bluuebunny/crossref_metadata_2025_split huggingface dataset:
NO-Induced Biofilm Dispersion in Pseudomonas aeruginosa Is Mediated by an MHYT Domain-Coupled Phosphodiesterase
Authors: Li Yi , Heine Sabrina , Entian Michael , Sauer Karin , Frankenberg-Dinkel Nicole 
Published: June 2013

ABSTRACTDispersion is a process used by bacteria to successfully transit from a biofilm to a planktonic growth state and to spawn novel communities in new locales. Alterations inbis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) levels have been shown to be associated with biofilm dispersal in a number of different bacteria. The signaling molecule nitric oxide (NO) is known to induce biofilm dispersion through stimulation of c-di-GMP-degrading phosphodiesterase (PDE) activity. However, no c-di-GMP modulating enzyme directly involved in NO-induced dispersion has yet been described in the opportunistic pathogenPseudomonas aeruginosa. Here, we characterized MucR (PA1727) and NbdA (PA3311,NO-inducedbiofilmdispersion locusA), two membrane-bound proteins with identical domain organization consisting of MHYT-GGDEF-EAL, with respect to their role in NO-induced dispersion. Inactivation ofmucRimpaired biofilm dispersion in response to NO and glutamate, whereas inactivation ofnbdAonly impaired biofilm dispersion upon exposure to NO. A specific role of NbdA in NO-induced dispersion was supported by increased PDE activity, resulting in decreased c-di-GMP levels in biofilms expressingnbdAupon exposure to NO, a response that was absent in the ΔnbdAstrain. Moreover, increased PDE activity was mainly due to a transcriptional activation ofnbdAupon addition of NO. Biochemical analyses of recombinant protein variants lacking the membrane-anchored MHYT domain support NbdA being an active PDE. In contrast, MucR displayed both diguanylate cyclase and PDE activityin vitro, which seemed regulated in a growth-dependent mannerin vivo. This is the first description of a PDE specifically involved in NO-induced biofilm dispersion inP. aeruginosa.
Cortisol: ACTH ratio to test for primary hypoadrenalism: a pilot study
Authors: Lee Mark K V , Vasikaran Samuel , Doery James C G , Wijeratne Nilika , Prentice David 
Published: June 2013

Abstract

Introduction
A standard short Synacthen test (SST) is the conventional diagnostic test for primary hypoadrenalism. Measuring simultaneous plasma cortisol and adrenocorticotrophin hormone (ACTH) and using the cortisol: ACTH ratio as a first-line test may be safer and more convenient than performing a SST.

Methods
A retrospective study of 349 patients who had a SST with simultaneous baseline plasma cortisol and ACTH performed between 2005 and 2010 in two separate Australian health centres. The plasma cortisol: ACTH ratio was calculated for each patient and their final diagnosis was determined based on their SST result and a review of their clinical notes.

Results
Eighteen patients had primary hypoadrenalism, 46 patients had secondary hypoadrenalism and 285 patients had normal adrenal function. All the patients with primary hypoadrenalism had a plasma cortisol: ACTH ratio &lt;3, while none of the patients with normal adrenal function or secondary hypoadrenalism had a cortisol: ACTH ratio &lt;3. Therefore, a cortisol: ACTH ratio &lt;3 had a 100% sensitivity and specificity for the diagnosis of primary hypoadrenalism. Patients with secondary hypoadrenalism had a cortisol: ACTH ratio &gt;3, while subjects with normal adrenal function had a cortisol: ACTH ratio &gt;15. There was overlap in cortisol: ACTH ratios of patients with secondary hypoadrenalism and normal adrenal function.

