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Background Human papillomavirus (HPV) infection is known to promote the development of mucosal squamous cell carcinoma (mSCC), including pathologically high-grade lesions, but its role in cutaneous squamous cell carcinoma (cuSCC) remains unclear, particularly in lesions that are considered high risk. Objective We aimed to determine whether enhanced HPV transcriptional activity can be detected in high-risk cuSCC samples compared with low-grade SCC samples or normal skin. Methods We performed RNA sequencing of cuSCC across 23 risk-stratified skin lesions. A subset of samples was tested for the presence of HPV DNA. High-quality, non-human reads from each sample group were used for viral analysis using Microbiome Coverage Profiler. Results None of the samples analysed had detectable expression of HPV RNA, while 64% of samples tested positive for HPV DNA. All samples were found to have expression of human endogenous retrovirus, and multiple samples showed expression of other viruses. Conclusions Viral and prophage gene expression can be monitored in cuSCC or normal skin biopsies, yet no sample in our study showed evidence of active HPV gene expression despite evidence of HPV genome presence. This suggests HPV transcription does not play a role in differentiating high-risk cuSCCs from low-risk cuSCCs or normal skin.

Fine-needle aspiration (FNA) for serial hepatic sampling may be an efficient and less invasive alternative to core needle biopsy (CNB), the current standard for liver tissue sampling. In this randomized, open-label trial in 31 participants with hepatitis C virus genotype 1 infection (NCT01678131/Merck protocol PN048), we evaluated the feasibility of using FNA to obtain human liver tissue samples appropriate for measuring hepatic pharmacokinetics (PK), using vaniprevir as a tool compound. The primary end point was successful retrieval of liver tissue specimens with measurable vaniprevir concentrations at two of three specified FNA time points. Twenty-nine patients met the primary end point and, therefore, were included in the PK analyses. Hepatic vaniprevir concentrations obtained with FNA were consistent with known vaniprevir PK properties. The shape of liver FNA and CNB concentration-time profiles were comparable. In conclusion, FNA may be effective for serial tissue sampling to assess hepatic drug exposure in patients with liver disease.

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In the present paper a single valence tautomeric cobalt complex placed in a dc electric field is examined. Along with the interaction with the electric field the model employed accounts for intramolecular transfer of the excess electron, vibronic and exchange interactions. To obtain the energy spectrum of the valence tautomeric complex in the electric field, the vibronic problem of the pseudo-Jahn-Teller effect is solved. The vibronic (hybrid) wave-functions and energy levels are used for the calculation of the temperature and field dependence of the molecular magnetic moment, and the polarization and shape of the absorption band in the near infrared range that relates to the light-induced transfer of the electron from the cat ligand to the metal ion. It is predicted that the application of a dc electric field leads to the appearance of electric polarization and significant change in magnetic and spectroscopic properties. A unique possibility to control electrically the magnetic state and optical and polarization characteristics of a valence tautomeric molecule is predicted.

Potentielle biomedizinische Anwendungen von Graphenoxid (GO), z. B. als Trager von Biomolekulen, Reagentien fur die photothermische Therapie oder Biosensoren, werden durch die Zytotoxizitat und Mutagenitat dieses Materials eingeschrankt. Es wird davon ausgegangen, dass diese Eigenschaften zumindest zum Teil auf eine von GO verursachte Erhohung des oxidativen Stresses in Zellen zuruckzufuhren ist. Es ist jedoch nicht bekannt, auf welchen chemischen Fragmenten dieser ungunstige Effekt beruht. In dieser Arbeit wurden vier GOs entwickelt, welche verschiedene redoxaktive Gruppen wie Mn2+, C-zentrierte Radikale sowie Endoperoxide (EPs) auf der Oberflache besitzen. Der Vergleich der Fahigkeit der Materialien, reaktive Sauerstoffspezies in humanen Gebarmutterhalskrebszellen zu generieren, zeigt, dass EPs eine entscheidende Rolle im GO-induzierten oxidativen Stress spielen. Diese Ergebnisse konnen fur die gezielte Entwicklung von biokompatiblem und nicht-toxischem GO fur biomedizinische Anwendungen verwendet werden.

