Luminescence-based detection and identification of illicit drugs.

Luminescence-based sensing is capable of being used for the sensitive, rapid, and in some cases selective detection of chemicals. Furthermore, the method is amenable to incorporation into handheld low-power portable detectors that can be used in the field. Luminescence-based detectors are now commercially available for explosive detection with the technology built on a strong foundation of science. In contrast, there are fewer examples of luminescence-based detection of illicit drugs, despite the pervasive and global challenge of combating their manufacture, distribution and consumption and the need for handheld detection systems. This perspective describes the relatively nascent steps that have been reported in the use of luminescent materials for the detection of illicit drugs. Much of the published work has focused on detection of illicit drugs in solution with less work on vapour detection using thin luminescent sensing films. The latter are better suited for handheld sensing devices and detection in the field. Illicit drug detection has been achieved via different mechanisms, all of which change the luminescence of the sensing material. These include photoinduced hole transfer (PHT) leading to quenching of the luminescence, disruption of Förster energy transfer between different chromophores by a drug, and chemical reaction between the sensing material and a drug. The most promising of these is PHT, which can be used for rapid and reversible detection of illicit drugs in solution and film-based sensing of drugs in the vapour phase. However, there are still significant knowledge gaps, for example, how vapours of illicit drugs interact with the sensing films, and how to achieve selectivity for specific drugs.

A modeling approach to understanding OLED performance improvements arising from spatial variations in guest:host blend ratio.

Phosphorescent organic light emitting diodes (OLEDs) suffer from efficiency roll off, where device efficiency rapidly decays at higher luminance. One strategy to minimize this loss of efficiency at higher luminance is the use of non-uniform or graded guest:host blend ratios within the emissive layer. This work applies a multi-scale modeling framework to elucidate the mechanisms by which a non-uniform blend ratio can change the performance of an OLED. Mobility and exciton data are extracted from a kinetic Monte-Carlo model, which is then coupled to a drift diffusion model for fast sampling of the parameter space. The model is applied to OLEDs with uniform, linear, and stepwise graduations in the blend ratio in the emissive layer. The distribution of the guests in the film was found to affect the mobility of the charge carriers, and it was determined that having a graduated guest profile broadened the recombination zone, leading to a reduction in second order annihilation rates. That is, there was a reduction in triplet-triplet and triplet-polaron annihilation. Reducing triplet-triplet and triplet-polaron annihilation would lead to an improvement in device efficiency.

A multicentre assessment of prostate MRI quality and compliance with UK and international standards.

AIM: To assess prostate magnetic resonance imaging (MRI) image quality and compliance with technical standards between centres in the South West region of the UK. MATERIALS AND METHODS: Fifteen imaging sites in the region submitted seven consecutive anonymised MRI studies. These were assessed by two experienced radiologists in consensus. Overall, subjective image quality for T2-weighted imaging (T2W), diffusion weighted imaging (DWI), and dynamic contrast enhancement (DCE) was scored on a five-point Likert scale. Five additional quality parameters were also assessed visually, including image noise, motion, artefact, and distortion. The degree of compliance by each site with 21 published technical standards was also assessed. RESULTS: Ninety-four MRI examinations were reviewed from across all sites (mean 6.3 scans per site, range 5-7). Mean compliance with technical standards was 63% (range 38-86%). Forty-seven percent of sites did not perform DCE. One site used a 3 T scanner. The percentage of patients with overall quality scores of ≥3 (diagnostically acceptable) were 68% for T2W, 81% for DWI, and 60% for both T2W and DWI. Ninety-three percent of the 45 patients who underwent DCE had diagnostically acceptable studies. By scanner age, the percentage of patients with diagnostically acceptable T2W scores was 53% for scanners ≥7 years and 80% when <7 years (p=0.006). Comparing individual sites, the mean overall quality scores were 2.9 (range 2.2-4.2) for T2W, 3.2 (1.8-4.7) for DWI, and 3.4 (2.5-4.7) for DCE. CONCLUSION: There is wide variation in compliance with recognised technical standards and image quality across sites. If MRI is to replace biopsy in selected low-risk patients, improvements in image quality may be required.

Real-time fluorescence quenching-based detection of nitro-containing explosive vapours: what are the key processes?

The detection of explosives continues to be a pressing global challenge with many potential technologies being pursued by the scientific research community. Luminescence-based detection of explosive vapours with an organic semiconductor has attracted much interest because of its potential for detectors that have high sensitivity, compact form factor, simple operation and low-cost. Despite the abundance of literature on novel sensor materials systems there are relatively few mechanistic studies targeted towards vapour-based sensing. In this Perspective, we will review the progress that has been made in understanding the processes that control the real-time luminescence quenching of thin films by analyte vapours. These are the non-radiative quenching process by which the sensor exciton decays, the analyte-sensor intermolecular binding interaction, and the diffusion process for the analyte vapours in the film. We comment on the contributions of each of these processes towards the sensing response and, in particular, the relative roles of analyte diffusion and exciton diffusion. While the latter has been historically judged to be one of, if not the primary, causes for the high sensitivity of many conjugated polymers to nitrated vapours, recent evidence suggests that long exciton diffusion lengths are unnecessary. The implications of these results on the development of sensor materials for real-time detection are discussed.

Phosphorescence quenching of fac-tris(2-phenylpyridyl)iridium(iii) complexes in thin films on dielectric surfaces.

We study the influence of the film thickness on the time-resolved phosphorescence and the luminescence quantum yield of fac-tris(2-phenylpyridyl)iridium(iii) [Ir(ppy)3]-cored dendrimers deposited on dielectric substrates. A correlation is observed between the surface quenching velocity and the quenching rate by intermolecular interactions in the bulk film, which suggests that both processes are controlled by dipole-dipole interactions between Ir(ppy)3 complexes at the core of the dendrimers. It is also found that the surface quenching velocity decreases as the refractive index of the substrate is increased. This can be explained by partial screening of dipole-dipole interactions by the dielectric environment.

Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides.

Mutations reducing the functional activity of leptin, the leptin receptor, alpha-melanocyte stimulating hormones (alpha-MSH) and the melanocortin-4 receptor (Mc4r) all lead to obesity in mammals. Moreover, mutant mice that ectopically express either agouti (Ay/a mice) or agouti-related protein (Agrp), antagonists of melanocortin signalling, become obese. These data suggest that alpha-MSH signalling transduced by Mc4r tonically inhibits feeding; however, it is not known to what extent this pathway mediates leptin signalling. We show here that Mc4r-deficient (Mc4r-/-) mice do not respond to the anorectic actions of MTII, an MSH-like agonist, suggesting that alpha-MSH inhibits feeding primarily by activating Mc4r. Obese Mc4r-/-mice do not respond significantly to the inhibitory effects of leptin on feeding, whereas non-obese Mc4r-/- mice do. These data demonstrate that melanocortin signalling transduced by Mc4r is not an exclusive target of leptin action and that factors resulting from obesity contribute to leptin resistance. Leptin resistance of obese Mc4r-/- mice does not prevent their response to the anorectic actions of ciliary neurotrophic factor (CNTF), corticotropin releasing factor (CRF), or urocortin; or the orexigenic actions of neuropeptide Y (NPY) or peptide YY (PYY), indicating that these neuromodulators act independently or downstream of Mc4r signalling.

High power efficiency phosphorescent poly(dendrimer) OLEDs.

We show that it is possible to produce an efficient solution-processable phosphorescent poly(dendrimer) OLED with a 32 lm/W power efficiency at 100 cd/m2 without using a charge transporting host or any improvements in light extraction. This is achieved by using the dendrimer architecture to control inter-chromophore interactions. The effects of using 4,4',4″-tris(N-carbazolyl)triphenylamine (TCTA) as a charge transporting host and using a double dendron structure to further reduce inter-chromophore interactions are also reported.

Effects of fluorination on iridium(III) complex phosphorescence: magnetic circular dichroism and relativistic time-dependent density functional theory.

