Enhanced pinning and proliferation of matching effects in a superconducting film with a Penrose array of magnetic dots

The vortex dynamics in superconducting films deposited on top of a five-fold Penrose array of magnetic dots is studied by means of transport measurements. We show that in the low pinning regime (demagnetized dots) a few periodic and aperiodic matching features coexist. In the strong pinning regime (magnetized dots) a richer structure of unforeseen periodic and aperiodic vortex patterns appear giving rise to a clear enhancement of the critical current in a broader field range. Possible stable vortex configurations are determined by molecular dynamics simulations

Suppression of type 1 pilus assembly in uropathogenic Escherichia coli by chemical inhibition of subunit polymerization

OBJECTIVES: To identify and to characterize small-molecule inhibitors that target the subunit polymerization of the type 1 pilus assembly in uropathogenic Escherichia coli (UPEC). METHODS: Using an SDS-PAGE-based assay, in silico pre-filtered small-molecule compounds were screened for specific inhibitory activity against the critical subunit polymerization step of the chaperone-usher pathway during pilus biogenesis. The biological activity of one of the compounds was validated in assays monitoring UPEC type 1 pilus biogenesis, type 1 pilus-dependent biofilm formation and adherence to human bladder epithelial cells. The time dependence of the in vivo inhibitory activity and the overall effect of the compound on UPEC growth were determined. RESULTS: N-(4-chloro-phenyl)-2-{5-[4-(pyrrolidine-1-sulfonyl)-phenyl]-[1,3,4]oxadiazol-2-yl sulfanyl}-acetamide (AL1) inhibited in vitro pilus subunit polymerization. In bacterial cultures, AL1 disrupted UPEC type 1 pilus biogenesis and pilus-dependent biofilm formation, and resulted in the reduction of bacterial adherence to human bladder epithelial cells, without affecting bacterial cell growth. Bacterial exposure to the inhibitor led to an almost instantaneous loss of type 1 pili. CONCLUSIONS: We have identified and characterized a small molecule that interferes with the assembly of type 1 pili. The molecule targets the polymerization step during the subunit incorporation cycle of the chaperone-usher pathway. Our discovery provides new insight into the design and development of novel anti-virulence therapies targeting key virulence factors of bacterial pathogens

Cost-Effectiveness Analysis of Diagnostic Options for Pneumocystis Pneumonia (PCP)

Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented.We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90$189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68$109 per life-year gained) compared with several molecular diagnostic options.For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone

Almost Everywhere Convergence for Lebesgue Differentiation Processes Along Rectangles

In this paper, we study Lebesgue differentiation processes along rectangles R-k shrinking to the origin in the Euclidean plane, and the question of their almost everywhere convergence in L-p spaces. In particular, classes of examples of such processes failing to converge a.e., in L-8 are provided, for which R-k is known to be oriented along the slope k(-s) for s > 0, yielding an interesting counterpart to the fact that the directional maximal operator associated to the set {k(-s) : k ? N*} fails to be bounded in L-p for any 1 = p < 8

Crossover from intravalley to intervalley vortex motion in type-II superconductors with a periodic pinning array

We have determined the transition from intravalley vortex motion (Campbell regime) to intervalley motion (critical state regime) in Pb thin films with and without a square array of holes (antidots) by means of ac susceptibility chi(T,H) measurements. The Campbell regime is characterized by a maximum dissipation chi(')(max) dependent on the ac excitation h but nearly temperature independent. In contrast, in the critical state regime, the height of the dissipation peak remains constant, whereas its position shifts to lower temperatures with increasing h. We introduce an alternative way for determining the temperature dependence of the ac onset of the Bean critical state by analyzing the critical current density J(T) extracted from the chi(')(T) data at several h. We demonstrate that the presence of a periodic pinning array strongly affects the extension of the crossover area in the h-T diagram between these regimes. We show that this effect can be ascribed to the lower dispersion of the pinning energy together with the higher topological order for the antidot sample

Usefulness of gram staining of blood collected from total parenteral nutrition catheter for rapid diagnosis of catheter-related sepsis.

The accuracy of Gram staining of blood drawn from catheters used to administer total parenteral nutrition was compared with paired quantitative blood cultures for the diagnosis of catheter-related sepsis. Gram staining was positive in 11 of 18 episodes of catheter-related sepsis documented by quantitative culture (sensitivity, 61%) but in none of the 5 episodes of fever unrelated to catheter infection. Thus, this procedure enabled the rapid presumptive diagnosis and guidance of antimicrobial therapy for total parenteral nutrition catheter sepsis, with a positive predictive value of 100% and a negative predictive value of 42%

The F4 fimbrial chaperone FaeE is stable as a monomer that does not require self-capping of its pilin-interactive surfaces

Many Gram-negative bacteria use the chaperone-usher pathway to express adhesive surface structures, such as fimbriae, in order to mediate attachment to host cells. Periplasmic chaperones are required to shuttle fimbrial subunits or pilins through the periplasmic space in an assembly-competent form. The chaperones cap the hydrophobic surface of the pilins through a donor-strand complementation mechanism. FaeE is the periplasmic chaperone required for the assembly of the F4 fimbriae of enterotoxigenic Escherichia coli. The FaeE crystal structure shows a dimer formed by interaction between the pilin-binding interfaces of the two monomers. Dimerization and tetramerization have been observed previously in crystal structures of fimbrial chaperones and have been suggested to serve as a self-capping mechanism that protects the pilin-interactive surfaces in solution in the absence of the pilins. However, thermodynamic and biochemical data show that FaeE occurs as a stable monomer in solution. Other lines of evidence indicate that self-capping of the pilin-interactive interfaces is not a mechanism that is conservedly applied by all periplasmic chaperones, but is rather a case-specific solution to cap aggregation-prone surfaces

Structural insight in histo-blood group binding by the F18 fimbrial adhesin FedF

F18-positive enterotoxigenic and Shiga toxin-producing Escherichia coli are responsible for post-weaning diarrhoea and oedema disease in pigs and lead to severe production losses in the farming industry. F18 fimbriae attach to the small intestine of young piglets by latching onto glycosphingolipids with A/H blood group determinants on type 1 core. We demonstrate the N-terminal domain of the F18 fimbrial subunit FedF to be responsible for ABH-mediated attachment and present its X-ray structure in ligand-free form and bound to A and B type 1 hexaoses. The FedF lectin domain comprises a 10-stranded immunoglobulin-like β-sandwich. Three linear motives, Q(47) -N(50), H(88) -S(90) and R(117) -T(119), form a shallow glycan binding pocket near the tip of the domain that is selective for type 1 core glycans in extended conformation. In addition to the glycan binding pocket, a polybasic loop on the membrane proximal surface of FedF lectin domain is shown to be required for binding to piglet enterocytes. Although dispensable for ABH glycan recognition, the polybasic surface adds binding affinity in the context of the host cell membrane, a mechanism that is proposed to direct ABH-glycan binding to cell-bound glycosphingolipids and could allow bacteria to avoid clearance by secreted glycoproteins