Optimized Long-Range Corrected Density Functionals for Electronic and Optical Properties of Bare and Ligated CdSe Quantum Dots.

The reliable prediction of optical and fundamental gaps of finite size systems using density functional theory requires to account for the potential self-interaction error, which is notorious for degrading the description of charge transfer transitions. One solution is provided by parametrized long-range corrected functionals such as LC-BLYP, which can be tuned such as to describe certain properties of the particular system at hand. Here, bare and 3-mercaptoprotionic acid covered Cd33Se33 quantum dots are investigated using the optimally tuned LC-BLYP functional. The range separation parameter, which determines the switching on of the exact exchange contribution, is found to be 0.12 bohr-1 and 0.09 bohr-1 for the bare and covered quantum dot, respectively. It is shown that density functional optimization indeed yields optical and fundamental gaps and thus exciton binding energies, considerably different compared with standard functionals such as the popular PBE and B3LYP ones. This holds true, despite the well established fact that the leading transitions are localized on the quantum dot and do not show pronounced long-range charge transfer character.

Growing up on a farm leads to lifelong protection against allergic rhinitis.

BACKGROUND: Various studies have reported a low prevalence of allergic rhinitis in farmers and farmers' children. We sought to investigate whether the protective effect of childhood farm environment is conserved throughout adulthood and how it corresponds to different degrees of urbanization. METHODS: A questionnaire on respiratory health was mailed in 2008 to 30,000 randomly selected subjects aged 16-75 in West Sweden, 29,218 could be traced and 18,087 (62%) responded. The questionnaire included questions on allergic rhinitis, asthma, respiratory symptoms and possible determinants. RESULTS: When stratified into age groups of 15 years, subjects that lived on a farm during their first 5 years of life had a lower prevalence of allergic rhinitis in all groups, even among the oldest (61-75 years). The negative correlation between childhood farm living and prevalence of allergic rhinitis was similar in 46-75 years of age (OR 0.82; 95% CI 0.70-0.95) as in 16-45 years of age (OR 0.78; 0.64-0.95). There was a significant trend of increasing prevalence of allergic rhinitis with increasing degree of urbanization independent of the effect of childhood farm living. CONCLUSIONS: We found a lifelong protective effect of childhood farm living on the prevalence of allergic rhinitis. In addition, we found an increasing prevalence of allergic rhinitis with increasing degree of urbanization both in those raised on a farm and those not, thus emphasizing the influence of both childhood and adult exposure for the development of allergic disease.

Probing the strength of the system-bath interaction by three-pulse photon echoes.

We explore how the width of the three-pulse photon echo signal at long population times can be used to determine the strength of the system-bath interaction. Using simulation with finite pulses we show that a simple relation exist between the width of the echo signal, the coupling strength, and the pulse autocorrelation. The derived model is applied to Rhodamine 6G in alcoholic solution, a paradigm system for the study of solvation dynamics, and the results are compared to conventional methods. The independently determined coupling strength forms the basis for a computationally inexpensive route to determine the entire spectral density, the key parameter when considering system-bath interactions. Our method allows us to accurately estimate the relative amplitude of fast and slow components in the correlation function using only impulsive limit simulations. We show that the peak shift significantly overestimates the amplitude of the fastest decay component for our experimental data. Changing solvent from methanol to 1-hexanol we observe a narrowing of the width of the echo profile. The changes in the echo width allow us to estimate the changes of the coupling strength in various solvents.

Comparison of the efficacy of salmeterol/fluticasone propionate combination in Japanese and Caucasian asthmatics.