Mid-thigh cross-sectional muscle area (CSA), muscle attenuation, and greater trochanter soft tissue thickness have been shown to be independent risk factors of hip fracture. Our aim was to determine whether muscle and adipose tissue measures derived from dual-energy X-ray absorptiometry (DXA) scans would have a similar risk association as those measured using other imaging methods. Using a case-cohort study design, we identified 169 incident hip fracture cases over an average of 13.5 years among participants from the Health ABC Study, a prospective study of 3075 individuals initially aged 70 to 79 years. We modeled the thigh 3D geometry and compared DXA and computed tomography (CT) measures. DXA-derived thigh CSA, muscle attenuation, and subcutaneous fat thickness were found to be highly correlated to their CT counterparts (Pearson's r = 0.82, 0.45, and 0.91, respectively; p < 0.05). The fracture risk of men and women were calculated separately. We found that decreased subcutaneous fat, CT thigh muscle attenuation, and appendicular lean mass by height squared (ALM/Ht2) were associated with fracture risk in men; hazard ratios (HR) = 1.44 (1.02, 2.02), 1.40 (1.05, 1.85), and 0.58 (0.36, 0.91), respectively, after adjusting for age, race, clinical site, body mass index (BMI), chronic disease, hip bone mineral density (BMD), self-reported health, alcohol use, smoking status, education, physical activity, and cognitive function. In a similar model for women, only decreases in subcutaneous fat and DXA CSA were associated with hip fracture risk; HR = 1.39 (1.07, 1.82) and 0.78 (0.62, 0.97), respectively. Men with a high ALM/Ht2 and low subcutaneous fat thickness had greater than 8 times higher risk for hip fracture compared with those with low ALM/Ht2 and high subcutaneous fat. In women, ALM/Ht2 did not improve the model when subcutaneous fat was included. We conclude that the DXA-derived subcutaneous fat thickness is a strong marker for hip fracture risk in both men and women, especially in men with high ALM/Ht2. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research

Purpose To evaluate the test performance of perfusion-weighted Fourier-decomposition (pw-FD) magnetic resonance imaging (MRI) in comparison to dynamic contrast-enhanced (DCE)-MRI as a reference standard in patients with known or suspected chronic pulmonary embolism (PE). Materials and Methods In 64 patients, chronic PE was ruled out or confirmed by DCE-MRI using a time-resolved angiography with stochastic trajectories (TWIST) sequence in one breath-hold. Pw-FD-MRI was performed using a 2D fast low-angle shot (FLASH) sequence in free-breathing. After a nonrigid image registration, FD was applied to generate pw-images. Lungs were scored by two radiologists (2 and 12 years of lung MRI experience) visually for each lobe and segment for hypoperfused areas. For intra- and interobserver variability, the MR images were analyzed 2 months after the first analysis, blinded to the results of the first reader. Results PE was diagnosed by DCE-MRI in 39 patients. For the pw-FD MRI sensitivity, specificity, accuracy, and positive and negative predictive value for diagnosis of PE were 100%, 95%, 98%, 98%, and 100% on a per-patient basis, 94%, 94%, 94%, 95%, 94% on a per-lobe basis, and 82%, 92%, 88%, 88%, 88% on a segmental basis, respectively. Detection of subsegmental and segmental hypoperfusion using pw-FD MRI showed a moderate agreement with DCE-MRI (kappa of 0.68; 95% confidence interval: 0.64; 0.72). Conclusion Pw-FD of the lung is a feasible test to diagnose chronic PE on a per-patient level during free-breathing without the use of ionizing radiation or contrast agents. J. Magn. Reson. Imaging 2015;42:72–79. © 2014 Wiley Periodicals, Inc.

A series of four 1,2,3-triazolium-based poly(ionic liquid)s (TPILs) is synthesized from the polyaddition of different tailor-made α-azide-ω-alkyne monomers by copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC), followed by quaternization with methyl iodide and subsequent anion exchange with lithium bis(trifluoromethylsulfonyl)imide. Whereas the chemical structures of the bis(trifluoromethylsulfonyl)imide counter anion and the N-3 methyl group are common to all TPILs, the structural features of the repeating units, i.e., triethylene glycol or undecanoyl spacers with either ester or ether linkages, are varied and compared. Their impact on the physical and ion-conducting properties of the obtained TPILs is established based on 1H NMR, DSC, thermogravimetric analysis (TGA), and broadband di­electric spectroscopy (BDS) characterization techniques. Most importantly, the replacement of an ether by an ester group at the C-4 position of the 1,2,3-triazolium ring significantly decreases the thermal stability and ionic conductivity of TPILs, whereas the chemical nature of the triethylene glycol or undec­anoyl spacers has little influence on the materials properties.

We investigated the influence of hydrophilic and hydrophobic imidazolium ionic liquids on the curing kinetic, mechanical, morphological and ionic conductivity properties of nitrile rubber composites. Two room temperature ionic liquids with a common cation—1-ethyl-3-methylimidazolium thiocyanate (EMIM SCN; hydrophilic) and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIM TFSI; hydrophobic)—were used. Magnesium–aluminium layered double hydroxide (MgAl-LDH; also known as hydrotalcite) was added to carboxylated acrylonitrile–butadiene rubber (XNBR) whereas fumed silica Aerosil 380 was used in acrylonitrile–butadiene rubber (NBR) as reinforcing fillers. NBR compounds were vulcanized with a conventional sulfur-based crosslinking system whereas XNBR compounds were cured with MgAl-LDH. The optimum cure time reduction and tensile properties improvement were obtained when both ionic liquids were added at 5 parts per hundred rubber (phr). The results revealed that EMIM SCN and EMIM TFSI induced an increase in the AC conductivity of nitrile rubber composites from 10−10 to 10−8 and to 10−7 S cm−1, respectively (at 15 phr ionic liquid concentration). The presence of ionic liquids in NBR slightly affected the glass transition temperature (Tg) whereas the presence of EMIM TFSI in XNBR contributed to a shift in Tg towards lower temperatures from −23 to −31 °C, at 15 phr loading, which can be attributed to the plasticizing behaviour of EMIM TFSI in the XNBR/MgAl-LDH system. Dynamic mechanical analysis was also carried out and the related parameters, such as the mechanical loss factor and storage modulus, were determined. © 2013 Society of Chemical Industry

Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood- and pre-erythrocytic liver stages of the parasite. P. falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial type II fatty acid biosynthesis (FAS II). It has been shown to be essential for liver-stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood-stage parasite growth with IC(50) values of 1.7 and 3.0 μM and lead to a more prominent developmental attenuation of liver-stage parasites than the gold-standard drug, primaquine.

This article challenges some deep-rooted assumptions of project management. Inspired by the work of the German philosopher, Arthur Schopenhauer, it calls for looking at projects through two complementary lenses: one that accounts for cognitive and representational aspects and one that accounts for material and volitional aspects. Understanding the many ways in which these aspects transpire and interact in projects sheds new light on project organizations, as imperfect and fragile representations that chase a shifting nexus of intractable human, social, technical, and material processes. This, in turn, can bring about a new grasp of notions such as value, knowledge, complexity, and risk.

