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Wastewater surveillance has been widely used as a supplemental method to track the community infection levels of severe acute respiratory syndrome coronavirus 2. A gap exists in standardized reporting for fecal indicator concentrations, which can be used to calibrate the primary outcome concentrations from wastewater monitoring for use in epidemiological models. To address this, measurements of fecal indicator concentration among wastewater samples collected from sewers and treatment centers in four counties of Kentucky (N = 650) were examined. Results from the untransformed wastewater data over 4months of sampling indicated that the fecal indicator concentration of human ribonuclease P (RNase P) ranged from 5.1 × 10¹ to 1.15 × 106 copies/ml, pepper mild mottle virus (PMMoV) ranged from7.23× 10³ to 3.53 ×107 copies/ml, and cross-assembly phage (CrAssphage) ranged from9.69×10³ to 1.85 × 108 copies/ml. The results showed both regional and temporal variability. If fecal indicators are used as normalization factors, knowing the daily sewer system flow of the sample location may matter more than rainfall. RNase P, while it may be suitable as an internal amplification and sample adequacy control, has less utility than PMMoV and CrAssphage as a fecal indicator in wastewater sampleswhenworking at different sizes of catchment area. The choice of fecal indicator will impact the results of surveillance studies using this indicator to represent fecal load. Our results contribute broadly to an applicable standard normalization factor and assist in interpreting wastewater data in epidemiological modeling and monitoring. [ABSTRACT FROM AUTHOR] more...

Wastewater monitoring for virus infections within communities can complement conventional clinical surveillance. Currently, most SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2) clinical testing is voluntary and inconsistently available, except for a few occupational and educational settings, and therefore likely underrepresents actual population prevalence. Randomized testing on a regular basis to estimate accurate population‐level infection rates is prohibitively costly and is hampered by a range of limitations and barriers associated with participation in clinical research. In comparison, community‐level fecal monitoring can be performed through wastewater surveillance to effectively surveil communities. However, epidemiologically defined protocols for wastewater sample site selection are lacking. Herein, we describe methods for developing a geographically resolved population‐level wastewater sampling approach in Jefferson County, Kentucky, and present preliminary results. Utilizing this site selection protocol, samples (n = 237) were collected from 17 wastewater catchment areas, September 8 to October 30, 2020 from one to four times per week in each area and compared to concurrent clinical data aggregated to wastewater catchment areas and county level. SARS‐CoV‐2 RNA was consistently present in wastewater during the studied period, and varied by area. Data obtained using the site selection protocol showed variation in geographically resolved wastewater SARS‐CoV‐2 RNA concentration compared to clinical rates. These findings highlight the importance of neighborhood‐equivalent spatial scales and provide a promising approach for viral epidemic surveillance, thus better guiding spatially targeted public health mitigation strategies. Plain Language Summary: The SARS‐CoV‐2 virus, which causes COVID‐19, is shed in the stool of infected persons. Samples collected from public sewers can be used for anonymous community monitoring to identify COVID‐19 "hot spots" that are not subject to the many limitations of clinical testing records, which are the standard method of COVID‐19 surveillance. Here, we describe methods for developing a sewer system sampling approach at the community scale by selection and sampling of wastewater from street lines, pumping stations, and treatment facilities in Jefferson County, Kentucky. Our preliminary data indicates that our sampling design allows for much higher spatial surveillance than the county scale, with fewer limitations than surveillance based on clinical testing records. This work outlines a viable approach to guide targeted public health response strategies for cities by taking advantage of wastewater sampling. Key Points: Epidemiologically defined protocols for wastewater sample site selection are lackingDemographically distinct catchment areas were selected with high spatial resolutionOur protocol may inform disease surveillance for geographically targeted scales [ABSTRACT FROM AUTHOR] more...

