DNA looping and translocation provide an optimal cleavage mechanism for the type III restriction enzymes

EcoP15I is a type III restriction enzyme that requires two recognition sites in a defined orientation separated by up to 3.5 kbp to efficiently cleave DNA. The mechanism through which site- bound EcoP15I enzymes communicate between the two sites is unclear. Here, we use atomic force microscopy to study EcoP15I-DNA pre-cleavage complexes. From the number and size distribution of loops formed, we conclude that the loops observed do not result from translocation, but are instead formed by a contact between site- bound EcoP15I and a nonspecific region of DNA. This conclusion is confirmed by a theoretical polymer model. It is further shown that translocation must play some role, because when translocation is blocked by a Lac repressor protein, DNA cleavage is similarly blocked. On the basis of these results, we present a model for restriction by type III restriction enzymes and highlight the similarities between this and other classes of restriction enzymes.

Testing and Modeling of MR Damper and Its Application to SDOF Systems Using Integral Backstepping Technique

Magnetorheological dampers are intrinsically nonlinear devices, which make the modeling and design of a suitable control algorithm an interesting and challenging task. To evaluate the potential of magnetorheological (MR) dampers in control applications and to take full advantages of its unique features, a mathematical model to accurately reproduce its dynamic behavior has to be developed and then a proper control strategy has to be taken that is implementable and can fully utilize their capabilities as a semi-active control device. The present paper focuses on both the aspects. First, the paper reports the testing of a magnetorheological damper with an universal testing machine, for a set of frequency, amplitude, and current. A modified Bouc-Wen model considering the amplitude and input current dependence of the damper parameters has been proposed. It has been shown that the damper response can be satisfactorily predicted with this model. Second, a backstepping based nonlinear current monitoring of magnetorheological dampers for semi-active control of structures under earthquakes has been developed. It provides a stable nonlinear magnetorheological damper current monitoring directly based on system feedback such that current change in magnetorheological damper is gradual. Unlike other MR damper control techniques available in literature, the main advantage of the proposed technique lies in its current input prediction directly based on system feedback and smooth update of input current. Furthermore, while developing the proposed semi-active algorithm, the dynamics of the supplied and commanded current to the damper has been considered. The efficiency of the proposed technique has been shown taking a base isolated three story building under a set of seismic excitation. Comparison with widely used clipped-optimal strategy has also been shown.

Ventricular repolarization during cardiovascular autonomic function testing

The autonomic nervous system is an important modulator of ventricular repolarization and arrhythmia vulnerability. This study explored the effects of cardiovascular autonomic function tests on repolarization and its heterogeneity, with a special reference to congenital arrhythmogenic disorders typically associated with stress-induced fatal ventricular arrhythmias. The first part explored the effects of standardized autonomic tests on QT intervals in a 12-lead electrocardiogram and in multichannel magnetocardiography in 10 healthy adults. The second part studied the effects of deep breathing, Valsalva manouvre, mental stress, sustained handgrip and mild exercise on QT intervals in asymptomatic patients with LQT1 subtype of the hereditary long QT syndrome (n=9) and in patients with arrhythmogenic right ventricular dysplasia (ARVD, n=9). Even strong sympathetic activation had no effects on spatial QT interval dispersion in healthy subjects, but deep respiratory efforts and Valsalva influenced it in ways that were opposite in electrocardiographic and magnetocardiographic recordings. LQT1 patients showed blunted QT interval and sinus nodal responses to sympathetic challenge, as well as an exaggerated QT prolongation during the recovery phases. LQT1 patients showed a QT interval recovery overshoot in 2.4 ± 1.7 tests compared with 0.8 ± 0.7 in healthy controls (P = 0.02). Valsalva strain prolonged the T wave peak to T wave end interval only in the LQT1 patients, considered to reflect the arrhythmogenic substrate in this syndrome. ARVD patients showed signs of abnormal repolarization in the right ventricle, modulated by abrupt sympathetic activation. An electrocardiographic marker reflecting interventricular dispersion of repolarization was introduced. It showed that LQT1 patients exhibit a repolarization gradient from the left ventricle towards the right ventricle, significantly larger than in controls. In contrast, ARVD patients showed a repolarization gradient from the right ventricle towards the left. Valsalva strain amplified the repolarization gradient in LQT1 patients whereas it transiently reversed it in patients with ARVD. In conclusion, intrathoracic volume and pressure changes influence regional electrocardiographic and magnetocardiographic QT interval measurements differently. Especially recovery phases of standard cardiovascular autonomic functions tests and Valsalva manoeuvre reveal the abnormal repolarization in asymptomatic LQT1 patients. Both LQT1 and ARVD patients have abnormal interventricular repolarization gradients, modulated by abrupt sympathetic activation. Autonomic testing and in particular the Valsalva manoeuvre are potentially useful in unmasking abnormal repolarization in these syndromes.

Leveraging Partially Enhanced Scan for Improved Observability in Delay Fault Testing

Enhanced Scan design can significantly improve the fault coverage for two pattern delay tests at the cost of exorbitantly high area overhead. The redundant flip-flops introduced in the scan chains have traditionally only been used to launch the two-pattern delay test inputs, not to capture tests results. This paper presents a new, much lower cost partial Enhanced Scan methodology with both improved controllability and observability. Facilitating observation of some hard to observe internal nodes by capturing their response in the already available and underutilized redundant flip-flops improves delay fault coverage with minimal or almost negligible cost. Experimental results on ISCAS'89 benchmark circuits show significant improvement in TDF fault coverage for this new partial enhance scan methodology.

Multi-Tone Testing of Linear and Nonlinear Analog Circuits using Polynomial Coefficients

A method of testing for parametric faults of analog circuits based on a polynomial representation of fault-free function of the circuit is presented. The response of the circuit under test (CUT) is estimated as a polynomial in the applied input voltage at relevant frequencies in addition to DC. Classification or Cur is based on a comparison of the estimated polynomial coefficients with those of the fault free circuit. This testing method requires no design for test hardware as might be added to the circuit fly some other methods. The proposed method is illustrated for a benchmark elliptic filter. It is shown to uncover several parametric faults causing deviations as small as 5% from the nominal values.

Developing and testing readability measurements for second language learners

This research constructed a readability measurement for French speakers who view English as a second language. It identified the true cognates, which are the similar words from these two languages, as an indicator of the difficulty of an English text for French people. A multilingual lexical resource is used to detect true cognates in text, and Statistical Language Modelling to predict the predict the readability level. The proposed enhanced statistical language model is making a step in the right direction by improving the accuracy of readability predictions for French speakers by up to 10% compared to state of the art approaches. The outcome of this study could accelerate the learning process for French speakers who are studying English. More importantly, this study also benefits the readability estimation research community, presenting an approach and evaluation at sentence level as well as innovating with the use of cognates as a new text feature.

Testing against changing correlation

A test for time-varying correlation is developed within the framework of a dynamic conditional score (DCS) model for both Gaussian and Student t-distributions. The test may be interpreted as a Lagrange multiplier test and modified to allow for the estimation of models for time-varying volatility in the individual series. Unlike standard moment-based tests, the score-based test statistic includes information on the level of correlation under the null hypothesis and local power arguments indicate the benefits of doing so. A simulation study shows that the performance of the score-based test is strong relative to existing tests across a range of data generating processes. An application to the Hong Kong and South Korean equity markets shows that the new test reveals changes in correlation that are not detected by the standard moment-based test.

Synthesis of Cu@ZnO Core−Shell Nanocomposite through Digestive Ripening of Cu and Zn Nanoparticles

The synthesis of colloids of copper and zinc nanoparticles by solvated metal atom dispersion (SMAD) is described. The as-prepared colloids with a large size distribution of the particles are transformed into colloidal nanoparticles of a narrow size distribution by the digestive ripening process which involves refluxing the colloid at or near the boiling point of the solvent in the presence of a passivating ligand. The copper nanoparticles of 2.1 ± 0.3 nm and zinc nanoparticles of 3.9 ± 0.3 nm diameters have thus been obtained. Digestive ripening of the as-prepared copper and zinc colloids together in the presence of a passivating agent gave Cu@ZnO core−shell nanoparticles, with an average diameter of 3.0 ± 0.7 nm. Particles synthesized in this manner were characterized by UV−visible spectroscopy, high-resolution electron microscopy, energy-filtered electron microscopy, and powder X-ray diffraction methods which confirm the core−shell structure.

Boarding control system for improved accessibility to offshore wind turbines: Full-scale testing

This paper considers the dynamic modelling and motion control of a Surface Effect Ship (SES) for safer transfer of personnel and equipment from vessel to-and-from an offshore wind-turbine. The control system designed is referred to as Boarding Control System (BCS). The performance of this system is investigated for a specific wind-farm service vessel—The Wave Craft. On a SES, the pressurized air cushion supports the majority of the weight of the vessel. The control problem considered relates to the actuation of the pressure such that wave-induced vessel motions are minimized. Results are given through simulation, model- and full-scale experimental testing.

Metabolic enzymes as potential drug targets in Plasmodium falciparum.

Plasmodium falciparum causes the most severe form of malaria that is fatal in many cases. Emergence of drug resistant strains of P. falciparum requires that new drug targets be-identified. This review considers in detail enzymes of the glycolytic pathway, purine salvage pathway, pyrimidine biosynthesis and proteases involved in catabolism of haemoglobin. Structural features of P. falciparum triosephosphate isomerase which could be exploited for parasite specific drug development have been highlighted. Utility of P. falciparum hypoxanthine-guanine-phosphoribosyltransferase, adenylosuccinate synthase, dihydroorotate dehydrogenase, thymidylate synthase-dihydrofolate reductase, cysteine and aspartic proteases have been elaborated in detail. The review also briefly touches upon other potential targets in P. falciparum