Classical solutions of the leading-logarithm approximation with non-trivial topology

Exact solutions of the classical equations corresponding to the leading-logarithm approximation are obtained. They are classified by an (integer) topological number.

On The Spot Damage Detection Methodology for Highway Bridges, July 2010

Vibration-based damage identification (VBDI) techniques have been developed in part to address the problems associated with an aging civil infrastructure. To assess the potential of VBDI as it applies to highway bridges in Iowa, three applications of VBDI techniques were considered in this study: numerical simulation, laboratory structures, and field structures. VBDI techniques were found to be highly capable of locating and quantifying damage in numerical simulations. These same techniques were found to be accurate in locating various types of damage in a laboratory setting with actual structures. Although there is the potential for these techniques to quantify damage in a laboratory setting, the ability of the methods to quantify low-level damage in the laboratory is not robust. When applying these techniques to an actual bridge, it was found that some traditional applications of VBDI methods are capable of describing the global behavior of the structure but are most likely not suited for the identification of typical damage scenarios found in civil infrastructure. Measurement noise, boundary conditions, complications due to substructures and multiple material types, and transducer sensitivity make it very difficult for present VBDI techniques to identify, much less quantify, highly localized damage (such as small cracks and minor changes in thickness). However, while investigating VBDI techniques in the field, it was found that if the frequency-domain response of the structure can be generated from operating traffic load, the structural response can be animated and used to develop a holistic view of the bridge’s response to various automobile loadings. By animating the response of a field bridge, concrete cracking (in the abutment and deck) was correlated with structural motion and problem frequencies (i.e., those that cause significant torsion or tension-compression at beam ends) were identified. Furthermore, a frequency-domain study of operational traffic was used to identify both common and extreme frequencies for a given structure and loading. Common traffic frequencies can be compared to problem frequencies so that cost-effective, preventative solutions (either structural or usage-based) can be developed for a wide range of IDOT bridges. Further work should (1) perfect the process of collecting high-quality operational frequency response data; (2) expand and simplify the process of correlating frequency response animations with damage; and (3) develop efficient, economical, preemptive solutions to common damage types.

Rapid transgene expression in multiple precursor cell types of adult rat subventricular zone mediated by adeno-associated type 1 vectors.

Abstract The adult rat brain subventricular zone (SVZ) contains proliferative precursors that migrate to the olfactory bulb (OB) and differentiate into mature neurons. Recruitment of precursors constitutes a potential avenue for brain repair. We have investigated the kinetics and cellular specificity of transgene expression mediated by AAV2/1 vectors (i.e., adeno-associated virus type 2 pseudotyped with AAV1 capsid) in the SVZ. Self-complementary (sc) and single-stranded (ss) AAV2/1 vectors mediated efficient GFP expression, respectively, at 17 and 24 hr postinjection. Transgene expression was efficient in all the rapidly proliferating cells types, that is, Mash1(+) precursors (30% of the GFP(+) cells), Dlx2(+) neuronal progenitors (55%), Olig2(+) oligodendrocyte progenitors (35%), and doublecortin-positive (Dcx(+)) migrating cells (40%), but not in the slowly proliferating glial fibrillary acidic protein-positive (GFAP(+)) neural stem cell pool (5%). Because cell cycle arrest by wild-type and recombinant AAV has been described in primary cultures, we examined SVZ proliferative activity after vector injection. Indeed, cell proliferation was reduced immediately after vector injection but was normal after 1 month. In contrast, migration and differentiation of GFP(+) precursors were unaltered. Indeed, the proportion of Dcx(+) cells was similar in the injected and contralateral hemispheres. Furthermore, 1 month after vector injection into the SVZ, GFP(+) cells, found, as expected, in the OB granular cell layer, were mature GABAergic neurons. In conclusion, the rapid and efficient transgene expression in SVZ neural precursors mediated by scAAV2/1 vectors underlines their potential usefulness for brain repair via recruitment of immature cells. The observed transient precursor proliferation inhibition, not affecting their migration and differentiation, will likely not compromise this strategy.

Signatures of CP violation in the presence of multiple b-pair production at hadron colliders

We calculate the production of two b-quark pairs in hadron collisions. Sources of multiple pairs are multiple interactions and higher order perturbative QCD mechanisms. We subsequently investigate the competing effects of multiple b-pair production on measurements of CP violation: (i) the increase in event rate with multiple b-pair cross sections which may reach values of the order of 1 b in the presence of multiple interactions and (ii) the dilution of b versus b tagging efficiency because of the presence of events with four B mesons. The impact of multiple B-meson production is small unless the cross section for producing a single pair exceeds 1 mb. We show that even for larger values of the cross section the competing effects (i) and (ii) roughly compensate so that there is no loss in the precision with which CP-violating CKM angles can be determined.

Guide to Cement-Based Integrated Pavement Solutions, August 2011

This guide provides a clear, concise, and cohesive presentation of cement-bound materials options for 10 specific engineering pavement applications: new concrete pavements, concrete overlays, previous concrete, precast pavements, roller-compacted concrete, cement-treated base, full-depth reclamation with cement, cement-modified soils, recycled concrete aggregates, and repair and restoration. Each application is presented as a method for meeting specific design and construction objectives that today’s pavement practitioners must accomplish. The benefits, considerations, brief description, and summary of materials, design, and construction requirements, as well as a list of sustainable attributes, are provided for every solution. This guide is intended to be short, simple, and easy to understand. It was designed so that the most up-to-date and relevant information is easily extractable. It is not intended to be used as a design guide for any of the applications identified herein. Recommendations for additional information that can provide such details are given at the end of each solution discussion. The intended audience is practitioners, including engineers and managers who face decisions regarding what materials to specify in the pavement systems they design or manage. The audience also includes city and county engineers, along with the A/E firms that often represent them, and state DOT engineers at all levels who are seeking alternatives in this era of changing markets.

RANKL expression, function, and therapeutic targeting in multiple myeloma and chronic lymphocytic leukemia.

Bone destruction is a prominent feature of multiple myeloma, but conflicting data exist on the expression and pathophysiologic involvement of the bone remodeling ligand RANKL in this disease and the potential therapeutic benefits of its targeted inhibition. Here, we show that RANKL is expressed by primary multiple myeloma and chronic lymphocytic leukemia (CLL) cells, whereas release of soluble RANKL was observed exclusively with multiple myeloma cells and was strongly influenced by posttranscriptional/posttranslational regulation. Signaling via RANKL into multiple myeloma and CLL cells induced release of cytokines involved in disease pathophysiology. Both the effects of RANKL on osteoclastogenesis and cytokine production by malignant cells could be blocked by disruption of RANK-RANKL interaction with denosumab. As we aimed to combine neutralization of RANKL with induction of antibody-dependent cellular cytotoxicity of natural killer (NK) cells against RANKL-expressing malignant cells and as denosumab does not stimulate NK reactivity, we generated RANK-Fc fusion proteins with modified Fc moieties. The latter displayed similar capacity compared with denosumab to neutralize the effects of RANKL on osteoclastogenesis in vitro, but also potently stimulated NK cell reactivity against primary RANKL-expressing malignant B cells, which was dependent on their engineered affinity to CD16. Our findings introduce Fc-optimized RANK-Ig fusion proteins as attractive tools to neutralize the detrimental function of RANKL while at the same time potently stimulating NK cell antitumor immunity.

MP2RAGE Multiple Sclerosis Magnetic Resonance Imaging at 3 T.

