Vibronic Spectra of Jet-Cooled 2-Aminopurine center dot H2O Clusters Studied by UV Resonant Two-Photon Ionization Spectroscopy and Quantum Chemical Calculations

For understanding the major- and minor-groove hydration patterns of DNAs and RNAs, it is important to understand the local solvation of individual nucleobases at the molecular level. We have investigated the 2-aminopurine center dot H2O. monohydrate by two-color resonant two-photon ionization and UV/UV hole-burning spectroscopies, which reveal two isomers, denoted A and B. The electronic spectral shift delta nu of the S-1 <- S-0 transition relative to bare 9H-2-aminopurine (9H-2AP) is small for isomer A (-70 cm(-1)), while that of isomer B is much larger (delta nu = 889 cm(-1)). B3LYP geometry optimizations with the TZVP basis set predict four cluster isomers, of which three are doubly H-bonded, with H2O acting as an acceptor to a N-H or -NH2 group and as a donor to either of the pyrimidine N sites. The "sugar-edge" isomer A is calculated to be the most stable form with binding energy D-e = 56.4 kJ/mol. Isomers B and C are H-bonded between the -NH2 group and pyrimidine moieties and are 2.5 and 6.9 kJ/mol less stable, respectively. Time-dependent (TD) B3LYP/TZVP calculations predict the adiabatic energies of the lowest (1)pi pi* states of A and B in excellent agreement with the observed 0(0)(0) bands; also, the relative intensities of the A and B origin bands agree well with the calculated S-0 state relative energies. This allows unequivocal identification of the isomers. The R2PI spectra of 9H-2AP and of isomer A exhibit intense low-frequency out-of-plane overtone and combination bands, which is interpreted as a coupling of the optically excited (1)pi pi* state to the lower-lying (1)n pi* dark state. In contrast, these overtone and combination bands are much weaker for isomer B, implying that the (1)pi pi* state of B is planar and decoupled from the (1)n pi* state. These observations agree with the calculations, which predict the (1)n pi* above the (1)pi pi* state for isomer B but below the (1)pi pi* for both 9H-2AP and isomer A.

Regulatory mechanism of the light-activable allosteric switch LOV-TAP for the control of DNA binding: a computer simulation study

The spatio-temporal control of gene expression is fundamental to elucidate cell proliferation and deregulation phenomena in living systems. Novel approaches based on light-sensitive multiprotein complexes have recently been devised, showing promising perspectives for the noninvasive and reversible modulation of the DNA-transcriptional activity in vivo. This has lately been demonstrated in a striking way through the generation of the artificial protein construct light-oxygen-voltage (LOV)-tryptophan-activated protein (TAP), in which the LOV-2-Jα photoswitch of phototropin1 from Avena sativa (AsLOV2-Jα) has been ligated to the tryptophan-repressor (TrpR) protein from Escherichia coli. Although tremendous progress has been achieved on the generation of such protein constructs, a detailed understanding of their functioning as opto-genetical tools is still in its infancy. Here, we elucidate the early stages of the light-induced regulatory mechanism of LOV-TAP at the molecular level, using the noninvasive molecular dynamics simulation technique. More specifically, we find that Cys450-FMN-adduct formation in the AsLOV2-Jα-binding pocket after photoexcitation induces the cleavage of the peripheral Jα-helix from the LOV core, causing a change of its polarity and electrostatic attraction of the photoswitch onto the DNA surface. This goes along with the flexibilization through unfolding of a hairpin-like helix-loop-helix region interlinking the AsLOV2-Jα- and TrpR-domains, ultimately enabling the condensation of LOV-TAP onto the DNA surface. By contrast, in the dark state the AsLOV2-Jα photoswitch remains inactive and exerts a repulsive electrostatic force on the DNA surface. This leads to a distortion of the hairpin region, which finally relieves its tension by causing the disruption of LOV-TAP from the DNA.

Morphological and biochemical T2 evaluation of cartilage repair tissue based on a hybrid double echo at steady state (DESS-T2d) approach

To use a new approach which provides, based on the widely used three-dimensional double-echo steady-state (DESS) sequence, in addition to the morphological information, the generation of biochemical T2 maps in one hybrid sequence.

Postprandial effects of dark chocolate on portal hypertension in patients with cirrhosis: results of a phase 2, double-blind, randomized controlled trial

In cirrhosis, hepatic endothelial dysfunction as a result of oxidative stress contributes to the postprandial increase in hepatic venous pressure gradient (HVPG).