The impetus for dislocation motion in thin films is generally understood in terms of Peach-Koehler forces. For the case of III-nitride films grown on step-free 4H-SiC mesas, however, it is the gradient of the strain energy from the mesa edge that is capable of driving misfit dislocations. Using the strain profile as a function of the distance from the mesa edge and the line tension of the c-plane threading arms, we have calculated the excess stress driving the half loop from the mesa edge into the mesa interior. We have also compared the half-loop excess stress with the excess stress driving the tilt of threading edge dislocations, which has been proposed as one of the principal strain relief mechanisms in III-nitride films. The excess stress driving c-plane half loops ranges from a few 1000 MPa at the mesa edge to few 100 MPa towards the mesa interior, while the excess stress driving the tilt of threading edge dislocations is in excess of 20 000 MPa. The greater excess stress driving dislocation tilt, however, does not dominate strain relief for III-nitride films on step-free SiC mesas due to the difficulty in nucleating threading dislocations in the absence of interfacial steps. [ABSTRACT FROM AUTHOR] more...

Focuses on a study which determined the infrared dielectric constant of gallium arsenide (GaAs). Description of the GaAs wafers; Efficiency of error estimates technique in refractive indices determination; Considerations in the selection of parameters for the dielectric function expression. more...

Identifies the real dielectric constant for chemical vapor deposition 3C-SiC grown on silicon from an analytic fit to interference fringes in transmission over the spectral range from the near infrared to the submillimeter region. Samples used in the study; Equation for the transmission of a nonconducting wafer in air. more...

Presents a study that examined the dependence of morphology and transport of YBa[sub2]Cu[sub3]O[sub7-x] sputtered in argon, oxygen and hydrogen on deposition temperature. Description of the thin films used in the investigation; Analysis of the surface morphology for selected films using scanning electron microscopy; Measurement of surface profile and roughness. more...

Investigates the photoresponse of shallow step, weak-link bridges using inverted cylindrical magnetron-sputtered yttrium compound thin films. Substrates used in the fabrication of the thin films; Details on the device fabrication; Characterization of the device. more...

Presents information on a study that evaluated cubic SiC films grown by chemical vapor deposition on silicon substrates. Brief summary of the materials preparation; Calculation of infrared spectra for ideal SiC, in semi-infinite, thick-film, and thin-film forms; Calculation of spectra for films on semi-infinite and on slablike substrates and for free-standing films. more...

While several maternal exposures have been associated with an increased risk of atopic dermatitis (AD) in offspring, the effect of alcohol use during pregnancy on the risk of AD in offspring is unclear. Furthermore, it is unclear whether adults with AD have an increased alcohol use, although other poor health behaviours have been associated with AD including smoking and physical inactivity as well as psychiatric disease. In this systematic review and meta-analysis, the association between alcohol use and AD was investigated in two ways: 1) whether alcohol use (drinkers versus abstainers) during pregnancy is associated with AD in offspring and 2) whether AD is associated with increased alcohol use. The medical databases PubMed, EMBASE and Web of Science were searched, and data extraction was carried out by two independent reviewers. Eighteen studies were included in the qualitative analysis (comparing alcohol drinkers to abstainers), and 12 studies were included in the quantitative analysis. There was a positive association between alcohol use during pregnancy and development of AD in offspring (pooled odds ratio [OR] 1.16; 95% confidence interval [CI] 1.09-1.24). However, there was no consistent association between AD in adults and adolescents and alcohol use (pooled OR 1.06; 95% CI 0.92-1.23). There is a need for future well-designed prospective studies to firmly establish the association between alcohol use and AD. [ABSTRACT FROM AUTHOR] more...

The previously reported carbon dioxide fixation reaction by the planar terminal hydroxide complex [Ni(pyN2 Me2)(OH)]1- in DMF has been further characterized by determination of the equilibrium constants Keq298 = 2.4 ± 0.2 × 105 M-1 and Keq223 = 1.3 ± 0.1 × 107 M-1, as well as the volume of activation for the CO2 binding (ΔV≠on223 = -21 ± 3 cm3 mol-1) and back decarboxylation (ΔV≠off223 = -13 ± 1 cm3 mol-1) by high-pressure kinetics. The data are consistent with an earlier DFT computation, including the probable nature of the transition state, and support designating the reaction as one of the most completely investigated carbon dioxide fixation reactions of any type. [ABSTRACT FROM AUTHOR] more...

