In two three-dimensional models a Shil’nikov homoclinic bifurcati

In two three-dimensional models a Shil’nikov homoclinic bifurcation functions as the organising centre of chaos, while tangencies of homoclinic cycle-to-cycle connections ‘cut’ the chaotic attractors, which is associated with boundary crises. In one model this leads to extinction of the top predator, while

in the other model hysteresis occurs. The types of ecological events occurring because of a global bifurcation will be categorized. Global bifurcations are always catastrophic, leading to the disappearance or merging of attractors. However, there is no 1-on-1 coupling between global bifurcation type and the possible ecological consequences. This only emphasizes the importance of including global bifurcations in the analysis of food chain models. (C) 2010 learn more Elsevier Inc. All rights reserved.”
“Background: The acronym “ASHT” stands for “Alerting System and Development of a Health Surveillance Combretastatin A4 System for the Deliberate Release of Chemicals by Terrorists”. Imagine this scenario: 15 patients with respiratory symptoms following a concert in Rome and 12 patients coughing after lunch in a cafeteria in the Czech Republic; are these events related? Today these events would never be connected as there is no mechanism to allow EU Member States to share this type of information effectively. The main objective of the ASHT project

was to improve data sharing between EU Member States. In part, this was achieved by an internet accessible EU-wide alerting system with the aim to detect the deliberate (i.e. criminal or terrorist) or accidental release of chemicals. Nevertheless more information from police, fire brigades and health professionals is needed.\n\nMethods: Description of the design, development, functionality and testing of the relational database

system called “RAS-CHEM” (Rapid Alert System for Chemicals).\n\nResults: A database structure appropriate for the description of “events” with sophisticated retrieval functions was developed. For evaluation purposes 37 events were entered into the database including 29 scenarios and 8 selleck chemicals llc historical mass intoxications. The alert level was “background information” for 21 events, “suspected mass intoxication” for 6 cases and “confirmed mass intoxication” for 10 events.\n\nConclusion: The RAS-CHEM database works and will be integrated into the Health Emergency Operations Facility (HEOF) with other European Rapid Alert Systems. Poisons centres receive a large number of enquiries and could be important sentinels in this field of toxicovigilance. (C) 2011 European Federation of Internal Medicine. Published by Elsevier B. V. All rights reserved.”
“This review is focused on the advancements in biomedical engineering regarding the elaboration of new prototypes of optical fiber catheters to be applied in spectroscopic analysis, such as Raman and fluorescence spectroscopy.

The requirements for aerosol therapy

The requirements for aerosol therapy selleck chemical depend on the target site of action and the underlying disease. Medication to treat airways disease should deposit on the conducting airways. Effective deposition of airway particles generally requires

particle size between 0.5 and 5 mu m mass median aerodynamic diameter; however, a smaller particle size neither equates to greater side effects nor greater effectiveness. However, medications like peptides intended for systemic absorption, need to deposit on the alveolar capillary bed. Thus ultrafine particles, a slow inhalation, and relatively normal airways that do not hinder aerosol penetration will optimize systemic delivery. Aerosolized antimicrobials are often used for the treatment of cystic fibrosis or bronchiectasis, and mucoactive agents to promote mucus clearance have been delivered by aerosol. As technology improves, a greater variety of novel medications are being developed for aerosol delivery, including

for therapy of pulmonary hypertension, as vaccines, for decreasing dyspnea, to treat airway inflammation, for migraine headache, for nicotine and drug addiction, and ultimately for gene therapy. Common reasons for therapeutic failure of aerosol medications include the use of inactive or depleted medications, inappropriate use of the aerosol device, and, most importantly, poor adherence to prescribed therapy. The respiratory therapist plays a key role in patient education, device selection, and outcomes assessment.”
“Firefly oxyluciferin is a prime example in which pi-pi stacking interactions

