bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turbulent Mixing in the Red Sea Outflow Plume from a High-Resolution Nonhydrostatic Model
Authors: Özgökmen Tamay M. , Johns William E. , Peters Hartmut , Matt Silvia 
Published: February 2011

Abstract
Given the motivation that overflow processes, which supply source waters for most of the deep and intermediate water masses in the ocean, pose significant numerical and dynamical challenges for ocean general circulation models, an intercomparison study is conducted between field data collected in the Red Sea overflow and a high-resolution, nonhydrostatic process model. The investigation is focused on the part of the outflow that flows along a long narrow channel, referred to as the “northern channel,” that naturally restricts motion in the lateral direction such that the use of a two-dimensional model provides a reasonable approximation to the dynamics. This channel carries about two-thirds of the total Red Sea overflow transport, after the overflow splits into two branches in the western Gulf of Aden. The evolution of the overflow in the numerical simulations can be characterized in two phases: the first phase is highly time dependent, during which the density front associated with the overflow propagates along the channel. The second phase corresponds to that of a statistically steady state. The primary accomplishment of this study is that the model adequately captures the general characteristics of the system: (i) the gradual thickening of the overflow with downstream distance, (ii) the advection of high salinity and temperature signals at the bottom along the channel with little dilution, and (iii) ambient water masses sandwiched between the overflow and surface mixed layer. To quantify mixing of the overflow with the ambient water masses, an entrainment parameter is determined from the transport increase along the slope and is expressed explicitly as a function of mean slope angle. Bulk Richardson numbers are estimated both from data and model and are related to the entrainment parameter. The range of entrainment parameter and its functional dependence on bulk Richardson number in this study are found to be in reasonable agreement with those reported from various laboratory experiments and that based on measurements of the Mediterranean overflow. The results reveal a complex dynamical interaction between shear-induced mixing and internal waves and illustrate the high computational and modeling requirements for numerical simulation of overflows to capture (at least in part) turbulent transports explicitly.
Direct Numerical Simulation of Differential Scalar Diffusion in Three-Dimensional Stratified Turbulence
Authors: Gargett Ann E. , Merryfield William J. , Holloway Greg 
Published: February 2011

Abstract
The potential for differential turbulent transport of oceanic temperature (T) and salinity (𝒮) is explored using three-dimensional direct numerical simulations of decaying stratified turbulence. The simulations employ a realistic molecular diffusion coefficient for T, and one for a “salt” scalar S that is 10 times smaller. Initially, a uniformly stratified medium is disturbed by a turbulent burst whose initial energy is assigned a range of values. In each instance, transports of T integrated over the subsequent decay of the burst exceed those of S. The more energetic cases occupy parameter ranges similar to, and exhibit spectral characteristics that are essentially indistinguishable from, those of direct observations of turbulence in the stratified ocean interior. In these cases, the turbulent diffusivity of T exceeds that of S by 6%–22%. These simulations underestimate the degree of differential diffusion between T and salinity 𝒮 (which has a molecular diffusivity 100 times less than T); thus at the Reynolds numbers attained by the simulations these results constitute lower bounds for differential diffusion associated with sporadic turbulence in the ocean. The simulation results are consistent with previous laboratory and two-dimensional numerical experiments and suggest that the assumption of equal turbulent diffusivities for T and 𝒮, commonly used in circulation modeling and in interpreting oceanic mixing measurements, should be reconsidered.
Laboratory Measurements of Differential Diffusion in a Diffusively Stable, Turbulent Flow
Authors: Jackson P. Ryan , Rehmann Chris R. 
Published: February 2011