INTRODUCTION: The effect of ethnicity on the efficacy of salmeterol (S)+fluticasone propionate (FP) has not been examined in Japanese and Caucasian asthmatics. In this study, the efficacy of combination treatment with S and FP from a single inhaler (SFC) was compared with concurrent treatment with S and FP administration from separate inhalers (S+FP) in Japanese and Caucasian asthmatics. METHODS: This was a randomised, double-blind, crossover study in male and female Japanese (n=18) and Caucasian (n=17) asthmatics (50-100% predicted FEV(1); >35% reversibility in sGaw). Subjects received SFC (S 50 mcg/FP 250 mcg b.i.d.) and S+FP (S 50 mcg b.i.d.+FP 250 mcg b.i.d.) for 14 days. sGaw and FEV(1) were determined 0-12h after the first and last doses. RESULTS: Treatment with both SFC and S+FP produced marked bronchodilation, which was maintained 0-12h after the first dose. Baseline sGaw and FEV(1) increased up to 51% and 180 mL, respectively, in Japanese subjects over 2 weeks of treatment, with similar improvements in Caucasian subjects. On Day 14 the 0-12h S+FP:SFC treatment ratios (90% CI) for sGaw AUC and peak were 1.05 (0.98, 1.12) and 1.05 (0.97, 1.14), respectively, in Japanese subjects, and 0.99 (0.92, 1.07) and 0.98 (0.89, 1.07), respectively, in Caucasian subjects, with no difference between the two ethnic groups. CONCLUSIONS: The finding of a similar significant bronchodilator response in Japanese and Caucasian asthmatics following concurrent and combination treatment with salmeterol and FP suggests that the therapeutic response to these agents is comparable and independent of ethnicity in Japanese and Caucasian asthma patients.

Effects of pollen and nasal glucocorticoid on FOXP3+, GATA-3+ and T-bet+ cells in allergic rhinitis.

BACKGROUND: T-regulatory cells (Treg) affect the balance of T(H)2 and T(H)1 cells. Treg, T(H)2 and T(H)1 cells are regulated by the FOXP3, GATA-3 and T-bet transcription factors respectively. Our aim was to determine the number of FOXP3(+), GATA-3(+) and T-bet(+) cells in nasal mucosa in symptom-free allergic rhinitis (AR) patients vs healthy controls, as well as the effects of natural pollen exposure and concomitant nasal glucocorticoid treatment on these cells. METHODS: Nasal biopsies were taken from healthy controls and patients with grass-pollen AR preseason. The AR patients were randomized to receive treatment with either fluticasone propionate (FP) or a placebo, and additional biopsies were taken during the pollen season. FOXP3(+), GATA-3(+) and T-bet(+) cells in nasal mucosa were quantified by immunohistochemistry. RESULTS: The number of FOXP3(+) and GATA-3(+) cells, but not T-bet(+) cells, was significantly higher in AR patients vs controls preseason. The number of FOXP3(+) cells remained unchanged in the former group after the pollen season but decreased significantly in the nasal mucosa as a result of FP treatment. The pollen season substantially increased the number of GATA-3(+) cells, which was inhibited by FP. The number of T-bet(+) cells was not affected by pollen or FP. CONCLUSION: These data suggest that nasal glucocorticoids attenuate the allergic inflammation partly by reducing the number of T(H)2 cells, but not by means of local upregulation of Treg cells. The local relationship between T(H)1 and T(H)2 cells as well as between Treg and T(H)2 is maintained by nasal glucocorticoid treatment.

Increased number of CD34+ cells in nasal mucosa of allergic rhinitis patients: inhibition by a local corticosteroid.

BACKGROUND: Eosinophils develop from CD34+ haematopoietic progenitor cells. Allergen exposure in susceptible individuals is known to induce a local eosinophilic inflammation, but the effect on progenitor cells is much less understood. OBJECTIVE: We aimed to evaluate how allergen exposure affects the number of tissue CD34+ cells and CD34+ eosinophils in allergic rhinitis (AR) patients and whether any such effect is influenced by local corticosteroid treatment. Also, we evaluated changes in the number of CXC receptor 4-positive cells (CXCR4+), since the CXCR4 ligand (stromal cell-derived factor-1 (SDF-1)) is a potent chemoattractant for haematopoietic progenitors. METHODS: In a double-blind, randomized study, pollen-sensitized AR patients were treated with a nasal corticosteroid fluticasone propionate (FP, 200 microg/day) or placebo throughout the pollen season. Nasal biopsies were taken before and during the season. CD34 and CXCR4 were stained using immunohistochemistry. RESULTS: The pollen season significantly increased the number of CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in placebo-treated patients, but not in FP-treated patients. The mean pollen season-induced increase in CD34+ cells, CD34+/CXCR4+ cells and CD34+ eosinophils in FP-treated patients was lower compared with placebo-treated patients. CONCLUSION: A pollen season increases the number of CD34+ cells in nasal tissue accompanied by an increase in the number of CD34+/CXCR4+ haematopoietic progenitors and also the number of CD34+ eosinophils in subjects with AR. Treatment with a local corticosteroid provides protection against this pollen-induced increase in tissue CD34+ cells and CD34+ eosinophils possibly via inhibition of allergen-induced CXCR4-mediated recruitment of CD34+ haematopoietic progenitors into airways and their further differentiation into eosinophils within the tissue.

Conformational fluctuations and large fluorescence spectral diffusion in conjugated polymer single chains at low temperatures.

The fluorescence of single chains of the conductive polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene vinylene] (MEH-PPV) was studied by means of single-molecule spectroscopy at 15 K. MEH-PPV was deposited onto a surface from a toluene solution and covered with a polymer cap layer of poly(vinyl alcohol) spin-coated from an aqueous solution for protection against air. Because MEH-PPV is insoluble in water, such sample preparation guarantees that MEH-PPV chains do not mix with the cap polymer. We found that this "host matrix free" environment results in substantially stronger fluorescence spectral diffusion than that observed for conjugated polymer single chains embedded into polymer matrices. The average spectral diffusion range was 500 cm(-1), and the maximum registered value reached 1100 cm(-1), which is approximately 6 times larger than the values reported before. We analyzed spectral diffusion by observation of temporal evolution of the fluorescence intensity, the position of the maximum, and the width of fluorescence spectra. We propose that the transition energy shifts are caused by the differences of the London dispersive forces in slightly different polymer chain conformations. Such conformational changes are possible even at low temperatures because the MEH-PPV single chains in our samples have more freedom for fluctuations than in the usual "in host" arrangement.

Effect of seasonal allergen exposure on mucosal IL-16 and CD4+ cells in patients with allergic rhinitis.

BACKGROUND: CD4+ T cells constitute a major source of cytokines in allergic diseases such as allergic rhinitis. Interleukin (IL)-16 selectively recruits CD4+ cells. METHODS: We evaluated the effect of natural allergen exposure during a grass-pollen season on IL-16 expression and number of CD4+ cells in nasal mucosa. Patients with allergic rhinitis (n=16) were treated with either a nasal glucocorticoid beclomethasone (BDP; 400 microg/day) or placebo, and gave nasal biopsies prior to and during the grass-pollen season. The evaluated markers in allergic rhinitis patients were also compared to those in healthy control subjects (n=5). RESULTS: Prior to the pollen season, the expression of IL-16, but not the number of CD4+ cells, was significantly higher in patients with allergic rhinitis than in healthy control subjects. The grass-pollen season further increased IL-16 expression and also increased the number of CD4+ cells in placebo-treated, but not in BDP-treated, allergic rhinitis patients. The pollen-season-induced change in IL-16 expression and in CD4+ cells was significantly more pronounced in placebo- than in BDP-treated patients. There was a significant correlation between the change in IL-16 expression and the number of CD4+ cells. CONCLUSIONS: These data suggest that local upregulation of IL-16 expression contributes to the inflammation observed in seasonal allergic rhinitis. Hypothetically, inhibition of IL-16 expression can be one of several mechanisms by which nasal glucocorticoids achieve their anti-inflammatory effect in allergic rhinitis.

Exciton delocalization probed by excitation annihilation in the light-harvesting antenna LH2.