Background and Purpose Intestinal nutrient transporters may mediate the uptake of drugs. The aim of this study was to investigate whether sertraline interacts with the intestinal proton-coupled amino acid transporter 1 PAT1 ( SLC36A1). Experimental Approach In vitro investigations of interactions between sertraline and human ( h)PAT1, hSGLT1 (sodium-glucose linked transporter 1) and hPepT1 (proton-coupled di-/tri-peptide transporter 1) were conducted in Caco-2 cells using radiolabelled substrates. In vivo pharmacokinetic investigations were conducted in male Sprague- Dawley rats using gaboxadol (10 mg·kg−1, p.o.) as a PAT1 substrate and sertraline (0-30.6 mg·kg−1). Gaboxadol was quantified by hydrophilic interaction chromatography followed by MS/ MS detection. Key Results Sertraline inhibited hPAT1-mediated L-[ 3H]- Pro uptake in Caco-2 cells. This interaction between sertraline and PAT1 appeared to be non-competitive. The uptake of the hSGLT1 substrate [ 14C]-α-methyl-D-glycopyranoside and the hPepT1 substrate [ 14C]- Gly- Sar in Caco-2 cells was also decreased in the presence of 0.3 mM sertraline. In rats, the administration of sertraline (0.1-10 mM, corresponding to 0.3-30.6 mg·kg−1, p.o.) significantly reduced the maximal gaboxadol plasma concentration and AUC after its administration p.o. Conclusions and Implications Sertraline is an apparent non-competitive inhibitor of hPAT1-mediated transport in vitro. This inhibitory effect of sertraline is not specific to hPAT1 as substrate transport via hPepT1 and hSGLT1 was also reduced in the presence of sertraline. In vivo, sertraline reduced the amount of gaboxadol absorbed, suggesting that the inhibitory effect of sertraline on PAT1 occurs both in vitro and in vivo. Hence, sertraline could alter the bioavailability of drugs absorbed via PAT1. [ABSTRACT FROM AUTHOR] more...

BACKGROUND AND PURPOSE Intestinal absorption via membrane transporters may determine the pharmacokinetics of drug compounds. The hypothesis is that oral absorption of gaboxadol (4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-ol) in rats occurs via the proton-coupled amino acid transporter, rPAT1 (encoded by the gene rSlc36a1). Consequently, we aimed to elucidate the in vivo role of rPAT1 in the absorption of gaboxadol from various intestinal segments obtained from Sprague-Dawley rats. EXPERIMENTAL APPROACH The absorption of gaboxadol was investigated following its administration into four different intestinal segments. The intestinal expression of rSlc36a1 mRNA was measured by quantitative real-time PCR. Furthermore, the hPAT1-/rPAT1-mediated transport of gaboxadol or L-proline was studied in hPAT1-expressing Xenopus laevis oocytes, Caco-2 cell monolayers and excised segments of the rat intestine. KEY RESULTS The absorption fraction of gaboxadol was high (81.3-91.3%) following its administration into the stomach, duodenum and jejunum, but low (4.2%) after administration into the colon. The pharmacokinetics of gaboxadol were modified by the co-administration of L-tryptophan (an hPAT1 inhibitor) and L-proline (an hPAT1 substrate). The in vitro carrier-mediated uptake rate of L-proline in the excised intestinal segments was highest in the mid jejunum and lowest in the colon. The in vitro uptake and the in vivo absorption correlated with the expression of rSlc36a1 mRNA along the rat intestine. CONCLUSIONS AND IMPLICATIONS These results suggest that PAT1 mediates the intestinal absorption of gaboxadol and therefore determines its oral bioavailability. This has implications for the in vivo role of PAT1 and may have an influence on the design of pharmaceutical formulations of PAT1 substrates. [ABSTRACT FROM AUTHOR] more...

