New infectious mammary tumor virus superantigen with V beta-specificity identical to staphylococcal enterotoxin B (SEB).

Only few infectious mouse mammary tumor viruses (MMTV) have been characterized which induce a potent superantigen response in vivo. Here we describe the characterization of an MMTV which was isolated from milk of the highly mammary tumor-prone SHN mouse strain. Exposure of newborn mice to milk-borne MMTV (SHN) results in a very slow deletion of V beta 7, 8.1, 8.2 and 8.3 expressing peripheral T cells. Subcutaneous injection of adult mice with this virus induces a rapid and strong stimulation of all four affected V beta-subsets in vivo. Besides the strong T cell effect we observed an early proliferation and activation of the local B cell pool leading to the initial secretion of IgM followed by preferential secretion of IgG2a by day 6. Sequence comparison of the polymorphic C terminus with known open reading frames revealed high homology to the endogenous provirus Mtv-RCS. This is the first report of a virus having a complete overlap in V beta-specificity with a bacterial superantigen stimulating as many as 35% of the whole CD4+ T cell repertoire including V beta 8.2.

Fragile-glass behavior of a short-range p-spin model

We propose a short-range generalization of the p-spin interaction spin-glass model. The model is well suited to test the idea that an entropy collapse is at the bottom line of the dynamical singularity encountered in structural glasses. The model is studied in three dimensions through Monte Carlo simulations, which put in evidence fragile glass behavior with stretched exponential relaxation and super-Arrhenius behavior of the relaxation time. Our data are in favor of a Vogel-Fulcher behavior of the relaxation time, related to an entropy collapse at the Kauzmann temperature. We, however, encounter difficulties analogous to those found in experimental systems when extrapolating thermodynamical data at low temperatures. We study the spin-glass susceptibility, investigating the behavior of the correlation length in the system. We find that the increase of the relaxation time is accompanied by a very slow growth of the correlation length. We discuss the scaling properties of off-equilibrium dynamics in the glassy regime, finding qualitative agreement with the mean-field theory.

Erasing the glassy state in magnetic fine particles

BaFe10.4Co0.8Ti0.8O19 magnetic fine particles exhibit most of the features attributed to glassy behavior, e.g., irreversibility in the hysteresis loops and in the zero-field-cooling and field-cooling curves extends up to very high fields, and aging and magnetic training phenomena occur. However, the multivalley energy structure of the glassy state can be strongly modified by a field-cooling process at a moderate field. Slow relaxation experiments demonstrate that the intrinsic energy barriers of the individual particles dominate the behavior of the system at high cooling fields, while the energy states corresponding to collective glassy behavior play the dominant role at low cooling fields.

Neoadjuvant therapy with denosumab in a giant cell tumour. A case report

Introduction: Giant cell tumour (GCT) is a benign but locally aggressive primary osteolytic bone tumour, prone to local recurrence after surgery. Denosumab is a human antibody against RANKL, an over-expressed ligand present on normal multinucleated cells, responsible for bone destruction in GCT. We report the case of a patient with an advanced GCT of the distal radius. The lesion was treated with adjuvant denosumab , followed by curettage. Clinical case: A 28 years old patient presented with a classical honeycomb osteolytic lesion in the left distal radius. Core-needle biopsy confirmed the diagnosis of GCT. Due to the proximity to the radio-carpal joint and advanced scalloping of the metaphyseal cortical bone, joint-salvage surgery was not possible. We initiated a neo-adjuvant treatment with denosumab (XGEVA), 120mg/ week for 1 month, followed by monthly injections for 6 months. During this time, a substantial bone recorticalization, without progression of the size of the tumour was noted. No local or systemic side effects were observed. We performed intra-lesional (curettage) excision and bone grafting after 6 months. Histological analysis revealed islets (10%) of viable tumour cells within fibrous tissue. Post-op evolution was eventless. Discussion: While surgery remains the treatment of choice for GCT, joint-salvage may not always be possible in case of extensive epiphyseal involvement. The presence of osteoclast-like giant cells seems to make those lesions prone to the specific anti-RANKL treatment with denosumab. Denosumab appears to slow down tumour growth and promote recorticalization of eroded bone. It might allow less aggressive surgery in selected cases.

Classical anisotropies in models of open inflation

In the simplest model of open inflation there are two inflaton fields decoupled from each other. One of them, the tunneling field, produces a first stage of inflation which prepares the ground for the nucleation of a highly symmetric bubble. The other, a free field, drives a second period of slow-roll inflation inside the bubble. However, the second field also evolves during the first stage of inflation, which to some extent breaks the needed symmetry. We show that this generates large supercurvature anisotropies which, together with the results of Tanaka and Sasaki, rule out this class of simple models (unless, of course, Omega0 is sufficiently close to 1). The problem does not arise in modified models where the second field does not evolve in the first stage of inflation.