Conclusions
Although the cortisol: ACTH ratio predicts primary hypoadrenalism, its value is limited to diagnosing primary hypoadrenalism as it does not distinguish secondary hypoadrenalism from normal adrenal function. Larger prospective studies that include patients with early primary hypoadrenalism are needed to confirm the reliability of plasma cortisol: ACTH ratio as a diagnostic test for primary hypoadrenalism.
Temporal and Spatial Evolution of Therapy-Induced Tumor Apoptosis Detected by Caspase-3–Selective Molecular Imaging
Authors: Nguyen Quang-Dé , Lavdas Ioannis , Gubbins James , Smith Graham , Fortt Robin , Carroll Laurence S. , Graham Martin A. , Aboagye Eric O. 
Published: June 2013

Abstract
Purpose: Induction of apoptosis in tumors is considered a desired goal of anticancer therapy. We investigated whether the dynamic temporal and spatial evolution of apoptosis in response to cytotoxic and mechanism-based therapeutics could be detected noninvasively by the caspase-3 radiotracer [18F]ICMT-11 and positron emission tomography (PET).
Experimental Design: The effects of a single dose of the alkylating agent cyclophosphamide (CPA or 4-hydroperoxycyclophosphamide), or the mechanism-based small molecule SMAC mimetic birinapant on caspase-3 activation was assessed in vitro and by [18F]ICMT-11–PET in mice bearing 38C13 B-cell lymphoma, HCT116 colon carcinoma, or MDA-MB-231 breast adenocarcinoma tumors. Ex vivo analysis of caspase-3 was compared to the in vivo PET imaging data.
Results: Drug treatment increased the mean [18F]ICMT-11 tumor uptake with a peak at 24 hours for CPA (40 mg/kg; AUC40–60: 8.04 ± 1.33 and 16.05 ± 3.35 %ID/mL × min at baseline and 24 hours, respectively) and 6 hours for birinapant (15 mg/kg; AUC40–60: 20.29 ± 0.82 and 31.07 ± 5.66 %ID/mL × min, at baseline and 6 hours, respectively). Voxel-based spatiotemporal analysis of tumor-intrinsic heterogeneity suggested that discrete pockets of caspase-3 activation could be detected by [18F]ICMT-11. Increased tumor [18F]ICMT-11 uptake was associated with caspase-3 activation measured ex vivo, and early radiotracer uptake predicted apoptosis, distinct from the glucose metabolism with [18F]fluorodeoxyglucose-PET, which depicted continuous loss of cell viability.
Conclusion: The proapoptotic effects of CPA and birinapant resulted in a time-dependent increase in [18F]ICMT-11 uptake detected by PET. [18F]ICMT-11–PET holds promise as a noninvasive pharmacodynamic biomarker of caspase-3–associated apoptosis in tumors. Clin Cancer Res; 19(14); 3914–24. ©2013 AACR.
BIBF 1120 (Nintedanib), a Triple Angiokinase Inhibitor, Induces Hypoxia but not EMT and Blocks Progression of Preclinical Models of Lung and Pancreatic Cancer
Authors: Kutluk Cenik Bercin , Ostapoff Katherine T. , Gerber David E. , Brekken Rolf A. 
Published: June 2013

Abstract
Signaling from other angiokinases may underlie resistance to VEGF-directed therapy. We evaluated the antitumor and biologic effects of BIBF 1120 (nintedanib), a tyrosine kinase inhibitor that targets VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor in preclinical models of lung and pancreatic cancer, including models resistant to VEGF-targeted treatments. In vitro, BIBF 1120 did not show antiproliferative effects, nor did it sensitize tumor cells to chemotherapy. However, in vivo BIBF 1120 inhibited primary tumor growth in all models as a single agent and in combination with standard chemotherapy. Analysis of tumor tissue posttreatment revealed that BIBF 1120 reduced proliferation (phospho-histone 3) and elevated apoptosis (cleaved caspase-3) to a greater extent than chemotherapy alone. Furthermore, BIBF 1120 showed potent antiangiogenic effects, including decreases in microvessel density (CD31), pericyte coverage (NG2), vessel permeability, and perfusion, while increasing hypoxia. Despite the induction of hypoxia, markers of epithelial-to-mesenchymal transition (EMT) were not elevated in BIBF 1120–treated tumors. In summary, BIBF 1120 showed potent antitumor and antiangiogenic activity in preclinical models of lung and pancreatic cancer where it induced hypoxia but not EMT. The absence of EMT induction, which has been implicated in resistance to antiangiogenic therapies, is noteworthy. Together, these results warrant further clinical studies of BIBF 1120. Mol Cancer Ther; 12(6); 992–1001. ©2013 AACR.
The Role of Discrete Terms in the Theory of the Properties of Terms
Authors: Brumberg-Chaumont Julie 
Published: June 2013

