Measuring the transmission phase of a quantum dot in a closed interferometer

The electron transmission through a closed Aharonov-Bohm mesoscopic solid-state interferometer, with a quantum dot (QD) on one of the paths, is calculated exactly for a simple model. Although the conductance is an even function of the magnetic flux (due to Onsager's relations), in many cases one can use the measured conductance to extract both the amplitude and the phase of the "intrinsic" transmission amplitude t(D)=-i|t(D)|e(ialpha(D)) through the "bare" QD. We also propose to compare this indirect measurement with the (hitherto untested) direct relation sin((2)(alpha(D)) identical with |t(D)|(2)/max((|t(D)|(2)).     

Hydrolytic reactions of guanosyl-(3',3')-uridine and guanosyl-(3',3')-(2',5'-di-O-methyluridine)

Hydrolytic reactions of guanosyl-(3',3')-uridine and guanosyl-(3',3')-(2',5'-di-O-methyluridine) have been followed by RP HPLC over a wide pH range at 363.2 K in order to elucidate the role of the 2'-hydroxyl group as a hydrogen-bond donor upon departure of the 3'-uridine moiety. Under neutral and basic conditions, guanosyl-(3',3')-uridine undergoes hydroxide ion-catalyzed cleavage (first order in [OH(-)]) of the P-O3' bonds, giving uridine and guanosine 2',3'-cyclic monophosphates, which are subsequently hydrolyzed to a mixture of 2'- and 3'-monophosphates. This bond rupture is 23 times as fast as the corresponding cleavage of the P-O3' bond of guanosyl-(3',3')-(2',5'-di-O-methyluridine) to yield 2',5'-O-dimethyluridine and guanosine 2',3'-cyclic phosphate. Under acidic conditions, where the reactivity differences are smaller, depurination and isomerization compete with the cleavage. The effect of Zn(2+) on the cleavage of the P-O3' bonds of guanosyl-(3',3')-uridine is modest: about 6-fold acceleration was observed at [Zn(2+)] = 5 mmol L(-)(1) and pH 5.6. With guanosyl-(3',3')-(2',5'-di-O-methyluridine) the rate-acceleration effect is greater: a 37-fold acceleration was observed. The mechanisms of the partial reactions, in particular the effects of the 2'-hydroxyl group on the departure of the 3'-linked nucleoside, are discussed.     

THE ROLE OF CYCLIC ELECTRON FLOW AROUND PHOTOSYSTEM I and EXCITATION ENERGY DISTRIBUTION BETWEEN THE PHOTOSYSTEMS UPON ACCLIMATION TO HIGH IONIC STRESS IN Dunaliella salina

Abstract— The distribution of excitation energy between the two photosystems in the halophylic alga Dunaliella salina has been analyzed under ionic stress. In the transition from state 1 to state 2, it was found that a, the absorption cross-section of photosystem (PS) I increased from 42 to 49% until an equal distribution between PS I and PS II was obtained in state 2. Acclimation of the algae to different salt concentrations did not change the fractions of light absorbed in PS II and PS I, but slowed down the transition time from state 1 to state 2. A large increase in ΔpH induced fluorescence quenching was observed which was abolished by the uncoupler nigericin. Photoacoustic quantum yield spectra of energy storage indicated a larger energy storage at 700 nm induced upon stress. The additional ΔpH quenching of fluorescence and the additional quantum yield of energy storage at 700 nm, in the stressed algae, are consistent with the operation of a cyclic, energy-storing pathway in PS I which is uncoupler sensitive.     