play an important role, by being the basis for the formation of GNS-1480 manufacturer sandwich-like oxyluciferin complexes. In the present study, we have used a theoretical methodology to further understand the effect of pi-pi stacking interactions in the properties of oxyluciferin molecule. More NVP-BSK805 specifically, we have analysed the effect of resonance changes in oxyluciferin pi-pi stacking dimers. We have found that resonance changes have little effect on the ground state properties of the dimmers. More interestingly, by modulating the resonance of the dimmers we can obtain different transition energies and efficiencies. This results in changes in the degree of contributions made by the different orbital excitations that compose the excitation transition. (C) 2013 Elsevier B.V. All rights reserved.”
“The complement (C’) cascade is an important part of the innate immunity. It acts through three major pathways: classical (CP), alternative (AP) and mannose-binding-lectin (MP). C’ reduction is a key feature in systemic lupus erythematosus (SLE), for its pathogenesis and for disease relapse. The aims of our study are to correlate C’ variations with disease activity and verify the presence of C’ deficiencies. We tested for three C’ pathways 52 sera from 20 patients affected by SLE. A significant correlation between the ECLAM score and the degree of activation of the CP (Mann-Whitney; P = 0.


“Complex electromagnetic structures can be designed by usi


“Complex electromagnetic structures can be designed by using the powerful concept of transformation electromagnetics. In this study, we define a spatial coordinate transformation that shows the possibility

of designing a device capable of producing an illusion on an antenna radiation pattern. Indeed, by compressing the space containing a radiating element, we show that it is able to change the radiation pattern and to make the radiation location appear outside the latter space. Both continuous and discretized models with calculated electromagnetic parameter values are presented. A SRT2104 molecular weight reduction of the electromagnetic material parameters is also proposed for a possible physical fabrication of the device with achievable values of permittivity and permeability that can be obtained from existing well-known metamaterials. Following that, the design selleck of the proposed antenna using a layered metamaterial is presented. Full wave numerical simulations using Finite Element Method are performed to demonstrate the performances of such a device. (C) 2015 AIP

Publishing LLC.”
“Chemotherapy is a traditional therapeutic approach for the treatment of many solid tumors, but the poor solubility and low bioavailability of hydrophobic anti-cancer drugs greatly limit their applications. In this article, DOX-loaded micelles were fabricated based on an amphiphilic graft polymer composed of hydrophilic poly(gamma-glutamic acid) (gamma-PGA) and hydrophobic poly (L-lactide) (PLLA). The structure of the copolymers and the characteristic of the micelles were studied. The release profiles of doxorubicin as a model drug from the micelles were measured. Due to the protonation of the amino group of DOX and the conformational alteration of gamma-PGA, the release of DOX from gamma-PGA-g-PLLA micelle was faster

in the acid condition, which is beneficial to tumor therapy. The cellular uptake of the DOX-loaded gamma-PGA-g-PLLA micelle was proved to be a GGT-mediated process.”
“The biofilm formation of Pseudomonas aeruginosa, GW4869 nmr an opportunistic human pathogen, is developed by cell-to-cell signaling, so-called quorum sensing (QS). To control the biofilm formation, we designed and synthesized new QS inhibitors of P. aeruginosa based on the structure of the previously known QS inhibitor, furanone. Newly synthesized compounds were a series of analogs of (5-oxo-2,5-dihydrofuran-3-yl)methyl alkanoate, and the structures of all six synthesized compounds was confirmed by NMR and GC/MS analyses. These new QS inhibitor candidates could remarkably inhibit both Pseudomonas QS signaling and biofilm formation, which were assayed by using the recombinant reporter system and flow cell confocal microscopy. The degree of QS inhibition by these new inhibitors varied from 20% to 90%.

The use of conjugated enynes circumvented possible side rections,

The use of conjugated enynes circumvented possible side rections, such as oligomerizations and cyclotrimerizations. The isolation of reaction intermediate complexes revealed that the eta(3)-butadienyl coordination

is the key for the selective formation of cyclobutene.”
“Objective: Faith Moves Mountains assessed the effectiveness of a faith-placed lay health advisor (LHA) intervention to increase Papanicolaou (Pap) test use among middle-aged and older women in a region disproportionately affected by cervical cancer and low screening rates (regionally, only 68% screened in prior 3 years).\n\nMethod: This community-based RCT was conducted in four Appalachian Kentucky counties (December 2005-June 2008). Women aged 40-64 and overdue for screening were recruited from churches and Bucladesine individually randomized to treatment (n = 176) or wait-list control

