide and considered to be influenced by inherited and environmental factors. Recently, we demonstrated a genome-wide association study for the susceptibility to POAG by comparing patients and controls. In addition, the serum cytokine levels, which are affected by environmental and postnatal factors, could be also obtained in patients as well as in controls, simultaneously. Here, in order to predict the effective diagnosis of POAG, we developed an “integration approach” using different attribute data which were integrated simply with several machine learning methods and random sampling. Two data sets were prepared for this study. The one is the “training data set”, which consisted of 42 POAG and 42 controls. The other is the “test data set” consisted of 73 POAG and 52 controls. We first examined for genotype and cytokine data using the training data set with general machine learning methods. After the integration approach was applied, we obtained the stable accuracy, using the support vector machine method with the radial basis function. Although our approach was based on well-known machine learning methods and a simple process, we demonstrated that the integration with two kinds of attributes, genotype and cytokines, was effective and helpful in diagnostic prediction of POAG.
Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement
Authors: Horneff Gerd , Fitter Sigrid , Foeldvari Ivan , Minden Kirsten , Kuemmerle-Deschner Jasmin , Tzaribacev Nicolay , Thon Angelika , Borte Michael , Ganser Gerd , Trauzeddel Rolf , Huppertz Hans-Iko 
Published: October 2012

Abstract
Introduction
While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS).

Methods
A total of 32 patients aged 12 to 17 years with severe, active and refractory JoAS were enrolled in a multicenter, randomized, double-blind, placebo-controlled parallel study of 12 weeks, followed by open-label adalimumab until week 24 for all patients. ASAS40 was used as the primary, and ASAS20, PedACR and single items were used as the secondary outcome measures for the intention to treat population.

Results
A total of 17 patients were randomized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo. Two patients (one of each group) discontinued prematurely due to insufficient efficacy and were labeled as non-responders. In the double-blind part, more patients on adalimumab achieved an ASAS40 at week 4 (41%), week 8 (53%) and week 12 (53%) than on placebo (20%, 33%, 33%), while differences at week 8 only reached borderline significance (P = 0.05). Also, at 4, 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group (53%/53%/29%; 59%/76%/41%; 53%/65%/53%) compared to placebo (27%/27%/7%; 27%/33%/13%; 33%/40%/27%). In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24. At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65% (P <0.001), the back pain score decreased by 50% (P <0.005), the Bath AS Functional Index (BASFI) score decreased by 47% (P <0.02), while the Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) score improved by 65% (P <0.005). ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity, parents' global assessment of subject's overall well-being, active joint count (all P <0.05) and erythrocyte sedimentation rate (ESR) (P <0.01).
During the 12-week controlled phase, 29 AEs occurred in 10 patients on placebo compared to 27 AEs in 11 patients on adalimumab. Injection site reactions were the most common adverse events. There were 17 various infections occurring in the double-blind phase, 8 on placebo, 9 on adalimumab and a further 19 in the open label period.

Conclusions
Adalimumab was well tolerated and highly effective in a double-blind randomized trial in patients with JoAS. Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment.

Trial registration
EudraCT 2007-003358-27.
Sp1 and Sp3 Transcription Factors Mediate Leptin-Induced Collagen α1(I) Gene Expression in Primary Culture of Male Rat Hepatic Stellate Cells
Authors: García-Ruiz Inmaculada , Gómez-Izquierdo Erica , Díaz-Sanjuán Teresa , Grau Montserrat , Solís-Muñoz Pablo , Muñoz-Yagüe Teresa , Solís-Herruzo José A. 
Published: October 2012

AbstractMechanisms by which leptin stimulates collagen α1(I) [Col1a(I)] gene expression are unclear. The purposes of this study were to identify the trans-acting factors and cis-acting elements in Col1a(I) promoter involved in this effect as well as the pathways that are implicated. In primary cultures of rat hepatic stellate cells (HSCs), we measured the effects of leptin on Col1a(I) gene and protein expression and on the binding of nuclear proteins to the Col1a(I) promoter. We found that leptin increased Col1a(I) gene and protein expression in activated HSCs. Transient transfections showed that leptin exerted its effects through elements located between −220 and −112 bp of the Col1a(I) promoter. Gel retardation assays demonstrated that leptin induced the binding of transcription factors specific protein (Sp)-1 and Sp3 to two elements located between −161 and −110 bp of the Col1a(I) promoter. Leptin-induced Sp1/Sp3 phosphorylation, but this effect was suppressed by inhibiting or silencing Janus kinase-2, phosphatidylinositol-3-kinase, nonphagocytic adenine dinucleotide phosphate (NADPH) oxidase, or ERK1/2, by the use of antioxidants or catalase, or by preventing protein-aldehyde adduct formation. Leptin provoked oxidative stress, aldehyde-protein adduct formation, and increased gene expression of some components of the NADPH oxidase complex. In conclusion, in HSCs, leptin up-regulates Col1a(I) gene expression after activating NADPH oxidase, inducing oxidative stress, aldehyde-protein adduct formation, and ERK1/2 phosphorylation, which in turn activates Sp1/Sp3 and provokes the binding of these two factors to regulatory elements located between −161 and −110 bp of the Col1a(I) promoter. These findings may contribute to a better understanding of mechanisms involved in the leptin-induced liver fibrosis.
Body dynamics and hydrodynamics of swimming fish larvae: a computational study
Authors: Li Gen , Müller Ulrike K. , van Leeuwen Johan L. , Liu Hao 
Published: October 2012

SUMMARYTo understand the mechanics of fish swimming, we need to know the forces exerted by the fluid and how these forces affect the motion of the fish. To this end, we developed a 3-D computational approach that integrates hydrodynamics and body dynamics. This study quantifies the flow around a swimming zebrafish (Danio rerio) larva. We used morphological and kinematics data from actual fish larvae aged 3 and 5 days post fertilization as input for a computational model that predicted free-swimming dynamics from prescribed changes in body shape. We simulated cyclic swimming and a spontaneous C-start. A rigorous comparison with 2-D particle image velocimetry and kinematics data revealed that the computational model accurately predicted the motion of the fish's centre of mass as well as the spatial and temporal characteristics of the flow. The distribution of pressure and shear forces along the body showed that thrust is mainly produced in the posterior half of the body. We also explored the effect of the body wave amplitude on swimming performance by considering wave amplitudes that were up to 40% larger or smaller than the experimentally observed value. Increasing the body wave amplitude increased forward swimming speed from 7 to 21 body lengths per second, which is consistent with experimental observations. The model also predicted a non-linear increase in propulsive efficiency from 0.22 to 0.32 while the required mechanical power quadrupled. The efficiency increase was only minor for wave amplitudes above the experimental reference value, whereas the cost of transport rose significantly.
Performance and scaling of a novel locomotor structure: adhesive capacity of climbing gobiid fishes
Authors: Maie Takashi , Schoenfuss Heiko L. , Blob Richard W. 
Published: October 2012

SUMMARY
Many species of gobiid fishes adhere to surfaces using a sucker formed from fusion of the pelvic fins. Juveniles of many amphidromous species use this pelvic sucker to scale waterfalls during migrations to upstream habitats after an oceanic larval phase. However, adults may still use suckers to re-scale waterfalls if displaced. If attachment force is proportional to sucker area and if growth of the sucker is isometric, then increases in the forces that climbing fish must resist might outpace adhesive capacity, causing climbing performance to decline through ontogeny. To test for such trends, we measured pressure differentials and adhesive suction forces generated by the pelvic sucker across wide size ranges in six goby species, including climbing and non-climbing taxa. Suction was achieved via two distinct growth strategies: (1) small suckers with isometric (or negatively allometric) scaling among climbing gobies and (2) large suckers with positively allometric growth in non-climbing gobies. Species using the first strategy show a high baseline of adhesive capacity that may aid climbing performance throughout ontogeny, with pressure differentials and suction forces much greater than expected if adhesion were a passive function of sucker area. In contrast, large suckers possessed by non-climbing species may help compensate for reduced pressure differentials, thereby producing suction sufficient to support body weight. Climbing Sicyopterus species also use oral suckers during climbing waterfalls, and these exhibited scaling patterns similar to those for pelvic suckers. However, oral suction force was considerably lower than that for pelvic suckers, reducing the ability for these fish to attach to substrates by the oral sucker alone.
Honeybees consolidate navigation memory during sleep
Authors: Beyaert Lisa , Greggers Uwe , Menzel Randolf 
Published: October 2012