Targeting an Interaction Between Two Disordered Domains by Using a Designed Peptide

Intrinsically disordered regions in proteins (IDRs) mediate many disease-related protein–protein interactions. However, the unfolded character and continuous conformational changes of IDRs make them difficult to target for therapeutic purposes. Here, we show that a designed peptide based on the disordered p53 linker domain can be used to target a partner IDR from the anti-apoptotic iASPP protein, promoting apoptosis of cancer cells. The p53 linker forms a hairpin-like structure with its two termini in close proximity. We designed a peptide derived from the disordered termini without the hairpin, designated as p53 LinkTer. The LinkTer peptide binds the disordered RT loop of iASPP with the same affinity as the parent p53 linker peptide, and inhibits the p53–iASPP interaction in vitro. The LinkTer peptide shows increased stability to proteolysis, penetrates cancer cells, causes nuclei shrinkage, and compromises the viability of cells. We conclude that a designed peptide comprising only the IDR from a peptide sequence can serve as an improved inhibitor since it binds its target protein without the need for pre-folding, paving the way for therapeutic targeting of IDRs.     

The statistics of words on rings

We analyze sequences of letters on a ring. Our objective is to determine the statistics of the occurrences of a set of r‐letter words when the sequence is chosen as a periodic Markov chain of order ≤ r ? 1. We first obtain a generating function for the associated probability distribution and then display its Poisson limit. For an i.i.d. letter sequence, correction terms to the Poisson limit are given. Finally, we indicate how a hidden Markov chain fits into this scheme. © 2005 Wiley Periodicals, Inc.     

2‐[(Acetyloxy)methyl]‐4‐(acetylsulfanyl)‐2‐(ethoxycarbonyl)‐3‐oxobutyl Group: A Thermolabile Protecting Group for Phosphodiesters

The phosphodiester linkage of 3′‐O‐levulinoylthymidine 5′‐methylphosphate ( 5 ) has been protected with 2‐[(acetyloxy)methyl]‐4‐(acetylsulfanyl)‐2‐(ethoxycarbonyl)‐3‐oxobutyl group (to give 1 ) to study the potential of this group as an esterase‐ and thermolabile protecting group. The group turned out to be unexpectedly thermolabile, being removed as ethyl 3‐(acetyloxy)‐4‐(acetylsulfanyl)‐2‐methylidenebut‐3‐enoate ( 10 ) without accumulation of any intermediates. The half‐life of this reaction at pH 7.5 and 37° is 14 min. Hog liver esterase (HLE), in turn, removes the protecting group as ethyl 4‐(acetylsulfanyl)‐2‐methylidene‐3‐oxobutanoate ( 12 ). On using 2.6 units of HLE in 1 ml, the rate of the enzymatic deprotection was still only one third of that of the nonenzymatic reaction. The mechanisms of both reactions have been studied and discussed. The crucial step seems to be removal of the O‐bound Ac group, either by esterase or by migration to the neighboring 3‐oxo group (nonenzymatic removal). This triggers the removal by retro‐aldol condensation/elimination mechanism. No alkylation of glutathione (GSH) upon the deprotection of 1 could be detected.     

Hydrolytic reactions of diribonucleoside 3',5'-(3'-N-phosphoramidates): kinetics and mechanisms for the P-O and P-N bond cleavage of 3'-amino-3'-deoxyuridylyl-3',5'-uridine

Hydrolytic reactions of 3'-amino-3'-deoxyuridylyl-3',5'-uridine (2a), an analogue of uridylyl-3',5'-uridine having the 3'-bridging oxygen replaced with nitrogen, have been followed by RP HPLC over a wide pH range. The only reaction taking place under alkaline conditions (pH > 9) is hydroxide ion-catalyzed hydrolysis (first-order in [OH(-)]) to a mixture of 3'-amino-3'-deoxyuridine 3'-phosphoramidate (7) and uridine (4). The reaction proceeds without detectable accumulation of any intermediates. At pH 6-8, a pH-independent formation of 3'-amino-3'-deoxyuridine 2'-phosphate (3) competes with the base-catalyzed cleavage. Both 3 and in particular 7 are, however, rather rapidly dephosphorylated under these conditions to 3'-amino-3'-deoxyuridine (5). In all likelihood, both 3 and 7 are formed by an intramolecular nucleophilic attack of the 2'-hydroxy function on the phosphorus atom, giving a phosphorane-like intermediate or transition state. Under moderately acidic conditions (pH 2-6), the predominant reaction is acid-catalyzed cleavage of the P-N3' bond (first-order in [H(+)]) that yields an equimolar mixture of 5 and uridine 5'-phosphate (6). The reaction is proposed to proceed without intramolecular participation of the neighboring 2'-hydroxyl group. Under more acidic conditions (pH < 2), hydrolysis to 3 and 4 starts to compete with the cleavage of the P-N bond, and this reaction is even the fastest one at pH < 1. Formation of 2'-O,3'-N-cyclic phosphoramidate as an intermediate appears probable, although its appearance cannot be experimentally verified. The rate constants for various partial reactions have been determined. The reaction mechanisms and the effect that replacing the 3'-oxygen with nitrogen has on the behavior of the phosphorane intermediate are discussed.     