Preliminary assessment of rockslide and rockfall hazards using a DEM (Oppstadhornet, Norway)

The increasing availability and precision of digital elevation model (DEM) helps in the assessment of landslide prone areas where only few data are available. This approach is performed in 6 main steps which include: DEM creation; identification of geomorphologic features; determination of the main sets of discontinuities; mapping of the most likely dangerous structures; preliminary rock-fall assessment; estimation of the large instabilities volumes. The method is applied to two the cases studies in the Oppstadhornet mountain (730m alt): (1) a 10 millions m3 slow-moving rockslide and (2) a potential high-energy rock falling prone area. The orientations of the foliation and of the major discontinuities have been determined directly from the DEM. These results are in very good agreement with field measurements. Spatial arrangements of discontinuities and foliation with the topography revealed hazardous structures. Maps of potential occurrence of these hazardous structures show highly probable sliding areas at the foot of the main landslide and potential rock falls in the eastern part of the mountain.

Hygroscopicity and ammonia volatilization losses from nitrogen sources in coated urea

Hygroscopic fertilizers tend to absorb moisture from the air and may have undesirable characteristics such as moistness, clumping and lower fluidity, hampering the application. The increasing use of urea is due to its numerous advantages, although this nitrogen (N) source is highly susceptible to volatilization losses, particularly when applied to the soil surface of management systems with conservation of crop residues. The volatilization losses can be minimized by slow or controlled-release fertilizers, with controlled water solubility of the urea-coating materials; and by stabilized fertilizers, which prolong the period during which N remains in the amide or ammonia forms by urease inhibitors. This study evaluated the hygroscopicity of and ammonia volatilization from urea coated with boric acid and copper sulfate or with sulfur. The hygroscopicity of the sources was evaluated over time after exposure to five levels of relative humidity (RH) and volatilization evaluated after application to the soil surface covered with sugarcane trash. Ammonium nitrate has a low potential for volatilization losses, but is highly hygroscopic. Although coating with boric acid and copper sulfate or elemental sulfur reduced the critical humidity level of urea, the delay in the volatilization process is a potential positive factor.

Sunitinib-eluting beads for chemoembolization: methods for in vitro evaluation of drug release.

Drug-eluting microspheres are used for embolization of hypervascular tumors and allow for local controlled drug release. Although the drug release from the microspheres relies on fast ion-exchange, so far only slow-releasing in vitro dissolution methods have been correlated to in vivo data. Three in vitro release methods are assessed in this study for their potential to predict slow in vivo release of sunitinib from chemoembolization spheres to the plasma, and fast local in vivo release obtained in an earlier study in rabbits. Release in an orbital shaker was slow (t50%=4.5h, 84% release) compared to fast release in USP 4 flow-through implant cells (t50%=1h, 100% release). Sunitinib release in saline from microspheres enclosed in dialysis inserts was prolonged and incomplete (t50%=9 days, 68% release) due to low drug diffusion through the dialysis membrane. The slow-release profile fitted best to low sunitinib plasma AUC following injection of sunitinib-eluting spheres. Although limited by lack of standardization, release in the orbital shaker fitted best to local in vivo sunitinib concentrations. Drug release in USP flow-through implant cells was too fast to correlate with local concentrations, although this method is preferred to discriminate between different sphere types.

Sleep function: current questions and new approaches.

The mammalian brain oscillates through three distinct global activity states: wakefulness, non-rapid eye movement (NREM) sleep and REM sleep. The regulation and function of these 'vigilance' or 'behavioural' states can be investigated over a broad range of temporal and spatial scales and at different levels of functional organization, i.e. from gene expression to memory, in single neurons, cortical columns or the whole brain and organism. We summarize some basic questions that have arisen from recent approaches in the quest for the functions of sleep. Whereas traditionally sleep was viewed to be regulated through top-down control mechanisms, recent approaches have emphasized that sleep is emerging locally and regulated in a use-dependent (homeostatic) manner. Traditional markers of sleep homeostasis, such as the electroencephalogram slow-wave activity, have been linked to changes in connectivity and plasticity in local neuronal networks. Thus waking experience-induced local network changes may be sensed by the sleep homeostatic process and used to mediate sleep-dependent events, benefiting network stabilization and memory consolidation. Although many questions remain unanswered, the available data suggest that sleep function will best be understood by an analysis which integrates sleep's many functional levels with its local homeostatic regulation.