(n = 169). The intervention provided LHA home visits and newsletters addressing barriers to screening. Self-reported Pap test receipt was the primary outcome.\n\nResults: Intention-to-treat analyses revealed that treatment group participants (17.6% screened) had over twice the odds of wait-list controls (11.2% screened) of reporting Pap test receipt post-intervention, OR = 2.56, 95% Cl: 1.03-638, p = 0.04. Independent of group, recently screened participants (last Pap >1 but <5 years ago) had significantly higher odds of obtaining screening during the study than rarely or never screened participants (last Pap >= 5 years ago), OR = 2.50. 95% Cl: 1.48-425, p = 0.001.\n\nConclusions: The intervention was associated find more IPI-145 datasheet with increased cervical cancer screening. The faith-placed LHA addressing barriers comprises a novel approach to reducing cervical cancer disparities among Appalachian women. (C) 2012 Elsevier Inc. All rights reserved.”
“Background. Definitive evidence that exercise interventions that improve gait also reduce disability is lacking. A task-oriented, motor sequence learning exercise intervention has been shown to reduce the energy cost of walking and improve gait speed, but whether the

intervention also improves activity and participation has not been demonstrated.\n\nObjective. The objective of this study was to compare the impact of a task-oriented, motor sequence learning exercise (TO) intervention and the impact of an impairment-oriented, multicomponent exercise (IO) intervention on activity and participation outcomes in older adults with mobility limitations. The mediating effects of a change in the energy cost of walking on changes in activity and participation also were determined.\n\nDesign. This study was a single-blind, randomized controlled trial.\n\nSetting. The study was conducted in an ambulatory clinical research training center.\n\nParticipants. The study participants were 47 older adults (mean age = 77.2 years, SD = 5.5) with slow and variable gait.

Palmitate-induced apoptosis was observed to increase levels of in

Palmitate-induced apoptosis was observed to increase levels of intracellular ROS production and p-ERK1/2 and decrease p-Akt significantly. Consistent with these results, palmitate-induced apoptosis was Proteases inhibitor attenuated by the ERK1/2 inhibitor, U0126, through partial reduction of intracellular ROS generation. Collectively, these results indicate that palmitate-induced apoptosis in

H9c2 cells is mediated by activation of the ERK1/2 signaling pathway and increased ROS generation.”
“Integrative biology currently undergoes a deep renewal as we witness the increasing influence of systems biology, which explores life’s logic, and of synthetic biology, which exploits it.”
“We have measured the temperature dependence of the physical aging rate beta of thick (2430 rim) and thin (29 nm) polystyrene (PS) films supported on silicon using a new streamlined ellipsometry procedure that we have recently developed. The physical aging rates beta(T) for the similar to 30 nm thick films are found to be reduced at all temperatures, which is not consistent with a simple shift in beta corresponding to the average reduced glass transition temperature (T(g)) of these films. Instead, the beta(T) results correspond well with there being a gradient in dynamics near the

free surface. Our beta(T) results can be well fit by both a two-layer model and a gradient model. The temperature-dependent length scale (of order 10 nm) that characterizes the depth to which the enhanced dynamics near ATM/ATR targets the free surface propagate into the film is similar to that found previously by Forrest and Mattsson [Phys. Res. E 2000, 61, R53-R56] for the molecular weight (MW)-independent T(g) reductions of low-MW find protocol free-standing PS films, strongly suggesting that the same mechanism is responsible for both effects. This length scale grows with decreasing temperature,

suggesting that the mechanism is cooperative in nature.”
“Wild species are essential hosts for maintaining Ixodes ticks and the tick-borne diseases. The aim of our study was to estimate the prevalence, the rate of co-infection with Babesia, Bartonella, and Anaplasma phagocytophilum, and the molecular diversity of tick-borne pathogens in roe deer in Poland. Almost half of the tested samples provided evidence of infection with at least 1 species. A. phagocytophilum (37.3%) was the most common and Bartonella (13.4%) the rarest infection. A total of 18.3% of all positive samples from roe deer were infected with at least 2 pathogens, and one-third of those were co-infected with A. phagocytophilum, Bartonella, and Babesia species. On the basis of multilocus molecular studies we conclude that: (1) Two different genetic variants of A. phagocytophilum, zoonotic and nonzoonotic, are widely distributed in Polish roe deer population; (2) the roe deer is the host for zoonotic Babesia (Bab. venatorum, Bab.

NBR1 is a ubiquitin-binding scaffold protein importantly particip

NBR1 is a ubiquitin-binding scaffold protein importantly participating in autophagic degradation of ubiquitinated proteins. Whereas abnormalities of p62, a ubiquitin-binding protein, were previously described in s-IBM, abnormalities of NBR1 have not been reported in s-IBM. We have now identified in s-IBM muscle biopsies that NBR1, by: (a) immunohistochemistry, was strongly accumulated

within s-IBM muscle-fiber aggregates, where it closely co-localized with p62, ubiquitin, and phosphorylated tau; (b) immunoblots, was increased threefold (p < 0.001); and (c) immunoprecipitation, was associated with p62 and LC3. By real-time PCR, NBR1 mRNA was increased twofold (p < 0.01). None of the various disease- and www.selleckchem.com/B-Raf.html normal-control muscle biopsies had any NBR1 abnormality. In cultured human muscle fibers, NBR1 also physically associated Nocodazole solubility dmso with both p62 and LC3, and experimental inhibition of either the 26S proteasome or the lysosomal activity resulted in NBR1 increase. Our demonstration of NBR1 abnormalities in s-IBM provides further evidence that altered protein degradation pathways may be critically involved in the s-IBM pathogenesis. Accordingly, attempts to unblock defective protein degradation might be a therapeutic strategy for s-IBM patients.”
“OBJECTIVE: Reconstruction of the cranial base using vascularized tissue promotes rapid and complete healing, thus

avoiding complications caused by persistent communication between the cranial cavity and the sinonasal tract. The Hadad-Bassagasteguy

flap (HBF), a neurovascular pedicled flap Nutlin-3 molecular weight of the nasal septum mucoperiosteurn and mucoperichondrium based on the nasoseptal artery, seems to be advantageous for the reconstruction of the cranial base after endonasal cranial base surgery.\n\nMETHODS: We performed a retrospective review of patients who underwent endonasal cranial base surgery at the University of Pittsburgh Medical Center from January 30, 2006 to January 30, 2007, identifying patients who experienced reconstruction with a vascularized septal mucosal flap (HBF). We analyzed the demographic data, pathological characteristics, site and extent of resection, use of cerebrospinal fluid (CSF) diversion techniques, and outcome.\n\nRESULTS: Seventy-five patients who underwent endonasal cranial base endoscopic surgery received repair with the HBF In this population, we encountered eight postoperative CSF leaks (10.66%), all in patients who required intra-arachnoidal dissection. When we correct the statistical analysis to include only patients with intra-arachnoidal lesions, the postoperative CSF leak rate is 14.5% (eight of 55 patients). It is notable that six CSF (33%) leaks occurred in our first 25 repairs, whereas we encountered only two postoperative leaks (4%) in the last 50 patients. The corrected CSF leak rate, considering only intra-arachnoidal lesions, was two (5.4%) of 37 patients.

We used the median as the point estimate and the 2 5th and 97 5th

We used the median as the point estimate and the 2.5th and 97.5th percentiles as the confidence interval. We compared case-chaos matched odds ratios with their respective case-control odds ratios in terms of statistical significance. Using Spearman’s correlation, we estimated the correlation between matched odds ratios and the proportion of cases exposed to each exposure and quantified the relationship between the 2 using a normal linear mixed model. Each case-control study identified an outbreak vehicle (odds ratios = 4.9-45).