We use a combination of low temperature, high field magnetic circular dichroism, absorption, and emission spectroscopy with relativistic time-dependent density functional calculations to reveal a subtle interplay between the effects of chemical substitution and spin-orbit coupling (SOC) in a family of iridium(III) complexes. Fluorination at the ortho and para positions of the phenyl group of fac-tris(1-methyl-5-phenyl-3-n-propyl-[1,2,4]triazolyl)iridium(III) cause changes that are independent of whether the other position is fluorinated or protonated. This is demonstrated by a simple linear relationship found for a range of measured and calculated properties of these complexes. Further, we show that the phosphorescent radiative rate, k(r), is determined by the degree to which SOC is able to hybridize T(1) to S(3) and that k(r) is proportional to the inverse fourth power of the energy gap between these excitations. We show that fluorination in the para position leads to a much larger increase of the energy gap than fluorination at the ortho position. Theory is used to trace this back to the fact that fluorination at the para position increases the difference in electron density between the phenyl and triazolyl groups, which distorts the complex further from octahedral symmetry, and increases the energy separation between the highest occupied molecular orbital (HOMO) and the HOMO-1. This provides a new design criterion for phosphorescent iridium(III) complexes for organic optoelectronic applications. In contrast, the nonradiative rate is greatly enhanced by fluorination at the ortho position. This may be connected to a significant redistribution of spectral weight. We also show that the lowest energy excitation, 1A, has almost no oscillator strength; therefore, the second lowest excitation, 2E, is the dominant emissive state at room temperature. Nevertheless the mirror image rule between absorption and emission is obeyed, as 2E is responsible for both absorption and emission at all but very low (<10 K) temperatures.

Photophysical properties of 9,10-disubstituted anthracene derivatives in solution and films.

We have carried out absorption, time-resolved fluorescence, and fluorescence quantum yield measurements of four new soluble anthracene derivatives. They show natural radiative lifetimes in the range of 2.5-4.4 ns, which is 5-10 times shorter than those reported for unsubstituted anthracene. The 9,10-bis(phenylethynyl)anthracene (BPEA) derivatives show the largest fluorescence transition dipoles, which is attributed to extended π-conjugation between anthracene and phenyls through acetylene linkages. Spin-cast films of the BPEA derivatives show strong fluorescence quenching by weakly emitting low energy excitations, which is attributed to excimer-like traps. Quenching is significantly reduced when bulky dendrons are attached so that they give maximum coverage of the emitting chromophore and prevent their aggregation. The results show that anthracene derivatives can be developed into efficient solution-processable fluorescent emitters for the blue and green spectral regions.

Ischaemic bowel perforation secondary to a gravid uterus in a patient with treated inflammatory bowel disease and an ileoanal pouch: a case report.

The diagnosis of visceral perforation during pregnancy is often delayed and the management complex. A 32-year-old primigravid woman in her second trimester presented with abdominal pain and a pre-existing ileoanal pouch. Initial imaging was negative but later imaging was suggestive of serious pathology. At laparotomy, a caesarean section was performed. Peritonitis was encountered secondary to two discrete perforations in the small bowel separate from her pouch. Histology found an ischaemic perforation secondary to a pressure effect from the gravid uterus. In pregnancy, ileoanal pouches may make the interconnected bowel vulnerable to the pressure effect of the gravid uterus and perforation. Pregnant women with such a surgical history who develop symptoms suggestive of bowel perforation should have rapid imaging and their clinical team should consider early definitive surgical intervention.

Floquet spin states in OLEDs.

Electron and hole spins in organic light-emitting diodes constitute prototypical two-level systems for the exploration of the ultrastrong-drive regime of light-matter interactions. Floquet solutions to the time-dependent Hamiltonian of pairs of electron and hole spins reveal that, under non-perturbative resonant drive, when spin-Rabi frequencies become comparable to the Larmor frequencies, hybrid light-matter states emerge that enable dipole-forbidden multi-quantum transitions at integer and fractional g-factors. To probe these phenomena experimentally, we develop an electrically detected magnetic-resonance experiment supporting oscillating driving fields comparable in amplitude to the static field defining the Zeeman splitting; and an organic semiconductor characterized by minimal local hyperfine fields allowing the non-perturbative light-matter interactions to be resolved. The experimental confirmation of the predicted Floquet states under strong-drive conditions demonstrates the presence of hybrid light-matter spin excitations at room temperature. These dressed states are insensitive to power broadening, display Bloch-Siegert-like shifts, and are suggestive of long spin coherence times, implying potential applicability for quantum sensing.

The cytoskeletal protein vinculin contains transformation-sensitive, covalently bound lipid.

Vinculin, which is associated with the cytoskeleton of many cells, has been suggested as a possible linker between microfilament bundles and the plasma membrane. Here it will be shown that fatty acid is covalently attached to vinculin in vivo. Furthermore, in chicken embryo fibroblasts infected with a temperature-sensitive mutant of Rous sarcoma virus, tsNY68, the acylation of vinculin at the permissive temperature was less than one-third that at the nonpermissive temperature. Thus, the covalent binding of lipid to vinculin is a transformation-sensitive event. The covalent modification of vinculin by lipids could be directly or indirectly involved in its reversible association with membranes. This modification may also provide a mechanism to alter the organization of vinculin within cells and thereby play a regulatory role in anchoring or stabilizing microfilament bundles at plasma membranes.

Strategies and potential molecular targets for obesity treatment.

Obesity is an increasingly prevalent and important health problem. Although treatment is available, the long-term maintenance of medically significant weight loss (5 to 10 percent of initial body weight) is rare. Since 1995 there has been an explosion of research focused on the regulation of energy balance and fat mass. Characterization of obesity-associated gene products has revealed new biochemical pathways and molecular targets for pharmacological intervention that will likely lead to new treatments. Ideally, these treatments will be viewed as adjuncts to behavioral and lifestyle changes aimed at maintenance of weight loss and improved health.

Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks.

The recent positional cloning of the mouse ob gene and its human homology has provided the basis to investigate the potential role of the ob gene product in body weight regulation. A biologically active form of recombinant mouse OB protein was overexpressed and purified to near homogeneity from a bacterial expression system. Peripheral and central administration of microgram doses of OB protein reduced food intake and body weight of ob/ob and diet-induced obese mice but not in db/db obese mice. The behavioral effects after brain administration suggest that OB protein can act directly on neuronal networks that control feeding and energy balance.

Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation.

The hematopoietically expressed product of the vav proto-oncogene, Vav, shared homology with guanine nucleotide releasing factors (GRFs) [also called guanosine diphosphate-dissociation stimulators (GDSs)] that activate Ras-related small guanosine triphosphate (GTP)-binding proteins. Human T cell lysates or Vav immunoprecipitates possessed GRF activity that increased after T cell antigen receptor (TCR)-CD3 triggering; an in vitro-translated Vav fragment that contained the putative GRF domain was also active. Vav-associated GRF stimulation after TCR-CD3 ligation paralleled its tyrosine phosphorylation; both were blocked by a protein tyrosine kinase (PTK) inhibitor. Vav also was a substrate for the p56lck PTK. Thus, Vav is a PTK-regulated GRF that may be important in TCR-CD3-initiated signal transduction through the activation of Ras.

Interaction of Shc with the zeta chain of the T cell receptor upon T cell activation.

The shc oncogene product is tyrosine-phosphorylated by Src family kinases and after its phosphorylation interacts with the adapter protein Grb2 (growth factor receptor-bound protein 2). In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Because several Src family kinases participate in T cell activation and Shc functions upstream of Ras, the role of Shc in T cell signaling was examined. Shc was phosphorylated on tyrosine after activation through the T cell receptor (TCR), and subsequently interacted with Grb2 and mSOS. The Src homology region 2 (SH2) domain of Shc directly interacted with the tyrosine-phosphorylated zeta chain of the TCR. Thus, Shc may couple TCR activation to the Ras signaling pathway.

Regulation of src family tyrosine kinases in lymphocytes.

An immune response is initiated by activation of antigen-specific lymphoid cells via receptors on the cell surface. Recent advances have begun to unravel the molecular pathways by which the signals from these surface receptors are transduced into the cells and affect the cell's behavior. Phosphorylation of key regulatory proteins on specific tyrosine residues is emerging as a central mechanism to activate, modulate or translocate these regulatory proteins. In this review, we summarize the current picture on the role and regulation of the src family of protein tyrosine kinases thought to be involved in lymphocyte activation, and put forward a working hypothesis that might serve as a basis for further experimentation.

Influence of the dendron chemical structure on the photophysical properties of bisfluorene-cored dendrimers.

A detailed study of the photophysics of a family of bisfluorene-cored dendrimers is reported. Polarized time-resolved fluorescence, singlet-singlet exciton annihilation and fluorescence quantum yield measurements were performed and used to understand how the dendron structure affects the light-emitting properties of the materials. The exciton diffusion rate is similar in all films studied. An increase in the nonradiative deactivation rate by nearly one order of magnitude is observed in films of dendrimers with stilbenyl and carbazolyl based dendrons as compared to solutions, whereas the dendrimers with biphenyl and diphenylethylenyl dendrons showed highly efficient emission (photoluminescence quantum yields of 90%) in both solution and the solid state. The results of the materials that show fluorescence quenching can be explained by the presence of quenching sites at a concentration of just a fraction of a percent of all macromolecules. A possible explanation of this quenching is hole transfer from the emissive chromophore to the dendron in a face-to-face geometry. These results are important for the design of efficient blue emitters for optoelectronic applications.

Identification of targets of leptin action in rat hypothalamus.

The hypothesis that leptin (OB protein) acts in the hypothalamus to reduce food intake and body weight is based primarily on evidence from leptin-deficient, ob/ob mice. To investigate whether leptin exerts similar effects in normal animals, we administered leptin intracerebroventricularly (icv) to Long-Evans rats. Leptin administration (3.5 microg icv) at the onset of nocturnal feeding reduced food intake by 50% at 1 h and by 42% at 4 h, as compared with vehicle-treated controls (both P < 0.05). To investigate the basis for this effect, we used in situ hybridization (ISH) to determine whether leptin alters expression of hypothalamic neuropeptides involved in energy homeostasis. Two injections of leptin (3.5 microg icv) during a 40 h fast significantly decreased levels of mRNA for neuropeptide Y (NPY, which stimulates food intake) in the arcuate nucleus (-24%) and increased levels of mRNA for corticotrophin releasing hormone (CRH, an inhibitor of food intake) in the paraventricular nucleus (by 38%) (both P < 0.05 vs. vehicle-treated controls). To investigate the anatomic basis for these effects, we measured leptin receptor gene expression in rat brain by ISH using a probe complementary to mRNA for all leptin receptor splice variants. Leptin receptor mRNA was densely concentrated in the arcuate nucleus, with lower levels present in the ventromedial and dorsomedial hypothalamic nuclei and other brain areas involved in energy balance. These findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting.

Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.

Src family protein tyrosine kinases (PTKs) play an essential role in antigen receptor-initiated lymphocyte activation. Their activity is largely regulated by a negative regulatory tyrosine which is a substrate for the activating action of the CD45 phosphotyrosine phosphatase (PTPase) or, conversely, the suppressing action of the cytosolic p50csk PTK. Here we report that CD45 was phosphorylated by p50csk on two tyrosine residues, one of them identified as Tyr-1193. This residue was not phosphorylated by T-cell PTKs p56lck and p59fyn. Tyr-1193 was phosphorylated in intact T cells, and phosphorylation increased upon treatment with PTPase inhibitors, indicating that this tyrosine is a target for a constitutively active PTK. Cotransfection of CD45 and csk into COS-1 cells caused tyrosine phosphorylation of CD45 in the intact cells. Tyrosine-phosphorylated CD45 bound p56lck through the SH2 domain of the kinase. Finally, p50csk-mediated phosphorylation of CD45 caused a severalfold increase in its PTPase activity. Our results show that direct tyrosine phosphorylation of CD45 can affect its activity and association with Src family PTKs and that this phosphorylation could be mediated by p50csk. If this is also true in the intact cells, it adds a new dimension to the physiological function of p50csk in T lymphocytes.