Competitive sorption and desorption of phosphate and citrate in clayey and sandy loam soils

The increase of organic acids in soils can reduce phosphorus sorption. The objective of the study was to evaluate the competitive sorption of P and citrate in clayey and sandy loam soils, using a stirred-flow system. Three experiments were performed with soil samples (0-20 cm layer) of clayey (RYL-cl) and sandy loam (RYL-sl) Red Yellow Latosols (Oxisols). In the first study, the treatments were arranged in a 2 × 5 factorial design, with two soil types and five combinations of phosphorus and citrate application (only P; P + citrate; and citrate applied 7, 22, 52 min before P); in the second, the treatments were arranged in a 2 × 2 factorial design, corresponding to two soils and two forms of P and citrate application (only citrate and citrate + P); and in the third study, the treatments in a 2 × 2 × 6 factorial design consisted of two soils, two extractors (citrate and water) and six incubation times. In the RYL-cl and RYL-sl, P sorption was highest (44 and 25 % of P application, respectively), in the absence of citrate application. Under citrate application, P sorption was reduced in all treatments. The combined application of citrate and P reduced P sorption to 25.8 % of the initially applied P in RYL-cl and to 16.7 % in RYL-sl, in comparison to P without citrate. Citrate sorption in RYL-cl and RYL-sl was highest in the absence of P application, corresponding to 32.0 and 30.2 % of the citrate applied, respectively. With P application, citrate sorption was reduced to 26.4 and 19.7 % of the initially applied citrate in RYL-cl and RYL-sl, respectively. Phosphorus desorption was greater when citrate was used. Phosphorus desorption with citrate and water was higher in the beginning (until 24 h of incubation of P) in RYL-cl and RYL-sl, indicating a rapid initial phase, followed by a slow release phase. This suggests that according to the contact time of P with the soil colloids, the previously adsorbed P can be released to the soil solution in the presence of competing ligands such as citrate. In conclusion, a soil management with continuous input of organic acids is desirable, in view of their potential to compete for P sorption sites, especially in rather weathered soils.

Dark energy equation of state and anthropic selection

We explore the possibility that the dark energy is due to a potential of a scalar field and that the magnitude and the slope of this potential in our part of the Universe are largely determined by anthropic selection effects. We find that, in some models, the most probable values of the slope are very small, implying that the dark energy density stays constant to very high accuracy throughout cosmological evolution. In other models, however, the most probable values of the slope are such that the slow roll condition is only marginally satisfied, leading to a recollapse of the local universe on a time scale comparable to the lifetime of the Sun. In the latter case, the effective equation of state varies appreciably with the redshift, leading to a number of testable predictions.

Statistical description of rotating Kaluza-Klein black holes

We extend the recent microscopic analysis of extremal dyonic Kaluza-Klein (D0-D6) black holes to cover the regime of fast rotation in addition to slow rotation. Fastly rotating black holes, in contrast to slow ones, have nonzero angular velocity and possess ergospheres, so they are more similar to the Kerr black hole. The D-brane model reproduces their entropy exactly, but the mass gets renormalized from weak to strong coupling, in agreement with recent macroscopic analyses of rotating attractors. We discuss how the existence of the ergosphere and superradiance manifest themselves within the microscopic model. In addition, we show in full generality how Myers-Perry black holes are obtained as a limit of Kaluza-Klein black holes, and discuss the slow and fast rotation regimes and superradiance in this context.

Classical cross sections for relativistic spinning particles

We propose a definition of classical differential cross sections for particles with essentially nonplanar orbits, such as spinning ones. We give also a method for its computation. The calculations are carried out explicitly for electromagnetic, gravitational, and short-range scalar interactions up to the linear terms in the slow-motion approximation. The contribution of the spin-spin terms is found to be at best 10-6 times the post-Newtonian ones for the gravitational interaction.

Glassiness in a model without energy barriers

We propose a microscopic model without energy barriers in order to explain some generic features observed in structural glasses. The statics can be exactly solved while the dynamics has been clarified using Monte Carlo calculations. Although the model has no thermodynamic transition, it captures some of the essential features of real glasses, i.e., extremely slow relaxation, time dependent hysteresis effects, anomalous increase of the relaxation time, and aging. This suggests that the effect of entropy barriers can be an important ingredient to account for the behavior observed in real glasses.

Diagnosis and treatment of follicular lymphoma.

Follicular lymphoma is a slow-growing disease exhibiting a heterogeneous clinical course, with a subset of patients experiencing a rapid disease course in the first two years and some developing disease transformation to a more aggressive phenotype. The advent of highly effective therapies has resulted in an increasing number of patients who achieve long-term progression-free survival alongside a good quality of life. Monoclonal antibodies, such as rituximab, either alone or in combination with chemotherapy regimens or radioimmunotherapy have been used with significant improvements in outcome. New treatment strategies such as new antibodies, biologic agents or vaccination therapy are also under investigation for the treatment of relapsed or refractory disease, further expanding the available options for patients and physicians alike. This article presents an overview of the current therapeutic strategies for the management of follicular lymphoma, focusing on the issues encountered in clinical practice.