Abstract
Laboratory experiments were performed to determine the conditions under which differential diffusion occurs and to evaluate its effect on the mixing efficiency. Diffusively stable profiles of temperature and salinity were stirred steadily by horizontally oscillating vertical rods. The two-component stratification ensures that both scalars experience the same stratification and forcing, or Richardson and Reynolds numbers. The eddy diffusivities KT and KS, for temperature and salinity, were estimated by fitting theoretical solutions of diffusion equations to measured profiles, and the mixing efficiency was computed as the ratio of the potential energy change during a stirring interval to the work done in that interval. Differential diffusion occurred for ɛa/νN2 &lt; 300–500, where ɛa is an average dissipation rate computed from an integrated energy budget. The diffusivity ratio d = KS/KT varied between 0.5 and 1 in the range 50 &lt; ɛa/νN2 &lt; 500. The experiments also show that differential diffusion can significantly affect the mixing efficiency. An important dimensionless parameter is the density ratio Rρ, which is the ratio of the density change due to temperature to that due to salinity. Measurements in cases with low density ratio (Rρ ≈ 0.25) and high density ratio (Rρ ≈ 5) showed that the mixing efficiencies agreed well for weak stratification, or small Richardson number. For larger Richardson number, the efficiency for the high-density-ratio case exceeded that for the low-density-ratio case by as much as a factor of 1.5.
Observational Evidence for Flow between the Subtropical and Tropical Atlantic: The Atlantic Subtropical Cells*
Authors: Zhang Dongxiao , McPhaden Michael J. , Johns William E. 
Published: February 2011

Abstract
This study determines the mean pathways and volume transports in the pycnocline and surface layer for water flowing between the subtropical and tropical Atlantic Ocean, using potential vorticity, salinity, geostrophic flow maps on isopycnal surfaces, and surface drifter velocities. In both hemispheres, subducted salinity maximum waters flow into the Tropics in the pycnocline along both interior and western boundary pathways. The North Atlantic ventilating trajectories are confined to densities between about 23.2 and 26.0 σθ, and only about 2 Sv (Sv ≡ 106 m3 s–1) of water reaches the Tropics through the interior pathway, whereas the western boundary contributes about 3 Sv to the equatorward thermocline flow. Flow on shallower surfaces of this density range originates from the central Atlantic near 40°W between 12° and 16°N whereas flow on the deeper surfaces originates from near 20°W just off the coast of Africa at higher latitudes. The pathways skirt around the potential vorticity barrier located under the intertropical convergence zone and reach their westernmost location at about 10°N. In the South Atlantic, about 10 Sv of thermocline water reaches the equator through the combination of interior (4 Sv) and western boundary (6 Sv) routes in a slightly higher density range than in the North Atlantic. Similar to the North Atlantic, the shallower layers originate in the central part of the basin (along 10°–30°W at 10°–15°S) and the deeper layers originate at higher latitudes from the eastern part of the basin. However, the ventilation pathways are spread over a much wider interior window in the Southern Hemisphere than in the Northern Hemisphere that at 6°S extends from 10°W to the western boundary. The equatorward convergent flows in the thermocline upwell into the surface layer and return to the subtropics through surface poleward divergence. As much as 70% of the tropical Atlantic upwelling into the surface layer is associated with these subtropical circulation cells, with the remainder contributed by the warm return flow of the large-scale thermohaline overturning circulation.
A Model Study on the 1988–89 Warming Event in the Northern North Pacific
Authors: Luo Jing-Jia , Yamagata Toshio 
Published: February 2011

Abstract
Using outputs of a high-resolution ocean general circulation model, upper-ocean heat content budget and mixed layer heat budget are analyzed to investigate the reason for the 1988–89 decadal warming event in the northern North Pacific. The model reproduces realistic upper-ocean temperature changes in comparison with observational data. This analysis suggests that the horizontal mean geostrophic advection of anomalous temperature is the main contributor to the heat content increase around 1988–89, and surface heat flux forcing is the main contributor to increasing mixed layer temperature. The anomalous geostrophic advection of mean temperature plays a negative role in the increase of both the upper-ocean heat content and mixed layer temperature in midlatitudes around 1988–89. Another negative contribution to the mixed layer temperature increase is provided by the Ekman advection. In the Kuroshio Extension region, the warm upper-ocean heat content anomaly appears in 1987–88, in which the mean geostrophic advection also plays a dominant role. South of Japan the decadal warming appears even earlier, around 1985–86. The anomalous Kuroshio transport shows a decadal decreasing trend since the early 1980s and therefore cannot explain the late 1980s warming event in midlatitudes. The 1988–89 event is found to be closely linked with the decadal change of the Kuroshio path south of Japan. It is found that subtropical Rossby waves may influence the decadal temperature changes south of Japan.
Onabotulinum toxin A treatment of cervicogenic headache: A randomised, double-blind, placebo-controlled crossover study
Authors: Linde Mattias , Hagen Knut , Salvesen Øyvind , Gravdahl Gøril Bruvik , Helde Grethe , Stovner Lars Jacob 
Published: February 2011

