238 research outputs found
Parameter Mismatches and Perfect Anticipating Synchronization in bi-directionally coupled external cavity laser diodes
We study perfect chaos synchronization between two bi-directionally coupled
external cavity semiconductor lasers and demonstrate for the first time that
mismatches in laser photon decay rates can explain the experimentally observed
anticipating time in synchronization.Comment: Latex 4 page
Service innovation - lessons from modularization and open innovation - a new service value
The traditional manufacturing model of volume-variety influencing the conduct of business is not entirely representative of service-centric business. The latter has two key differences â it is much more end-user centric and individualistic in experience. The complex nature of service attributes also make it much more convoluted. The notion of product being the centre of interaction is being replaced with service processes involving participants and generally defined between a service provider and service consumer. The aim of this paper is to validate the service innovation hypotheses put forward based on significant developments in value networks, open interfaces, and business models recently. In doing so, this theoretical paper substantiates the claim that prescriptive volume-variety relationships are little meaningful in service delivery environment
Inverse Anticipating Synchronization
We report a new type of chaos synchronization:inverse anticipating
synchronization, where a time delay chaotic system can drive another system in
such a way that the driven system anticipates the driver by synchronizing with
its inverse future state. We extend the concept of inverse anticipating chaos
synchronization to cascaded systems. We propose means for the experimental
observation of inverse anticipating chaos synchronization in external cavity
lasers.Comment: LaTex 6 pages, resubmitted to PR
Lag time and parameter mismatches in synchronization of unidirectionally coupled chaotic external cavity semiconductor lasers
We report an analysis of synchronization between two unidirectionally coupled
chaotic external cavity master/slave semiconductor lasers with two
characteristic delay times, where the delay time in the coupling is different
from the delay time in the coupled systems themselves. We demonstrate for the
first time that parameter mismatches in photon decay rates for the master and
slave lasers can explain the experimental observation that the lag time is
equal to the coupling delay time.Comment: LaTex, 5 pages, submitted to PRE(R
Anticipating the dynamics of chaotic maps
We study the regime of anticipated synchronization in unidirectionally
coupled chaotic maps such that the slave map has its own output reinjected
after a certain delay. For a class of simple maps, we give analytic conditions
for the stability of the synchronized solution, and present results of
numerical simulations of coupled 1D Bernoulli-like maps and 2D Baker maps, that
agree well with the analytic predictions.Comment: Uses the elsart.cls (v2000) style (included). 9 pages, including 4
figures. New version contains minor modifications to text and figure
Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation
BACKGROUND
Polyomavirus-associated nephropathy is a leading cause of kidney allograft failure. Therapeutic options are limited and prompt reduction of the net state of immunosuppression represents the mainstay of treatment. More recent application of aggressive screening and management protocols for BK-virus infection after renal transplantation has shown encouraging results. Nevertheless, long-term outcome for patients with BK-viremia and nephropathy remains obscure. Risk factors for BK-virus infection are also unclear.
AIM
To investigate incidence, risk factors, and outcome of BK-virus infection after kidney transplantation.
METHODS
This single-centre observational study with a median follow up of 57 (31-80) mo comprises 629 consecutive adult patients who underwent kidney transplantation between 2007 and 2013. Data were prospectively recorded and annually reviewed until 2016. Recipients were periodically screened for BK-virus by plasma quantitative polymerized chain reaction. Patients with BK viral load >= 1000 copies/mL were diagnosed BK-viremia and underwent histological assessment to rule out nephropathy. In case of BK-viremia, immunosuppression was minimized according to a prespecified protocol. The following outcomes were evaluated: patient survival, overall graft survival, graft failure considering death as a competing risk, 30-d-event-censored graft failure, response to treatment, rejection, renal function, urologic complications, opportunistic infections, new-onset diabetes after transplantation, and malignancies. We used a multivariable model to analyse risk factors for BK-viremia and nephropathy.
RESULTS
BK-viremia was detected in 9.5% recipients. Initial viral load was high (>= 10000 copies/mL) in 66.7% and low (= 50% (30% vs 14.6%, P = 0.0047), human leukocyte antigen (HLA) mismatching > 4 (26.7% vs 13.4%, P = 0.0110), and rejection within thirty days of transplant (21.7% vs 9.5%; P = 0.0073) was higher in the viremic group. Five-year patient and overall graft survival rates for patients with or without BK-viremia were similar. However, viremic recipients showed higher 5-year crude cumulative (22.5% vs 12.2%, P = 0.0270) and 30-d-event-censored (22.5% vs 7.1%, P = 0.001) incidences of graft failure than control. In the viremic group we also observed higher proportions of recipients with 5-year estimated glomerular filtration rate 50%, HLA mismatching > 4, and rejection were independent risk factors for BK-virus viremia whereas cytomegalovirus prophylaxis was protective.
CONCLUSION
Current treatment of BK-virus infection offers sub-optimal results. Initial viremia is a valuable parameter to detect patients at increased risk of nephropathy. Panel-reactive antibody > 50% and Afro-Caribbean ethnicity are independent predictors of BK-virus infection whereas cytomegalovirus prophylaxis has a protective effect
2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase
Renewed interest in covalent inhibitors of enzymes implicated in disease states has afforded several agents targeted at protein kinases of relevance to cancers. We now report the design, synthesis and biological evaluation of 6-ethynylpurines that act as covalent inhibitors of Nek2 by capturing a cysteine residue (Cys22) close to the catalytic domain of this protein kinase. Examination of the crystal structure of the non-covalent inhibitor 3-((6-cyclohexylmethoxy-7H-purin-2-yl)amino)benzamide in complex with Nek2 indicated that replacing the alkoxy with an ethynyl group places the terminus of the alkyne close to Cys22 and in a position compatible with the stereoelectronic requirements of a Michael addition. A series of 6-ethynylpurines was prepared and a structure activity relationship (SAR) established for inhibition of Nek2. 6-Ethynyl-N-phenyl-7H-purin-2-amine [IC50 0.15 μM (Nek2)] and 4-((6-ethynyl-7H-purin-2-yl)amino)benzenesulfonamide (IC50 0.14 μM) were selected for determination of the mode of inhibition of Nek2, which was shown to be time-dependent, not reversed by addition of ATP and negated by site directed mutagenesis of Cys22 to alanine. Replacement of the ethynyl group by ethyl or cyano abrogated activity. Variation of substituents on the N-phenyl moiety for 6-ethynylpurines gave further SAR data for Nek2 inhibition. The data showed little correlation of activity with the nature of the substituent, indicating that after sufficient initial competitive binding to Nek2 subsequent covalent modification of Cys22 occurs in all cases. A typical activity profile was that for 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide [IC50 0.06 μM (Nek2); GI50 (SKBR3) 2.2 μM] which exhibited >5–10-fold selectivity for Nek2 over other kinases; it also showed > 50% growth inhibition at 10 μM concentration against selected breast and leukaemia cell lines. X-ray crystallographic analysis confirmed that binding of the compound to the Nek2 ATP-binding site resulted in covalent modification of Cys22. Further studies confirmed that 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide has the attributes of a drug-like compound with good aqueous solubility, no inhibition of hERG at 25 μM and a good stability profile in human liver microsomes. It is concluded that 6-ethynylpurines are promising agents for cancer treatment by virtue of their selective inhibition of Nek2
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