Case-chaos methodology identified the outbreak vehicle 3 out of 5 times. It identified significant associations in 22 OSI-744 order of 113 exposures that were not associated with outcome and 5 of 18 exposures that were significantly associated with outcome. Log matched odds ratios correlated with their respective proportion of cases exposed (Spearman rho = 0.91) and increased significantly with the proportion of cases exposed (b = 0.054). Case-chaos methodology missed the outbreak source 2 of 5 times and identified spurious associations between a number of exposures and outcome. Measures of association correlated with the proportion of cases exposed. We recommended against using case-chaos analysis during outbreak investigations.”
“FAR-RED ELONGATED HYPOCOTYLS3 (FHY3) and FAR-RED-IMPAIRED RESPONSE1 (FARM initially identified as crucial components of phytochrome

A (phyA)-mediated far-red (FR) light signaling in Arabidopsis thaliana, are the founding members of the FAR1-related sequence (FRS) family PI3K inhibitor of transcription factors present in most angiosperms. These proteins share extensive similarity with the Mutator-like transposases, indicative of their evolutionary history of ‘molecular

domestication’. Here we review emerging multifaceted roles of FHY3/FAR1 in diverse developmental and physiological processes, including UV-B signaling, circadian clock entrainment, flowering, chloroplast biogenesis, chlorophyll biosynthesis, programmed cell death, reactive oxygen species (ROS) homeostasis, abscisic acid (ABA) signaling, and branching. The domestication of FHY3/FAR1 may enable angiosperms to better integrate various endogenous and exogenous signals for coordinated regulation of growth and development, thus enhancing their AZD9291 fitness and adaptation.”
“The role of human Fc gamma receptors (Fc gamma R) has been recognized considerably over the last years. These receptors vary in their affinity for IgG subclasses and the intracellular signals elicited by them. Allelic variants of Fc gamma R genes may influence the biological phagocyte activity, accounting for an inherited pre-disposition to disease. The specific Fc gamma RIIa (CD32) contains a polymorphic variant (H/R131) that has been associated to a reduced risk for developing dengue hemorrhagic fever (DHF).

In the other 3 cases, peripheral intravenous thrombolysis failed,

In the other 3 cases, peripheral intravenous thrombolysis failed, followed by successful transcatheter thrombolysis. The average duration of therapy was (7.25 +/- 5.31) hours (1-17 hours). The average doses of heparin and urokinase were (1600 +/- 723) U (800-3000 U) and (268 571 +/- 177 240) U (50 000-500 000 U), respectively. There were no statistically significant differences in partial thromboplastin time before and during urokinase therapy ((40.6 +/- 22.3) to (49.9 +/- 39.2) seconds). However, the prothrombin

time was significantly longer ((12.7 +/- 2.58) to (48.1 +/- 18.6) seconds, P<0.05). Patency of the target vessel was evaluated in all the patients selleck for 2 weeks and no occlusion recurred.\n\nConclusion Thrombolytic therapy with urokinase is a safe and useful modality in children with femoral artery thrombosis after left cardiac catheterization.”
“The aim of our study was to evaluate volumetric capnography (VCap) in the differentiation between chronic obstructive pulmonary disease (COPD) patients and normal subjects. Thirty-nine healthy male volunteers and 60 male COPD patients were

enrolled. Regression equations between VCap indices and age, weight, height, and tidal volume in healthy volunteers were established by stepwise regression analysis. Sotrastaurin Predicted normal values of VCap indices in COPD patients were calculated. A paired t test was used to compare the difference between observed and predicted values for VCap indices in COPD patients. Receiver operating characteristic (ROC) curve analysis was used to evaluate the power of each VCap index alone in differentiating COPD patients and normal subjects. The power of the combination

of VCap indices was assessed by discriminant analysis. All regression equations were significant (P smaller than 0.01) as were the differences between the observed and predicted normal VCap indices in COPD patients (P smaller than 0.001). ROC curve analysis showed that the volume between 25 and 50 % of F CO2et (Vm25-50), slope of Phase II (dC2/dV), Selleckchem SHP099 and slope of Phase III (dC3/dV) were valuable predictors. Nearly all (90.9 %) subjects were correctly classified by discriminant analysis. Vm25-50, dC2/dV, or dC3/dV alone are valuable for differentiating COPD patients and normal subjects, but more powerful are the combinations of Vm25-50, dC2/dV, and dC3/dV, the ratio of dC2/dV to dC3/dV (SR23), dead space according to the Bohr method (VDB), and dead space according to the Wolff and Brunner methods (PIE).”
“Objective To determine if a low-cost, automated motion analysis system using Microsoft Kinect could accurately measure shoulder motion and detect motion impairments in women following breast cancer surgery. Design Descriptive study of motion measured via 2 methods. Setting Academic cancer center oncology clinic.

