Kinetic characterization of the critical step in HIV-1 protease maturation

HIV maturation requires multiple cleavage of long polyprotein chains into functional proteins that include the viral protease itself. Initial cleavage by the protease dimer occurs from within these precursors, and yet only a single protease monomer is embedded in each polyprotein chain. Self-activation has been proposed to start from a partially dimerized protease formed from monomers of different chains binding its own N termini by self-association to the active site, but a complete structural understanding of this critical step in HIV maturation is missing. Here, we captured the critical self-association of immature HIV-1 protease to its extended amino-terminal recognition motif using large-scale molecular dynamics simulations, thus confirming the postulated intramolecular mechanism in atomic detail. We show that self-association to a catalytically viable state requires structural cooperativity of the flexible β-hairpin “flap” regions of the enzyme and that the major transition pathway is first via self-association in the semiopen/open enzyme states, followed by enzyme conformational transition into a catalytically viable closed state. Furthermore, partial N-terminal threading can play a role in self-association, whereas wide opening of the flaps in concert with self-association is not observed. We estimate the association rate constant (k(on)) to be on the order of ∼1 × 10(4) s(−1), suggesting that N-terminal self-association is not the rate-limiting step in the process. The shown mechanism also provides an interesting example of molecular conformational transitions along the association pathway

Coherent states for polynomial su(1,1) algebra and a conditionally solvable system

In a previous paper [{\it J. Phys. A: Math. Theor.} {\bf 40} (2007) 11105], we constructed a class of coherent states for a polynomially deformed $su(2)$ algebra. In this paper, we first prepare the discrete representations of the nonlinearly deformed $su(1,1)$ algebra. Then we extend the previous procedure to construct a discrete class of coherent states for a polynomial su(1,1) algebra which contains the Barut-Girardello set and the Perelomov set of the SU(1,1) coherent states as special cases. We also construct coherent states for the cubic algebra related to the conditionally solvable radial oscillator problem.Comment: 2 figure

Hepatitis B testing and treatment in HIV patients in The Gambia - compliance with international guidelines and clinical outcomes

Background Compliance with WHO guidelines on HBV screening and treatment in HIV-coinfected patients is often challenging in resource limited countries and has been poorly assessed in sub-Saharan Africa. Methods Between 2015 and 2016, we assessed physician’s compliance with WHO guidelines on HIV-HBV coinfection in the largest HIV clinic in The Gambia, and the hepatic outcomes in HIV-HBV coinfected patients as compared to randomly selected HIV-monoinfected controls. Results 870 HIV-infected patients regularly seen in this clinic agreed to participate in our study. Only 187 (21.5%, 95% CI 18.8–24.3) had previously been screened for HBsAg, 23 (12.3%, 95% CI 8.0–17.9) were positive of whom none had liver assessment and only 6 (26.1%) had received Tenofovir. Our HBV testing intervention was accepted by all participants and found 94/870 (10.8%, 95% CI 8.8–13.1) positive, 78 of whom underwent full liver assessment along with 40 HBsAg-negative controls. At the time of liver assessment, 61/78 (78.2%) HIV-HBV coinfected patients received ART with 7 (11.5%) on Tenofovir and 54 (88.5%) on Lamivudine alone. HIV-HBV coinfected patients had higher APRI score compared to controls (0.58 vs 0.42, p = 0.002). HBV DNA was detectable in 52/53 (98.1%) coinfected patients with 14/53 (26.4%) having HBV DNA >20,000 IU/L. 10/12 (83.3%) had at least one detectable 3TC-associated HBV resistance, which tended to be associated with increase in liver fibrosis after adjusting for age and sex (p = 0.05). Conclusions Compliance with HBV testing and treatment guidelines is poor in this Gambian HIV programme putting coinfected patients at risk of liver complications. However, the excellent uptake of HBV screening and linkage to care in our study suggests feasible improvements

Anisotropic dynamical scaling in a spin model with competing interactions

Results are presented for the kinetics of domain growth of a two-dimensional Ising spin model with competing interactions quenched from a disordered to a striped phase. The domain growth exponent are $\beta=1/2$ and $\beta=1/3$ for single-spin-flip and spin-exchange dynamics, as found in previous simulations. However the correlation functions measured in the direction parallel and transversal to the stripes are different as suggested by the existence of different interface energies between the ground states of the model. In the case of single-spin-flip dynamics an anisotropic version of the Ohta-Jasnow-Kawasaki theory for the pair scaling function can be used to fit our data.Comment: 4 pages, REVTeX fil

Efficient Compliance Checking Using BPMN-Q and Temporal Logic

Abstract. Compliance rules describe regulations, policies and quality constraints business processes must adhere to. Given the large number of rules and their frequency of change, manual compliance checking can be-come a time-consuming task. Automated compliance checking of process activities and their ordering is an alternative whenever business pro-cesses and compliance rules are described in a formal way. This paper introduces an approach for automated compliance checking. Compliance rules are translated into temporal logic formulae that serve as input to model checkers which in turn verify whether a process model satisfies the requested compliance rule. To address the problem of state-space explo-sion we employ a set of reduction rules. The approach is prototypically realized and evaluated.

High Level Synthesis of Controllers for Communication Protocols

Petri nets are popular in the communication protocol community for modelling and analysis purposes. This paper gives a procedure for implementation of controllers in hardware from a high level Petri net model. With this the entire design-analysis-implementation cycle for protocols can be petri net based. It is especially suited for data link, network, transport layer protocols

VLSI Implementation of Controllers for Communication Protocols from their Petri Net Models

Petri nets are popular in the communication protocol community for modelling and analysis purposees. This paper gives a procedure for extraction and implementation of controllers of protocols from thier Petri net model. IOt adds another dimension tot he use of Petri nets and is suited for Network, Transport and Data link protocols

A novel technique for fast multiplication

In this paper we present the design of a new high-speed multiplication unit. The design is based on non-overlapped scanning of 3-bit ® elds of the multiplier. In this technique the partial products of the multiplicand and three bits of the multiplier are pre-calculated using only hardwired shifts. These partial products are then added using a tree of carry-save-adders, and ® nally the sum and carry vectors are added using a carry-lookahead adder. In the case of 2 s complement multiplication the tree of carry-save-adders also receives a correction output produced in parallel with the partial products. The algorithm is modelled in a hardware description language and its VLSI chip implemented. The performance of the new design is comparedwith that of other recent ones proposed in literature