SUMMARY 1. The metabolic balance of plankton communities, commonly assessed by the photosynthesis-torespiration ratio (P : R), has received much attention recently in connection with allochthonous organic subsidies to lakes, while the role of physical, climate-related forces has received less attention. 2. Here we evaluated the effects of wind and upwelling events on plankton metabolism and the potential of stable oxygen isotopes to characterise P, R and P : R on the scales necessary to characterise properly physical forcing effects in large lakes. 3. We measured the 18 O ⁄ 16 O ratio of dissolved oxygen and water in a large productive embayment of Lake Ontario (Hamilton Harbour, Canada) and estimated P, R and P : R from the steady state solutions of a widely accepted mass balance model, together with estimates of wind-driven gas exchange, and compared the results with those from experimental incubations of plankton samples. 4. Estimates of P, but not R, from the isotope model were significantly correlated with bottle estimates while average P : R was similar by both methods. Closer examination of physical forcing events led to a model of how wind events induce mixing, upwelling, exchange and consequent changes in P and R. These physical forcing events were captured more by the isotope model than by the bottle estimates, as episodes of immediately increased R and decreased P : R, with a subsequent stimulation of P. 5. The oxygen isotope approach provided valuable measures of plankton metabolism and helped to characterise more effectively the substantial effects on P : R of physical forcing and, in particular, mixing and exchange events.

Suggesting that bioartificial vascular scaffolds cannot but tissue-engineered vessels can withstand biomechanical stress, we developed in vitro methods for preclinical biological material testings. The aim of the study was to evaluate the influence of revitalization of xenogenous scaffolds on biomechanical stability of tissue-engineered vessels. For measurement of radial distensibility, a salt-solution inflation method was used. The longitudinal tensile strength test (DIN 50145) was applied on bone-shaped specimen: tensile/tear strength (SigmaB/R), elongation at maximum yield stress/rupture (DeltaB/R), and modulus of elasticity were determined of native (NAs; n = 6), decellularized (DAs; n = 6), and decellularized carotid arteries reseeded with human vascular smooth muscle cells and human vascular endothelial cells (RAs; n = 7). Radial distensibility of DAs was significantly lower (113) than for NAs (135) (P < 0.001) or RAs (127) (P = 0.018). At levels of 120 mm Hg and more, decellularized matrices burst (120, 160 n = 2 and 200 mm Hg). Although RAs withstood levels up to 300 mm Hg, ANOVA revealed a significant difference from NA (P = 0.018). Compared with native vessels (NAs), SigmaB/R values were lower in DAs (44%; 57%) (P = 0.014 and P = 0.002, respectively) and were significantly higher in RAs (71%; 83%) (both P < 0.001). Similarly, DeltaB/R values were much higher in DAs compared with NAs (94%; 88%) (P < 0.001) and RAs (87%; 103%) (P < 0.001), but equivalent in NAs and RAs. Modulus of elasticity (2.6/1.1/3.7 to 16.6 N/mm(2)) of NAs, DAs, RAs was comparable (P = 0.088). Using newly developed in vitro methods for small-caliber vascular graft testing, this study proved that revitalization of decellularized connective tissue scaffolds led to vascular graft stability able to withstand biomechanical stress mimicking the human circulation. This tissue engineering approach provides a sufficiently stable autologized graft.

Starting from the optically pure [6]helicene-like alcohol(P,3S)-3-methyl-4-(4-methylphenyl)-1,3,6,7-tetrahydrobenzo[c]benzo[5,6]phenanthro[4,3-e]oxepin-14-ol, four helical phosphites were prepared from the corresponding chlorophosphites. These ligands containing parent or substituted 1,3,2-dioxaphospholan-2-yl or dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl moieties were applied to the asymmetric hydroformylation of terminal alkenes catalyzed by Rh(acac)(CO)2 and the asymmetric allylic amination of cinnamyl-type carbonates catalyzed by [Ir(cod)Cl]2. The helical phosphite containing the dibenzo[d,f][1,3,2]dioxaphosphepin-6-yl group was most successful in the asymmetric hydroformylation of styrene, leading to moderate enantiomeric excess values (up to 32 % ee), high regioselectivity in favor of the branched product, and mostly high conversion, whereas the helical ligand containing the 4,4,5,5-tetramethyl-1,3,2-dioxaphospholan-2-yl fragment was most effective in asymmetric allylic aminations, exhibiting high enantioselectivity (up to 94 % ee), excellent regioselectivity in favor of the branched products, and good reactivity. This study represents the first use of helicene-like ligands in asymmetric reactions, including hydroformylation and allylic amination, and the promising results indicate the potential of the helicene moieties as chiral inductors.