Aims: Preliminary reports regarding injections in the neck of onabotulinum toxin A have been positive in cervicogenic headache (CeH). The aim was to perform the first methodologically rigorous trial. Methods: A randomised, placebo-controlled, patient-, injector- and evaluator-blinded crossover study included 28 adult patients with a long-standing and treatment-resistant CeH. After a baseline period, injections of either onabotulinum toxin A or placebo were given in fixed sites in the neck muscles on the pain side. Second injections were given after ≥8 weeks. Patients were thereafter followed for another 8 weeks. A detailed headache calendar was filled in, and patients were followed with quality-of-life (QoL) questionnaires, algometry and neck mobility measurements. Results: There was no significant difference between verum and placebo in a mixed linear model analysis ( p = 0.084) with regard to the primary end-point, reduction of days with moderate to severe headache. Six patients withdrew from the study before the second injections, but an intention-to-treat (ITT) analysis gave a similar result ( p = 0.27). There were no significant differences favouring verum in any of the secondary efficacy measures. Side-effects of onabotulinum toxin A were minor and short-lasting. Conclusion: Onabotulinum toxin A in neck muscles does not seem to be beneficial in CeH.
The Influence of Arm and Shoulder Position on the Bear-Hug, Belly-Press, and Lift-Off Tests
Authors: Pennock Andrew T. , Pennington W. Wesley , Torry Michael R. , Decker Michael J. , Vaishnav Suketu B. , Provencher Matthew T. , Millett Peter J. , Hackett Thomas R. 
Published: February 2011

Background: Clinical testing for the integrity of the subscapularis muscle includes the belly-press, lift-off, and bear-hug examinations. While these tests have been widely applied in clinical practice, there is considerable variation in arm positioning within each clinical examination. Hypothesis: To determine the ideal arm and shoulder positions for isolating the subscapularis muscle while performing the bear-hug, belly-press, and lift-off tests. Study Design: Controlled laboratory study. Methods: The activity of 7 muscles was monitored in 20 healthy participants: upper and lower divisions of the subscapularis, supraspinatus, infraspinatus, latissimus dorsi, teres major, triceps, pectoralis major. Electromyogram data were collected and compared across each clinical test at varying arm positions: bear-hug (ideal position, 10° superior, 10° inferior to the shoulder line), belly-press (ideal position, maximum shoulder external rotation, and maximal shoulder internal rotation), and lift-off (ideal position, hand position 5 in. [12.7 cm] superior and 5 in. [12.7 cm] inferior to the midlumbar spine). Results: Regardless of arm and shoulder position, the upper and lower subscapularis muscle activities were significantly greater than all other muscles while performing each test. No significant differences were observed between the upper and lower subscapularis divisions at any position within and across the 3 tests. There were no significant differences in subscapularis electromyogram activities across the 3 tests. Conclusion: The level of subscapularis muscle activation was similar among the bear-hug, belly-press, and lift-off tests. The 3 tests activated the subscapularis significantly more than all other muscles tested but were not different from one another when compared across tests and positions. Although the bear-hug and lift-off tests have been described to activate differential portions of the subscapularis, the findings of this study do not support the preferential testing of a specific subscapular division across the 3 tests. As such, all 3 tests are effective in testing the integrity of the entire subscapularis muscle, although there does not appear to be an ideal position for selectively testing its divisions. Clinical Relevance: Clinicians may feel comfortable in using any of the 3 tests, depending on the patient, to isolate the function of the subscapularis as a single muscle. Furthermore, clinicians should not solely focus on a patient’s arm position when administering an examination but also compare the affected arm to the contralateral shoulder when appropriate.
Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients
Authors: Garcia-Martin E , Pueyo V , Ara JR , Almarcegui C , Martin J , Pablo L , Dolz I , Sancho E , Fernandez FJ 
Published: February 2011

