On the asymptotic reduction of a bifurcation equation for edge-buckling instabilities

Weakly clamped uniformly stretched thin elastic plates can experience edge buckling when subjected to a transverse pressure. This situation is revisited here for a circular plate, under the assumption of finite rotations and negligible bending stiffness in the pre-buckling range. The eigenproblem describing this instability is formulated in terms of two singularly perturbed fourth-order differential equations involving the non-dimensional bending stiffness ε>0. By using an extension of the asymptotic reduction technique proposed by Coman and Haughton (Acta Mech 55:179–200, 2006), these equations are formally reduced to a simple second-order ordinary differential equation in the limit ε→0+. It is further shown that the predictions of this reduced problem are in excellent agreement with the direct numerical simulations of the original bifurcation equations

Inverse spin-s portrait and representation of qudit states by single probability vectors

Using the tomographic probability representation of qudit states and the inverse spin-portrait method, we suggest a bijective map of the qudit density operator onto a single probability distribution. Within the framework of the approach proposed, any quantum spin-j state is associated with the (2j+1)(4j+1)-dimensional probability vector whose components are labeled by spin projections and points on the sphere. Such a vector has a clear physical meaning and can be relatively easily measured. Quantum states form a convex subset of the 2j(4j+3) simplex, with the boundary being illustrated for qubits (j=1/2) and qutrits (j=1). A relation to the (2j+1)^2- and (2j+1)(2j+2)-dimensional probability vectors is established in terms of spin-s portraits. We also address an auxiliary problem of the optimum reconstruction of qudit states, where the optimality implies a minimum relative error of the density matrix due to the errors in measured probabilities.Comment: 23 pages, 4 figures, PDF LaTeX, submitted to the Journal of Russian Laser Researc

Current trends in the cardiovascular clinical trial arena (I)

The existence of effective therapies for most cardiovascular disease states, coupled with increased requirements that potential benefits of new drugs be evaluated on clinical rather than surrogate endpoints, makes it increasingly difficult to substantiate any incremental improvements in efficacy that these new drugs might offer. Compounding the problem is the highly controversial issue of comparing new agents with placebos rather than active pharmaceuticals in drug efficacy trials. Despite the recent consensus that placebos may be used ethically in well-defined, justifiable circumstances, the problem persists, in part because of increased scrutiny by ethics committees but also because of considerable lingering disagreement regarding the propriety and scientific value of placebo-controlled trials (and trials of antihypertensive drugs in particular). The disagreement also substantially affects the most viable alternative to placebo-controlled trials: actively controlled equivalence/noninferiority trials. To a great extent, this situation was prompted by numerous previous trials of this type that were marked by fundamental methodological flaws and consequent false claims, inconsistencies, and potential harm to patients. As the development and use of generic drugs continue to escalate, along with concurrent pressure to control medical costs by substituting less-expensive therapies for established ones, any claim that a new drug, intervention, or therapy is "equivalent" to another should not be accepted without close scrutiny. Adherence to proper methods in conducting studies of equivalence will help investigators to avoid false claims and inconsistencies. These matters will be addressed in the third article of this three-part series

Set-optimization meets variational inequalities

We study necessary and sufficient conditions to attain solutions of set-optimization problems in therms of variational inequalities of Stampacchia and Minty type. The notion of a solution we deal with has been introduced Heyde and Loehne, for convex set-valued objective functions. To define the set-valued variational inequality, we introduce a set-valued directional derivative and we relate it to the Dini derivatives of a family of linearly scalarized problems. The optimality conditions are given by Stampacchia and Minty type Variational inequalities, defined both by the set valued directional derivative and by the Dini derivatives of the scalarizations. The main results allow to obtain known variational characterizations for vector valued optimization problems

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

High energy emission from microquasars

The microquasar phenomenon is associated with the production of jets by X-ray binaries and, as such, may be associated with the majority of such systems. In this chapter we briefly outline the associations, definite, probable, possible, and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng and G.E. Romero (eds.), to be published by Kluwer Academic Publishers, Dordrecht, 2004. (19 pages

Ethanol seeking triggered by environmental context is attenuated by blocking dopamine D1 receptors in the nucleus accumbens core and shell in rats

Conditioned behavioral responses to discrete drug-associated cues can be modulated by the environmental context in which those cues are experienced, a process that may facilitate relapse in humans. Rodent models of drug self-administration have been adapted to reveal the capacity of contexts to trigger drug seeking, thereby enabling neurobiological investigations of this effect. We tested the hypothesis that dopamine transmission in the nucleus accumbens, a neural structure that mediates reinforcement, is necessary for context-induced reinstatement of responding for ethanol-associated cues. Rats pressed one lever (active) for oral ethanol (0.1 ml; 10% v/v) in operant conditioning chambers distinguished by specific visual, olfactory, and tactile contextual stimuli. Ethanol delivery was paired with a discrete (4 s) light-noise stimulus. Responses on a second lever (inactive) were not reinforced. Behavior was then extinguished by withholding ethanol but not the discrete stimulus in a different context. Reinstatement, expressed as elevated responding for the discrete stimulus without ethanol delivery, was tested by placing rats into the prior self-administration context after administration of saline or the dopamine D1 receptor antagonist, SCH 23390 (0.006, 0.06, and 0.6 μg/side), into the nucleus accumbens core or shell. Compared with extinction responding, active lever pressing in saline-pretreated rats was enhanced by placement into the prior ethanol self-administration context. SCH 23390 dose-dependently reduced reinstatement after infusion into the core or shell. These findings suggest a critical role for dopamine acting via D1 receptors in the nucleus accumbens in the reinstatement of responding for ethanol cues triggered by placement into an ethanol-associated context

On the renormalization of multiparton webs

We consider the recently developed diagrammatic approach to soft-gluon exponentiation in multiparton scattering amplitudes, where the exponent is written as a sum of webs - closed sets of diagrams whose colour and kinematic parts are entangled via mixing matrices. A complementary approach to exponentiation is based on the multiplicative renormalizability of intersecting Wilson lines, and their subsequent finite anomalous dimension. Relating this framework to that of webs, we derive renormalization constraints expressing all multiple poles of any given web in terms of lower-order webs. We examine these constraints explicitly up to four loops, and find that they are realised through the action of the web mixing matrices in conjunction with the fact that multiple pole terms in each diagram reduce to sums of products of lower-loop integrals. Relevant singularities of multi-eikonal amplitudes up to three loops are calculated in dimensional regularization using an exponential infrared regulator. Finally, we formulate a new conjecture for web mixing matrices, involving a weighted sum over column entries. Our results form an important step in understanding non-Abelian exponentiation in multiparton amplitudes, and pave the way for higher-loop computations of the soft anomalous dimension.Comment: 60 pages, 15 figure

Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect Model

Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments