bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Iterative EnKF for Strongly Nonlinear Systems
Authors: Sakov Pavel , Oliver Dean S. , Bertino Laurent 
Published: February 2012

Abstract
The study considers an iterative formulation of the ensemble Kalman filter (EnKF) for strongly nonlinear systems in the perfect-model framework. In the first part, a scheme is introduced that is similar to the ensemble randomized maximal likelihood (EnRML) filter by Gu and Oliver. The two new elements in the scheme are the use of the ensemble square root filter instead of the traditional (perturbed observations) EnKF and rescaling of the ensemble anomalies with the ensemble transform matrix from the previous iteration instead of estimating sensitivities between the ensemble observations and ensemble anomalies at the start of the assimilation cycle by linear regression. A simple modification turns the scheme into an ensemble formulation of the iterative extended Kalman filter. The two versions of the algorithm are referred to as the iterative EnKF (IEnKF) and the iterative extended Kalman filter (IEKF).
In the second part, the performance of the IEnKF and IEKF is tested in five numerical experiments: two with the 3-element Lorenz model and three with the 40-element Lorenz model. Both the IEnKF and IEKF show a considerable advantage over the EnKF in strongly nonlinear systems when the quality or density of observations are sufficient to constrain the model to the regime of mainly linear propagation of the ensemble anomalies as well as constraining the fast-growing modes, with a much smaller advantage otherwise.
The IEnKF and IEKF can potentially be used with large-scale models, and can represent a robust and scalable alternative to particle filter (PF) and hybrid PF–EnKF schemes in strongly nonlinear systems.
Synthetic Aperture Radar Remote Sensing of Shear-Driven Atmospheric Internal Gravity Waves in the Vicinity of a Warm Front
Authors: Swales Dustin J. , Young George S. , Sikora Todd D. , Winstead Nathaniel S. , Shirer Hampton N. 
Published: February 2012

Abstract
The synthetic aperture radar ocean surface signature of atmospheric internal gravity waves in the vicinity of a synoptic-scale warm front is examined via a classic Kelvin–Helmholtz velocity profile with a rigid lower boundary and a sloping interface. The horizontal distance that the waves extend from the surface warm front is consistent with a bifurcation along the warm frontal inversion from unstable to neutral solutions. Similarity theories are derived for the wave span and the location of maximum growth rate relative to the surface front position. The theoretical maximum wave growth rate is demonstrated to occur near this bifurcation point and, hence, to explain the observed pattern of wave amplitude. Finally, a wave crest-tracing procedure is developed to explain the observed acute orientation of waves with respect to the surface warm front.
The Influence of Shallow Convection on Tropical Cyclone Track Forecasts
Authors: Torn Ryan D. , Davis Christopher A. 
Published: February 2012

ABSTRACTAccurate tropical cyclone (TC) track forecasts depend on having skillful numerical model predictions of the environmental wind field. Given that wind and temperature are related through thermal wind balance, structural errors in the processes that determine the tropical temperature profile, such as shallow convection, can therefore lead to biases in TC position. This paper evaluates the influence of shallow convection on Advanced Hurricane Weather Research and Forecasting Model (AHW) TC track forecasts by cycling an ensemble data assimilation during a 1-month period in 2008 where cumulus convection is parameterized on the coarse-resolution domain using the Kain–Fritsch scheme or the modified Tiedtke scheme, which contains a more appropriate treatment of oceanic shallow convection. Short-term forecasts with the Kain–Fritsch scheme are characterized by a 1-K, 700-hPa temperature bias over much of the western Atlantic Ocean, which is attributed to a lack of shallow convection within that scheme. In turn, the horizontal gradients in this temperature bias are associated with wind biases in the region where multiple TCs move during this period. By contrast, the Tiedtke scheme does not suffer from this temperature bias, thus the wind biases are smaller. AHW forecasts initialized from the data assimilation system that uses the Tiedtke scheme have track errors that are up to 25% smaller than forecasts initialized from the data assimilation system that uses Kain–Fritsch.
A New Thiopurine S‐Methyltransferase Haplotype Associated With Intolerance to Azathioprine
Authors: Colleoni Lara , Kapetis Dimos , Maggi Lorenzo , Camera Giorgia , Canioni Eleonora , Cavalcante Paola , Kerlero de Rosbo Nicole , Baggi Fulvio , Antozzi Carlo , Confalonieri Paolo , Mantegazza Renato , Bernasconi Pia 
Published: February 2012

AbstractThe authors have analyzed single nucleotide polymorphisms in the thiopurine S‐methyltransferase (TPMT) gene in the context of efficacy and toxicity of azathioprine (AZA) to determine possible genotype‐phenotype correlations between TPMT allelic variants and response to AZA treatment in 76 Italian patients with myasthenia gravis. They confirm known intronic and exonic TPMT polymorphisms that do not correlate with AZA responses and demonstrate a novel intronic polymorphism in a patient intolerant to AZA. Most importantly, they show that of the 22 AZA‐intolerant patients, all 5 who carried mutations of the intolerance‐linked haplotype TPMT*3A also carried the intronic T140+114A (rs3931660), all 3 mutations being part of a new haplotype designated TMPT*3E. TPMT*3E was not observed in unresponsive or responsive patients. The association of TPMT*3E with AZA intolerance and its frequency must be ascertained in larger, ethnically different cohorts. Nevertheless, in view of the highly significant association (Psim = 0.0026) between TPMT*3E and AZA intolerance in the study, this new haplotype should be taken into consideration in pharmacogenetic profiling for AZA.
¡Indígnate!: The 2011 popular protests and the limits to democracy in Spain
Authors: Charnock Greig , Purcell Thomas , Ribera-Fumaz Ramon 
Published: February 2012

We are the unemployed, the poorly remunerated, the subcontracted, the precarious, the young … we want change and a dignified future. We are fed up with antisocial reforms, those that leave us unemployed, those with which the bankers that have provoked the crisis raise our mortgages or take our homes, those laws that they impose upon us that limit our liberty for the benefit of the powerful. We blame the political economic and economic powers for our precarious situation and we demand a change of direction. ¡Democracia Real YA! website, 2011 Thus explains one of the principal organisations behind the ‘movement of the indignant’ that has re-awakened popular political consciousness in Spain since 15 May 2011. 1 From its origins in a network of activists utilising new social media to coordinate a series of protest marches in cities across Spain, the ‘15-M’ movement has since staged camp-outs in several main city squares, and in the space of a month mobilised 40,000 protestors in Madrid and 80,000 in Barcelona to march against high unemployment, the policies and conduct of Spain’s political class, and to demand ‘real democracy NOW!’ As an important case of potential interest to Capital & Class readers in its own right, but also as one example of contemporary European mass movements like that of the aganaktismenoi in Greece, this report explains the motives and actions of los indignados, while also contextualising it within a critical materialist analysis of the political economy of Spain since the mid-20th century. It concludes with some open questions about the limits to the movement itself and its demands for real democracy and systemic change.
Clinical and Radiographic Outcomes After Arthroscopic Repair of Massive Rotator Cuff Tears Using a Suture Bridge Technique
Authors: Kim Jung Ryul , Cho Yong Suk , Ryu Keun Jung , Kim Jae Hwa 
Published: February 2012

Background: High retear rates of arthroscopic massive rotator cuff repair have been reported with relatively satisfactory functional outcomes. Purpose: To assess the clinical and radiological outcomes of an arthroscopic repair of massive rotator cuff tears using a suture bridge technique. We also aimed to explore the various factors that may affect retears. Study Design: Case-control study; Level of evidence, 3. Methods: Sixty-six patients included in the study were divided into 2 groups according to the presence of retears on magnetic resonance imaging (MRI) evaluation at a minimum of 1 year after surgery. We evaluated the visual analog scale (VAS) for pain during motions, the University of California, Los Angeles (UCLA) score, and the absolute and relative Constant scores (mean follow-up, 25.4 months). Results: Twenty-eight of the 66 patients (42.4%) in this study had a retear. At the final follow-up visit, pain VAS, UCLA score, and absolute and relative Constant scores in the completely healed group were significantly superior to those in the retear group, with 2, 29.5, 76.0, and 95.2 points and 4, 26.0, 70.6, and 87.3 points, respectively ( P < .05). From univariate analysis, the preoperative mean acromiohumeral distance, extent of retraction, and degree of fatty infiltration of the supraspinatus and infraspinatus were significantly different between the completely healed (7.83 mm, 2.97 cm, 1.74, and 0.71, respectively) and the retear group (6.36 mm, 3.97 cm, 2.54, and 2.07, respectively; P < .05). From multivariate logistic regression analysis, the preoperative degree of fatty infiltration of the infraspinatus and extent of retraction were the 2 most important factors associated with retears. Conclusion: Arthroscopic repair of massive rotator cuff tears using a suture bridge technique has a relatively high retear rate, and these structural failures appear to have a significant difference in clinical outcomes compared with the healed group. Degree of fatty infiltration of the infraspinatus and extent of retraction are the 2 most important factors associated with a retear. Orthopaedic surgeons should predict the possibility of retear before surgery and counsel patients about their expected functional results.
Arthroscopic Debridement Versus Refixation of the Acetabular Labrum Associated With Femoroacetabular Impingement
Authors: Larson Christopher M. , Giveans M. Russell , Stone Rebecca M. 
Published: February 2012