Abstract
Discrete supposition occurs whenever a discrete term, such as ‘Socrates‘, is the subject of a given proposition. I propose to examine this apparently simple notion. I shall draw attention to the incongruity, within a general theory of the semantic variation of terms in a propositional context, of the notion of discrete supposition, in which a term usually has a single semantic correlate. The incongruity comes to the fore in those treatises that attempt to describe discrete supposition as a sort of personal supposition, although the same term cannot be in simple supposition in another propositional context, because it has no significate distinct from its suppositum. This shows a fundamental link between common signification, simple supposition and predicability, three notions that rely on the existence of a significate distinct and independent from the suppositum of the term. The connection is to be seen especially in William of Sherwood’s Introductiones, the only author of a terminist Summa who recognizes the existence of simple supposition for discrete terms.
Richard Brinkley on Supposition
Authors: Cesalli Laurent 
Published: June 2013

Abstract
This study comments on six notabilia found in the general observations (praemittenda) with which Brinkley begins his treatise on supposition in his Summa logicae: i) the logico-metaphysical explanation of the distinction between significatio and suppositio, ii) the ontic division principle of supposition, iii) the relationship between supposita and truth-makers, iv) what seems to be a late (and English) resurgence of natural supposition, v) a pragmatic suspension of the regula appellationum and vi) Brinkley’s apparently incompatible claims that there are communicable things and that there are only singular things, a position that is a medieval form of immanent realism. Based on the two manuscripts that contain the treatise on supposition, an appendix offers a provisional edition of part of Brinkley’s Summa, a collaboration between the author and Joël Lonfat.
The Role of ‘Denotatur’ in Ockham’s Theory of Supposition
Authors: Dutilh Novaes Catarina 
Published: June 2013

Abstract
In the scholarship on medieval logic and semantics of the last decades, Ockham’s theory of supposition is probably the most extensively studied version of such theories; yet, it seems that we still do not fully understand all its intricacies. In this paper, I focus on a phrase that occurs countless times throughout Ockham’s writings, but in particular in the sections dedicated to supposition in the Summa logicae: the phrase ‘denotatur’. I claim that an adequate understanding of the role of the concept of denotatur within Ockham’s supposition theory shall yield a deeper understanding of the theory as a whole. Here, I first examine a few uses of the term ‘denotatur’ and its variants by other authors. I then turn to Ockham: first I briefly mention some uses of the term in contexts other than his theory of supposition. Following that, I focus on his supposition theory, in particular on how ‘denotatur’ allows him to deal with two crucial puzzles, namely the supposition of empty terms and the supposition of terms in false affirmative propositions. The treatment of these two puzzles suggests that Ockham’s theory of supposition must be understood as a theory chiefly intended for the generation of the meanings of propositions.
When the Inference ‘p is true, therefore p’ Fails: John Buridan on the Evaluation of Propositions
Authors: Perini-Santos Ernesto 
Published: June 2013

Abstract
For John Buridan, truth-bearers are assertions. This fact explains why the inference ‘p is true, therefore p’ may fail. On the one hand, the tense of the verb plus the time of utterance do not determine the time about which a sentence is intended to be true: the intention of the speaker is needed. On the other hand, since the meaning of vocal and written words is conventional, it may seem that they can be used with different meanings on each side of the inference. While the antecedent may talk about a situation different from the present one, this doesn’t make it the actual situation of utterance, and the words have meanings only in the actual situation of use. Although such situations are different, in both of them we are asked to see the importance of identifying features of which the disquotational schema doesn’t keep track and that can only be specified in the context of use.
The Hermeneutical Rehabilitation of Supposition Theory in Seventeenth-Century Protestant Logic
Authors: Meier-Oeser Stephan 
Published: June 2013

