Successful Conversions Research Articles

Metal Ion Microwave-Assisted Depolymerization of Poly(Ethylene Terephthalate): A Zinc Salts-Based Deep Eutectic Solvent as Case Study

In this study, a new and very quick method to depolymerize PET plastics is reported. The depolymerization experiments were conducted using a type-IV deep eutectic solvent containing ZnCl2 and urea, and a microwave oven as reactor. Different combinations of power and reaction times were employed while keeping the total energy constant. Successful conversions were obtained carrying out the process at 180 W for 2 min and 360 W for 1 min, whereas at higher powers and shorter times, an inclusion likely occurs of some solvent into the structure of the recovered PET flakes, as suggested by the porosity of the flakes, imaged by SEM microscopy. The flakes increase their crystalline character during the treatment, as indicated by the appearance of narrow diffraction peaks in the XRD patterns, at variance with the broad signals observed in the case of the pristine amorphous polymer. The NMR analysis of the supernatant liquid above the partially solubilized PET shows the presence of terephthalic acid peaks. The infrared spectra of the solid powder achieved upon the acidic treatment of the extract reveal the presence of C=O stretching peaks and the absence of typical CH2 wagging absorptions that satisfactorily comply with the presence of terephthalic acid.

Performance metrics that matter: assessing winning and losing teams in women’s Rugby union

ABSTRACT The aim of this study was to identify key performance indicators (KPI) that differentiated winning and losing teams, and how KPI may vary in balanced and unbalanced matches in Australian domestic women’s Rugby Union (RU). Four seasons of the Buildcorp Super W competition (2019–2022), round and final matches (n = 47) were analysed by an experienced performance analyst using computerised notational analysis software (Hudl SportsCode) to identify various KPI that occurred throughout a match. Findings showed that winning teams had greater ball-carrying efficiency, quick ruck speed, greater field-based tactics, greater successful conversions, and created more scoring opportunities while losing teams had poorer goal-kicking performance, greater number of rucks lost, and unsuccessful set piece performance. However, in balanced matches, only greater scoring opportunities, possession, and kicking performance discriminated between winning and losing teams. Winning teams in unbalanced matches had greater scoring opportunities, kicking performance, possession, territory, ball-carrying efficiency, and ruck performance, whilst losing teams had a greater number of rucks lost and lineouts lost. These results suggest some performance metrics can differ between balanced and unbalanced matches. Coaches may use these findings to help evaluate match performances based on scoring differential, as well as influence possession-in-territory, and kicking tactics, to increase scoring opportunities.

Early Successful Experiences of Surgical Conversion of Endoscopic Gastric Plication to Roux-en-Y Gastric Bypass.

The primary obesity surgery endoluminal (POSE) procedure is an innovative incision-less endoscopic bariatric procedure that is increasingly used. However, variable weight loss response and recurrence post-endoscopic bariatric procedures have at times necessitated laparoscopic bariatric conversion. The safety and approach of conversion to laparoscopic sleeve gastrectomy (LSG) or Roux-en-Y gastric bypass (RYGB), however, have been an active point of discussion within revisional bariatric surgery. This retrospective review of four consecutive patients is the largest description of medium-term postoperative outcomes and technical highlights of a laparoscopic conversion of POSE to RYGB. Chart review was completed to evaluate patients' post-POSE clinical course and perioperative outcomes after surgical conversion. Early data suggests varied weight loss trajectory with POSE and marked improvement in weight response after surgical conversion. Qualitative review reveals successful single-staged conversions contrary to previous smaller case series describing staged conversions involving endoscopic removal of plications followed by RYGB. Review additionally reveals key perioperative considerations for successful conversions to include intraoperative endoscopy, upper gastrointestinal fluoroscopic studies, and at times computed tomography. The latter study and laparoscopic view of the post-POSE stomach challenge the prior notion that distal POSE allows for easy revision to LSG. Our case series underscores the complex multifactorial nature of metabolic disease and the increasing importance of a conscientious approach to conversion bariatric surgery as the adoption of POSE and the bariatric patient population continues to grow.

Improving the Conversion Success Rate of Hepatocellular Carcinoma: Focus on the Use of Combination Therapy with a High Objective Response Rate.

The high mortality rate in hepatocellular carcinoma (HCC) is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage, with surgical treatment options unavailable. Conversion therapy, which involves both locoregional and systemic treatments, has the potential to downstage tumors in selected patients with initially unresectable HCC, thereby making surgical treatment a possibility and potentially increasing long-term survival. To optimize the conversion rate, it is necessary to maximize successful conversions and clearly define the target population for conversion treatment through a collaborative effort. In this review article, we summarize the clinical experience and evidence for conversion therapy in patients with 'potentially resectable' HCC from four perspectives: 1) defining the target population for conversion therapy, 2) selecting the appropriate conversion strategy, placing emphasis on the utilization of combination therapy that exhibits a significant objective response rate, 3) determining the timing and urgency of surgical resection, 4) promoting the adoption of a multidisciplinary team model. The authors are optimistic that with the continuous progress in treatment and a deeper understanding of HCC, the success rate of HCC conversion therapy will increase, and the overall survival of HCC patients will be prolonged.

Impact of targeted subsidies on access to resilient sanitation for climate-vulnerable households in rural Cambodia

Abstract Access to safe sanitation is a basic requirement for human well-being and is critical for protecting public health and preventing environmental contamination at the community level. The increasing global risk of climate-related disasters exacerbates the likelihood of traditional sanitation solutions failing and exposing communities to harmful pathogens. This risk is ubiquitous in Cambodia's flood-prone Tonle Sap Lake region, which has some of the lowest rates of sanitation coverage in the country. This study sought to design and test a targeted mechanism in the region to deliver sanitation subsidies to households in a vulnerable position due to climate and socioeconomic characteristics. Subsidy eligibility was evaluated using the poverty probability index for Cambodia, with thresholds set according to households' individual and community-level climate vulnerability. In a randomized controlled trial, offering subsidies increased the likelihood of successful sales conversions for climate-resilient latrine products among targeted households by 32 percentage points, indicating effectiveness for increasing market-based sanitation uptake. The research did not find evidence of widespread or sustained market distortion due to the subsidy program.

All-Optical Modulation Format Conversions from PAM4 to QPSK and 16QAM Using Silicon-Rich Nitride Waveguides

Quadrature phase-shift keying (QPSK) and 16-quadrature amplitude modulation (16QAM) formats are deployed in inter-data center networks where high transmission capacity and spectral efficiency are required. However, in intra-data center networks, a four-level pulse amplitude modulation (PAM4) format is deployed to satisfy the requirements for a simple and low-cost transceiver configuration. For the seamless and effective connection of such heterogeneous networks without an optical-electrical-optical conversion, an all-optical modulation format conversion technique is required. In this paper, we propose all-optical PAM4 to QPSK and 16QAM modulation format conversions using silicon-rich nitride waveguides. The successful conversions from 50-Gbps-class PAM4 signals to 50-Gbps-class QPSK and 100-Gbps-class 16QAM signals are demonstrated via numerical simulations.

Cationic ruthenium(II)-CNC pincer complexes as phosphine-free catalysts for nitrile hydration to amides in aqueous medium

We report the synthesis, characterization, and catalytic activity of a series of electron-rich, phosphine-free complexes featuring multiple N-heterocyclic carbene (NHC) ligands, namely [Ru(CNCi-Pr)(CNMe)I]PF6 (1a), [Ru(CNCi-Pr)(CNi-Pr)I]PF6 (1b), [Ru(CNCCy)(CNMe)I]PF6 (2a), [Ru(CNCCy)(CNi-Pr)I]PF6 (2b), [Ru(CNCt-Bu)(CNMe)I]PF6 (3a), and [Ru(CNCt-Bu)(CNi-Pr)I]PF6 (3b) (where CNC = 2,6-bis(alkylimidazol-2-ylidene)-pyridine and CN = 2-(3-alkylimidazol-2-ylidene)-pyridine). Spectroscopic characterization using multinuclear NMR and high-resolution mass spectrometry (HRMS) confirms the composition of all complexes. The molecular structures of 1a and 2a were further confirmed by single-crystal X-ray diffraction. The catalytic activity of these ruthenium(II) complexes in the hydration of nitriles under mild reaction conditions and in the aqueous medium have been explored, with complex 1a exhibiting superior reactivity among the studied complexes. Mechanistic investigations revealed a catalytic pathway initiated by a [Ru-OH] species, facilitated by the hemilability of a pyridine ligand. The versatility of these ruthenium(II) complexes as catalysts for nitrile hydration has been demonstrated through successful conversions of a diverse range of nitriles, containing electron-releasing or electron-withdrawing groups, and heterocyclic nitriles into the corresponding amides with high reactivity and good to excellent yields.

Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Multi-stage pre-treatment of lignocellulosic biomass for multi-product biorefinery: A review

With increasing population worldwide and the consumption of greenhouse gases (GHGs) emitting limited fossil fuel resources, the indispensable need of seeking sustainable energy sources and conversion methods have been realized that can offer possible alternative ways to substantially minimize biomass wastes and even pre-treatments assisted biorefinery systems to convert those wastes into biofuels and other bioproducts. Considerable attention, therefore, has been given to the generation of biofuels from lignocellulosic biomass including the agricultural wastes. Biochemical and biological methods for converting lignocellulosic biomass to biofuels are challenging because of their unreactive nature, and pre-treatments are the key for their successful and efficient conversions. This review explored, compared, and highlighted the significance of multi-stage pre-treatment over the single-step biorefinery systems for biofuels production from different sources. The multi-stage methods have exhibited to demand less energy consumption and reaction time, to enhance productivity of lignocellulose deconstruction. However, optimized and engineered multi-stage pre-treatment methods for multi-product biorefinery from specific feedstocks have not been fully investigated yet. The authors present the future research direction for potential industrial application of multi-stage pre-treatments with key technical considerations as well.

Conversion of Appointments to Televisits in a Minimally Invasive Practice during the COVID-19 Pandemic

Study ObjectiveTo determine rate of conversion of in-person visits, scheduled before COVID-19 pandemic, to televisits in a minimally invasive gynecology surgery (MIGS) practice and identify factors that predict successful conversion.DesignRetrospective review of appointments scheduled over a 11-week period between March 17th and May 29th, 2020, in the MIGS division of an academic obstetrics and gynecology department. During this period, the office was closed except for emergency visits due to the restrictions secondary to COVID-19. Successful conversion from in-person to televisits was defined as appointments rescheduled within 2 months of the initial in-person visit.SettingN/A.Patients or ParticipantsAll patients scheduled for in-person visits during this time were included. Patients were excluded from the analysis if they were seen emergently in person or newly scheduled as a televisit.InterventionsN/A.Measurements and Main ResultsData extracted included age, race/ethnicity, primary language, insurance type, appointment type, reason for visit, and time to rescheduled visit. 132 patients were originally scheduled during 11 weeks. 32 (24.2%) appointments were newly scheduled televisits and 20 (15.2%) were emergent in-person visits, leaving 87 visits. 21 (24%) appointments were rescheduled as televisits; 14 (66.7%) via telephone and 7 (33.3)% of these as video. There were no significant differences between age, race, primary language. insurance type, appointment type and the reason seen between the converted and non-converted groups. Median time to rescheduled appointments was sooner in successful conversions (16 days (-7 to 73) versus 96 days (8-234), p<.001).ConclusionConversion to televisits was reasonable for a telemedicine naïve practice, despite having an overall low conversion rate to televisits. Utilizing telemedicine allowed patients to receive care sooner when compared to the non-converted group. The lack of difference in demographic/clinical factors between the two groups provides hope that technology can be utilized by diverse groups of MIGS patients.

INFORMATION TECHNOLOGY FOR INTERNET RESOURCES PROMOTION IN SEARCH SYSTEMS BASED ON CONTENT ANALYSIS OF WEB-PAGE KEYWORDS

Context. Timely and correct analysis of the process of visiting Internet resources, which led to the overall conversion of e-business, is fundamental and relevant for successfully managing the website. Appropriate, accurate traffic analysis, which brings both successful and unsuccessful conversions, will identify the cause of the impact on conversion metrics and criteria and will measure the effectiveness of changes made to the site to increase traffic conversions. It is necessary to collect information on the activities of system users on the website and determine specific performance indicators of the website to improve e-business strategy further to solve these problems and achieve the relevant goals of e-commerce. Thus, it is necessary to develop and implement an analytical method of text content support for e-commerce Internet resources based on the analysis of key performance indicators of the website, paying particular attention to determining the set of relevant and relevant keywords used by regular users and led to an increase in e-business conversions.&#x0D; Objective of the study is to develop a technology for promoting Internet resources of e-commerce based on the results of Web-analytics of critical indicators of pages as KPI and KSI through forming a relevant set of keywords as feedback activity of a regular audience.&#x0D; Method. An analytical method for promoting Internet resources based on the analysis of key performance indicators of the website, which is based on three main algorithms аlgorithm for identifying problem areas of the site structure for further optimization, аlgorithm for optimizing search engine marketing activities (SEM), аlgorithm for site promotion and calculation of its efficiency.&#x0D; General recommendations for the design of information resources processing systems have been developed, different from the existing ones, by the presence of additional modules that significantly affect promoting the website on the Internet to further the success of ecommerce or improve the values of these indicators. Among them is the module of online shopping, marketing, module-copywriter and Web-master. For each of them, calculate their own KRI. It will allow you to effectively implement the processing of information resources at the level of system developers (reducing resources and time for development, improving the quality of information processing systems).&#x0D; Results. The paper develops and describes in detail, based on the results of Web-analytics, the parameters and criteria for assessing the level of success of e-business. Software tools for monitoring the textual content of Internet resources based on the analysis of key performance indicators of the website have also been developed. For a detailed analysis of the functioning and promotion of Internet ecommerce systems such as Internet newspaper and Internet magazine, 12 different methods have been developed and implemented, respectively, with support for each of them with a different number of stages of the content life cycle. A computer experiment of analysis of key performance indicators of the website was conducted. The service of keeping statistics of visits to the Web resource allows you to estimate the increase in sales of textual content in direct proportion to the rise in the number of visits to the Web resource, the number of regular users, the prospects of marketing activities.&#x0D; Conclusions. It was found that the presence of appropriate modules in the systems of information resources processing increases the sales of textual content to the regular user by 9%, active involvement of unique visitors, potential users and expanding the target and regional audience by 11%, viewed pages by 12%, resources by 7%.

Water-Mediated Catalytic Decarboxylation Enabled Polysubstituted Furans and Allylic Alcohols with Exclusive (E)-Configurations.

A water-mediated catalytic decarboxylation process toward the formation of polysubstituted furans and (E)-allylic alcohols has been reported. This protocol features wide functional group tolerance, easy operation, and only CO2-byproduct generation. These reactions can be performed on a large scale open to air under extremely ambient conditions. A range of control experiments revealed the crucial role of the water for the successful conversions as well as the origin of the chemoselectivity and exclusive stereoselectivity.

On-Chip Template-Directed Conversion of Metal Hydroxides to Metal-Organic Framework Films with Enhanced Adhesion.

Interfacial compatibility between metal-organic framework (MOF) films and the underlying substrates determines the integrity of MOF films and their associated functions, and thus it has been gaining growing attention. Herein, we present a comparison of adhesion properties at the chip level of two disparate nickel (Ni)-MOF films, respectively, obtained by direct hydro/solvothermal growth and template-directed conversion approaches. We demonstrate that the on-chip delamination/corrugation of the films obtained by the direct growth approach can be circumvented by adopting the template-directed approach, which enables delicate dissolution of primarily grown nanoflaked nickel hydroxide (Ni(OH)2) films and thus triggers the controllable formation of Ni-MOF films. Successful on-chip conversions of Ni(OH)2 layers to different Ni-MOF thin films with good homogeneity, compactness, and appreciable affinity to the substrates are verified by multiple microscopic and spectroscopic techniques. Notably, the resultant Ni-MOF films do not show delamination even after activation with additional treatments, such as solvent soaking, nitrogen (N2) blowing for 1 h, and scotch-tape tests. As a demonstration of the application of MOF films, a Ni-NDC (NDC stands for 2,6-naphthalenedicarboxylate) MOF-coated sensor exhibits selective detection toward benzene vapor. This study highlights the importance of interfaces between MOF films and substrates and provides new perspectives for integrating MOF films onto microelectronic devices with robust adhesion for practical applications.

Are you still online or are you already mobile? – Predicting the path to successful conversions across different devices

As digitalization increases, retail firms must invest in online and mobile commerce to attract customers to their website or mobile store. Since the type of device used to access marketing channels influences conversions, this research examines the different impacts of different devices such as desktop computers, tablets, and smartphones on the success of various marketing channels. We find customer experience (CX) to be important in improving attribution outcomes (e.g., conversion rates) by combining clickstream and survey data to understand consumers’ decision processes. Therefore, this paper also conceptualizes and measures perceptions of CX of clickstream-data participants. We identify the central implications of using each device.

Total Syntheses of Ningalins D and G.

A flexible synthetic strategy for the total syntheses of ningalins D and G is described. The highly effective TMS-OTf/2,6-lutidine-mediated [3,3]-sigmatropic rearrangement of densely loaded dinaphthyl hydrazides and cyclization of the resulting 2,2'-diamino-1,1'-dinaphthyls afforded the key 7H-dibenzo[c,g]carbazole intermediates. Successful conversions to biphenylene quinone methides followed by regioselective brominations completed the total syntheses of the titled marine alkaloids.

No Heir apparent? Exploring the Worker Co-operative Model as a Solution to Family Business Continuity

Family businesses, with no apparent heir, face the risk of discontinuity. While a number of family businesses rely heavily on non-family employees, the role of non-family employees in the continuity of family businesses is under-researched. The workers’ co-operative model offers one way to address this gap as it represents a model whereby non-family employees gain a stake in ownership whilst the family remains involved. In practice, conversion to ensure continuity is actively promoted in a number of countries. In this paper, the authors explore the role of the workers’ co-operative model as one possible solution to succession difficulties facing family firms. Based on the reported experiences in a number of countries, we identify the motivations behind conversion, the barriers faced and the benefits accruing. We find that, in theory, the worker co-operative model merits the attention of family business scholars as a means of securing continuity and survival of family business. We explore the factors that appear to aid or hinder successful conversions in practice and we make recommendations to policy-makers surrounding the supports required to encourage and facilitate successful conversion.

Abstract 13503: Efficacy of Subcutaneous Implantable Cardioverter Defibrillator Defibrillation Testing in Hypertrophic Cardiomyopathy Patients at High Risk of Sudden Cardiac Death

Introduction: Subcutaneous ICD (S-ICD) is a promising option for Hypertrophic Cardiomyopathy (HCM) patients at high-risk of Sudden Cardiac Death (SCD). However, its efficacy in terminating ventricular arrhythmias in HCM is yet unresolved. Hypothesis: To determine the efficacy of post-implantation S-ICD defibrillation testing (DT) of Ventricular Fibrillation (VF) in HCM patients and assess possible predictors of failure. Methods: Consecutive HCM patients referred for S-ICD implantation at seven Italian Centers from June 2014 to May 2016 were prospectively enrolled. At S-ICD implantation, patients underwent one or two attempts of VF induction by programmed electrical stimulation. Successful conversion was defined as any 65j shock that terminated VF and did not require rescue shocks. Clinical, ECG and Echocardiographic findings were analyzed to study potential predictors of conversion failure. Results: We evaluated 50 HCM patients (34 males, mean age 40±16) with a mean BMI of 25.2±4.4 kg/m 2 [18.1-36]. Two patients (4%) had a history of cardiac arrest, whereas 48 (96%) were implanted in primary prevention. Mean calculated risk of SCD at 5 years by the ESC score was 6.5±3.9% and all patients had at least one major risk factor. Maximal LV wall thickness (LVMWT) was &gt;25 mm in 19 (38%) patients and ≥ 30 mm in 13 (26 %). In 2/50 patients (4%) no arrhythmias were inducible, while in 7 (14%) only polymorphic sustained ventricular tachycardia (SVT) was induced and correctly cardioverted by the S-ICD. In the remaining 41 (82%) patients, 70 VF episodes were induced (2 VF in 29 and 1 VF in 12 patients), all correctly recognized by the device. Of the 70 VFs, 4 (6%) spontaneously converted into sinus rhythm. In 65/66 (98%) the S-ICD performed successful conversions, but failed in 1 (2%) patient, who needed rescue defibrillation. This patient was severely obese, with a BMI 36 kg/m 2 and LVMWT of 25 mm. VF was induced again and successfully converted by 80j shock with inverted polarity. Conclusions: Acute defibrillation testing at 65j shows the efficacy of S-ICD in terminating VF or polymorphic SVT in HCM patients, despite the presence of extreme LV hypertrophy. Severe obesity was possibly responsible for the single failure observed at 65j in our series.

Monofunctionalized Cobaltocenium Compounds by Dediazoniation Reactions of Cobaltoceniumdiazonium Bis(hexafluorophosphate)

Monofunctionalized cobaltocenium salts are obtained for the first time from cobaltoceniumdiazonium bis(hexafluorophosphate) with various nucleophiles via Sandmeyer-type and related reactions. For successful conversions, reaction conditions are quite critical: either standard solution chemistry in nitromethane or solvent-free ball milling proved necessary, depending on the type of reactant. By this synthetic approach valuable synthons such as iodocobaltocenium and azidocobaltocenium salts are accessible that open up new vistas in cobaltocenium chemistry. Spectroscopic characterization by NMR, IR, HRMS, and single-crystal structure analysis as well as the results of electrochemical studies are reported. Derivatives with two reversible reductions show the expected relation of the half-wave potentials with the Hammett substituent parameter σp of the respective substituent with a slightly larger slope for the first reduction. The carboxylic acid (reductive deprotonation of the −COOH functionality), the iodo (p...

Asymmetric Functional Conversion of Eubacterial Light-driven Ion Pumps

In addition to the well-known light-driven outward proton pumps, novel ion-pumping rhodopsins functioning as outward Na(+) and inward Cl(-) pumps have been recently found in eubacteria. They convert light energy into transmembrane electrochemical potential difference, similar to the prototypical archaeal H(+) pump bacteriorhodopsin (BR) and Cl(-) pump halorhodopsin (HR). The H(+), Na(+), and Cl(-) pumps possess the conserved respective DTE, NDQ, and NTQ motifs in the helix C, which likely serve as their functional determinants. To verify this hypothesis, we attempted functional interconversion between selected pumps from each category by mutagenesis. Introduction of the proton-pumping motif resulted in successful Na(+) → H(+) functional conversion. Introduction of the respective characteristic motifs with several additional mutations leads to successful Na(+) → Cl(-) and Cl(-) → H(+) functional conversions, whereas remaining conversions (H(+) → Na(+), H(+) → Cl(-), Cl(-) → Na(+)) were unsuccessful when mutagenesis of 4-6 residues was used. Phylogenetic analysis suggests that a H(+) pump is the common ancestor of all of these rhodopsins, from which Cl(-) pumps emerged followed by Na(+) pumps. We propose that successful functional conversions of these ion pumps are achieved exclusively when mutagenesis reverses the evolutionary amino acid sequence changes. Dependence of the observed functional conversions on the direction of evolution strongly suggests that the essential structural mechanism of an ancestral function is retained even after the gain of a new function during natural evolution, which can be evoked by a few mutations. By contrast, the gain of a new function needs accumulation of multiple mutations, which may not be easily reproduced by limited mutagenesis in vitro.

Type 1 Ring-Opening Reactions of Cyclopropanated 7-Azabenzonorbornadienes with Organocuprates.

The first nucleophilic ring-opening reactions of cyclopropanated 7-azabenzonorbornadienes have been achieved using organocuprates. Tricyclic or tetracyclic γ-lactams were obtained as the sole product in good yields of up to 98% when alkoxycarbonyl groups occupied the N-substituent position. Successful conversions to lactams were observed for primary, secondary, tertiary, and aromatic nucleophiles, as well as for a variety of substrates functionalized on the benzene ring. A possible mechanism for these transformations is discussed.