OBJECTIVES: Lesion detection and characterization in multiple sclerosis (MS) are an essential part of its clinical diagnosis and an important research field. In this pilot study, we applied the recently introduced two inversion-contrast magnetization-prepared rapid gradient echo sequence (MP2RAGE) to patients with early-stage MS.¦MATERIALS AND METHODS: The MP2RAGE is a 3-dimensional (3D) magnetization-prepared rapid gradient echo derivative providing homogeneous T1 weighting and simultaneous T1 mapping. The MP2RAGE performance was compared with that of 2 clinical routine sequences (2D fluid-attenuated inversion recovery [FLAIR] and 3D magnetization-prepared rapid gradient echo [MP-RAGE]) and 2 state-of-the art clinical research sequences (the 3D FLAIR-SPACE [sampling perfection with application-optimized contrasts by using different flip-angle evolutions], a fluid-attenuated variable flip-angle fast spin echo technique, and the 3D double-inversion recovery SPACE). A cohort of 10 early-stage female MS patients (age, 31.6 ± 4.7 years; disease duration, 3.8 ± 1.9 years; median expanded disability status scale score, 1.75) and 10 age- and gender-matched controls were enrolled after approval of the local institutional review board was obtained. Multiple sclerosis lesions were identified and assigned to brain locations and tissue types by two experienced physicians in all 5 contrasts. Subsequently, lesions were manually delineated for comparison and statistical analysis of lesion count, volume and quantitative measures.¦RESULTS AND CONCLUSIONS: The results show that the 3D T1-weighted high-resolution MP2RAGE contrast provides a sensitive means for MS lesion assessment. The additional quantitative T1 relaxation time maps obtained with the MP2RAGE provide further potential diagnostic and prognostic information that could help (a) to better discriminate lesion subtypes and (b) to stage and predict the activity and the evolution of MS. Results also indicate that the T2-weighted double-inversion recovery and FLAIR-SPACE contrasts are attractive complements to the MP2RAGE for lesion detection.

HLA-B7-Restricted EBV-Specific CD8+ T Cells Are Dysregulated in Multiple Sclerosis.

It was hypothesized that the EBV-specific CD8(+) T cell response may be dysregulated in multiple sclerosis (MS) patients, possibly leading to a suboptimal control of this virus. To examine the CD8(+) T cell response in greater detail, we analyzed the HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and CMV-specific CD8(+) T cell responses in a high number of MS patients and control subjects using tetramers. Content in cytolytic granules, as well as cytotoxic activity, of EBV- and CMV-specific CD8(+) T cells was assessed. We found that MS patients had a lower or a higher prevalence of HLA-A2 and HLA-B7, respectively. Using HLA class I tetramers in HLA-B7(+) MS patients, there was a higher prevalence of MS patients with HLA-B*0702/EBV(RPP)-specific CD8(+) T cells ex vivo. However, the magnitude of the HLA-B*0702/EBV(RPP)-specific and HLA-B*0702/CMV(TPR)-specific CD8(+) T cell response (i.e., the percentage of tetramer(+) CD8(+) T cells in a study subject harboring CD8(+) T cells specific for the given epitope) was lower in MS patients. No differences were found using other tetramers. After stimulation with the HLA-B*0702/EBV(RPP) peptide, the production of IL-2, perforin, and granzyme B and the cytotoxicity of HLA-B*0702/EBV(RPP)-specific CD8(+) T cells were decreased. Altogether, our findings suggest that the HLA-B*0702-restricted viral (in particular the EBV one)-specific CD8(+) T cell response is dysregulated in MS patients. This observation is particularly interesting knowing that the HLA-B7 allele is more frequently expressed in MS patients and considering that EBV is associated with MS.

Ballistic and diffusive corrections to front propagation in the presence of multiplicative noise

We study the dynamics of reaction-diffusion fronts under the influence of multiplicative noise. An approximate theoretical scheme is introduced to compute the velocity of the front and its diffusive wandering due to the presence of noise. The theoretical approach is based on a multiple scale analysis rather than on a small noise expansion and is confirmed with numerical simulations for a wide range of the noise intensity. We report on the possibility of noise sustained solutions with a continuum of possible velocities, in situations where only a single velocity is allowed without noise.