Abstract
The paper focuses on some aspects of the early modern aftermath of supposition theory within the framework of the protestant logical tradition. Due to the growing influence of Humanism, supposition theory from the third decade of the sixteenth century was the object of general neglect and contempt. While in the late sixteenth-century a number of standard textbooks of post-Tridentine scholastic logic reintegrated this doctrine, although in a bowdlerized version, it remained for a century out of the scope of Protestant logic. The situation changed when the Strasburg Lutheran theologian J.C. Dannhauer, who in 1630 developed and propagated the program of a new discipline which he called ‘general hermeneutics’ (hermeneutica generalis), accentuating the importance of supposition theory as an indispensable device for the purpose of textual interpretation. Due to Dannhauer’s influence on later developments of hermeneutics, which in the seventeenth and early eighteenth centuries was regarded as a logical discipline, supposition theory is still present in several logical treatises of the eighteenth century. The explication of the underlying views on the notion of supposition and its logico-semantic function may give at least some clues as to how to answer the question of what supposition theory was all about.
A Quantified Temporal Logic for Ampliation and Restriction
Authors: Uckelman Sara L. 
Published: June 2013

Abstract
Temporal logic as a modern discipline is separate from classical logic; it is seen as an addition or expansion of the more basic propositional and predicate logics. This approach is in contrast with logic in the Middle Ages, which was primarily intended as a tool for the analysis of natural language. Because all natural language sentences have tensed verbs, medieval logic is inherently a temporal logic. This fact is most clearly exemplified in medieval theories of supposition. As a case study, we look at the supposition theory of Lambert of Lagny (Auxerre), extracting from it a temporal logic and providing a formalization of that logic.
Directional Control-Response Compatibility Relationships Assessed by Physical Simulation of an Underground Bolting Machine
Authors: Steiner Lisa , Burgess-Limerick Robin , Porter William 
Published: June 2013

Objective: The authors examine the pattern of direction errors made during the manipulation of a physical simulation of an underground coal mine bolting machine to assess the directional control-response compatibility relationships associated with the device and to compare these results to data obtained from a virtual simulation of a generic device. Background: Directional errors during the manual control of underground coal roof bolting equipment are associated with serious injuries. Directional control-response relationships have previously been examined using a virtual simulation of a generic device; however, the applicability of these results to a specific physical device may be questioned. Method: Forty-eight participants randomly assigned to different directional control-response relationships manipulated horizontal or vertical control levers to move a simulated bolter arm in three directions (elevation, slew, and sump) as well as to cause a light to become illuminated and raise or lower a stabilizing jack. Directional errors were recorded during the completion of 240 trials by each participant. Results: Directional error rates are increased when the control and response are in opposite directions or if the direction of the control and response are perpendicular. The pattern of direction error rates was consistent with experiments obtained from a generic device in a virtual environment. Conclusion: Error rates are increased by incompatible directional control-response relationships. Application: Ensuring that the design of equipment controls maintains compatible directional control-response relationships has potential to reduce the errors made in high-risk situations, such as underground coal mining.
Influence of Sex on the Outcome of Autologous Chondrocyte Implantation in Chondral Defects of the Knee
Authors: Kreuz Peter C. , Müller Sebastian , von Keudell Arvind , Tischer Thomas , Kaps Christian , Niemeyer Philipp , Erggelet Christoph 
Published: June 2013