We report the first single-molecule magnet (SMM) to incorporate the [Os(CN)(6)](3-) moiety. The compound (1) has a trimeric, cyanide-bridged Mn(III)-Os(III)-Mn(III) skeleton in which Mn(III) designates a [Mn(5-Brsalen)(MeOH)](+) unit (5-Brsalen=N,N'-ethylenebis(5-bromosalicylideneiminato)). X-ray crystallographic experiments reveal that 1 is isostructural with the Mn(III)-Fe(III)-Mn(III) analogue (2). Both compounds exhibit a frequency-dependent out-of-phase χ''(T) alternating current (ac) susceptibility signal that is suggestive of SMM behaviour. From the Arrhenius expression, the effective barrier for 1 is found to be Δ(eff)/k(B)=19 K (τ(0)=5.0×10(-7) s; k(B)=Boltzmann constant), whereas only the onset (1.5 kHz, 1.8 K) of χ''(T) is observed for 2, thus indicating a higher blocking temperature for 1. The strong spin-orbit coupling present in Os(III) isolates the E'(1g(1/2))(O(h)*) Kramers doublet that exhibits orbital contributions to the single-ion anisotropy. Magnetic susceptibility and inelastic neutron-scattering measurements reveal that substitution of [Fe(CN)(6)](3-) by the [Os(CN)(6)](3-) anion results in larger ferromagnetic, anisotropic exchange interactions going from quasi-Ising exchange interactions in 2 to pure Ising exchange for 1 with J(parallel)(MnOs)=-30.6 cm(-1). The combination of diffuse magnetic orbitals and the Ising-type exchange interaction effectively contributes to a higher blocking temperature. This result is in accordance with theoretical predictions and paves the way for the design of a new generation of SMMs with enhanced SMM properties.

Summary 1. Despite the recognition of its importance, benthic primary production is seldom reported, especially for large lakes. We measured in situ benthic net primary production by monitoring flux in dissolved inorganic carbon (DIC) concentration in benthic incubation chambers, based on continuous measurements of CO2(aq) flux, alkalinity, and the temperature-dependent dissociation constants of carbonic acid (K1 and K2). This methodology has the advantages of monitoring net primary production directly as change in carbon, maintaining continuous water recirculation, and having sufficient precision to detect change in DIC over short (i.e. 15 min) incubations, even in alkaline waters. 2. Benthic primary production on Cladophora-dominated rocky substrata in western Lake Ontario was measured biweekly. Maximum biomass-specific net photosynthetic rates were highest in the spring (2.39 mgC g Dry Mass−1 h−1), decreased to negative rates by early summer (−0.76 mgC g DM−1 h−1), and exhibited a regrowth in late summer (1.98 mgC g DM−1 h−1). 3. A Cladophora growth model (CGM), previously validated to predict Cladophora biomass accrual in Lake Ontario, successfully simulated the seasonality and magnitude of biomass-specific primary production during the first cohort of Cladophora growth. Averaged over this growing season (May–Aug), mean areal net benthic production at the estimated depth of peak biomass (2 m) was 405 mg C m−2 d−1. 4. We measured planktonic primary production in proximity to the benthic study and constructed a depth-resolved model of planktonic production. Using the CGM, benthic primary production was compared with planktonic primary production for the period May–Aug. Net benthic production from the shoreline to the 12 m contour (1–2 km offshore) equalled planktonic production. Closer to shore, benthic primary production exceeded planktonic primary production. Failure to account for benthic primary production, at least during abundant Cladophora growth, will lead to large underestimates in carbon and nutrient flows in the nearshore zone of this Great Lake.