Background: The acetabular labrum provides a sealing function and a degree of hip joint stability. Limited, short-term follow-up studies suggest that labral refixation/preservation leads to superior outcomes compared with labral debridement/excision. Purpose: To compare the results of labral refixation versus focal labral excision/debridement in a cohort of patients who underwent arthroscopic correction of femoroacetabular impingement (FAI). Study Design: Cohort study; Level of evidence, 3. Methods: We reported on patients who underwent labral debridement/focal labral excision during a period before the development of labral repair techniques. Patients with labral tears thought to be repairable with our current arthroscopic technique were compared with a cohort of patients who underwent labral refixation. To better match the 2 groups, only patients with labral pincer- or combined-type FAI were included. In the first 44 hips, the labrum was focally excised/debrided (group 1); in the next 50 hips, the labrum was refixed (group 2). Outcomes were measured with the modified Harris Hip Score (HHS), Short Form 12 (SF-12), and a visual analog scale (VAS) for pain preoperatively and postoperatively. Preoperative and postoperative radiographs were obtained to evaluate bony resection. Results: The mean age was 32 years in group 1 and 28 years in group 2 with a mean follow-up of 42 months (range, 24-72 months). Preoperative mean subjective outcome scores were not significantly different between groups. At a mean 3.5 years’ follow-up, subjective outcomes were significantly improved ( P < .01) for both groups compared with preoperative scores. The HHS ( P = .001), SF-12 ( P = .041), and VAS pain scores ( P = .004) were all significantly better for the refixation group compared with the debridement group at the most recent follow-up. At a mean 3.5 years’ follow-up, good to excellent results were noted in 68% of the focal excision/debridement group and 92% of the refixation group ( P = .004). Conclusion: Although other factors may have influenced these results, labral refixation compared with an earlier cohort of focal labral excision/debridement resulted in better HHS, SF-12, and VAS pain outcomes and a greater percentage of good to excellent results at a mean 3.5-year follow-up.
Distribution of Bone Mineral Density at Osteochondral Donor Sites in the Patellofemoral Joint Among Baseball Players and Controls
Authors: Nishida Kinya , Iwasaki Norimasa , Fujisaki Kazuhiro , Funakoshi Tadanao , Kamishima Tamotsu , Tadano Shigeru , Minami Akio 
Published: February 2012

Background: To theoretically minimize complications of osteochondral graft harvest from the knee, grafts should be obtained from the site of lowest stress distribution across the joint. Hypothesis: Long-term stress distribution over the patellofemoral (PF) joint surface is not equal in athletes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Measurement of subchondral bone density can determine long-term resultant stress acting on an articular surface in living joints. Our analysis was performed using computed tomography (CT) image data obtained from bilateral knees of 10 college baseball fielders (fielder group) and 10 college baseball pitchers (pitcher group) and 2 control groups, including 10 college soccer players (soccer group) and 10 nonathletes (nonathlete group). The distribution pattern of subchondral bone density throughout the articular surface of the PF joint was assessed using the CT osteoabsorptiometry method. The quantitative analysis focused on the location of the low-density area at the articular surface to assess potential osteochondral donor sites. Results: All participants in the pitcher and fielder groups demonstrated a low-density area widely distributed in the proximal part of the lateral trochlea. On the other hand, a high-density area was located in the distal part of the lateral notch, of the medial notch, and of the medial trochlea. No apparent differences in the distribution pattern were found between the baseball groups and the control groups. Conclusion: Our analysis, based on CT osteoabsorptiometry, indicates that the proximal lateral trochlea of the distal femur has the highest percentage area of low bone density at the PF joint level in donor knees of baseball players, soccer players, and nonathlete controls. Clinical Relevance: From a biomechanical viewpoint, the proximal lateral trochlea is the optimal site for harvesting osteochondral grafts in performing mosaicplasty for baseball players. This selection for the donor site may minimize postoperative PF joint symptoms.
Prediction of the Graft Size of 4-Stranded Semitendinosus Tendon and 4-Stranded Gracilis Tendon for Anterior Cruciate Ligament Reconstruction
Authors: Xie Guoming , Huangfu Xiaoqiao , Zhao Jinzhong 
Published: February 2012

Background: Little information is available regarding parameters that would enable a surgeon to predict the size and length of 4-stranded semitendinosus (ST) and 4-stranded gracilis tendon (GT) grafts. Purpose: To evaluate whether certain preoperative anthropometric data enable prediction of the size of 4-stranded ST and GT autograft for anterior cruciate ligament (ACL) reconstruction. Study Design: Cohort study (prevalence); Level of evidence, 2. Methods: This study involved 235 Chinese Han patients who underwent double-bundle ACL reconstruction with 4-stranded autogenous ST and GT grafts. Preoperatively, the authors recorded height, weight, body mass index (BMI), gender, age, and sports activity. During surgery, the usable length of the ST and GT and the diameter of the 4-stranded grafts made of ST and GT were measured. Multiple regression analysis was used to determine relationships between anthropometric measurements and the length and diameter of intraoperatively measured ST and GT grafts. Results: Strongest correlations for ST and GT length and GT graft diameter were height and weight. The strongest correlations for ST graft diameter were gender and weight. Body mass index had only moderate correlations with ST and GT graft size. Self-reported activity level was not correlated. Women had significantly smaller GT and ST graft diameters and shorter tendon lengths than did men. Semitendinosus graft size was significantly larger and longer than was the GT graft (7.4 ± 0.7 mm vs 5.9 ± 0.6 mm and 279.9 ± 20.8 mm vs 251.5 ± 20.8 mm, respectively). Simple regression analysis demonstrated that height, weight, and BMI can be used to predict ST and GT autograft length and diameter. Conclusion: Several preoperative anthropometric measurements showed correlation with the length of the ST and GT and diameter of 4-stranded ST and GT grafts. The current data may provide surgeons with important preoperative information about size of ST and GT grafts and would be useful for patient counseling and alternative graft source planning.
The mitochondrial ATP-dependent Lon protease: a novel target in lymphoma death mediated by the synthetic triterpenoid CDDO and its derivatives
Authors: Bernstein Steven H. , Venkatesh Sundararajan , Li Min , Lee Jae , Lu Bin , Hilchey Shannon P. , Morse Kimberly M. , Metcalfe Hollie M. , Skalska Jolanta , Andreeff Michael , Brookes Paul S. , Suzuki Carolyn K. 
Published: February 2012

Abstract
Synthetic triterpenoids are multitarget compounds exhibiting promise as preventative and therapeutic agents for cancer. Their proposed mechanism of action is by forming Michael adducts with reactive nucleophilic groups on target proteins. Our previous work demonstrates that the 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivatives promote B-lymphoid cell apoptosis through a mitochondria-mediated pathway linked to mitochondrial protein aggregation. As one function of the Lon protease is to eliminate abnormal mitochondrial proteins, we hypothesized that CDDO-induced protein aggregation and lymphoma apoptosis occur by inactivating this enzyme. Here, we show that CDDO and its derivatives directly and selectively inhibit Lon. CDDO blocks Lon-mediated proteolysis in biochemical and cellular assays, but does not inhibit the 20S proteasome. Furthermore, a biotinylated-CDDO conjugate modifies mitochondrial Lon. A striking common phenotype of CDDO-treated lymphoma cells and Lon-knockdown cells is the accumulation of electron-dense aggregates within mitochondria. We also show that Lon protein levels are substantially elevated in malignant lymphoma cells, compared with resting or activated B cells. Finally, we demonstrate that Lon knockdown leads to lymphoma cell death. Together, these findings suggest that Lon inhibition plays a contributory role in CDDO-induced lymphoma cell death, and support the concept that mitochondrial Lon is a novel anticancer drug target.
Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex
Authors: Kurowska Mathieu , Goudin Nicolas , Nehme Nadine T. , Court Magali , Garin Jérôme , Fischer Alain , de Saint Basile Geneviève , Ménasché Gaël 
Published: February 2012

