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Xie, Qingyi, Chunfeng Ma, Guangzhao Zhang, and Christine Bressy. "Poly(ester)–poly(silyl methacrylate) copolymers: synthesis and hydrolytic degradation kinetics." Polymer Chemistry 9, no. 12 (2018): 1448–54. http://dx.doi.org/10.1039/c8py00052b.
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Folini, Jenny, Chao-Hung Huang, James C. Anderson, Wolfgang P. Meier, and Jens Gaitzsch. "Novel monomers in radical ring-opening polymerisation for biodegradable and pH responsive nanoparticles." Polymer Chemistry 10, no. 39 (2019): 5285–88. http://dx.doi.org/10.1039/c9py01103j.
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We report the first amine-bearing cyclic ketene acetals (CKAs) for radical ring-opening polymerisation (RROP). The resulting polyesters and their corresponding nanoparticles were biodegradable and showed the desired pH sensitive behaviour.
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Lin, Si-Ting, Chung-Chi Wang, Chi-Jung Chang, Yasuyuki Nakamura, Kun-Yi Andrew Lin, and Chih-Feng Huang. "Progress in the Preparation of Functional and (Bio)Degradable Polymers via Living Polymerizations." International Journal of Molecular Sciences 21, no. 24 (December 16, 2020): 9581. http://dx.doi.org/10.3390/ijms21249581.
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This review presents the latest developments in (bio)degradable approaches and functional aliphatic polyesters and polycarbonates prepared by typical ring-opening polymerization (ROP) of lactones and trimethylene carbonates. It also considers several recent innovative synthetic methods including radical ring-opening polymerization (RROP), atom transfer radical polyaddition (ATRPA), and simultaneous chain- and step-growth radical polymerization (SCSRP) that produce aliphatic polyesters. With regard to (bio)degradable approaches, we have summarized several representative cleavable linkages that make it possible to obtain cleavable polymers. In the section on functional aliphatic polyesters, we explore the syntheses of specific functional lactones, which can be performed by ring-opening copolymerization of typical lactone/lactide monomers. Last but not the least, in the recent innovative methods section, three interesting synthetic methodologies, RROP, ATRPA, and SCSRP are discussed in detail with regard to their reaction mechanisms and polymer functionalities.
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Singha, Nikhil Kumar, Amalin Kavitha, Prodip Sarker, and Stephen Rimmer. "Copper-mediated controlled radical ring-opening polymerization (RROP) of a vinylcycloalkane." Chemical Communications, no. 26 (2008): 3049. http://dx.doi.org/10.1039/b801149d.
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Jackson, Alexander W., Srinivasa Reddy Mothe, Lohitha Rao Chennamaneni, Alexander van Herk, and Praveen Thoniyot. "Unraveling the History and Revisiting the Synthesis of Degradable Polystyrene Analogues via Radical Ring-Opening Copolymerization with Cyclic Ketene Acetals." Materials 13, no. 10 (May 19, 2020): 2325. http://dx.doi.org/10.3390/ma13102325.
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Degradable analogues of polystyrene are synthesized via radical ring-opening (co)polymerization (rROP) between styrene and two cyclic ketene acetals, namely 2-methylene-1,3-dioxepane (MDO) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO). This approach periodically inserts ester bonds throughout the main chain of polystyrene, imparting a degradation pathway via ester hydrolysis. We discuss the historical record of this approach, with careful attention paid to the conflicting findings previously reported. We have found a common 1H NMR characterization error, repeated throughout the existing body of work. This misinterpretation is responsible for the discrepancies within the cyclic ketene acetal (CKA)-based degradable polystyrene literature. These inconsistencies, for the first time, are now understood and resolved through optimization of the polymerization conditions, and detailed characterization of the degradable copolymers and their corresponding oligomers after hydrolytic degradation.
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Dishop, Megan K. "Robbins Review of Pathology." Archives of Pathology & Laboratory Medicine 125, no. 3 (March 1, 2001): 456–57. http://dx.doi.org/10.5858/2001-125-456b-rrop.
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Popović, Zoran B., Kent A. Mowrey, Youhua Zhang, Shaowei Zhuang, Tomotsugu Tabata, Don W. Wallick, Richard A. Grimm, James D. Thomas, and Todor N. Mazgalev. "Slow rate during AF improves ventricular performance by reducing sensitivity to cycle length irregularity." American Journal of Physiology-Heart and Circulatory Physiology 283, no. 6 (December 1, 2002): H2706—H2713. http://dx.doi.org/10.1152/ajpheart.00571.2002.
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Atrial fibrillation (AF) is characterized by short and irregular ventricular cycle lengths (VCL). While the beneficial effects of heart rate slowing (i.e., the prolongation of VCL) in AF are well recognized, little is known about the impact of irregularity. In 10 anesthetized dogs, R-R intervals, left ventricular (LV) pressure, and aortic flow were collected for >500 beats during fast AF and when the average VCL was prolonged to 75%, 100%, and 125% of the intrinsic sinus cycle length by selective atrioventricular (AV) nodal vagal stimulation. We used the ratio of the preceding and prepreceding R-R intervals (RRp/RRpp) as an index of cycle length irregularity and assessed its effects on the maximum LV power, the minimum of the first derivative of LV pressure, and the time constant of relaxation by using nonlinear fitting with monoexponential functions. During prolongation of VCL, there was a pronounced decrease in curvature with the formation of a plateau, indicating a lesser dependence on RRp/RRpp. We conclude that prolongation of the VCL during AF reduces the sensitivity of the LV performance parameters to irregularity.
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Reddy Mothe, Srinivasa, Jacqueline S. J. Tan, Lohitha R. Chennamaneni, Farhan Aidil, Yi Su, Hway C. Kang, Freda C. H. Lim, and Praveen Thoniyot. "A systematic investigation of the ring size effects on the free radical ring‐opening polymerization ( rROP ) of cyclic ketene acetal ( CKA ) using both experimental and theoretical approach." Journal of Polymer Science 58, no. 12 (May 21, 2020): 1728–38. http://dx.doi.org/10.1002/pol.20200210.
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Garnett, Holly Ann. "Referendum Resource Officers in the 2007 Ontario Referendum on Electoral Reform." Canadian Political Science Review 8, no. 1 (August 12, 2014): 63–84. http://dx.doi.org/10.24124/c677/2014387.
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On October 10th, 2007, Ontarians overwhelmingly rejected a proposed change to their electoral system in a province-wide referendum on a new mixed-member proportional (MMP) system. Many commentators and academics blamed this failure of MMP on the quality of Election Ontario’s public education campaign, which was comprised of advertisements, an information hotline, a website, and public outreach activities. Elections Ontario’s public outreach element contained a unique program of grassroots education through local liaison officers. Elections Ontario chose to hire one Referendum Resource Officer (RRO) for each electoral district, who was tasked with providing referendum information through presentations and public meetings in their communities.
This paper examines the feedback of one-third of these RROs collected through telephone and email interviews. Many of these RROs felt that the referendum education program fell short of its aim to provide local education on the referendum question and made suggestions as to the reasons behind the shortcomings of Elections Ontario’s referendum education campaign. They commented that their work was not supported by appropriate timelines, budgets and materials. In addition, many were displeased with the restrictions placed on RROs in efforts of keep the Elections Ontario campaign neutral. This case study supports previous referendum education and voting research that demonstrates that referendum education campaigns should not only provide timely and accessible information, but also encourage debate in order to provide citizens with the competence needed to make their “big decision.”
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Onders, Richard J., Steven D. Mims, Changzheng Wang, and William D. Pearson. "Reservoir Ranching of Paddlefish." North American Journal of Aquaculture 63, no. 3 (July 2001): 179–90. http://dx.doi.org/10.1577/1548-8454(2001)063<0179:rrop>2.0.co;2.
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Day, Stephanie L., and Carol McDonald Connor. "Examining the Relations Between Self-Regulation and Achievement in Third-Grade Students." Assessment for Effective Intervention 42, no. 2 (September 28, 2016): 97–109. http://dx.doi.org/10.1177/1534508416670367.
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Children with stronger self-regulation skills generally demonstrate greater overall success in school both academically and socially. However, there are few valid and reliable measures of self-regulation in middle elementary school. Such a measure could help identify whether a child is truly having difficulties. Thus, the Remembering Rules and Regulation Picture Task (RRRP) was developed. The aim of this study was to develop scoring systems for the RRRP and then to examine the associations between RRRP and independent measures of self-regulation and academic achievement in mathematics and reading. Children ( N = 282) from 34 third-grade classrooms in Florida participated in this study. Results revealed that the RRRP captured three constructs: working memory, attentional flexibility, and inhibitory control. Hierarchical linear modeling (HLM) demonstrated that the RRRP was significantly and positively associated with other measures of self-regulation. The RRRP was significantly and positively associated with mathematics and reading as well. The RRRP appears to be a promising measure of children’s self-regulation skills.