This work reports the possibility of controlling the sense of enantio- and diastereoinductions in the sequential hydroformylation and aldol reactions via the judicious combination of a chiral metal catalyst with a chiral organocatalyst. The diastereoselectivity of the reaction between styrene, syngas and acetone can be increased by using a matched pair of catalysts, [rhodium/(2S,4S)-Chiraphite]/(S)-organocatalyst and decreased, but not inverted, by using a mismatched pair of catalysts, [rhodium/(2R,4R)-Chiraphite]/(S)-organocatalyst.

Detergents are powerful agents for tissue decellularization. Despite this, the high toxicity of detergent residua can be a major limitation. This study evaluated the efficacy of detergent removal from decellularized pulmonary valves (PVs) and the consequences of repopulation with human endothelial cells (HECs). Porcine PVs were treated with 1% sodium deoxycholate (SDC), group A; 1% sodium dodecyl sulfate (SDS), group B; and a mixture of 0.5% SDC/0.5% SDS, group C (n = 5 each). After each of 10 succeeding wash cycles (WCs), samples of the washing solution (WS) were analyzed by solid phase extraction and high performance liquid chromatography for the presence of detergents. Metabolic activity of HEC was also assessed in the WS samples (cytotoxicity and MTS assays). Decellularized and washed PVs were reseeded with HEC. Histological analysis demonstrated efficient tissue decellularization in all groups. Detergents' concentration in all WSs decreased exponentially and was below 50 mg/L after 6, 8, and 4 WCs in groups A, B, and C, respectively. This concentration resulted in no significant toxic influence on cell cultures, and scaffolds could be efficiently reseeded with HEC. In conclusion, intensive washing of detergent decellularized valvular scaffolds lowers the residual contamination below a hazardous threshold and allows their successful repopulation with HEC for tissue engineering purposes.

Purpose: Mammography has a low sensitivity in dense breasts due to low contrast between malignant and normal tissue confounded by the predominant water density of the breast. Water is found in both adipose and fibroglandular tissue and constitutes most of the mass of a breast. However, significant protein mass is mainly found in the fibroglandular tissue where most cancers originate. If the protein compartment in a mammogram could be imaged without the influence of water, the sensitivity and specificity of the mammogram may be improved. This article describes a novel approach to dual-energy mammography, full-field digital compositional mammography (FFDCM), which can independently image the three compositional components of breast tissue: water, lipid, and protein. Methods: Dual-energy attenuation and breast shape measures are used together to solve for the three compositional thicknesses. Dual-energy measurements were performed on breast-mimicking phantoms using a full-field digital mammography unit. The phantoms were made of materials shown to have similar x-ray attenuation properties of the compositional compartments. They were made of two main stacks of thicknesses around 2 and 4 cm. Twenty-six thickness and composition combinations were used to derive the compositional calibration using a least-squares fitting approach. Results: Very high accuracy was achieved with a simple cubic fitting function with root mean square errors of 0.023, 0.011, and 0.012 cm for the water, lipid, and protein thicknesses, respectively. The repeatability (percent coefficient of variation) of these measures was tested using sequential images and was found to be 0.5%, 0.5%, and 3.3% for water, lipid, and protein, respectively. However, swapping the location of the two stacks of the phantom on the imaging plate introduced further errors showing the need for more complete system uniformity corrections. Finally, a preliminary breast image is presented of each of the compositional compartments separately. Conclusions: FFDCM has been derived and exhibited good compositional thickness accuracy on phantoms. Preliminary breast images demonstrated the feasibility of creating individual compositional diagnostic images in a clinical environment.

Purpose: This study describes the design and characteristics of a highly accurate, precise, and automated single-energy method to quantify percent fibroglandular tissue volume (%FGV) and fibroglandular tissue volume (FGV) using digital screening mammography. Methods: The method uses a breast tissue-equivalent phantom in the unused portion of the mammogram as a reference to estimate breast composition. The phantom is used to calculate breast thickness and composition for each image regardless of x-ray technique or the presence of paddle tilt. The phantom adheres to the top of the mammographic compression paddle and stays in place for both craniocaudal and mediolateral oblique screening views. We describe the automated method to identify the phantom and paddle orientation with a three-dimensional reconstruction least-squares technique. A series of test phantoms, with a breast thickness range of 0.5–8 cm and a %FGV of 0%–100%, were made to test the accuracy and precision of the technique. Results: Using test phantoms, the estimated repeatability standard deviation equaled 2%, with a ±2% accuracy for the entire thickness and density ranges. Without correction, paddle tilt was found to create large errors in the measured density values of up to 7%/mm difference from actual breast thickness. This new density measurement is stable over time, with no significant drifts in calibration noted during a four-month period. Comparisons of %FGV to mammographic percent density and left to right breast %FGV were highly correlated ( r = 0.83 and 0.94, respectively). Conclusions: An automated method for quantifying fibroglandular tissue volume has been developed. It exhibited good accuracy and precision for a broad range of breast thicknesses, paddle tilt angles, and %FGV values. Clinical testing showed high correlation to mammographic density and between left and right breasts.

Metal-catalysed hydroformylation is successfully combined with an organocatalysed stereoselective Mannich reaction in a tandem reaction sequence. This novel type of "tandem catalysis" allows access to complex molecular systems with high levels of enantioselectivity, using simple starting materials and an amino acid as the chiral catalyst.

Summary 1. Planktonic metabolic balance (PMBm) of the surface mixed layer (SML) was measured as the ratio of areal rates of gross photosynthesis (AGP) to community respiration (AR) to test the idea that previously neglected allochthonous inputs of organic matter may support chronic excess respiration relative to photosynthesis even in very large lakes during the summer (May–October) season. Four Laurentian Great Lakes coastal sites of varying trophic status, physical structure and dissolved organic carbon (DOC) concentration were studied with oxygen light-and dark bottle and 14C methods, with excess respiration anticipated in the higher DOC sites. 2. Planktonic metabolic balance was net autotrophic in 73% of the observations. The calculated mixing depth at which respiration would predominate over photosynthesis was greater than typically observed mixing depths, varying from 11 to 25 m in the more transparent, low DOC (

We develop a theoretical framework for understanding why firms adopt specific approaches for the management of innovation project portfolios. Our theory focuses on a key contingency factor for innovation, namely the dynamics of competitive environments. We use four dimensions to characterize the patterns of environmental dynamics: velocity, turbulence, growth and instability. The paper then proposes the concept of dynamic risk as a determinant of portfolio management processes. Dynamic risk results from second-order learning by a firm confronted with a specific dynamic pattern in its environment. This learning concerns the likely nature of threats and the required updating of cognitive frameworks in such environments. Attempts to deal with dynamic risk enable various actors inside the firm to understand what kind of dynamic capabilities are needed in their innovation portfolio management processes. As a result of this diffuse learning, firms tend to favor certain common characteristics in their concrete portfolio management activities. To advance the theorizing of these characteristics, the paper also proposes four dimensions of portfolio management: structure, commitment, emergence and integration. Based on arguments inspired by the dynamic capability and related literatures, we advance a series of hypotheses, that relate environmental dynamics dimensions and portfolio management dimensions. These hypotheses are tested based on a survey of 795 firms in a variety of sectors and on four continents, using original scales and structural equation modeling methods. The results show, among other findings, that high-velocity environments favor structured as well as integrated portfolio management approaches, while high-growth environments favor approaches that are structured but commit significant resources to each project as well. Turbulent environments favor approaches that are emergent, but also, contrary to our expectations, have high resource commitment levels. Finally, firms in unstable environments have a marginal preference for emergent approaches. Results could help advance the dynamic contingency theoretical perspective on dynamic capabilities, as well as improve the practice of innovation portfolio management.

This work is focused on the glassy dynamics of polymers under conditions of one-dimensional confinement (in thin films). Several important topics are addressed: (a) preparative factors with large impact on the molecular dynamics of thin polymer films (oxidative degradation, plasticizing effects, residual stresses leading to metastable states); (b) it is emphasized the necessity to characterize the glass transition by measuring relaxation time distribution functions; (c) it is shown that different experimental techniques do not necessarily deliver converging results when applied to characterise the dynamics of confined polymers; (d) a novel approach is demonstrated which grants a direct experimental access to interfacial polymer dynamics; (e) measurements on nearly isolated polymer chains are presented.

The dynamic glass transition and the dilatometric glass transition temperature are simultaneously characterized in thin films of hyperbranched aromatic polyesters by broadband dielectric spectroscopy and capacitive scanning dilatometry. A diverging thickness dependence is detected: while the temperature position of the alpha relaxation peak Tα decreases by ∼30 K, the dilatometric Tg increases by ∼10 K with decreasing film thickness. This emphasizes the subtle character of the glass transition phenomenon—as manifested in the molecular dynamics and in the (structural) thermal expansion—and proves that, in contrast to the bulk, different experimental techniques do not necessarily deliver similar results in confinement. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3006–3010, 2006

An alignment of serotonin [5-hydroxytryptamine (5-HT)] G protein-coupled receptors identified a lysine at position 4.45 (helix 4) and a small polar residue (serine or cysteine) at 7.45 (helix 7) that occur exclusively in the 5-HT2 receptor family. Other serotonin receptors have a hydrophobic amino acid, typically a methionine, at 4.45 and an invariant asparagine at 7.45. The functional significance of these class-specific substitutions was tested by site-directed mutagenesis of two distantly related 5-HT2 receptors, Caenorhabditis elegans 5-HT2ce and rat 5-HT2C. Residues 4.45 and 7.45 were each mutated to a methionine and asparagine, respectively, or an alanine and the resulting constructs were tested for activity. A K4.45M mutation decreased serotonin-dependent activity (Emax) of the rat 5-HT2C receptor by 60% and that of the C. elegans homologue by 40%, as determined by a fluorometric plate-based calcium assay. The rat mutant also exhibited nearly sixfold higher agonist binding affinity and significantly lower constitutive activity compared with wildtype. Mutagenesis of S7.45 in the C. elegans receptor increased serotonin binding affinity by up to 25-fold and decreased Emax by up to 65%. The same mutations of the cognate C7.45 in rat 5-HT2C produced a smaller fourfold change in the affinity for serotonin and decreased agonist efficacy by up to 50%. Substitutions of S/C7.45 did not produce a significant change in the basal activity of either receptor. All mutants tested exhibited levels of receptor expression similar to the corresponding wildtype based on measurements of specific [3H]-mesulergine binding or flow cytometry analyses. Taken together, these results suggest that K4.45 and S/C7.45 play an important role in the conformational rearrangements leading to agonist-induced activation of 5-HT2 receptors.

This paper uses a combination of grounded theorising and exploratory quantitative analysis to compare the patterns of organising and managing innovation in the New and Old Economies. The results show that firms in the NE put in place structures and processes that give the R&D function a more strategic position, link it directly to customers and accelerate innovation throughput inside the firm.

It is shown that in many cases an adequate description of optical spectra of semiconductor quantum dots requires a treatment beyond the commonly used adiabatic approximation. We have developed a theory of phonon-assisted optical transitions in semiconductor quantum dots, which takes into account non-adiabaticity of the exciton–phonon system. Effects of non-adiabaticity lead to a mixing of different exciton and phonon states that provides a key to the understanding of surprisingly high intensities of phonon satellites observed in photoluminescence spectra of quantum dots. A breakdown of the adiabatic approximation gives an explanation also for discrepancies between the serial law, observed in multi-phonon optical spectra of some quantum dots, and the Franck–Condon progression, prescribed by the adiabatic approach.