Objective: The objective of this research was to study the effect of optic neuritis (ON) on axonal damage in multiple sclerosis (MS) patients. Specifically, we compared changes over 2 years in the retinal nerve fibre layer (RNFL) between affected and contralateral eyes in MS patients with a prior history of ON. Methods: Thirty-four patients with one unilateral definitive episode of ON were included and underwent a complete ophthalmic examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials (VEP) and pattern electroretinogram (pERG). All patients were re-evaluated at 12 and 24 months. Parameters were compared between ON-affected and contralateral eyes in an initial exploration and over the course of the follow-up. Correlations between parameter changes were analysed. Results: RNFL thickness and functional parameters showed more affection in ON eyes ( p ≤ 0.05), but changes in measurements during the study were similar between both groups of eyes. Conclusions: Progressive axonal loss can be detected in the optic nerve, but ON is not a risk factor for increased chronic damage in MS patients without ophthalmic relapses. Loss of the RNFL is caused by progressive degeneration associated with the disease.
The potential for inhaled treprostinil in the treatment of pulmonary arterial hypertension
Authors: Gessler Tobias , Seeger Werner , Schmehl Thomas 
Published: February 2011

Inhaled treprostinil is a safe and well-tolerated approved pharmaceutical for the treatment of pulmonary arterial hypertension. In a series of open-label studies and in the pivotal trial with 253 patients, this long-acting prostacyclin analogue demonstrated pronounced pulmonary selectivity of vasodilatory effects, improved physical capacity and excellent tolerability and safety following aerosol administration. For efficient treatment, only four daily inhalations of treprostinil are necessary compared with six to nine in iloprost aerosol therapy. This review describes in detail the development of inhaled treprostinil, starting with intravenous epoprostenol followed by inhaled iloprost and subcutaneous treprostinil, all three representing well-established and widely approved prostanoid therapies for pulmonary hypertension. In order to circumvent the drawbacks of intravenous epoprostenol, stable prostacyclin analogues with similar pharmacological properties have been investigated. In addition, alternative routes of administration have been proposed and evaluated, mainly inhaled and subcutaneous delivery. The concept of inhaled treprostinil was to combine the pulmonary selectivity of an aerosolized vasodilator with the long-acting effects of a stable prostacyclin analogue. Pulmonary arterial hypertension remains, however, a severe, life-threatening disease, in spite of the enormous progress in specific drug therapy over the last decade. Therefore, further improvement of drug therapy will be essential, with clear potential for inhaled treprostinil: a reduction of inhalation frequency and duration would markedly improve quality of life and compliance, and a longer-lasting local prostanoid effect might further enhance the efficacy of inhaled treprostinil. The advantageous pharmacological properties of treprostinil offer the opportunity to establish a convenient metered dose inhaler as a delivery system, to combine inhaled treprostinil with available or future drugs for pulmonary arterial hypertension, or to develop sustained release formulations of treprostinil suitable for inhalation based on liposomes or biodegradable nanoparticles.
Application of dual affinity retargeting molecules to achieve optimal redirected T-cell killing of B-cell lymphoma
Authors: Moore Paul A. , Zhang Wenjun , Rainey G. Jonah , Burke Steve , Li Hua , Huang Ling , Gorlatov Sergey , Veri Maria Concetta , Aggarwal Sudeepta , Yang Yinhua , Shah Kalpana , Jin Linda , Zhang Sunan , He Leilei , Zhang Tengfei , Ciccarone Valentina , Koenig Scott , Bonvini Ezio , Johnson Syd 
Published: February 2011