Rapid estimation of cartilage T2 based on double echo at steady state (DESS) with 3 Tesla

The double-echo-steady-state (DESS) sequence generates two signal echoes that are characterized by a different contrast behavior. Based on these two contrasts, the underlying T2 can be calculated. For a flip-angle of 90 degrees , the calculated T2 becomes independent of T1, but with very low signal-to-noise ratio. In the present study, the estimation of cartilage T2, based on DESS with a reduced flip-angle, was investigated, with the goal of optimizing SNR, and simultaneously minimizing the error in T2. This approach was validated in phantoms and on volunteers. T2 estimations based on DESS at different flip-angles were compared with standard multiecho, spin-echo T2. Furthermore, DESS-T2 estimations were used in a volunteer and in an initial study on patients after cartilage repair of the knee. A flip-angle of 33 degrees was the best compromise for the combination of DESS-T2 mapping and morphological imaging. For this flip angle, the Pearson correlation was 0.993 in the phantom study (approximately 20% relative difference between SE-T2 and DESS-T2); and varied between 0.429 and 0.514 in the volunteer study. Measurements in patients showed comparable results for both techniques with regard to zonal assessment. This DESS-T2 approach represents an opportunity to combine morphological and quantitative cartilage MRI in a rapid one-step examination.

The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis

Background: The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown. Methods: Meta-analysis of the pretest risk of psychosis in help-seeking patients selected to undergo CHR assessment: total transitions to psychosis over the pool of patients assessed for potential risk and deemed at risk (CHR+) or not at risk (CHR−). Recruitment strategies (number of outreach activities per study, main target of outreach campaign, and proportion of self-referrals) were the moderators examined in meta-regressions. Results: 11 independent studies met the inclusion criteria, for a total of 2519 (CHR+: n = 1359; CHR−: n = 1160) help-seeking patients undergoing CHR assessment (mean follow-up: 38 months). The overall meta-analytical pretest risk for psychosis in help-seeking patients was 15%, with high heterogeneity (95% CI: 9%–24%, I 2 = 96, P < .001). Recruitment strategies were heterogeneous and opportunistic. Heterogeneity was largely explained by intensive (n = 11, β = −.166, Q = 9.441, P = .002) outreach campaigns primarily targeting the general public (n = 11, β = −1.15, Q = 21.35, P < .001) along with higher proportions of self-referrals (n = 10, β = −.029, Q = 4.262, P = .039), which diluted pretest risk for psychosis in patients undergoing CHR assessment. Conclusions: There is meta-analytical evidence for overall risk enrichment (pretest risk for psychosis at 38monhts = 15%) in help-seeking samples selected for CHR assessment as compared to the general population (pretest risk of psychosis at 38monhts=0.1%). Intensive outreach campaigns predominantly targeting the general population and a higher proportion of self-referrals diluted the pretest risk for psychosis.

A double role of sperm in scorpions: the mating plug of Euscorpius italicus (Scorpiones: Euscorpiidae) consists of sperm

Mating plugs occluding the female gonopore after mating are a widespread phenomenon. In scorpions, two main types of mating plugs are found: sclerotized mating plugs being parts of the spermatophore that break off during mating, and gel-like mating plugs being gelatinous fluids that harden in the female genital tract. In this study, the gel-like mating plug of Euscorpius italicus was investigated with respect to its composition, fine structure, and changes over time. Sperm forms the major component of the mating plug, a phenomenon previously unknown in arachnids. Three parts of the mating plug can be distinguished. The part facing the outside of the female (outer part) contains sperm packages containing inactive spermatozoa. In this state, sperm is transferred. In the median part, the sperm packages get uncoiled to single spermatozoa. In the inner part, free sperm is embedded in a large amount of secretions. Fresh mating plugs are soft gelatinous, later they harden from outside toward inside. This process is completed after 3-5 days. Sperm from artificially triggered spermatophores could be activated by immersion in insect Ringer's solution indicating that the fluid condition in the females' genital tract or females' secretions causes sperm activation. Because of the male origin of the mating plug, it has likely evolved under sperm competition or sexual conflict. As females refused to remate irrespective of the presence or absence of a mating plug, females may have changed their mating behavior in the course of evolution from polyandry to monandry.

Collimated Field Emission Beams from Metal Double-Gate Nanotip Arrays Optically Excited via Surface Plasmon Resonance

The generation of collimated electron beams from metal double-gate nanotip arrays excited by near infrared laser pulses is studied. Using electromagnetic and particle tracking simulations, we showed that electron pulses with small rms transverse velocities are efficiently produced from nanotip arrays by laser-induced field emission with the laser wavelength tuned to surface plasmon polariton resonance of the stacked double-gate structure. The result indicates the possibility of realizing a metal nanotip array cathode that outperforms state-of-the-art photocathodes.

The dark side of the moon

When talking about flow, most people probably think of a highly desirable state associated with a broad variety of positive outcomes in terms of positive motivation, well-being, and performance. In contrast, this chapter suggests that the characteristics of flow also have the potential to be evil. First, we will explain how flow can lead to addiction when exercising, playing games, and using the Internet. Then we will consider how flow is linked to impaired risk perception and risky behavior. As a third negative facet of flow, we will outline how it can also be experienced in antisocial contexts and during combat. This chapter ends with some broader comments on the dark and bright sides of flow, including flow as a universal experience, the implications for practical interventions, ethical questions related to flow, and future research questions.

Three Shades of Embeddedness, State Capitalism as the Informal Economy, Emic Notions of the Anti-Market, and Counterfeit Garments in the Mauritian Export Processing Zone

Purpose This paper furthers the analysis of patterns regulating capitalist accumulation based on a historical anthropology of economic activities revolving around and within the Mauritian Export Processing Zone (EPZ). Design/methodology/approach This paper uses fieldwork in Mauritius to interrogate and critique two important concepts in contemporary social theory – “embeddedness” and “the informal economy.” These are viewed in the wider frame of social anthropology’s engagement with (neoliberal) capitalism. Findings A process-oriented revision of Polanyi’s work on embeddedness and the “double movement” is proposed to help us situate EPZs within ongoing power struggles found throughout the history of capitalism. This helps us to challenge the notion of economic informality as supplied by Hart and others. Social implications Scholars and policymakers have tended to see economic informality as a force from below, able to disrupt the legal-rational nature of capitalism as practiced from on high. Similarly, there is a view that a precapitalist embeddedness, a “human economy,” has many good things to offer. However, this paper shows that the practices of the state and multinational capitalism, in EPZs and elsewhere, exactly match the practices that are envisioned as the cure to the pitfalls of capitalism. Value of the paper Setting aside the formal-informal distinction in favor of a process-oriented analysis of embeddedness allows us better to understand the shifting struggles among the state, capital, and labor.

Excited-State Structure, Vibrations, and Nonradiative Relaxation of Jet-Cooled 5-Fluorocytosine

The S0 → S1 vibronic spectrum and S1 state nonradiative relaxation of jet-cooled keto-amino 5-fluorocytosine (5FCyt) are investigated by two-color resonant two-photon ionization spectroscopy at 0.3 and 0.05 cm–1 resolution. The 000 rotational band contour is polarized in-plane, implying that the electronic transition is 1ππ*. The electronic transition dipole moment orientation and the changes of rotational constants agree closely with the SCS-CC2 calculated values for the 1ππ* (S1) transition of 5FCyt. The spectral region from 0 to 300 cm–1 is dominated by overtone and combination bands of the out-of-plane ν1′ (boat), ν2′ (butterfly), and ν3′ (HN–C6H twist) vibrations, implying that the pyrimidinone frame is distorted out-of-plane by the 1ππ* excitation, in agreement with SCS-CC2 calculations. The number of vibronic bands rises strongly around +350 cm–1; this is attributed to the 1ππ* state barrier to planarity that corresponds to the central maximum of the double-minimum out-of-plane vibrational potentials along the ν1′, ν2′, and ν3′ coordinates, which gives rise to a high density of vibronic excitations. At +1200 cm–1, rapid nonradiative relaxation (knr ≥ 1012 s–1) sets in, which we interpret as the height of the 1ππ* state barrier in front of the lowest S1/S0 conical intersection. This barrier in 5FCyt is 3 times higher than that in cytosine. The lifetimes of the ν′ = 0, 2ν1′, 2ν2′, 2ν1′ + 2ν2′, 4ν2′, and 2ν1′ + 4ν2′ levels are determined from Lorentzian widths fitted to the rotational band contours and are τ ≥ 75 ps for ν′ = 0, decreasing to τ ≥ 55 ps at the 2ν1′ + 4ν2′ level at +234 cm–1. These gas-phase lifetimes are twice those of S1 state cytosine and 10–100 times those of the other canonical nucleobases in the gas phase. On the other hand, the 5FCyt gas-phase lifetime is close to the 73 ps lifetime in room-temperature solvents. This lack of dependence on temperature and on the surrounding medium implies that the 5FCyt nonradiative relaxation from its S1 (1ππ*) state is essentially controlled by the same ∼1200 cm–1 barrier and conical intersection both in the gas phase and in solution.

Three-State Single-Molecule Naphthalenediimide Switch: Integration of a Pendant Redox Unit for Conductance Tuning

We studied charge transport through core-substituted naphthalenediimide (NDI) single-molecule junctions using the electrochemical STM-based break-junction technique in combination with DFT calculations. Conductance switching among three well-defined states was demonstrated by electrochemically controlling the redox state of the pendent diimide unit of the molecule in an ionic liquid. The electrical conductances of the dianion and neutral states differ by more than one order of magnitude. The potential-dependence of the charge-transport characteristics of the NDI molecules was confirmed by DFT calculations, which account for electrochemical double-layer effects on the conductance of the NDI junctions. This study suggests that integration of a pendant redox unit with strong coupling to a molecular backbone enables the tuning of charge transport through single-molecule devices by controlling their redox states.