SUMMARY
Sleep is known to support memory consolidation in animals, including humans. Here we ask whether consolidation of novel navigation memory in honeybees depends on sleep. Foragers were exposed to a forced navigation task in which they learned to home more efficiently from an unexpected release site by acquiring navigational memory during the successful homing flight. This task was quantified using harmonic radar tracking and applied to bees that were equipped with a radio frequency identification device (RFID). The RFID was used to record their outbound and inbound flights and continuously monitor their behavior inside the colony, including their rest during the day and sleep at night. Bees marked with the RFID behaved normally inside and outside the hive. Bees slept longer during the night following forced navigation tasks, but foraging flights of different lengths did not lead to different rest times during the day or total sleep time during the night. Sleep deprivation before the forced navigation task did not alter learning and memory acquired during the task. However, sleep deprivation during the night after forced navigation learning reduced the probability of returning successfully to the hive from the same release site. It is concluded that consolidation of novel navigation memory is facilitated by night sleep in bees.
Diagnosis of acetabular labral tears: Comparison of three-dimensional intermediate-weighted fast spin-echo MR arthrography with two-dimensional MR arthrography at 3.0 T
Authors: Park So Young , Park Ji Seon , Jin Wook , Rhyu Kee Hyung , Ryu Kyung Nam 
Published: October 2012

Background Magnetic resonance (MR) arthrography is the ideal imaging modality for the acetabular labrum. Three-dimensional (3D) fast spin-echo (FSE) sequences have similar diagnostic performance as two-dimensional (2D) conventional MR imaging for ligaments, menisci, or bone marrow edema in the knee. Purpose To compare the diagnostic accuracy and inter-observer reliability of 3D intermediate-weighted FSE sequence and 2D FSE sequences for the diagnosis of acetabular labral tears. Material and Methods Institutional review board approval was obtained and informed consent was waived for 45 patients (47 hips) who underwent 3D and 2D MR arthrography and subsequent arthroscopic surgery. The 3D sequences were performed using volumetric intermediate-weighted fast spin-echo imaging with fat suppression (voxel size, 0.6 × 0.6 × 1.2 mm; imaging time, 6 min 38 s). Labral tear was retrospectively and independently evaluated by two radiologists in four areas of the labrum (anterosuperior, posterosuperior, anteroinferior, and posteroinferior) on 3D and 2D FSE sequences. Statistical differences between the sensitivity and specificity of the methods were analyzed with the McNemar test, using arthroscopic findings as the reference standard. Inter-observer agreement was calculated using kappa statistics. Results Arthroscopic findings confirmed labral tears at 40 anterosuperior, 23 posterosuperior, 0 anteroinferior, and 2 posteroinferior quadrants. Sensitivity and specificity were 74% and 89% for 2D FSE sequences, and 78% and 92% for 3D FSE sequences, respectively. Sensitivities and specificities for the methods were not different statistically (P > 0.05). Inter-observer agreement for labral tear was substantial for 2D FSE sequences (k = 0.774) and almost perfect for 3D FSE sequences (k = 0.842). Conclusion 3D intermediate-weighted FSE MR arthrography is excellent for diagnosing acetabular labral tears. Sensitivity, specificity, and inter-observer reliability were similar to conventional 2D MR arthrography. For evaluation of the labrum, 3D FSE MR arthrography is more time-efficient than 2D FSE MR arthrography.
Type 2 diabetes care for patients in a tertiary care setting in UAE: a retrospective cohort study
Authors: Alhyas Layla , Cai Yutong , Majeed Azeem 
Published: October 2012

Objective We aimed to examine the quality of type 2 diabetes mellitus (T2DM) care in Al-Ain, in the United Arab Emirates (UAE). Design A retrospective cohort study from 2008 to 2010. Setting A diabetes centre located in a tertiary care hospital in Al-Ain, UAE. Participants People with T2DM receiving care from the diabetes centre. Results 382 Emirates patients with T2DM were included in the analysis. Overall in 2010, proportions of people with T2DM reaching the following targets were: glycated haemoglobin (HbA1c) 41%, low-density lipoprotein (LDL) 72%, systolic and diastolic blood pressure (SBP/DBP) 47% and 73%, respectively. There was a significant improvement from 2008 to 2010, respectively, in the mean for the following: (1) HbA1c (8.5% [95% confidence interval, CI: 8.33–8.67] versus 7.5% [95% CI: 7.36–7.63]); (2) LDL (2.60 mmol/L [95% CI: 2.51–2.70] versus 2.27 mmol/L [95% CI: 2.21–2.33]); and (3) SBP (133.1 mmHg [95% CI: 131.7–134.4] versus 131.0 [95% CI: 130.1–131.9]). Glycaemic and lipid control were similar in men and women; however, HbA1c levels in men and women aged 60+ years were significantly lower by (0.7% [ P = 0.01] versus 0.8% [ P < 0.001], respectively) than for those aged between 18 and 39 years. Conclusion This study demonstrates that there is encouraging progress in diabetes care in Al-Ain, UAE as reflected by the overall improvement in the mean of HbA1c, LDL and SBP, and the increase in the number of people reaching the target for the same indicators from 2008 to 2010. The results however show that there is scope for additional enhancement of care, especially for better glycaemic control among young patients and better SBP control among men.
Combination Therapy for the Treatment and Prevention of Hepatic Encephalopathy
Authors: Mohammad Rima A , Regal Randolph E , Alaniz Cesar 
Published: October 2012

OBJECTIVE: To evaluate the efficacy and safety of combination therapy for the treatment and prevention of hepatic encephalopathy (HE). DATA SOURCES: A PubMed MEDLINE search was conducted (1947-June 2012) using the key terms lactulose, lactitol, nonabsorbable disaccharide, metronidazole, rifaximin, neomycin, probiotics, and hepatic encephalopathy. Searches were limited to include articles published in English. STUDY SELECTION AND DATA EXTRACTION: Study selection included published trials, case reports, and case series of humans with HE who were treated with combination therapy of rifaximin, lactulose, lactitol, metronidazole, neomycin, and/or probiotics. DATA SYNTHESIS: Only 6 studies that evaluated the benefits of combination drug therapy in the treatment or prevention of HE were available for review. Four studies addressed the treatment of HE, 2 found no significant difference between lactulose/neomycin versus placebo or rifaximin/lactulose, 1 assessed the use of rifaximin/lactulose without a control group, and the fourth found no significant difference between lactulose/probiotics versus either drug alone, although each group showed improvement from baseline. In the 2 prevention trials, both of which stemmed from the same data, the combination of rifaximin/lactulose was superior to lactulose alone, showing significant improvement in mental status, blood ammonia levels, and health-related quality of life and reductions in HE recurrence and hospitalization. Currently, there are no available clinical studies evaluating dual antibiotic therapy, metronidazole with nonabsorbable disaccharides, or antibiotics with probiotics. CONCLUSIONS: The evidence evaluating the use of combination therapy for the treatment of HE does not support its widespread use. The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy. The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence.