Catalytic site forms and controls in ATP synthase catalysis

AbstractA suggested minimal scheme for substrate binding by and interconversion of three forms of the catalytic sites of the ATP synthase is presented. Each binding change, that drives simultaneous interchange of the three catalytic site forms, requires a 120° rotation of the γ with respect to the β subunits. The binding of substrate(s) at two catalytic sites is regarded as sufficing for near maximal catalytic rates to be attained. Although three sites do not need to be filled for rapid catalysis, during rapid bisite catalysis some enzyme may be transiently present with three sites filled. Forms with preferential binding for ADP and Pi or for ATP are considered to arise from the transition state and participate in other steps of the catalysis. Intermediate forms and steps that may be involved are evaluated. Experimental evidence for energy-dependent steps and for control of coupling to proton translocation and transition state forms are reviewed. Impact of relevant past data on present understanding of catalytic events is considered. In synthesis a key step is suggested in which proton translocation begins to deform an open site so as to increase the affinity for ADP and Pi, that then bind and pass through the transition state, and yield tightly bound ATP in one binding change. ADP binding appears to be a key parameter controlling rotation during synthesis. In hydrolysis ATP binding to a loose site likely precedes any proton translocation, with proton movement occurring as the tight site form develops. Aspects needing further study are noted. Characteristics of the related MgADP inhibition of the F1 ATPases that have undermined many observations are summarized, and relations of three-site filling to catalysis are assessed

Squeezed Light and Entangled Images from Four-Wave-Mixing in Hot Rubidium Vapor

Entangled multi-spatial-mode fields have interesting applications in quantum information, such as parallel quantum information protocols, quantum computing, and quantum imaging. We study the use of a nondegenerate four-wave mixing process in rubidium vapor at 795 nm to demonstrate generation of quantum-entangled images. Owing to the lack of an optical resonator cavity, the four-wave mixing scheme generates inherently multi-spatial-mode output fields. We have verified the presence of entanglement between the multi-mode beams by analyzing the amplitude difference and the phase sum noise using a dual homodyne detection scheme, measuring more than 4 dB of squeezing in both cases. This paper will discuss the quantum properties of amplifiers based on four-wave-mixing, along with the multi mode properties of such devices.Comment: 11 pages, 8 figures. SPIE Optics and Photonics 2008 proceeding (San Diego, CA

Demonstration of images with negative group velocities

We report the experimental demonstration of the superluminal propagation of multi-spatial-mode images via four-wave mixing in hot atomic vapor, in which all spatial sub-regions propagate with negative group velocities. We investigate the spatial mode properties and temporal reshaping of the fast light images, and show large relative pulse peak advancements of up to 64% of the input pulse width. The degree of temporal reshaping is quantified and increases as the relative pulse peak advancement increases. When optimized for image quality or pulse advancement, negative group velocities of up to $v_{g}=-\frac{c}{880}$ and $v_{g}=-\frac{c}{2180}$, respectively, are demonstrated when integrating temporally over the entire image. The present results are applicable to temporal cloaking devices that require strong manipulation of the dispersion relation, where one can envision temporally cloaking various spatial regions of an image for different durations. Additionally, the modes involved in a four-wave mixing process similar to the present experiment have been shown to exhibit quantum correlations and entanglement. The results presented here provide insight into how to tailor experimental tests of the behavior of these quantum correlations and entanglement in the superluminal regime.Comment: 9 pages, 4 figure

Imaging using quantum noise properties of light

We show that it is possible to estimate the shape of an object by measuring only the fluctuations of a probing field, allowing us to expose the object to a minimal light intensity. This scheme, based on noise measurements through homodyne detection, is useful in the regime where the number of photons is low enough that direct detection with a photodiode is difficult but high enough such that photon counting is not an option. We generate a few-photon state of multi-spatial-mode vacuum-squeezed twin beams using four-wave mixing and direct one of these twin fields through a binary intensity mask whose shape is to be imaged. Exploiting either the classical fluctuations in a single beam or quantum correlations between the twin beams, we demonstrate that under some conditions quantum correlations can provide an enhancement in sensitivity when estimating the shape of the object

Extrapleural pneumonectomy for malignant pleural mesothelioma: Outcomes of treatment and prognostic factors

ObjectiveThis study aimed to evaluate the perioperative and long-term outcomes associated with extrapleural pneumonectomy for patients with malignant pleural mesothelioma.MethodsFrom October 1994 to April 2008, 70 patients were selected for extrapleural pneumonectomy. Univariate analysis was performed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analysis with entering and removing limits of P less than .10 and P greater than .05, respectively, was used. The prognostic factors included age, gender, side of disease, asbestos exposure, histology, positron emission tomography, date of surgery, neoadjuvant chemotherapy, completeness of cytoreduction, lymph node involvement, perioperative morbidity, adjuvant radiotherapy, and pemetrexed-based chemotherapy.ResultsThe mean age of patients was 55 years (standard deviation = 10). Fifty-eight patients had epithelial tumors. Six patients received neoadjuvant chemotherapy, 28 patients received adjuvant radiotherapy, and 16 patients received postoperative pemetrexed-based chemotherapy. Forty-four patients had no lymph node involvement. The perioperative morbidity and mortality were 37% and 5.7%, respectively. Complications included hemothorax (n = 7), atrial fibrillation (n = 6), empyema (n = 4), bronchopulmonary fistula (n = 3), right-sided heart failure (n = 2), pneumonia (n = 1), constrictive pericarditis (n = 1), acute pulmonary edema (n = 1), small bowel herniation (n = 1), and disseminated intravascular coagulopathy (n = 1). The median survival was 20 months, with a 3-year survival of 30%. Asbestos exposure, negative lymph node involvement, and receipt of adjuvant radiation or postoperative pemetrexed-based chemotherapy were associated with improved survival on both univariate and multivariate analyses.ConclusionThe present study supports the use of extrapleural pneumonectomy-based multimodal therapy in carefully selected patients with malignant pleural mesothelioma

Author Correction: Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Trends in Clinical, Demographic, and Biochemical Characteristics of Patients with Acute Myocardial Infarction from 2003 to 2008: A Report from the American Heart Association Get with the Guidelines Coronary Artery Disease Program

Background: An analysis of the changes in the clinical and demographic characteristics of patients with acute myocardial infarction could identify successes and failures of risk factor identification and treatment of patients at increased risk for cardiovascular events. Methods and results: We reviewed data collected from 138 122 patients with acute myocardial infarction admitted from 2003 to 2008 to hospitals participating in the American Heart Association Get With The Guidelines Coronary Artery Disease program. Clinical, demographic, and laboratory characteristics were analyzed for each year stratified on the electrocardiogram at presentation. Patients with non–ST-segment–elevation myocardial infarction were older, more likely to be women, and more likely to have hypertension, diabetes mellitus, and a history of past cardiovascular disease than were patients with ST-elevation myocardial infarction. In the overall patient sample, significant trends were observed of an increase over time in the proportions of non–ST-segment–elevation myocardial infarction, patient age of 45 to 65 years, obesity, and female sex. The prevalence of diabetes mellitus decreased over time, whereas the prevalences of hypertension and smoking were substantial and unchanging. The prevalence of “low” high-density lipoprotein increased over time, whereas that of “high” low-density lipoprotein decreased. Stratum-specific univariate analysis revealed quantitative and qualitative differences between strata in time trends for numerous demographic, clinical, and biochemical measures. On multivariable analysis, there was concordance between strata with regard to the increase in prevalence of patients 45 to 65 years of age, obesity, and “low” high-density lipoprotein and the decrease in prevalence of “high” low-density lipoprotein. However, changes in trends in age distribution, sex ratio, and prevalence of smokers and the magnitude of change in diabetes mellitus prevalence differed between strata. Conclusions: There were notable differences in risk factors and patient characteristics among patients with ST-elevation myocardial infarction and those with non–ST-segment–elevation myocardial infarction. The increasing prevalence of dysmetabolic markers in a growing proportion of patients with acute myocardial infarction suggests further opportunities for risk factor modification

Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design

HIV-1 reverse transcriptase (RT) is a primary target for anti-AIDS drugs. Structures of HIV-1 RT, usually determined at ∼2.5–3.0 Å resolution, are important for understanding enzyme function and mechanisms of drug resistance in addition to being helpful in the design of RT inhibitors. Despite hundreds of attempts, it was not possible to obtain the structure of a complex of HIV-1 RT with TMC278, a nonnucleoside RT inhibitor (NNRTI) in advanced clinical trials. A systematic and iterative protein crystal engineering approach was developed to optimize RT for obtaining crystals in complexes with TMC278 and other NNRTIs that diffract X-rays to 1.8 Å resolution. Another form of engineered RT was optimized to produce a high-resolution apo-RT crystal form, reported here at 1.85 Å resolution, with a distinct RT conformation. Engineered RTs were mutagenized using a new, flexible and cost effective method called methylated overlap-extension ligation independent cloning. Our analysis suggests that reducing the solvent content, increasing lattice contacts, and stabilizing the internal low-energy conformations of RT are critical for the growth of crystals that diffract to high resolution. The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs