Treating Chronic Wounds Using Photoactive Metabolites: Data Mining the Chinese Pharmacopoeia for Potential Lead Species (#)

Efficient wound treatment that addresses associated infections and inflammation remains one of the big unmet needs, especially in low- and middle-income countries. One strategy for securing better healthcare can be using medicinal plants if sufficient evidence on their safety and therapeutic benefits can be ascertained. A unique novel opportunity could be photo-enhanced wound treatment with a combination of light-sensitive plant preparations and local exposure to daylight. Data mining strategies using existing resources offer an excellent basis for developing such an approach with many potential plant candidates. In the present analysis, we researched the 535 botanical drugs included in the Chinese pharmacopeia and identified 183 medicinal plant species, 82 for treating open wounds caused by trauma and 101 for inflammatory skin conditions. After further screening for reports on the presence of known photoactive compounds, we determined a core group of 10 scientifically lesser-known botanical species that may potentially be developed into more widely used topical preparations for photodynamic treatment of infected wounds. Our predictive approach may contribute to developing a more evidence-based use of herbal medicines

Thomas-Fermi approach to resonant tunneling in delta-doped diodes

We study resonant tunneling in B-$\delta$-doped diodes grown by Si-molecular beam epitaxy. A Thomas-Fermi approach is used to obtain the conduction-band modulation. Using a scalar Hamiltonian within the effective-mass approximation we demonstrate that the occurrence of negative differential resistance (NDR) only involves conduction-band states, whereas interband tunneling effects seem to be negligible. Our theoretical results are in very good agreement with recent experimental observations of NDR in this type of diodes.Comment: 6 pages, REVTeX 3.0, 5 figures available from [email protected]

Influence of atmospheric vapour pressure deficit on ozone responses of snap bean (Phaseolus vulgaris L.) genotypes

Environmental conditions influence plant responses to ozone (O3), but few studies have evaluated individual factors directly. In this study, the effect of O3 at high and low atmospheric vapour pressure deficit (VPD) was evaluated in two genotypes of snap bean (Phaseolus vulgaris L.) (R123 and S156) used as O3 bioindicator plants. Plants were grown in outdoor controlled-environment chambers in charcoal-filtered air containing 0 or 60 nl l−1 O3 (12 h average) at two VPDs (1.26 and 1.96 kPa) and sampled for biomass, leaf area, daily water loss, and seed yield. VPD clearly influenced O3 effects. At low VPD, O3 reduced biomass, leaf area, and seed yield substantially in both genotypes, while at high VPD, O3 had no significant effect on these components. In clean air, high VPD reduced biomass and yield by similar fractions in both genotypes compared with low VPD. Data suggest that a stomatal response to VPD per se may be lacking in both genotypes and it is hypothesized that the high VPD resulted in unsustainable transpiration and water deficits that resulted in reduced growth and yield. High VPD- and water-stress-induced stomatal responses may have reduced the O3 flux into the leaves, which contributed to a higher yield compared to the low VPD treatment in both genotypes. At low VPD, transpiration increased in the O3 treatment relative to the clean air treatment, suggesting that whole-plant conductance was increased by O3 exposure. Ozone-related biomass reductions at low VPD were proportionally higher in S156 than in R123, indicating that differential O3 sensitivity of these bioindicator plants remained evident when environmental conditions were conducive for O3 effects. Assessments of potential O3 impacts on vegetation should incorporate interacting factors such as VPD

Criminal narrative experience: relating emotions to offence narrative roles during crime commission

A neglected area of research within criminality has been that of the experience of the offence for the offender. The present study investigates the emotions and narrative roles that are experienced by an offender while committing a broad range of crimes and proposes a model of Criminal Narrative Experience (CNE). Hypotheses were derived from the Circumplex of Emotions (Russell, 1997), Frye (1957), Narrative Theory (McAdams, 1988) and its link with Investigative Psychology (Canter, 1994). The analysis was based on 120 cases. Convicted for a variety of crimes, incarcerated criminals were interviewed and the data were subjected to Smallest Space Analysis (SSA). Four themes of Criminal Narrative Experience (CNE) were identified: Elated Hero, Calm Professional, Distressed Revenger and Depressed Victim in line with the recent theoretical framework posited for Narrative Offence Roles (Youngs & Canter, 2012). The theoretical implications for understanding crime on the basis of the Criminal Narrative Experience (CNE) as well as practical implications are discussed

Quantum-Enhanced Advanced LIGO Detectors in the Era of Gravitational-Wave Astronomy

The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1)

Convection in colloidal suspensions with particle-concentration-dependent viscosity

The onset of thermal convection in a horizontal layer of a colloidal suspension is investigated in terms of a continuum model for binary-fluid mixtures where the viscosity depends on the local concentration of colloidal particles. With an increasing difference between the viscosity at the warmer and the colder boundary the threshold of convection is reduced in the range of positive values of the separation ratio psi with the onset of stationary convection as well as in the range of negative values of psi with an oscillatory Hopf bifurcation. Additionally the convection rolls are shifted downwards with respect to the center of the horizontal layer for stationary convection (psi>0) and upwards for the Hopf bifurcation (psi<0).Comment: 8 pages, 6 figures, submitted to European Physical Journal

Harnessing evolutionary fitness in Plasmodium falciparum for drug discovery and suppressing resistance

Drug resistance emerges in an ecological context where fitness costs restrict the diversity of escape pathways. These pathways are targets for drug discovery, and here we demonstrate that we can identify small-molecule inhibitors that differentially target resistant parasites. Combining wild-type and mutant-type inhibitors may prevent the emergence of competitively viable resistance. We tested this hypothesis with a clinically derived chloroquine-resistant (CQr) malaria parasite and with parasites derived by in vitro selection with Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. We screened a chemical library against CQs and CQr lines and discovered a drug-like compound (IDI-3783) that was potent only in the CQr line. Surprisingly, in vitro selection of Plasmodium falciparum resistant to IDI-3783 restored CQ sensitivity, thereby indicating that CQ might once again be useful as a malaria therapy. In parallel experiments, we selected P. falciparum lines resistant to structurally unrelated PfDHODH inhibitors (Genz-666136 and DSM74). Both selections yielded resistant lines with the same point mutation in PfDHODH:E182D. We discovered a compound (IDI-6273) more potent against E182D than wild-type parasites. Selection of the E182D mutant with IDI-6273 yielded a reversion to the wild-type protein sequence and phenotype although the nucleotide sequence was different. Importantly, selection with a combination of Genz-669178, a wild-type PfDHODH inhibitor, and IDI-6273, a mutant-selective PfDHODH inhibitor, did not yield resistant parasites. These two examples demonstrate that the compromise between resistance and evolutionary fitness can be exploited to design therapies that prevent the emergence and spread of resistant organisms.Organismic and Evolutionary Biolog

A double-sided silicon micro-strip super-module for the ATLAS inner detector upgrade in the high-luminosity LHC

The ATLAS experiment is a general purpose detector aiming to fully exploit the discovery potential of the Large Hadron Collider (LHC) at CERN. It is foreseen that after several years of successful data-taking, the LHC physics programme will be extended in the so-called High-Luminosity LHC, where the instantaneous luminosity will be increased up to 5 × 1034 cm−2 s−1. For ATLAS, an upgrade scenario will imply the complete replacement of its internal tracker, as the existing detector will not provide the required performance due to the cumulated radiation damage and the increase in the detector occupancy. The current baseline layout for the new ATLAS tracker is an all-silicon-based detector, with pixel sensors in the inner layers and silicon micro-strip detectors at intermediate and outer radii. The super-module is an integration concept proposed for the strip region of the future ATLAS tracker, where double-sided stereo silicon micro-strip modules are assembled into a low-mass local support structure. An electrical super-module prototype for eight double-sided strip modules has been constructed. The aim is to exercise the multi-module readout chain and to investigate the noise performance of such a system. In this paper, the main components of the current super-module prototype are described and its electrical performance is presented in detail

A double-sided, shield-less stave prototype for the ATLAS upgrade strip tracker for the high luminosity LHC

A detailed description of the integration structures for the barrel region of the silicon strips tracker of the ATLAS Phase-II upgrade for the upgrade of the Large Hadron Collider, the so-called High Luminosity LHC (HL-LHC), is presented. This paper focuses on one of the latest demonstrator prototypes recently assembled, with numerous unique features. It consists of a shortened, shield-less, and double sided stave, with two candidate power distributions implemented. Thermal and electrical performances of the prototype are presented, as well as a description of the assembly procedures and tools