Hydrolysis and Desulfurization of the Diastereomeric Phosphoromonothioate Analogs of Uridine 2',3'-Cyclic Monophosphate

Hydrolyses of the two diastereomeric phosphoromonothioate analogs of uridine 2',3'-cyclic monophosphate [(R(P))- and (S(P))-2',3'-cUMPS] at 363.2 K have been followed by HPLC over pH-range 0-12. In aqueous alkali (pH > 9) only base-catalyzed endocyclic phosphoester hydrolysis to a nearly equimolar mixture of uridine 2'- and 3'-phosphoromonothioates (2'- and 3'-UMPS) takes place, analogously to the hydrolysis of uridine 2',3'-cyclic monophosphate (2',3'-cUMP). The (R(P))- and (S(P))-2',3'-cUMPS are hydrolyzed 50 and 30%, respectively, more slowly than 2',3'-cUMP. Under neutral and acidic conditions, desulfurization of the cyclic thiophosphates to 2',3'-cUMP competes with the phophoester hydrolysis, both reactions being acid-catalyzed at pH < 5. The desulfurization is most pronounced in strongly acidic solutions ([HCl] > 0.1 mol L(-)(1)), where more than 90% of the starting material is degraded via this route. At pH < 2, the thioates are considerably, i.e., more than 1 order of magnitude, more stable than 2',3'-cUMP. While the hydrolysis of 2',3'-cUMP is second-order in hydronium-ion concentration, that of 2',3'-cUMPS exhibits a first-order dependence. The reactivities of the two diastereomers are comparable with each other over the entire pH-range studied, the most significant difference being that the pH-independent desulfurization at pH > 5 is with the R(P)-isomer 5-fold faster than with the S(P)-isomer. In contrast to 2',3'-cUMP, depyrimidination of the starting material (i.e., release of the uracil base) competes with the hydrolysis of the thiophosphate moiety under neutral conditions (pH 6-8).     

Derivatization of phosphopeptides with mercapto- and amino-functionalized conjugate groups by phosphate elimination and subsequent Michael addition

Kinetics of the beta-elimination of the phosphate group from H-Tyr-Ser(PO3H2)-Phe-OH and H-Tyr-Thr(PO3H2)-Phe-OH and subsequent addition of thiols and amines to the dehydroalaninyl and beta-methyldehydroalaninyl residues formed, were followed by RP HPLC under alkaline conditions in the absence and presence of Ba2+ ions. By this reaction sequence, the phosphoserinyl peptide was conjugated with mono-N-(2-mercaptoethyl)amide of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (4), a mercapto-functionalized pentapeptide, H-His-Gly-Gly-His-Gly-NH(CH2)4SH, and an amino-functionalized fluorescent dye, 5-dimethylaminonaphthalene-1-[N-(5-aminopentyl)]sulfonamide (dansyl cadaverine). The beta-methyldehydroalanine residue was, in turn, observed to be a poor Michael acceptor.     

Models for queue length in clocked queueing networks

We analyze a discrete-time network of queues. The unit element of the network is the 2 × 2 buffered switch, which we regard as a system of two queues working in parallel. We show how to transform transition probability information from the output of one switch, or network stage, to the input of the next one. This is used to carry out a Markov time series input model to predict mean queue length at every stage of the system. Another model considered is a renewal process time series model, which we use to find the mean queue length of the second stage of the network. Numerical simulations fall within the narrow band spanned by the two models.