Singlet-singlet annihilation is used to study exciton delocalization in the light harvesting antenna complex LH2 (B800-B850) from the photosynthetic purple bacterium Rhodobacter sphaeroides. The characteristic femtosecond decay constants of the high intensity isotropic and the low intensity anisotropy kinetics of the B850 ring are related to the hopping time tau(h) and the coherence length N(coh) of the exciton. Our analysis yields N(coh) = 2.8+/-0.4 and tau(h) = 0.27+/-0.05 ps. This approach can be seen as an extension to the concept of the spectroscopic ruler.

Intermolecular hydrogen bonding between carotenoid and bacteriochlorophyll in LH2.

We have studied van der Waals contacts of the carotenoid rhodopin glucoside (RG) with the bacteriochlorophyll pigments absorbing at 800 nm (B800) in the crystal structure of Rhodopseudomonas acidophila, and the hydrogen positions were determined from quantum chemical calculations at the Hartree--Fock (6-31G) level. We have found strong evidence for hydrogen bonding between the B800 BChl and the RG from neighboring protomer units. The binding energy was estimated to be about 2 kcal/mol (700 cm(-1)). CI-singles approach and time-dependent density functional theory calculations of the B800--RG dimer indicate a red-shift (ca 2 nm) of the B800 Q(y) transition, along with a substantial increase of its oscillator strength, probably due to the hydrogen bonding.

Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid.

BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. OBJECTIVE: We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 microgram/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. CONCLUSION: Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.

B800-->B850 energy transfer mechanism in bacterial LH2 complexes investigated by B800 pigment exchange.

Femtosecond transient absorption measurements were performed on native and a series of reconstituted LH2 complexes from Rhodopseudomonas acidophila 10050 at room temperature. The reconstituted complexes contain chemically modified tetrapyrrole pigments in place of the native bacteriochlorophyll a-B800 molecules. The spectral characteristics of the modified pigments vary significantly, such that within the B800 binding sites the B800 Q(y) absorption maximum can be shifted incrementally from 800 to 670 nm. As the spectral overlap between the B800 and B850 Q(y) bands decreases, the rate of energy transfer (as determined by the time-dependent bleaching of the B850 absorption band) also decreases; the measured time constants range from 0.9 ps (bacteriochlorophyll a in the B800 sites, Q(y) absorption maximum at 800 nm) to 8.3 ps (chlorophyll a in the B800 sites, Q(y) absorption maximum at 670 nm). This correlation between energy transfer rate and spectral blue-shift of the B800 absorption band is in qualitative agreement with the trend predicted from Förster spectral overlap calculations, although the experimentally determined rates are approximately 5 times faster than those predicted by simulations. This discrepancy is attributed to an underestimation of the electronic coupling between the B800 and B850 molecules.

Bronchial hyperresponsiveness and airway wall remodelling induced by exposure to allergen for 9 weeks.

Prolonged exposure to allergen has been proposed to be important for the development of bronchial hyperresponsiveness and airway remodelling in asthma. The present study was designed to examine the effect of chronic allergen exposure on bronchial responsiveness, eosinophil infiltration, and airway remodelling. We sensitized brown Norway rats with the occupational allergen trimellitic anhydride (TMA) and exposed the animals to TMA conjugated to rat serum albumin (TMA-RSA) on 5 consecutive days each week for 9 weeks, starting 4 weeks after sensitization. IgE and IgG anti-TMA antibodies in serum and bronchial responsiveness to acetylcholine were evaluated before and at weeks 3, 6, and 9 of allergen exposure. Thickness of the airway wall, airway luminal narrowing, and the number of goblet cells and eosinophils in the airway wall were evaluated with an image analysis system in lungs resected after the last assessment of bronchial responsiveness, at the end of the 9-week allergen exposure. All rats developed IgE and IgG anti-TMA antibodies after sensitization. The levels of antibodies increased with allergen exposure until week 6, and then declined. Bronchial hyperresponsiveness to acetylcholine was induced in allergen-exposed rats without ongoing airway eosinophilia. Bronchial hyperresponsiveness induced by chronic allergen exposure via inhalation was accompanied by significantly increased thickness of smooth muscle and airway narrowing in the small airways, and goblet cell hyperplasia in the large airways. We conclude that chronic exposure to allergen can induce bronchial hyperresponsiveness and airway wall remodelling. Airway wall remodelling may contribute to bronchial hyperresponsiveness.

Treating asthma with anti-IgE or anti-IL5.

In the last decades, several key mechanisms driving asthma pathophysiooogy have been discovered. These include the role of IgE in allergic disease, and the role of IL-5 in eosinophilic inflammation. In the last few years, tools to block each of these have been developed. At this time, early clinical studies with neutralizing antibodies against both IgE and IL-5 have been performed in asthma patients, with promising results, and larger studies are underway. The mechanisms of, and possible role of, both anti-IgE and anti-IL-5 treatment in asthma are discussed in this review article.

Randomized placebo-controlled study comparing a leukotriene receptor antagonist and a nasal glucocorticoid in seasonal allergic rhinitis.

Allergic rhinitis is an inflammatory disorder associated with local leukotriene release during periods of symptoms. Therefore, it has been suggested that antileukotrienes may be beneficial in the treatment of this disease. Leukotriene receptor antagonists have recently become available for asthma treatment, but little is known of their effects on allergic rhinitis. We have evaluated the effects of the leukotriene receptor antagonist zafirlukast versus placebo in patients with allergic rhinitis during the grass pollen season, using the nasal glucocorticoid beclomethasone dipropionate (BDP) as a positive treatment control. Thirty-three patients with seasonal allergic rhinitis were in a double-blind, double-dummy fashion randomized to treatments with oral zafirlukast (20 mg twice a day), intranasal beclomethasone dipropionate (200 microg twice a day), or placebo. The treatment was initiated 3 wk prior to the expected beginning of the grass pollen season. Patients completed a daily symptom-score list for sneezing, rhinorrhea, nasal itch, and nasal blockage during the 50-d treatment period. Nasal biopsies for quantification of local tissue eosinophilia (immunohistochemistry; EG2) were taken 1 mo before initiation of treatment and immediately after the peak of grass pollen season. Patients receiving treatment with zafirlukast had degrees of nasal symptoms similar to those in the placebo group, whereas the BDP group had significantly less symptoms compared with both treatments (p = 0.01 and p = 0.005, respectively). The numbers of activated eosinophils in the nasal tissue increased significantly during the pollen season in both the zafirlukast and the placebo groups, but not in the BDP group. These results obtained with a limited number of patients do not support any clinical efficacy of regular treatment with an oral antileukotriene in seasonal allergic rhinitis but rather favor the use of a nasal glucocorticoid.

An IL-2-toxin, DAB389IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production.

BACKGROUND: Expression of high-affinity IL-2 receptor (IL-2R) on T lymphocytes, key cells in chronic inflammation, is a T-cell activation marker. OBJECTIVE: We sought to evaluate the effect of the fusion protein DAB389IL-2, which kills cells bearing IL-2R, on delayed-type hypersensitivity and antibody production in Brown Norway rats sensitized with trimellitic anhydride (TMA). METHODS: DAB389IL-2 (25 micrograms/kg/day) or placebo was administered intraperitoneally for 8 days over the period of sensitization, starting 2 days before sensitization. RESULTS: The administration of DAB389IL-2 resulted in a one-third reduction in the number of IL-2R-bearing cells and significant weight loss of animals. Delayed-type hypersensitivity, evaluated at 5 weeks after sensitization, was significantly inhibited by treatment with DAB389IL-2. In contrast, production of IgE anti-TMA antibodies after sensitization was increased by treatment with DAB389IL-2. DAB389IL-2 affected neither IgG anti-TMA antibody nor total IgE levels. CONCLUSION: These data imply that systemic administration of DAB389IL-2 in Brown Norway rats influences cells that have regulatory effects on the immune system, resulting in a switch from a TH1 to a TH2 type of immune response.

Bystander suppression of occupational hapten sensitization in rats made tolerant to ovalbumin.

Feeding a soluble antigen to an animal is known to cause a state of unresponsiveness against this antigen. If this antigen is given together with another antigen during the sensitization procedure, impairment of the response to the new antigen can also be seen, a phenomenon referred to as bystander suppression. The induction of tolerance against ovalbumin (OvA) and the effect of bystander suppression on the response to the hapten trimellitic anhydride (TMA), a cause of occupational asthma, were studied in Brown-Norway rats. Rats were fed either OvA-containing pellets or standard diet for 16 days before sensitization with the mixture of TMA and OvA. The animals were followed for 6 weeks after sensitization. Animals made tolerant to OvA showed a significantly suppressed delayed-type hypersensitivity (DTH) reaction against both OvA and TMA compared with the nontolerized control group at 5 weeks after sensitization, implying bystander suppression. By contrast, immunoglobulin (Ig)E and IgG antibody levels were suppressed only against OvA, whereas anti-TMA antibody levels were not affected. Airway eosinophilia after a single aerosol challenge at 6 weeks after sensitization using TMA conjugated to rat serum albumin, correlated with IgE anti-TMA levels in the group made tolerant to OvA and was not affected by OvA ingestion. In conclusion, suppressive factors released in ovalbumin-tolerant rats when they are challenged with ovalbumin, can suppress the response to trimellitic anhydride and this suppression is more pronounced for T-helper1-type responses.

Fluorescence and absorption spectroscopy of the weakly fluorescent chlorophyll a in cytochrome b6f of Synechocystis PCC6803.

A spectroscopic characterization of the chlorophyll a (Chl) molecule in the monomeric cytochrome b6f complex (Cytb6f) isolated from the cyanobacterium Synechocystis PCC6803 is presented. The fluorescence lifetime and quantum yield have been determined, and it is shown that Chl in Cytb6f has an excited-state lifetime that is 20 times smaller than that of Chl in methanol. This shortening of the Chl excited state lifetime is not caused by an increased rate of intersystem crossing. Most probably it is due to quenching by a nearby amino acid. It is suggested that this quenching is a mechanism for preventing the formation of Chl triplets, which can lead to the formation of harmful singlet oxygen. Using site-selected fluorescence spectroscopy, detailed information on vibrational frequencies in both the ground and Qy excited states has been obtained. The vibrational frequencies indicate that the Chl molecule has one axial ligand bound to its central magnesium and accepts a hydrogen bond to its 13(1)-keto carbonyl. The results show that the Chl binds to a well-defined pocket of the protein and experiences several close contacts with nearby amino acids. From the site-selected fluorescence spectra, it is further concluded that the electron-phonon coupling is moderately strong. Simulations of both the site-selected fluorescence spectra and the temperature dependence of absorption and fluorescence spectra are presented. These simulations indicate that the Huang-Rhys factor characterizing the electron-phonon coupling strength is between 0.6 and 0.9. The width of the Gaussian inhomogeneous distribution function is 210 +/- 10 cm-1.

Ultrafast carotenoid band shifts probe structure and dynamics in photosynthetic antenna complexes.

We report observations of ultrafast carotenoid band shifts correlated with energy transfer dynamics between bacteriochlorophyll (BChl) molecules within the peripheral light-harvesting complex (LH2) from the photosynthetic bacterium Rhodobacter sphaeroides. Direct excitation of the bacteriochlorophyll Qy bands yielded distinct changes in the carotenoid S2 absorption from 430 to 530 nm. Transient absorption spectra and kinetics were measured in a femtosecond pump-probe experiment, revealing the ultrafast carotenoid response to excited BChl pigments. These data are an indication of a new property of carotenoids that is manifested as a unique ability to detect and report changes in their immediate environment, thereby serving as sensitive probes of local structure and dynamics.