AbstractWe describe the application of a novel, bispecific antibody platform termed dual affinity retargeting (DART) to eradicate B-cell lymphoma through coengagement of the B cell–specific antigen CD19 and the TCR/CD3 complex on effector T cells. Comparison with a single-chain, bispecific antibody bearing identical CD19 and CD3 antibody Fv sequences revealed DART molecules to be more potent in directing B-cell lysis. The enhanced activity with the CD19xCD3 DART molecules was observed on all CD19-expressing target B cells evaluated using resting and prestimulated human PBMCs or purified effector T-cell populations. Characterization of a CD19xTCR bispecific DART molecule revealed equivalent potency with the CD19xCD3 DART molecule, demonstrating flexibility of the DART structure to support T-cell/B-cell associations for redirected T cell–killing applications. The enhanced level of killing mediated by DART molecules was not accompanied by any increase in nonspecific T-cell activation or lysis of CD19− cells. Cell-association studies indicated that the DART architecture is well suited for maintaining cell-to-cell contact, apparently contributing to the high level of target cell killing. Finally, the ability of the CD19xTCR DART to inhibit B-cell lymphoma in NOD/SCID mice when coadministered with human PBMCs supports further evaluation of DART molecules for the treatment of B-cell malignancies.
Deletion of cIAP1 and cIAP2 in murine B lymphocytes constitutively activates cell survival pathways and inactivates the germinal center response
Authors: Gardam Sandra , Turner Vivian M. , Anderton Holly , Limaye Sandhya , Basten Antony , Koentgen Frank , Vaux David L. , Silke John , Brink Robert 
Published: February 2011

Abstract
B cells require signals delivered through B-cell activating factor of the TNF family receptor (BAFF-R) and CD40 to survive and produce antibody responses in vivo. In vitro data indicate that these signals are controlled by the homologous RING finger proteins cIAP1 and cIAP2, in collaboration with TRAF2 and TRAF3. There is also mounting evidence that all 4 of these signaling molecules can act as tumor suppressors in human B-lineage malignancies. However, it has not been possible to identify the roles of cIAP1 and cIAP2 in controlling B-cell physiology because of the absence of an appropriate in vivo model. Here we describe a unique genetically modified mouse in which the linked cIap1 and cIap2 genes can be independently inactivated. Deletion of cIAP1 plus cIAP2 (but not either protein alone) rendered primary B cells independent of BAFF-R for their survival and led to their uncontrolled accumulation in vivo. B cells deficient in cIAP1 and cIAP2 were also incapable of forming germinal centers, a key step in antibody-mediated immunity. These data define a fundamental role for cIAP1/cIAP2 in regulating B-cell survival and responsiveness, show this requires direct binding to TRAF2, and suggest how mutations of TRAF2, TRAF3, and cIAP1/cIAP2 contribute to B-lineage malignancies, such as multiple myeloma.
Molecular identification of an MHC-independent ligand recognized by a human α/β T-cell receptor
Authors: Hanada Ken-ichi , Wang Qiong J. , Inozume Takashi , Yang James C. 
Published: February 2011

AbstractDuring an analysis of T-cell responses against human renal cell carcinoma (RCC), we identified a CD4+ T-cell line that showed TCR-mediated recognition and lysis of nearly all RCC lines regardless of MHC type. We have now elucidated the nature of the ligand for this α/β TCR, and it contains no MHC-related moiety and does not involve classic peptide processing. First, matrix metalloproteinase 14 (MMP14) expressed on RCC cells releases membrane-bound TRAIL expressed by the T cell; then, soluble TRAIL binds to its receptor DR4 (TRAIL-R1), which is expressed on tumor cells, and this TRAIL-DR4 complex is recognized by the TCR through a complementarity-determining region 3α (CDR3α)–mediated interaction. Direct and specific antigen-TCR interaction was demonstrated when the immobilized recombinant TRAIL/DR4 complex stimulated the TCR. In addition, amino acid substitutions in the CDR3α of the TCR either obliterated or enhanced target-specific recognition. This description of the molecular nature of a non-MHC target structure recognized by a naturally occurring α/β TCR not only broadens our concept of what the TCR can recognize, but also raises the question of whether such a T cell could be of clinical utility against RCC.