Background: Sex-specific outcomes have been reported in anterior cruciate ligament reconstruction as well as in osteoarthrosis progression, but there are currently no related published data on autologous chondrocyte implantation (ACI). The present prospective study was performed to investigate sex-dependent differences in the results after ACI. Hypothesis: The clinical and magnetic resonance imaging (MRI) results after ACI of the knee are influenced by the patient’s sex. Study Design: Cohort study; Level of evidence, 2. Methods: The midterm clinical and MRI results of a cell-based fibrin-polymer graft for the treatment of full-thickness cartilage defects were evaluated preoperatively and 6, 12, and 48 months after surgery in 52 patients (male:female ratio, 25:27; average age, 35.6 years). Depending on the sex and the location of the defects (femoral condyles, n = 32; patellofemoral compartment, n = 20), patients were assigned to 4 different groups. Baseline clinical scores were compared with follow-up data by paired Wilcoxon tests for the Lysholm score and the International Knee Documentation Committee (IKDC) scoring system. Sex-specific differences were evaluated with the Mann-Whitney U test. The MRI evaluation was performed with the Henderson score at final follow-up. Results: Clinical scores improved in all groups over the whole study period ( P < .05). Compared with female patients, male patients achieved significantly better results in the Lysholm score at all time intervals and in the IKDC score at 6 and 12 months after surgery ( P < .05). In a subgroup analysis, female patients with patellar defects had the worst results in both clinical scores. With the available number of patients, MRI evaluation at 48 months after surgery revealed no significant difference in defect fill between male and female patients ( P > .05). The Pearson correlation coefficient between both clinical scores and the MRI parameters of defect fill and cartilage signal was significant ( P < .05). Conclusion: Autologous chondrocyte implantation is a promising treatment option for full-thickness cartilage defects of male and female knee joints. Female patients with patellar defects have worse prognostic factors.
Parenting Interventions Implementation Science
Authors: Cotter Katie L. , Bacallao Martica , Smokowski Paul R. , Robertson Caroline I. B. 
Published: June 2013

Objectives: This study examines the implementation and effectiveness of Parenting Wisely, an Internet-based parenting skills intervention. The study assesses whether parents benefit from Parenting Wisely participation and whether the delivery format influences program effectiveness. Method: This study uses a quasi-experimental design. Participating parents ( N = 144) come from a rural, impoverished, ethnically diverse county in a Southeastern state. The intervention is delivered via four formats: parents-only intensive workshop, parents-only 5-week group, parent and adolescent 5-week group, and parent and adolescent online format. Results: Findings show an association between Parenting Wisely participation and improvements in family problem solving, family roles, family involvement, parenting self-efficacy, parenting sense of competence, and decreased adolescent violent behavior. Effect sizes vary by delivery format. Conclusion: Positive program effects vary by delivery format and outcome. Practice implications are discussed.
Relationship of Red Cell Distribution Width With the Presence and Severity of Preeclampsia
Authors: Kurt Raziye Keskin , Aras Zinnur , Silfeler Dilek Benk , Kunt Cigdem , Islimye Mine , Kosar Ozlem 
Published: June 2013

Aim: Although the relationship between red cell distribution width (RDW) and hypertension has been well documented, there is an absence of data on the association between RDW and preeclampsia. In the present study, we have aimed to investigate the correlation of RDW with preeclampsia and its severity. Methods: The study population consisted of 52 (35 mild and 17 severe) patients with preeclampsia and 50 control pregnancy patients. For the entire study population, baseline RDW was measured using an automatic blood counter. Results: Although there were no significant differences between the preeclampsia group and the control group in terms of hemoglobin and platelet counts, the RDW (14.1 ± 1.1 vs 16.9 ± 1.7, P < .001), systolic and diastolic blood pressure, proteinuria, white blood cell, and high-sensitivity C-reactive protein levels were significantly higher in the preeclampsia group. Moreover, subgroup analysis revealed that RDW levels were significantly increased in patients with severe preeclampsia when compared to the patients with mild preeclampsia (18 ± 1.5 vs 16.4 ± 1.5, P < .001). Conclusion: Our study results revealed that RDW levels were associated with both the presence and the severity of preeclampsia.
Determining Competencies for Frontline Sales Managers in For-Profit Organizations
Authors: Busch Tina K. 
Published: June 2013

The Problem With sales models evolving in response to the changing marketplace, knowing the skills required for sales effectiveness is key to organizational competitive advantage. Frontline sales managers are the most critical role in a productive sales force; however, empirical research focusing on sales manager competence is limited. The Solution Understanding the knowledge and skills necessary for success as a frontline sales manager can assist in improving individual, team, and organizational sales performance. This article adds to the knowledge base by providing a frontline sales manager competency model that can serve as a guide for human resources initiatives to increase sales force effectiveness and help bridge the gap between theory and practice. The Stakeholders Competency models are valuable across industries, and human resources professionals, senior leaders, sales organizations, and researchers can learn from the findings of this study and adapt them to their context.