AbstractCytotoxic T lymphocytes kill target cells via the polarized secretion of cytotoxic granules at the immune synapse. The lytic granules are initially recruited around the polarized microtubule-organizing center. In a dynein-dependent transport process, the granules move along microtubules toward the microtubule-organizing center in the minus-end direction. Here, we found that a kinesin-1–dependent process is required for terminal transport and secretion of polarized lytic granule to the immune synapse. We show that synaptotagmin-like protein 3 (Slp3) is an effector of Rab27a in cytotoxic T lymphocytes and interacts with kinesin-1 through the tetratricopeptide repeat of the kinesin-1 light chain. Inhibition of the Rab27a/Slp3/kinesin-1 transport complex impairs lytic granule secretion. Our data provide further molecular insights into the key functional and regulatory mechanisms underlying the terminal transport of cytotoxic granules and the latter's secretion at the immune synapse.
Hematopoietic stem cells: to be or Notch to be
Authors: Bigas Anna , Espinosa Lluis 
Published: February 2012

AbstractNotch is a well-conserved signaling pathway and its function in cell fate determination is crucial in embryonic development and in the maintenance of tissue homeostasis during adult life. Notch activation depends on cell-cell interactions that are essential for the generation of cell diversity from initially equivalent cell populations. In the adult hematopoiesis, Notch is undoubtedly a very efficient promoter of T-cell differentiation, and this has masked for a long time the effects of Notch on other blood lineages, which are gradually being identified. However, the adult hematopoietic stem cell (HSC) remains mostly refractory to Notch intervention in experimental systems. In contrast, Notch is essential for the generation of the HSCs, which takes place during embryonic development. This review summarizes the knowledge accumulated in recent years regarding the role of the Notch pathway in the different stages of HSC ontology from embryonic life to fetal and adult bone marrow stem cells. In addition, we briefly examine other systems where Notch regulates specific stem cell capacities, in an attempt to understand how Notch functions in stem cell biology.
CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results
Authors: Till Brian G. , Jensen Michael C. , Wang Jinjuan , Qian Xiaojun , Gopal Ajay K. , Maloney David G. , Lindgren Catherine G. , Lin Yukang , Pagel John M. , Budde Lihua E. , Raubitschek Andrew , Forman Stephen J. , Greenberg Philip D. , Riddell Stanley R. , Press Oliver W. 
Published: February 2012

AbstractCellular immune responses have the potential to elicit dramatic and sustained clinical remissions in lymphoma patients. Recent clinical trial data demonstrate that modification of T cells with chimeric antigen receptors (CARs) is a promising strategy. T cells containing CARs with costimulatory domains exhibit improved activity against tumors. We conducted a pilot clinical trial testing a “third-generation” CD20-specific CAR with CD28 and 4-1BB costimulatory domains in patients with relapsed indolent B-cell and mantle cell lymphomas. Four patients were enrolled, and 3 received T-cell infusions after cyclophosphamide lymphodepletion. Treatment was well tolerated, although one patient developed transient infusional symptoms. Two patients without evaluable disease remained progression-free for 12 and 24 months. The third patient had an objective partial remission and relapsed at 12 months after infusions. Modified T cells were detected by quantitative PCR at tumor sites and up to 1 year in peripheral blood, albeit at low levels. No evidence of host immune responses against infused cells was detected. In conclusion, adoptive immunotherapy with CD20-specific T cells was well tolerated and was associated with antitumor activity. We will pursue alternative gene transfer technologies and culture conditions in future studies to improve CAR expression and cell production efficiency. This study is registered at www.clinicaltrials.gov as NCT00621452.