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Sbergio, Stefanie-Grace, Peter Liang, Greg Beilhartz, Palak Patel, Arun Anguraj Vadivel, Roman Melnyk, and Cynthia Hawkins. "EXTH-47. TUMOUR-TARGETED PAN-RAS INHIBITION AS A NOVEL THERAPY FOR DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)." Neuro-Oncology 25, Supplement_5 (November 1, 2023): v235. http://dx.doi.org/10.1093/neuonc/noad179.0900.
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Abstract INTRODUCTION Diffuse Intrinsic Pontine Glioma (DIPG) has a median survival of 9 months following diagnosis in children 7-9 years old. Current therapeutic options are limited to radiation and thus tumour specific vulnerabilities are the subject of ongoing research. One such vulnerability is RAS signalling due to its upregulation in DIPG. RAS regulates cellular proliferation and survival making it an attractive target. Based on diphtheria toxin (DT), we have developed a molecular chimera which selectively binds a DIPG cell surface receptor and releases a RAS cleaving peptidase (RRSP). We hypothesize that using a DIPG targeted RRSP conjugated chimera will reduce tumour viability and improve survival in DIPG models. METHODS Viability of SU-DIPG XIII, XVII, XXV, 36 and 50 cell lines treated with RRSP-DTB, and a DIPG targeted RRSP conjugated chimera was measured using CellTiterGlo Luminescent Assay. Proteomic analysis and single-cell RNA sequencing was used to identify a cell surface receptor upregulated on tumour cell populations from patient samples. SU-DIPG 36 orthotopic xenograft mice were treated with our DIPG targeted RRSP conjugated chimera or vehicle for one week delivered into the pons via osmotic pump and monitored using bioluminescent imaging. RESULTS RRSP-DTB successfully reduces DIPG cell viability in vitro with an EC50 between 0-3 picomolar, demonstrating successful toxicity mediated by RRSP. This is supported by ablation of RAS verified on Western Blot. ANTXR1 receptor was identified as upregulated in tumour cell populations, and a TEM8 conjugated RRSP chimera was developed. RRSP-TEM8 has an EC50 of 5-70 picomolar in vitro and significantly improves survival in vivo with a median survival of 68 days (n = 14) compared to the vehicle control (n = 14) 57 days (p = 0.02). Our results present a successful novel therapeutic as our RRSP chimera, RRSP-TEM8, effectively targets DIPG cells and reduces cell viability to improve survival.
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Ogilvie, Richard Ian, and Danuta Zborowska-Sluis. "Vascular capacitance and cardiac output in pacing-induced canine models of acute and chronic heart failure." Canadian Journal of Physiology and Pharmacology 73, no. 11 (November 1, 1995): 1641–50. http://dx.doi.org/10.1139/y95-726.
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The relationship between stressed and total blood volume, total vascular capacitance, central blood volume, cardiac output (CO), and pulmonary capillary wedge pressure (Ppcw) was investigated in pacing-induced acute and chronic heart failure. Acute heart failure was induced in anesthetized splenectomized dogs by a volume load (20 mL/kg over 10 min) during rapid right ventricular pacing at 250 beats/min (RRVP) for 60 min. Chronic heart failure was induced by continuous RRVP for 2–6 weeks (average 24 ± 2 days). Total vascular compliance and capacitance were calculated from the mean circulatory filling pressure (Pmcf) during transient circulatory arrest after acetylcholine at three different circulating volumes. Stressed blood volume was calculated as a product of compliance and Pmcf, with the total blood volume measured by a dye dilution. Central blood volume (CBV) and CO were measured by thermodilution. Central (heart and lung) vascular capacitance was estimated from the plot of Ppcw against CBV. Acute volume loading without RRVP increased capacitance and CO, whereas after volume loading with RRVP, capacitance and CO were unaltered from baseline. Chronic RRVP reduced capacitance and CO. All interventions, volume ± RRVP or chronic RRVP, increased stressed and central blood volumes and Ppcw. Acute or chronic RRVP reduced central vascular capacitance. Cardiac output was increased when stressed and unstressed blood volumes increased proportionately as during volume loading alone. When CO was reduced and Ppcw increased, as during chronic RRVP or acute RRVP plus a volume load, stressed blood volume was increased and unstressed blood volume was decreased. Thus, interventions that reduced CO and increased Ppcw also increased stressed and reduced unstressed blood volume and total vascular capacitance.Key words: vascular capacitance, vascular compliance, central blood volume, rapid ventricular pacing, dogs, heart failure.
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Vidimar, Vania, Minyoung Park, Caleb K. Stubbs, Nana K. Ingram, Wenan Qiang, Shanshan Zhang, Demirkan Gursel, Roman A. Melnyk, and Karla J. F. Satchell. "Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts." Molecular Cancer Therapeutics 21, no. 5 (February 28, 2022): 810–20. http://dx.doi.org/10.1158/1535-7163.mct-21-0550.
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Abstract The lack of effective RAS inhibition represents a major unmet medical need in the treatment of pancreatic ductal adenocarcinoma (PDAC). Here, we investigate the anticancer activity of RRSP-DTB, an engineered biologic that cleaves the Switch I of all RAS isoforms, in KRAS-mutant PDAC cell lines and patient-derived xenografts (PDX). We first demonstrate that RRSP-DTB effectively engages RAS and impacts downstream ERK signaling in multiple KRAS-mutant PDAC cell lines inhibiting cell proliferation at picomolar concentrations. We next tested RRSP-DTB in immunodeficient mice bearing KRAS-mutant PDAC PDXs. Treatment with RRSP-DTB led to ≥95% tumor regression after 29 days. Residual tumors exhibited disrupted tissue architecture, increased fibrosis and fewer proliferating cells compared with controls. Intratumoral levels of phospho-ERK were also significantly lower, indicating in vivo target engagement. Importantly, tumors that started to regrow without RRSP-DTB shrank when treatment resumed, demonstrating resistance to RRSP-DTB had not developed. Tracking persistence of the toxin activity following intraperitoneal injection showed that RRSP-DTB is active in sera from immunocompetent mice for at least 1 hour, but absent after 16 hours, justifying use of daily dosing. Overall, we report that RRSP-DTB strongly regresses hard-to-treat KRAS-mutant PDX models of pancreatic cancer, warranting further development of this pan-RAS biologic for the management of RAS-addicted tumors.
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Seeliger, E., W. Boemke, M. Corea, T. Encke, and H. W. Reinhardt. "Mechanisms compensating Na and water retention induced by long-term reduction of renal perfusion pressure." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 273, no. 2 (August 1, 1997): R646—R654. http://dx.doi.org/10.1152/ajpregu.1997.273.2.r646.
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Endogenous downregulation of plasma aldosterone (Aldo) concentration, despite increased plasma renin activity (PRA), has been suggested to compensate Na and water retention, which is induced by long-term reduction of renal perfusion pressure (rRPP). To determine whether fixed plasma Aldo concentration would prevent equilibration of 24-h Na and water balances during rRPP, chronically instrumented, freely moving beagle dogs were kept under standardized conditions (daily intake 5.5 mmol Na/kg body wt) and studied for 4 consecutive days under the following conditions: control without rRPP (protocol 1) and rRPP + infusion of Aldo (rRPP + Aldo, protocol 2). Because Aldo administration reduces PRA and, thereby, angiotensin II (ANG II) levels ANG II was additionally infused in protocol 3 (rRPP + ANG II + Aldo). During rRPP + Aldo, 24-h Na balances were never equilibrated. Daily Na retention was approximately 3.5 mmol/kg body wt on day 1 and decreased to approximately 1.6 mmol/kg body wt on day 4; 24-h water balances changed in a similar manner. PRA decreased stepwise. On all rRPP + ANG II + Aldo days, Na and water retentions were more extensive than during rRPP + Aldo. Daily Na retention decreased from approximately 4.4 mmol/kg body wt on day 1 to approximately 3.0 mmol/kg body wt on day 4. Plasma atrial natriuretic peptide increased during both protocols. It is concluded that 1) endogenous downregulation of components of the renin-angiotensin-aldosterone system is a pivotal compensatory mechanism to reduce Na and water retention and 2) natriuretic and diuretic factors seem to be of minor potency, because not even the sum of all could counterbalances the Na- and water-retaining effects of Aldo and ANG II.
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Davenport, Paul W., Pei-Ying Sarah Chan, Weirong Zhang, and Yang-Ling Chou. "Detection threshold for inspiratory resistive loads and respiratory-related evoked potentials." Journal of Applied Physiology 102, no. 1 (January 2007): 276–85. http://dx.doi.org/10.1152/japplphysiol.01436.2005.
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The relationship between detection threshold of inspiratory resistive loads and the peaks of the respiratory-related evoked potential (RREP) is unknown. It was hypothesized that the short-latency and long-latency peaks of the RREP would only be elicited by inspiratory loads that exceeded the detection threshold. The detection threshold for inspiratory resistive loads was measured in healthy subjects with inspiratory-interruption or onset load presentations. In a separate protocol, the RREPs were recorded with resistive loads that spanned the detection threshold. The loads were presented in stimulus attend and ignore sessions. Onset and interruption load presentations had the same resistive load detection threshold. The P1, Nf, and N1 peaks of the RREP were observed with loads that exceeded the detection threshold in both attend and ignore conditions. The P300 was present with loads that exceeded the detection threshold only in the attend condition. No RREP components were elicited with subthreshold loads. The P1, Nf, and P300 amplitudes varied with resistive load magnitude. The results support the hypothesis that there is a resistive load threshold for eliciting the RREPs. The amplitude of the RREP peaks vary as a function of load magnitude. The cognitive P300 RREP peak is present only for detectable loads and when the subject attends to the stimulus. The absence of the RREP with loads below the detection threshold and the presence of the RREP elicited by suprathreshold loads are consistent with the gating of these neural measures of respiratory mechanosensory information processing.
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Reinhardt, H. W., M. Corea, W. Boemke, R. Pettker, L. Rothermund, A. Scholz, G. Schwietzer, and P. B. Persson. "Resetting of 24-h sodium and water balance during 4 days of servo-controlled reduction of renal perfusion pressure." American Journal of Physiology-Heart and Circulatory Physiology 266, no. 2 (February 1, 1994): H650—H657. http://dx.doi.org/10.1152/ajpheart.1994.266.2.h650.
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This study examines whether an increase in renal perfusion pressure (RPP) is necessary to escape endogenously stimulated Na- and water-retaining mechanisms. In seven dogs stimulation was accomplished by a servo-controlled reduction of RPP (rRPP) below the threshold for pressure-dependent renin release for 4 days. Oral intake was standardized. Plasma renin activity (PRA) rose from 2.5 in controls to approximately 5 ng ANG I.ml-1 x h-1 during rRPP days. Plasma aldosterone concentration (PAC) increased by approximately 50% only on day 1 of rRPP but fell at or below control levels thereafter. The PAC-to-PRA ratio decreased during rRPP days. Atrial natriuretic factor (ANF) rose to values three times higher than in controls. Mean systemic blood pressure (MABP) rose from 111 +/- 12 in controls to 142 +/- 14 mmHg on day 4 of rRPP. On day 1 of rRPP 60% of the Na and 24% of the water intake were retained. However, after 2–3 days the input-output balance was restored but on a higher level of total body Na and total body water (new “set point”). Because elevated systemic MABP could not exert direct pressure effects on the kidneys due to servo control of rRPP, there must be other factors, e.g., fall in PAC, increase in ANF, and changes in intrarenal hemodynamics and physical factors that may have contributed to the resetting of input-output balances during rRPP.
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Morelli, Eugenio, Mariateresa Fulciniti, Mehmet K. Samur, Caroline Ribeiro, Leon Wert-Lamas, Annamaria Gulla, Anil Aktas-Samur, et al. "RNA Regulator of Lipogenesis (RROL) Is a Novel Lncrna Mediating Protein-Protein Interaction at Gene Regulatory Loci Driving Lipogenic Programs in Multiple Myeloma." Blood 136, Supplement 1 (November 5, 2020): 20–21. http://dx.doi.org/10.1182/blood-2020-142514.
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Long noncoding RNA (lncRNAs) are key epigenetic factors that drive the origin and progression of human cancers via mechanisms that are largely unknown. We have previuosly reported the clinical significance of a lncRNA signature in multiple myeloma (MM) as independent risk predictor for clinical outcome; and recently identified a lncRNA RROL (RNA Regulator of Lipogenesis) with impact on MM cell proliferation. Here we describe a unique regulatory function for RROL in the control of gene networks involved in the de novo lipogenesis (DNL) pathway, ultimately impacting MM cell growth and survival. Based on growth and survival impact of RROL depletion, we performed integrated transcriptomic analysis of RNA-seq data after RROL depletion in MM cell lines and CD138+ patient MM cells, and identified a set of significantly modulated metabolic genes including the acetyl Co-A Carboxylase 1 (ACC1) gene, encoding a rate-limiting enzyme of the DNL pathway. This metabolic pathway converts nutrients into fatty acids serving for energy storage or biosynthesis of membranes and signaling molecules. Consistent with the transcriptional control of ACC1, we have observed that RROL inhibition in cell lines and primary MM cells significantly decreased the incorporation of C14-radiolabeled glucose into de novo synthesized lipids. Importantly, supplementation with exogenous palmitate, the main downstream product of DNL pathway, rescued the growth inhibitory effect of RROL depletion on MM cells, further confirming the importance of the DNL pathway in the oncogenic activity of RROL in MM. To understand the molecular mechanism through which RROL regulates ACC1 expression and its metabolic axis, we evaluated the RROL interactome in MM cells. RNA-Protein Pull Down (RPPD) and in vivo RNA yeast three-hybrid (Y3H) assays led to the identification of MYC as relevant direct partner of RROL. These results were further validated by qRT-PCR analysis of MYC-bound RNA obtained through RNA immunoprecipitation (RIP) assay. Using experimental model of conditional MYC KD (P493-6), we found that RROL exerts regulatory activity on ACC1 only in the presence of MYC. Mapping of MYC genomic occupancy by ChIP-seq and gene expression after MYC KD in MM cells revealed that ACC1 is a direct transcriptional target of MYC in cells expressing RROL. These data indicate that RROLand MYC cooperate in the transcriptional control of ACC1. Moreover, we found that RROL itself is transcriptionally regulated by MYC, suggesting the existence of a feed-forward regulatory loop in which MYC enhances the expression of RROL that, in turn, drives MYC transcriptional activity to ACC1. We hypothesized that RROL may shape the protein interacting network of MYC to confer specificity for ACC1 promoter. To this end, we performed mass spectrometry analysis of MYC interactome in three MM cell lines in the presence or in the absence of RROL and identified the transcriptional modulator WDR82 as RROL-dependent MYC partner. Interestingly, WDR82 directly interacts with RROL as assessed in the RPPD and RNA Y3H assays, and transcriptionally regulates ACC1 in RROL-dependent manner. These data indicate that RROL catalyzes the interaction of MYC with the transcriptional modulator WDR82 to form a transcriptional ternary complex regulating ACC1 expression. To therapeutically antagonize the RROL lipogenic signaling we have pre-clinically tested small molecule inhibitors of ACC1 (ACC1i). We have observed significant anti-MM activity of ACC1i in vitro in a large panel of MM cell lines and primary MM cells from patients; and in vivo in mouse models of human MM including the localized subcutaneous model and the disseminated model that establish a more aggressive systemic disease. Importantly, we have now developed clinically applicable ASOs and small molecule-like compounds to directly target RROL in MM cells. These studies are ongoing and will be presented. In conclusion, we here report a unique regulatory function of a novel lncRNA supporting MM cell growth via its control of the lipogenic metabolic axis. The availability of oral inhibitors of ACC1 as well as the ongoing development of RROL inhibitors may allow clinical application of this unique targeted therapy in MM. Disclosures Fulciniti: NIH: Research Funding. Chauhan:Oncopeptide AB: Consultancy; consultant to Stemline Therapeutics, Inc., and Equity owner in C4 Therapeutics.: Consultancy, Other: Equity owner in C4 Therapeutics.. Anderson:Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Oncopep and C4 Therapeutics.: Other: Scientific Founder of Oncopep and C4 Therapeutics.. Munshi:Takeda: Consultancy; Karyopharm: Consultancy; AbbVie: Consultancy; Amgen: Consultancy; Legend: Consultancy; Adaptive: Consultancy; Janssen: Consultancy; C4: Current equity holder in private company; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy.
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Huang, Chien Hui, A. Daniel Martin, and Paul W. Davenport. "Effect of inspiratory muscle strength training on inspiratory motor drive and RREP early peak components." Journal of Applied Physiology 94, no. 2 (February 1, 2003): 462–68. http://dx.doi.org/10.1152/japplphysiol.00364.2002.
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This study investigated the effect of inspiratory muscle strength training (IMST) on inspiratory motor drive [mouth occlusion pressure at 0.1 s (P0.1)] and respiratory-related evoked potentials (RREP). It was hypothesized that, if IMST increased inspiratory muscle strength, inspiratory motor drive would decrease. If motor drive were related to the RREP, it was further hypothesized that an IMST-related decrease in drive would change RREP latency and/or amplitude. Twenty-three subjects received IMST at 75% of their maximal inspiratory pressure (Pi max) with the use of a pressure threshold valve. IMST consisted of four sets of six breaths daily for 4 wk. P0.1 and the RREP were recorded before and after IMST. Posttraining, Pi maxincreased significantly by 36.0 ± 2.7%. P0.1decreased significantly by 21.9 ± 5.2%. The increase in Pi max was significantly correlated to the decrease in P0.1. RREP peaks P1a, Nf, P1, and N1 were identified pre- and post-IMST, and there was no difference in either amplitude or latency for those peaks. These results demonstrate that high-intensity IMST significantly increased Pi max, decreased P0.1, but did not change the RREP.
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Lin, Hota Chia-Sheng, Chia-Ling Huang, and Wei-Chang Yeh. "A Novel Constraints Model of Credibility-Fuzzy for Reliability Redundancy Allocation Problem by Simplified Swarm Optimization." Applied Sciences 11, no. 22 (November 15, 2021): 10765. http://dx.doi.org/10.3390/app112210765.
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A novel constraints model of credibility-fuzzy for the reliability redundancy allocation problem (RRAP) is studied in this work. The RRAP that must simultaneously decide reliability and redundancy of components is an effective approach in improving the system reliability. In practice various systems, the uncertainty condition of components used in the systems, which few studies have noticed this state over the years, is a concrete fact due to several reasons such as production conditions, different batches of raw materials, time reasons, and climatic factors. Therefore, this study adopts the fuzzy theory and credibility theory to solve the components uncertainty in the constraints of RRAP including cost, weight, and volume. Moreover, the simplified swarm optimization (SSO) algorithm has been adopted to solve the fuzzy constraints of RRAP. The effectiveness and performance of SSO algorithm have been experimented by four famous benchmarks of RRAP.
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Knafelc, Marie, and Paul W. Davenport. "Relationship between magnitude estimation of resistive loads, inspiratory pressures, and the RREP P1 peak." Journal of Applied Physiology 87, no. 2 (August 1, 1999): 516–22. http://dx.doi.org/10.1152/jappl.1999.87.2.516.
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This study investigated the relationship among resistive load magnitude (ΔR), the cortical evoked potential P1peak amplitude of the respiratory-related evoked potential (RREP), mouth pressure (Pm), esophageal pressure (Pes), transdiaphragmatic pressure (Pdi), and resistive load magnitude estimation (ME) in human subjects. The RREP, Pdi, Pes, Pm, and ME were recorded in response to three ΔR values. The RREP was recorded from C3 and C4, referenced to the vertex CZ. The group means of the Pdi, Pm, ME, and RREP P1 amplitude increased with increases in the ΔR. A log-log plot of the P1 amplitudes showed a relationship with ME as did Pes, Pdi, and Pm. There were linear log-log relationships between CZ-C3P1 amplitude, CZ-C4P1 amplitude, and Pdi to ME. Pdi had a linear log-log relationship with CZ-C3and CZ-C4. These results support the hypothesis that the estimated magnitude of the respiratory load is related to the P1 amplitude of the RREP. Pm, Pes, and Pdi are mechanically related and correlated with the P1 peak amplitude, suggesting that the mechanoreceptors mediating the P1 peak of the RREP are activated by changes in mechanical forces related to the inspiratory pump.
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Chou, Yang Ling, and Paul W. Davenport. "The effect of increased background resistance on the resistive load threshold for eliciting the respiratory-related evoked potential." Journal of Applied Physiology 103, no. 6 (December 2007): 2012–17. http://dx.doi.org/10.1152/japplphysiol.01232.2006.
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The detection threshold (ΔR50) of resistive (R) loads is a function of the total background resistance (R0). Increased R0 increases the ΔR50, but the ratio ΔR50/R0 remains constant. The respiratory-related evoked potential (RREP) is elicited only by R loads greater than the cognitive detection threshold, ΔR50. We hypothesized that the RREP Nf, P1, and N1 peaks will be elicited only when the added load ΔR/R0 is greater than the normal detection threshold, ΔR50/R0 = 0.30. We also hypothesized that when the R0 is increased by adding extrinsic R, the RREP will not be elicited if the ΔR/R0 is less than the 0.30 ratio. RREPs were recorded with healthy volunteers ( n = 20) respiring through a non-rebreathing valve. Three inspiratory R loads that spanned the ΔR50/R0 = 0.30 detection threshold were presented in two conditions: 1) no added R0 (R1 < 0.30, R2 > 0.30, R3 > 0.30); and 2) increased R0 = 13.3 cmH2O·l−1·s (R1 < 0.30, R2 < 0.30, R3 > 0.30). For the control R0, P1, Nf, and N1 peaks of the RREP were elicited by both R2 and R3, and not present with R1. The increased R0 decreased R2/R0 > 1.5 to R2/R0 < 0.15. With increased R0, the R1 and R2 loads did not elicit the RREP, but the Nf, P1, and N1 peaks were present for R3. These results demonstrate that the RREP is present if the ΔR is above the cognitive detection threshold, and the RREP is absent if the load is below the detection threshold. When the R0 is increased to make the ΔR/R0 less than the detection threshold, the ΔR no longer elicits the RREP.
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de Verneuil, Maylis. "L’apatridie rrom en Europe." Plein droit 128, no. 1 (March 26, 2021): 11–14. http://dx.doi.org/10.3917/pld.128.0013.
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Macre, Miriam de Souza, Márcio Pires, Luciana Regina Meireles, Sérgio O. Angel, and Heitor Franco de Andrade Jr. "Serology using rROP2 antigen in the diagnostic of toxoplasmosis in pregnant women." Revista do Instituto de Medicina Tropical de São Paulo 51, no. 5 (October 2009): 283–88. http://dx.doi.org/10.1590/s0036-46652009000500009.
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Toxoplasma gondii causes severe fetal disease during acute infection in pregnant women, thus demanding early diagnosis for effective treatment and fetus preservation. Fetal tests are inefficient and risky, and diagnosis is based on maternal IgM serology, which had weak screening ability due to increased sensitivity, with alternative IgG avidity tests. Here, we performed ELISA and avidity assays using a recombinant T. gondii antigen, rROP2, in samples from 160 pregnant women screened from a large public hospital who were referred due to positive IgM assays. IgG serology and avidity assays were compared using whole T. gondii extract or rROP2. ELISA IgG detection with rROP2 showed good agreement with assays performed with T. gondii extract, but rROP2 IgG avidity assays were unrelated to whole extract antigen IgG avidity, regardless of the chaotrope used. These data show that avidity maturation is specific to individual antigen prevalence and immune response during infection. ELISA rROP2 IgG assays may be an alternative serological test for the diagnosis of toxoplasmosis during pregnancy, although our data do not support their use in avidity assays.
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Martin, Valentina, Alicia Supanitsky, Pablo C. Echeverria, Silvana Litwin, Tamara Tanos, Adolfo R. De Roodt, Eduardo A. Guarnera, and Sergio O. Angel. "Recombinant GRA4 or ROP2 Protein Combined with Alum or the gra4 Gene Provides Partial Protection in Chronic Murine Models of Toxoplasmosis." Clinical Diagnostic Laboratory Immunology 11, no. 4 (July 2004): 704–10. http://dx.doi.org/10.1128/cdli.11.4.704-710.2004.
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ABSTRACT The efficacy of vaccination with Toxoplasma gondii recombinant GRA4 (rGRA4) and ROP2 (rRPO2) proteins and a mix of both combined with alum were evaluated in C57BL/6 and C3H mice. In C57BL/6 mice, rGRA4 and rGRA4-rROP2 immunizations generated similar levels of immunoglobulin G1 (IgG1) and IgG2a isotypes against GRA4, whereas immunizations with rROP2 and the mix induced a predominant IgG1 production against ROP2. All groups of C3H vaccinated mice exhibited higher levels of IgG1 than IgG2a. rGRA4-stimulated splenocytes from vaccinated mice produced primarily gamma interferon while those stimulated with rROP2 produced interleukin-4. Challenge of rGRA4- or rGRA4-rROP2-vaccinated mice from both strains with ME49 cysts resulted in fewer brain cysts than the controls, whereas vaccination with rROP2 alone only conferred protection to C3H mice. Immunization with a plasmid carrying the entire open reading frame of GRA4 showed a protective level similar to that of rGRA4 combined with alum. These results suggest that GRA4 can be a good candidate for a multiantigen anti-T. gondii vaccine based on the use of alum as an adjuvant.
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Kim, Chang-Hyun, Hyung-Chul Nam, and Soon-Man Kwon. "Pitting Life for RRP System." Transactions of the Korean Society of Mechanical Engineers A 36, no. 4 (April 1, 2012): 387–93. http://dx.doi.org/10.3795/ksme-a.2012.36.4.387.
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Xiong, Jin, Jie Tang, Penghua Guo, and Jingyin Li. "Flow Capacity Optimization of a Squirrel Cage Fan with a New Rounded Rectangle Volute under Size Limitation." Machines 11, no. 2 (February 13, 2023): 283. http://dx.doi.org/10.3390/machines11020283.
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Squirrel cage fans (SCFs) are widely used in a variety of household appliances. Due to the restriction on installation size, the design of high-efficiency SCFs with high flow capacities is an important topic. In this study, we proposed a novel rounded rectangle volute profile (RRVP) for the design of compact high-flow SCFs. At first, we used computational fluid dynamics (CFD) to simulate the aerodynamic performances of three SCFs having the same impeller but different volutes, which were the common logarithmic-spiral volute profile, the cutting volute profile, and the RRVP volute at the maximum flow rate working condition. The CFD simulations indicate that the fan with RRVP volute has the highest flow rate at the maximum flow rate working condition. Then, we proposed a parameterization method for the RRVP with 16 control variables. The multiobjective evolutionary algorithm based on decomposition (MOEA/D) and Kriging model was used to optimize the aerodynamic shape of the compact SCF with an RRVP volute. Twenty-three control variables were used in the multiobjective optimization process, including the optimization of the blade angles and the impeller position. Optimization results show that the maximum volumetric flow rate of the optimal SCF with an RRVP volute increases from 147.1 cubic feet per minute (CFM) to 191.1 CFM, and the fan efficiency also increases from 32.21% to 33.5%, compared with the original SCF with the common logarithmic-spiral volute. Two main factors were found to increase the flow capacity and efficiency of the optimal SCF under strict size constrains. First, the RRVP became smooth and large, which reduced the flow loss and increased the flow cross-section; second, the eccentrically mounted impeller of the optimal fan enlarged the flow section near the outlet of the volute.
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Chan, Pei-Ying Sarah, and Paul W. Davenport. "Respiratory-related evoked potential measures of respiratory sensory gating." Journal of Applied Physiology 105, no. 4 (October 2008): 1106–13. http://dx.doi.org/10.1152/japplphysiol.90722.2008.
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The purpose of this study was to demonstrate a neural respiratory gating system using a paired stimuli paradigm. The N1 peak of the respiratory-related evoked potential (RREP) represents early perceptual processing of respiratory sensory information. This is similar to the N100 peak shown with tactile sensation, where the second peak amplitude (S2) of the N100 peak from the somatosensory evoked potential (SEP) was smaller than the first peak amplitude (S1) when the stimuli were presented 500 ms apart. We hypothesized that paired inspiratory occlusions would result in a reduced amplitude of the S2 N1 RREP peak amplitude, indicating respiratory central neural gating. Twenty healthy subjects (10 men and 10 women; 25.8 ± 6.5 yr old) completed the paired inspiratory occlusion (RREP) trial. Thirteen of the subjects also completed the paired mouth air puffs [mouth-evoked potential (MEP) trial], and the paired hand air puffs (SEP) trial. All paired presentations were separated by 500 ms. The N1 peak amplitudes of the RREP trial and the N100 peak amplitudes of the MEP and SEP trials for S1 and S2 and the S2/S1 ratios were determined. The S1 RREP N1 peak amplitude was significantly greater than S2, and the S2/S1 ratio was 0.43. The S1 MEP and SEP N100 peak amplitudes were significantly greater than S2, and the N100 ratio was 0.49 and 0.49, respectively. These results are consistent with central neural gating of respiratory afferent input. The RREP gating response is similar to somatosensory mechanoreceptor gating.
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López-Fernández, Josu, Juan J. Barrero, M. Dolors Benaiges, and Francisco Valero. "Truncated Prosequence of Rhizopus oryzae Lipase: Key Factor for Production Improvement and Biocatalyst Stability." Catalysts 9, no. 11 (November 15, 2019): 961. http://dx.doi.org/10.3390/catal9110961.
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Recombinant Rhizopus oryzae lipase (mature sequence, rROL) was modified by adding to its N-terminal 28 additional amino acids from the C-terminal of the prosequence (proROL) to obtain a biocatalyst more suitable for the biodiesel industry. Both enzymes were expressed in Pichia pastoris and compared in terms of production bioprocess parameters, biochemical properties, and stability. Growth kinetics, production, and yields were better for proROL harboring strain than rROL one in batch cultures. When different fed-batch strategies were applied, lipase production and volumetric productivity of proROL-strain were always higher (5.4 and 4.4-fold, respectively) in the best case. rROL and proROL enzymatic activity was dependent on ionic strength and peaked in 200 mM Tris-HCl buffer. The optimum temperature and pH for rROL were influenced by ionic strength, but those for proROL were not. The presence of these amino acids altered lipase substrate specificity and increased proROL stability when different temperature, pH, and methanol/ethanol concentrations were employed. The 28 amino acids were found to be preferably removed by proteases, leading to the transformation of proROL into rROL. Nevertheless, the truncated prosequence enhanced Rhizopus oryzae lipase heterologous production and stability, making it more appropriate as industrial biocatalyst.
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Machalska, Ewa, Grzegorz Zajac, Monika Halat, Aleksandra J. Wierzba, Dorota Gryko, and Malgorzata Baranska. "Resonance Raman Optical Activity Spectroscopy in Probing Structural Changes Invisible to Circular Dichroism Spectroscopy: A Study on Truncated Vitamin B12 Derivatives." Molecules 25, no. 19 (September 24, 2020): 4386. http://dx.doi.org/10.3390/molecules25194386.
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This work demonstrates resonance Raman optical activity (RROA) spectra of three truncated vitamin B12 derivatives modified within the nucleotide loop. Since truncated cobalamins possess sufficiently high rotational strength in the range of ROA excitation (532 nm), it was possible to record their spectra in the resonance condition. They showed several distinct spectral features allowing for the distinguishing of studied compounds, in contrast to other methods, i.e., UV-Vis absorption, electronic circular dichroism, and resonance Raman spectroscopy. The improved capacity of the RROA method is based here on the excitation of molecules via more than two electronic states, giving rise to the bisignate RROA spectrum, significantly distinct from a parent Raman spectrum. This observation is an important step in the dissemination of using RROA spectroscopy in studying the complex structure of corrinoids which may prove crucial for a better understanding of their biological role.
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Novakovic, Daniel, Alan T. L. Cheng, Daron H. Cope, and Julia M. L. Brotherton. "Estimating the prevalence of and treatment patterns for juvenile onset recurrent respiratory papillomatosis in Australia pre-vaccination: a pilot study." Sexual Health 7, no. 3 (2010): 253. http://dx.doi.org/10.1071/sh09142.
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Background: Recurrent respiratory papillomatosis (RRP) causes serious morbidity. RRP in Australia may be eliminated in the near future following the implementation of a national vaccination program using a human papillomavirus (HPV) vaccine that protects against infection with HPV types 6 and 11, those responsible for RRP. Baseline data on RRP prevalence and disease burden in Australia are lacking. Methods: Three study methods were used to estimate the burden of juvenile onset RRP in Australia. We conducted a retrospective chart review of RRP cases treated at The Children’s Hospital at Westmead over 10 years, examined the coding of these cases, and then calculated and applied the positive predictive value of the codes to national data to estimate the prevalence of RRP in Australia. We also conducted an online survey of otolaryngologists in Australia who manage RRP. Results: Nineteen patients were treated at the hospital over 10 years, involving 359 admissions. We estimate that between 33 and 56 RRP cases aged <20 are being treated nationally per year (0.6–1.1 per 100 000 persons), with children 5–9 years having a higher estimated rate of 1.2–1.8 per 100 000. Among 39 otolaryngologists treating juvenile onset RRP, the majority (73%) treated RRP in a paediatric tertiary hospital, and used the microdebrider for ablation of lesions. Conclusions: Our estimates of RRP disease burden agree with international estimates. As a small number of clinicians treat RRP nationally, we believe that establishment of a national RRP register is both feasible and necessary to monitor the impact of vaccination.
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Webster, Kate E., and Ian M. Colrain. "Multichannel EEG analysis of respiratory evoked-potential components during wakefulness and NREM sleep." Journal of Applied Physiology 85, no. 5 (November 1, 1998): 1727–35. http://dx.doi.org/10.1152/jappl.1998.85.5.1727.
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Airway occlusion in awake humans produces a somatosensory evoked response called the respiratory-related evoked potential (RREP). In the present study, 29 channel evoked-potential recordings were obtained from seven men who were exposed to 250-ms inspiratory airway occlusions during wakefulness, stage 1, stage 2, and slow-wave sleep. The RREP recorded during wakefulness was similar to previous reports, with the unique observation of an additional short-latency positive peak with a mean latency of 25 ms. Short-latency RREP components were maintained in non-rapid-eye-movement (NREM) sleep. The clearly seen N1 vertex and late positive complex components during wakefulness were markedly attenuated during NREM sleep, and two large negative components (N300 and N550) dominated the sleep RREP. These findings indicate the maintenance of central nervous system monitoring of respiratory afferent information during NREM sleep, presumably to facilitate protective arousal responses to pathophysiological respiratory phenomena.
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Oliveira, Saulo Fernandes Melo de, Lúcia Inês Oliveira, and Manoel Costa. "Influência da resistência ao rolamento no desempenho de velocidade no rúgbi em cadeiras de rodas independente da classificação funcional." Journal of Physical Education 30, no. 1 (December 3, 2018): 3001. http://dx.doi.org/10.4025/jphyeduc.v30i1.3001.
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Nosso objetivo foi verificar as possíveis associações entre o desempenho de velocidade e a resistência ao rolamento (RROL) em atletas de rúgbi em cadeiras de rodas. Dessa forma, 16 jogadores foram avaliados nos próprios locais de treinamento das equipes. Foram coletados o peso dos sujeitos e das cadeiras de rodas, a RROL por um procedimento de campo e a velocidade pelo protocolo de sprint de 20 metros. Os dados foram analisados por meio de procedimentos de correlação de Pearson, correlação parcial e regressão linear simples. Os resultados demonstraram que há uma correlação negativa e significativa entre RROL, o desempenho no teste de velocidade de 20 metros (r= -0,825, p<0,001; R2= 0,680, p<0,001), e a potência propulsiva em 20 metros (r= 0,960, p<0,001; R2= 0,922, p<0,001). Após controle pela classificação funcional e a idade dos atletas, verificou-se que a RROL permaneceu correlacionando-se negativamente com o desempenho de velocidade (r= -0,790, p=0,001; R2= 0,624), e positivamente com a potência propulsiva (r= 0,963, p<0,001; R2= 0,928). Conclui-se que a RROL pode constituir-se em um elemento importante para controle do desempenho de velocidade no rúgbi em cadeiras de rodas, independente da classe funcional e da idade do atleta.
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Jiang, Guo-Liang, Thierry C. Marcel, Fernando Martínez, and Rients E. Niks. "Relative Ratio of Mature Pustules: A Simple Method to Assess Partial Resistance of Barley to Puccinia hordei." Plant Disease 91, no. 3 (March 2007): 301–7. http://dx.doi.org/10.1094/pdis-91-3-0301.
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In plant breeding and germplasm evaluation, large-scale assessment of quantitative resistance is desirable, but feasible only if a simple and accurate measure is available. In several plant-pathogen systems, latent period (LP) is a parameter that is well correlated with the level of partial resistance observed in field trials. However, measuring LP or relative LP (RLP), i.e., relative to the reference accessions, is laborious. We investigated the value of relative ratio of mature pustules (RRMP, relative to the susceptible control) as a simple and rapid alternative to replace LP estimation in barley to barley leaf rust (Puccinia hordei). A set of 103 F9 recombinant inbred lines (RILs) derived from a cross L94 × Vada was sown in a greenhouse compartment, and was inoculated at the seedling stage with isolate Uppsala or 24, and at the adult plant stage with isolate 24. In demarcated sections of leaves, the number of mature pustules was counted several times after inoculation. The ratio of mature pustules (RMP) and LP50 were calculated to assess RRMP and RLP, respectively, and to identify the quantitative trait loci (QTLs) contributing to the genetic variation. The contrasts in RRMP among accessions were highest when the susceptible reference line had developed 70 to 90% mature orange pustules, the immature infection sites being visible as pale flecks. At this optimal time of observation, the correlation between RRMP and RLP in both the seedling stage and the adult plant stage was highly significant (r = -0.82 ~-0.98). Compared with RLP, RRMP was much easier and simpler to measure and still showed good correspondence with RLP in the identification of QTLs for partial resistance. In another experiment at the seedling stage with 25 barley cultivars and lines inoculated with isolate 1.2.1, the coefficient of correlation between RRMP and RLP was -0.98. Therefore, we conclude that RRMP should have great application potential in breeding programs and germplasm screening and could be used in fundamental studies as well.
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Kim, Eung Sun, and Myongsoo Chong. "The Anti-depressive Effect of Rehmanniae Radix Preparata via Anti-inflammatory Activity." Journal of Korean Medicine 43, no. 1 (March 1, 2022): 99–111. http://dx.doi.org/10.13048/jkm.22009.
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Objectives: Rehmanniae Radix Preparata (RRP) has been used as a traditional remedy to treat gynecology and endocrine diseases. Recently, studies on antioxidant and anti-inflammatory effects of RRP have been reported, so it was judged that RRP extracts would have an anti-depressive effect.Methods: We investigated the anti-neuroinflammatory and anti-depressive effect of RRP on lipopolysaccharide (LPS)-induced depression and LPS-stimulated BV2 microglia. RRP inhibited the LPS-stimulated excessive release of nitrite in the BV2 cells. RRP also significantly inhibited the inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated BV2 microglial cells.Results: RRP significantly suppressed the LPS-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-κB activation. In addition, administration of RRP not only inhibited the immobility time in the forced swimming test (FST) but also increased the total travel distance in the open field test (OFT). Also, RRP inhibited the elevation of TNF-alpha, IL-1beta, and IL-6 in brain of LPS-injected mice.Conclusions: Considering the overall results, our study showed that RRP exhibited the anti-neuroinflammatory and anti-depressive activities via deactivation of MAPKs and NF-κB.
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Flenga, Maria G., and Maria J. Favvata. "The Effect of Magnitude Mw and Distance Rrup on the Fragility Assessment of a Multistory RC Frame Due to Earthquake-Induced Structural Pounding." Buildings 13, no. 7 (July 20, 2023): 1832. http://dx.doi.org/10.3390/buildings13071832.
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The effect of an intensity measure’s (IM’s) sufficiency property on the probabilistic assessment of reinforced concrete (RC) structures due to floor-to-floor structural pounding conditions is examined. In the first part of this investigation, efficiency and sufficiency properties of 23 scalar IMs are verified. Then, the magnitude Mw and the distance Rrup are examined as elements in a vector with an efficient scalar IM to evaluate whether they have any significant effect on the structural response. Subsequently, probabilistic seismic demand models (PSDMs) are developed using linear regression analyses based on a scalar IM and a vector-valued IM. Fragility curves are developed based on these PSDMs, and the influence of Mw and Rrup on the evaluation of the minimum required separation gap distance dg,min due to the pounding effect is examined. More than two hundred nonlinear time history analyses are performed based on the Cloud Analysis method. Seismic displacement demands that control of the global state of the structure, as well as the probability of structural pounding, are examined. The results of this research indicate that once Mw or Rrup is increased, fragility curves are shifted to greater values of IM, and the probability of the exceedance of a certain performance level is reduced. Also, the predictive power of Rrup seems to be greater than the one of Mw. On the other hand, it is revealed that Mw and Rrup induce variabilities in the demand solutions for adequate separation gap distance between the adjacent structures. Therefore, variation in Mw or Rrup may lead, in some cases, to unacceptable evaluations of the pounding effect in the capacity levels of structures.
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Biancucci, Marco, George Minasov, Avik Banerjee, Alfa Herrera, Patrick J. Woida, Matthew B. Kieffer, Lakshman Bindu, et al. "The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling." Science Signaling 11, no. 550 (October 2, 2018): eaat8335. http://dx.doi.org/10.1126/scisignal.aat8335.
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The Ras–extracellular signal–regulated kinase pathway is critical for controlling cell proliferation, and its aberrant activation drives the growth of various cancers. Because many pathogens produce toxins that inhibit Ras activity, efforts to develop effective Ras inhibitors to treat cancer could be informed by studies of Ras inhibition by pathogens.Vibrio vulnificuscauses fatal infections in a manner that depends on multifunctional autoprocessing repeats-in-toxin, a toxin that releases bacterial effector domains into host cells. One such domain is the Ras/Rap1-specific endopeptidase (RRSP), which site-specifically cleaves the Switch I domain of the small GTPases Ras and Rap1. We solved the crystal structure of RRSP and found that its backbone shares a structural fold with the EreA/ChaN-like superfamily of enzymes. Unlike other proteases in this family, RRSP is not a metalloprotease. Through nuclear magnetic resonance analysis and nucleotide exchange assays, we determined that the processing of KRAS by RRSP did not release any fragments or cause KRAS to dissociate from its bound nucleotide but instead only locally affected its structure. However, this structural alteration of KRAS was sufficient to disable guanine nucleotide exchange factor–mediated nucleotide exchange and prevent KRAS from binding to RAF. Thus, RRSP is a bacterial effector that represents a previously unrecognized class of protease that disconnects Ras from its signaling network while inducing limited structural disturbance in its target.
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Sims, Andrew, Kim Keltie, Emma Belilios, Julie Burn, Liz Brown, Aaron Jackson, Steven Powell, Sue Jones, and Adam Donne. "Our experience in developing and operating the Airway Intervention Registry for Recurrent Respiratory Papillomatosis (AIR-RRP): national data collection." NIHR Open Research 2 (February 24, 2022): 22. http://dx.doi.org/10.3310/nihropenres.13244.1.
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Recurrent respiratory papillomatosis (RRP) is characterised by benign wart-like growths in the respiratory tract caused by the human papillomavirus (HPV). These warts vary in size and grow quickly, causing voice changes and airway obstruction. Whilst the condition is rare, RRP is more common and aggressive in children. There is currently no curative treatment for HPV, therefore RRP is managed by maintaining a safe airway and a serviceable voice by repeated surgery to remove the growths. A lack of specific diagnostic codes prevents reliable case ascertainment of RRP from routine administrative databases such as Hospital Episode Statistics. To determine RRP burden in the UK, we conducted a cross-sectional survey of ENT consultants; 283 responded, identifying 918 RRP patients, half of whom received surgical intervention for RRP in the previous 12 months with 16 different interventions reported. Randomised controlled trials for RRP interventions are difficult due to the rarity of the disease, variation in severity and progression and non-standard care across the NHS. Consequently, there is a lack of definitive efficacy and safety evidence. The only national guidance for RRP interventions is “Radiofrequency cold ablation for respiratory papillomatosis” (NICE IPG434, 2017) which recommended further data collection due to lack of evidence. However, due to the wide variation in RRP management across the NHS, clinical opinion favoured that any data collection should include a comparison of safety and efficacy of all RRP interventions in order to advise which improved patient outcomes and quality of life. To address lack of evidence, and inform the future care of RRP patients, we developed a registry and used it to collect real-world data from patients receiving treatment for RRP in NHS hospitals across the UK. The purpose of this paper is to share lessons learned from this national data collection exercise to inform future clinical registry development.
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Shimokawaji, Tadasuke, Shoko Narita, Tomoyuki Naito, Hibiki Udagawa, Koichi Goto, Taichi Miyawaki, Nobuaki Mamesaya, et al. "Clinical characteristics of nivolumab-induced radiation recall pneumonitis in patients with non-small cell lung cancer: A multicenter real-world analysis of 669 patients." Journal of Clinical Oncology 38, no. 5_suppl (February 10, 2020): 88. http://dx.doi.org/10.1200/jco.2020.38.5_suppl.88.
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88 Background: Immune checkpoint inhibitors can cause immune-related pneumonitis in lung cancer patients. Some of those patients with history of previous thoracic radiation therapy (TRT) are reported to show radiation recall pneumonitis (RRP) pattern. In this multicenter retrospective study, we analyzed the patient background and clinical characteristics of RRP. Methods: Medical records of non-small cell lung cancer patients, who received nivolumab between December 2015 and March 2017, were retrospectively reviewed. Incidence of pneumonitis, and incidence, risk factors and clinical characteristics of RRP were analyzed at 5 institutions. Person’s chi-square test (age, sex, smoking history, performance status at the start of nivolumab treatment, background lung disease, history of previous radiation pneumonitis, total dose, volume receiving more than 20Gy, 30Gy, mean lung dose of TRT, and duration after TRT) was conducted to identify potential risk factors of RRP. RRP was defined as fibrosis or consolidation occurring in the previous TRT field, and imaging analysis was conducted by two individual radiologists. Results: A total of 669 patients were evaluated, and the incidences of all-grade and ≥ grade 3 pneumonitis were 8.8% (59/669) and 6.2% (18/669), respectively. Incidence of RRP was 5.4% (14/257) among patients with history of previous TRT. There were no significant risk factors for RRP. Although we did not find significant difference between the severity of RRP pattern and other radiological patterns of pneumonitis, patients with RRP showed better outcome. All patients recovered from RRP without no exacerbation or death, compared to 9.3% of exacerbation or death in other patterns of pneumonitis. Conclusions: Incidence of RRP was 5.4% among patients with history of previous TRT, although there were no significant risk factors of RRP. Patients with RRP pattern showed relatively better outcome.
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Skokov, O. I., O. H. Dyachenko, V. V. Volovschikova, and M. S. Khorolsky. "THE RUBBER REINFORCED SUPPORT PARTS FOR COMPLEITING DYNAMICS AND QUIESCENT LOADS OF BRIDGE CONSTRUCTIONS." Science and Transport Progress, no. 33 (August 25, 2010): 259–61. http://dx.doi.org/10.15802/stp2010/13358.
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The research of deformation characteristics of the rubber reinforced support parts (RRBP), which compensate static and dynamic loadings of elements of bridge constructions, is conducted. The technology for manufacturing RRBP using new materials is developed; their deformation characteristics are investigated with the purpose of determination of the predicted operation life.
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Chan, Pei-Ying Sarah, and P. W. Davenport. "The role of nicotine on respiratory sensory gating measured by respiratory-related evoked potentials." Journal of Applied Physiology 108, no. 3 (March 2010): 662–69. http://dx.doi.org/10.1152/japplphysiol.00798.2009.
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Respiratory perception can be altered by changes in emotional or psychological states. This may be due to affective (i.e., anxiety) modulation of respiratory sensory gating. Nicotine withdrawal induces elevated anxiety and decreased somatosensory gating. Respiratory sensory gating is evidenced by decreased amplitude of the respiratory-related evoked potentials (RREP) N1 peak for the second occlusion (S2) when two 150-ms occlusions are presented with a 500-ms interval during an inspiration. The N1 peak amplitude ratio of the S2 and first occlusion (S1) (S2/S1) is <0.5 and due to central neural sensory gating. We hypothesized that withdrawal from nicotine is anxiogenic and reduces respiratory gating in smokers. The RREP was recorded in smokers with 12-h withdrawal from nicotine and nonsmokers using a paired occlusion protocol. In smokers, the RREP was measured after nicotine withdrawal, then with either nicotine or placebo gum, followed by the second RREP trial. Nonsmokers received only placebo gum. After nicotine withdrawal, the smokers had a higher state anxiety compared with nonsmokers. There was a significant interaction between groups (nonsmokers vs. smokers with nicotine vs. smokers with placebo) and test (pre- vs. posttreatment) in RREP N1 peak amplitude S2/S1. The S2/S1 in the smokers were larger than in nonsmokers before treatment. After gum treatment, the smoker-with-placebo group had a significantly larger S2/S1 than the other two groups. The S2/S1 was significantly decreased after the administration of nicotine gum in smokers due to significantly decreased S2 amplitudes. The RREP Nf and P1 peaks were unaffected. These results demonstrated that respiratory sensory gating was decreased in smokers after nicotine withdrawal. Nicotine increased respiratory sensory gating in smokers with a S2/S1 similar to that of the nonsmokers. Nicotine did not change respiratory sensory information arrival, but secondary information processing in respiratory sensation.
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Zhao, Weiying, A. Daniel Martin, and Paul W. Davenport. "Respiratory-related evoked potentials elicited by inspiratory occlusions in double-lung transplant recipients." Journal of Applied Physiology 93, no. 3 (September 1, 2002): 894–902. http://dx.doi.org/10.1152/japplphysiol.01218.2001.
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This study investigated the role of lung vagal afferents in the respiratory-related evoked potential (RREP) response to inspiratory occlusions by using double-lung transplant recipients as a lung denervation model. Evoked potential recordings in response to inspiratory occlusions were obtained from 10 double-lung transplant (DLT) recipients with normal lung function and 12 healthy control (Nor) subjects under the attend, ignore, and unoccluded conditions. Results demonstrated that early-latency RREP components (P1, P1a, Nf, and N1) were not significantly different between the DLT and the Nor groups. The late-latency RREP component (P3) was identifiable in all DLT subjects during the attend trial. However, P3 latency was significantly longer in the DLT group compared with the Nor group. The zero-to-peak amplitude of P3 was also significantly smaller in the DLT group than that in the Nor group during the attend trial. These results suggest that lung vagal afferents were not essential to elicit RREP responses, but may contribute to the cognitive processing of respiratory stimuli.
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Davenport, P. W., I. M. Colrain, and P. M. Hill. "Scalp topography of the short-latency components of the respiratory-related evoked potential in children." Journal of Applied Physiology 80, no. 5 (May 1, 1996): 1785–91. http://dx.doi.org/10.1152/jappl.1996.80.5.1785.
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Respiratory-related evoked potentials (RREPs) have been elicited by inspiratory occlusion and recorded at electroencephalographic (EEG) sites overlying the somatosensory cortex in adults. The present study was the first to be conducted in normal children and was designed to identify the scalp distribution of the early RREP components. EEG responses to occlusion were recorded from CZ-C3, CZ-C4, and 17 sites referenced to the linked earlobes. The RREP was observed in all subjects in the CZ-C3 and CZ-C4 electrode pairs. The earlobe-referenced recordings revealed two RREP patterns. The P1 and N1 peaks were found in C3, C4, P3, P4, T3, and T4. The RREPs recorded from the F3, F4, F7, and F8 electrodes did not exhibit either the P1 or N1 peaks. A negative peak (NF) occurred approximately 13 ms after the P1 peak. The results show that the RREPs to inspiratory occlusions were present bilaterally but diminished greatly over midline sites. Furthermore, consistent with mechanically and electrically elicited somatosensory evoked potentials, the RREP displayed a polarity inversion over the central sulcus in the early component latency range.
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Davenport, Paul W., and Alastair A. Hutchison. "Cerebral cortical respiratory-related evoked potentials elicited by inspiratory occlusion in lambs." Journal of Applied Physiology 93, no. 1 (July 1, 2002): 31–36. http://dx.doi.org/10.1152/japplphysiol.00177.2001.
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Respiratory-related evoked potentials (RREP) elicited by inspiratory mechanical loads have been recorded in humans. Early RREP peaks were hypothesized to be generated by activation of neurons in the somatosensory cortex. An animal model was developed to test this hypothesis in chronically instrumented, awake, spontaneously breathing lambs. Electrocorticogram (ECoG) was recorded bilaterally with ball electrodes on the dural surface over the somatosensory region. Inspiratory occlusions were presented through a face mask or endotracheal tube as interruptions of inspiration. Occlusion-elicited evoked potentials were obtained by computer-signal averaging the ECoG activity. A short-latency positive peak was observed bilaterally in the averaged occlusion-elicited evoked potentials in all animals breathing with the facemask and 5 of 8 lambs with the endotracheal tube. Postmortem identification of the electrode location demonstrated that the ECoG was recorded in the caudal-lateral portion of the somatosensory cortex. These results demonstrate that inspiratory occlusion elicits an evoked potential in the somatosensory cortical region of awake, spontaneously breathing lambs. The lamb cortical RREP is similar to human RREP.
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Boemke, W., E. Seeliger, L. Rothermund, M. Corea, R. Pettker, G. Mollenhauer, and H. W. Reinhardt. "ACE inhibition prevents Na and water retention and MABP increase during reduction of renal perfusion pressure." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 269, no. 3 (September 1, 1995): R481—R489. http://dx.doi.org/10.1152/ajpregu.1995.269.3.r481.
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Two groups of six dogs were studied during 4 control days and 4 days of reduced renal perfusion pressure (rRPP) servo controlled at 20% below the individual dog's 24-h mean arterial blood pressure (MABP) during control days, i.e., below the threshold for renin release. On rRPP days, endogenous activation of plasma aldosterone and angiotensin II was inhibited by the angiotensin-converting enzyme inhibitor captopril. The dogs were kept on a high-Na and high-water intake. Unlike studies during rRPP alone, there was no Na and water retention during rRPP+captopril. Glomerular filtration rate dropped by approximately 9%, and MABP remained in the range of control days. Plasma renin activity rose to values 14 times greater than control, whereas plasma aldosterone decreased by approximately 60%. Atrial natriuretic peptide remained in the range of controls. In conclusion, angiotensin-converting enzyme inhibition can prevent the otherwise obligatory Na and water retention and systemic MABP increase during a 20% reduction in renal perfusion pressure. This is achieved most likely via the captopril-induced fall in angiotensin II and plasma aldosterone levels.
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Egido Piqueras, Marto. "Comunicación persuasiva como estrategia de neurocomunicación para las relaciones públicas." Miguel Hernández Communication Journal 14 (July 28, 2023): 339–60. http://dx.doi.org/10.21134/mhjournal.v14i.1961.
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El presente trabajo se enfoca en el estudio de la comunicación persuasiva como estrategia de neurocomunicación de gran utilidad para las Relaciones Públicas. La persuasión es una parte importante de la comunicación, en la que se busca influir en la opinión o comportamiento de un receptor, por lo que es posible considerarla como una estrategia que puede ser explicada desde la neurocomunicación para optimizar su aplicación en el ámbito de las RRPP. Así, el presente escrito tiene el objetivo de examinar cómo la comunicación persuasiva puede funcionar como estrategia efectiva en las RRPP para influir en la percepción y comportamiento de los destinatarios. Este fue cumplimentado mediante una revisión bibliográfica desde la cual se analizaron cualitativamente 19 artículos de investigación vinculados con la temática. Se han podido detectar numerosas estrategias de comunicación persuasiva que son de utilidad en el ámbito de las RRPP. De esta forma, se concluye que las RRPP y la comunicación persuasiva están estrechamente relacionadas y que la neurocomunicación posibilita la detección de elementos que pueden mejorarse para aumentar su efectividad.
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Stevens, Charles F., and James H. Williams. "Discharge of the Readily Releasable Pool With Action Potentials at Hippocampal Synapses." Journal of Neurophysiology 98, no. 6 (December 2007): 3221–29. http://dx.doi.org/10.1152/jn.00857.2007.
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A readily releasable pool (RRP) of synaptic vesicles has been identified at hippocampal synapses with application of hypertonic solution. RRP size correlates with important properties of synaptic function such as release probability. However, a discrepancy in RRP size has been reported depending on the method used to evoke synaptic release. This study was undertaken to determine quantitative relationships between the RRP defined with hypertonic solution and that released with trains of action potentials. We find that asynchronous release at cell culture synapses contributes significantly to the discharge of the RRP with trains of action potentials and that RRP size is the same when elicited by either nerve stimuli or hypertonic challenge.
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Durnez, Anne, Geert Vanderschueren, Luc Lateur, René Westhovens, and Patrick Verschueren. "Effectiveness of initial treatment allocation based on expert opinion for prevention of rapid radiographic progression in daily practice of an early RA cohort." Annals of the Rheumatic Diseases 70, no. 4 (December 21, 2010): 634–37. http://dx.doi.org/10.1136/ard.2010.135319.
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ObjectivesTo evaluate expert treatment selection for early rheumatoid arthritis and to validate a prediction model for rapid radiographic progression (RRP) in daily practice.MethodsPatients received initial combination therapy with steroids (ICTS) or disease-modifying antirheumatic drug monotherapy (IMT) after informal evaluation of prognostic factors, followed by a tight control strategy. Changes in Sharp/van der Heijde score (total Sharp score (TSS)) of >5 units over 1 year (=RRP) were documented. The mean change in TSS and proportion with RRP were compared between groups. Based on the 28 swollen joint count, rheumatoid factor titre and C reactive protein/erythrocyte sedimentation rate, patients were placed in the ASPIRE prediction matrix, yielding a RRP risk. Numbers needed to treat (NNT) intensively to avoid one RRP after 1 year were calculated.ResultsThe mean change in TSS after 1 year and the proportion with RRP was lower in the ICTS group (n=37) than in the IMT group (n=43). The mean calculated risk of RRP was higher in patients with radiographic progression. The mean NNT intensively to prevent RRP was lower in the ICTS group than in the IMT group. The positive predictive value of NNT for RRP prevention was 12.6%, but the negative predictive value reached 100%.ConclusionICTS seems more effective in preventing RRP than IMT. The predictive matrix model could be helpful in preventing overtreatment in practice.
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Ramaseshan, B., Jochen Wirtz, and Dominik Georgi. "The enhanced loyalty drivers of customers acquired through referral reward programs." Journal of Service Management 28, no. 4 (August 21, 2017): 687–706. http://dx.doi.org/10.1108/josm-07-2016-0190.
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Purpose The purpose of this paper is to extend prior research on referral reward programs (RRPs) by examining if and how the mode of customer acquisition (RRP-acquired customers vs non-RRP-acquired new customers) moderates the relationships between customer satisfaction and attitudinal loyalty, perceived switching costs and attitudinal loyalty, and attitudinal loyalty and behavioral loyalty (i.e. recommendations, cross-buying, and total spend). Design/methodology/approach Set in a banking context, this study is the first in an RRP context to link survey data with actual purchase data from a bank’s CRM records. Specifically, the survey captured customers’ satisfaction, perceived switching costs and attitudinal loyalty, whereas the CRM data provided actual loyalty behaviors (cross-buying and total spend). Findings The findings show that the effect of satisfaction on attitudinal loyalty, and the effects of attitudinal loyalty on recommendations, cross-buying, and total spend were stronger for RRP-acquired customers than for non-RRP-acquired new customers. Furthermore, perceived switching costs had a lower effect on attitudinal loyalty for RRP-acquired customers than for non-RRP-acquired new customers. Practical implications The findings offer managers a better understanding of how RRP-acquired customers differ from non-RRP-acquired new customers with regard to their satisfaction, perceived switching costs, and attitudinal and behavioral loyalty, thus enabling effective management of RRPs. Originality/value This is the first empirical study that explores the differences between RRP-acquired customers and non-RRP-acquired new customers with regard to the effects of satisfaction and perceived switching costs on attitudinal loyalty, and the effect of attitudinal loyalty on behavioral loyalty.
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Sims, Andrew, Kim Keltie, Emma Belilios, Julie Burn, Liz Brown, Aaron Jackson, Steven Powell, Sue Jones, and Adam Donne. "Our experience in developing and operating the Airway Intervention Registry for Recurrent Respiratory Papillomatosis (AIR-RRP): national data collection." NIHR Open Research 2 (January 12, 2023): 22. http://dx.doi.org/10.3310/nihropenres.13244.2.
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Recurrent respiratory papillomatosis (RRP) is characterised by benign wart-like growths in the respiratory tract caused by the human papillomavirus (HPV). These warts vary in size and grow quickly, causing voice changes and airway obstruction. Whilst the condition is rare, RRP is more common and aggressive in children. There is currently no curative treatment for HPV, therefore RRP is managed by maintaining a safe airway and a serviceable voice by repeated surgery to remove the growths. A lack of specific diagnostic codes prevents reliable case ascertainment of RRP from routine administrative databases such as Hospital Episode Statistics. In 2017 a cross-sectional survey identified 918 RRP patients in the UK, half of whom had received surgical intervention for RRP in the previous 12 months with 16 different interventions. Randomised controlled trials for RRP interventions are difficult due to the rarity of the disease, variation in severity and progression and non-standard care across the NHS. Consequently, there is a lack of definitive efficacy and safety evidence. The only national guidance for RRP interventions is “Radiofrequency cold ablation for respiratory papillomatosis” (NICE IPG434, 2017) which recommended further data collection due to lack of evidence. However, due to the wide variation in RRP management across the NHS, clinical opinion favoured that any data collection should include a comparison of safety and efficacy of all RRP interventions in order to advise which improved patient outcomes and quality of life. To address lack of evidence, and inform the future care of RRP patients, we developed a registry and used it to collect real-world data from patients receiving treatment for RRP in NHS hospitals across the UK. The purpose of this paper is to share lessons learned from this national data collection exercise to inform future clinical registry development.