The lymphocytes were identified as T cells, resulting in a final

The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis. 2012 Elsevier Ltd. All rights reserved.”
“Background\n\nAcute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and Cilengitide meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival.\n\nObjectives\n\nTo assess the safety/efficacy

of CSFs with regard to disease-related outcomes and survival in patients with AML.\n\nSearch methods\n\nWe conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December AZD8186 2009), databases of ongoing trials and relevant conference proceedings.\n\nSelection

criteria\n\nRandomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e. g. before and/or only for the duration of chemotherapy).\n\nData collection and analysis\n\nTwo review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs).\n\nMain results\n\nThe search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality selleck kinase inhibitor at 30 days and

at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival (HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates (RR 1.03; 95% CI 0.99 to 1.07), relapse rates (RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival (HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias (RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections (RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm (RR 1.33; 95% CI 1.00 to 1.56).\n\nAuthors’ conclusions\n\nIn summary, colony-stimulating factors should not be given routinely to acute myelogenous leukemia patients post-chemotherapy since they do not affect overall survival or infectious parameters including the rate of bacteremias and invasive fungal infections.

In addition, females that experienced unrestricted access to mate

In addition, females that experienced unrestricted access to mates maintained very high viability over their entire reproductive lives. Nevertheless, insects also performed better when allowed to mate four times compared with once or twice. 4. The present findings thus support NCT-501 cell line the hypothesis that multiple-mating behaviour is maintained owing to increased fitness benefits in the

current and the next generation. Selection for re-mating is, therefore, expected in field populations, which is likely to happen naturally owing to the aggregate lifestyle of O. communa.”
“The atrioventricular (AV) node is permanently damaged in approximately 3% of congenital heart surgery operations, requiring implantation of a permanent pacemaker. Improvements in pacemaker design and in alternative treatment modalities require an effective in vivo model of complete heart block (CHB)

before testing can be performed in humans. Such a model should enable accurate, reliable, and detectable Fludarabine datasheet induction of the surgical pathology. Through our laboratory’s efforts in developing a tissue engineering therapy for CHB, we describe here an improved in vivo model for inducing chronic AV block. The method employs a right thoracotomy in the adult rabbit, from which the right atrial appendage may be retracted to expose an access channel for the AV node. A novel injection device was designed, which both physically restricts needle depth and provides electrical information via electrocardiogram interface. This combination of features provides real-time guidance to the researcher for confirming contact with the AV node, and documents its ablation upon formalin injection. While all animals tested could be induced to acute AV block, those with ECG guidance were more likely to maintain chronic heart block

>12 h. Our model enables the researcher to reproduce both CHB and the associated peripheral fibrosis that would be present in an open congenital learn more heart surgery, and which would inevitably impact the design and utility of a tissue engineered AV node replacement.”
“Fibrin (Fn) enhances plasminogen (Pg) activation by tissue-type plasminogen activator(tPA) by serving as a template onto which Pg and tPA assemble. To explore the contribution of the Pg/Fn interaction to Fn cofactor activity, Pg variants were generated and their affinities for Fn were determined using surface plasmon resonance (SPR). Glu-Pg, Lys-Pg (des(1-77)), and Mini-Pg (lacking kringles 1-4) bound Fn with K-d values of 3.1, 0.21, and 24.5 mu M, respectively, whereas Micro-Pg (lacking all kringles) did not bind. The kinetics of activation of the Pg variants by tPA were then examined in the absence or presence of Fn. Whereas Fn had no effect on Micro-Pg activation, the catalytic efficiencies of Glu-Pg, Lys-Pg, and Mini-Pg activation in the presence of Fn were 300- to 600-fold higher than in its absence.