When predicting pressure gradients for the flow of sludges in pipes, the rheology of the fluid plays an important role, especially with increasing concentration of the suspended matter in the sludge. The f-Re relationship is often applied when designing pipelines, but it depends on the rheological parameters of the fluid and what definition of non-Newtonian Reynolds number is used. In this work, a database of 586 ΔP - Q points from tests with 10 different sludges of concentration 3.4 to 7.2% by mass, in 3 test pipe diameters, was established and used to rheologically characterise the sludges as Bingham plastic fluids. Five published definitions of the non-Newtonian Reynolds number were used to create composite power law correlations for the f-Re relationship covering all flow regimes. Pressure gradient predictions based on each correlation were compared and ranked, based on 2 different statistical estimates of error. The correlations using the Metzner-Reed Reynolds number (ReMR) and a Reynolds number proposed by Slatter and Lazarus in 1993 (Re2) yielded the lowest errors in comparison with the experimental values. It is shown that these correlations can be used to predict pressure drop to within ±20% for a given sludge concentration and operating condition. [ABSTRACT FROM AUTHOR] more...

Carbon dioxide may react with free or metal-bound hydroxide to afford products containing bicarbonate or carbonate, often captured as ligands bridging two or three metal sites. We report the kinetics and probable mechanism of an extremely rapid fixation reaction mediated by a planar nickel complex [NiII(NNN)(OH)]1- containing a tridentate 2,6-pyridinedicarboxamidate pincer ligand and a terminal hydroxide ligand. The minimal generalized reaction is M-OH + CO2 → M-OCO2H; with variant M, previous rate constants are ≲10³ M-1 s-1 in aqueous solution. For the present bimolecular reaction, the (extrapolated) rate constant is 9.5 × 105 M-1 s-1 in N, N'-dimethylformamide at 298 K, a value within the range of kcat/KM≈105-108 M-1 s-1 for carbonic anhydrase, the most efficient catalyst of CO2 fixation reactions. The enthalpy profile of the fixation reaction was calculated by density functional theory. The initial event is the formation of a weak precursor complex between the Ni-OH group and CO2, followed by insertion of a CO2 oxygen atom into the Ni-OH bond to generate a four center Ni(η²-OCO2H) transition state similar to that at the zinc site in carbonic anhydrase. Thereafter, the Ni-OH bond detaches to afford the Ni(η¹-OCO2H) fragment, after which the molecule passes through a second, lower energy transition state as the bicarbonate ligand rearranges to a conformation very similar to that in the crystalline product. Theoretical values of metric parameters and activation enthalpy are in good agreement with experimental values [ΔH‡ = 3.2(5) kcal/mol]. [ABSTRACT FROM AUTHOR] more...

BACKGROUND AND PURPOSE The intestinal proton-coupled amino acid transporter, SLC36A1, transports zwitterionic α-amino acids and drugs such as vigabatrin, gaboxadol and δ-aminolevulinic acid. We hypothesize that SLC36A1 might also transport some dipeptides. The aim of the present study was to investigate SLC36A1-mediated transport of Gly-Gly and Gly-Gly mimetics, and to investigate Gly-Sar transport via SLC36A1 and the proton-coupled dipeptide/tripeptide transporter, SLC15A1 in Caco-2 cells. EXPERIMENTAL APPROACH Transport of a compound via SLC36A1 was determined by its ability to induce an increase in the inward current of two-electrode voltage clamped SLC36A1 cRNA-injected Xenopus laevis oocytes. SLC36A1-mediated L-[³H]Pro uptake in Caco-2 cells was measured in the absence and presence of Gly-Gly or Gly-Sar. In addition, apical [¹⁴C]Gly-Sar uptake was measured in the absence and presence of the SLC36A1 inhibitor 5-hydroxy-L-tryptophan (5-HTP) or the SLC15A1 inhibitor L-4,4'-biphenylalanyl-L-proline (Bip-Pro). KEY RESULTS In SLC36A1-expressing oocytes, an inward current was induced by Gly-Sar, Gly-Gly, δ-aminolevulinic acid, β-aminoethylglycine, δ-aminopentanoic acid, GABA, Gly and Pro, whereas Val, Leu, mannitol, 5-HTP and the dipeptides Gly-Ala, Gly-Pro and Gly-Phe did not evoke currents. In Caco-2 cell monolayers, the apical uptake of 30 mM Gly-Sar was inhibited by 20 and 22% in the presence of 5-HTP or Bip-Pro, respectively, and by 48% in the presence of both. CONCLUSION AND IMPLICATIONS Our results suggest that whereas Gly-Gly amid bond bioisosteres are widely accepted by the hPAT1 carrier, dipeptides in general are not; and therefore, Gly-Sar might structurally define the size limit of dipeptide transport via SLC36A1. [ABSTRACT FROM AUTHOR] more...

Forescattered electron channeling contrast imaging (ECCI) offers the potential for imaging and analyzing extended defects in a scanning electron microscope (SEM). Indeed, it is shown that ECCI is able to determine the Burgers vector of threading dislocations with the aid of carefully determined experimental parameters and accompanying image simulations. Simulations are compared with ECC images from samples with features that are relatively easily studied and modeled: those based on specially engineered 4H-SiC mesa substrates. These mesas serve as substrates for both homoepitaxial 4H-SiC layers and heteroepitaxial GaN layers in which images of threading dislocations (TDs) have been recorded using ECCI and found to strongly resemble diffraction contrast simulations of TD intensity profiles. [ABSTRACT FROM AUTHOR] more...

An approach to fabricate a set of simultaneously operating dual-UV-wavelength detectors is described. The fabrication flow relies on the confined-epitaxy growth method. The confined epitaxial Alscript>α Ga1--α N-layer stacking approach is used to establish simultaneous multiple UV-wavelength detection. The chosen stoichiometries of specific epitaxial layers set the wavelength sensitivity at approximately 355 nm for pixel A and 320 nm for pixel B. Spectral responsivity plots of the detectors clearly show the dual-UV-color sensitivity of the pair. The detectors have signal-to-noise ratios of 15 and 17 and spectral responsivity values of 0.12 A/W and 0.05 A/W for pixel A and pixel B, respectively. [ABSTRACT FROM AUTHOR] more...

Background and Purpose: Gaboxadol has been in development for treatment of chronic pain and insomnia. The clinical use of gaboxadol has revealed that adverse effects seem related to peak serum concentrations. The aim of this study was to investigate the mechanism of intestinal absorption of gaboxadol in vitro and in vivo.Experimental Approach: In vitro transport investigations were performed in Caco-2 cell monolayers. In vivo pharmacokinetic investigations were conducted in beagle dogs. Gaboxadol doses of 2.5 mg.kg(-1) were given either as an intravenous injection (1.0 mL.kg(-1)) or as an oral solution (5.0 mL.kg(-1)).Key Results: Gaboxadol may be a substrate of the human proton-coupled amino acid transporter, hPAT1 and it inhibited the hPAT1-mediated L-[(3)H]proline uptake in Caco-2 cell monolayers with an inhibition constant K(i) of 6.6 mmol.L(-1). The transepithelial transport of gaboxadol was polarized in the apical to basolateral direction, and was dependent on gaboxadol concentration and pH of the apical buffer solution. In beagle dogs, the absorption of gaboxadol was almost complete (absolute bioavailability, F(a), of 85.3%) and T(max) was 0.46 h. Oral co-administration with 2.5-150 mg.kg(-1) of the PAT1 inhibitor, L-tryptophan, significantly decreased the absorption rate constant, k(a), and C(max), and increased T(max) of gaboxadol, whereas the area under the curve and clearance of gaboxadol were constant.Conclusions and Implications: The absorption of gaboxadol across the luminal membrane of the small intestinal enterocytes is probably mediated by PAT1. This knowledge is useful for reducing gaboxadol absorption rates in order to decrease peak plasma concentrations. [ABSTRACT FROM AUTHOR] more...

Aims: To determine the levels of expression of ZNF652 and its relevance to prognosis in vulvar squamous cell carcinomas. Methods: 22 cases of vulvar intraepithelial neoplasia (VIN) and tumours from 217 patients with vulvar squamous cell carcinomas were investigated for expression of ZNF652 using immunostaining methods. The effect of ZNF652 ectopic expression was determined in the vulvar carcinoma cell line SW954 by western and cell-based assays. Results: High levels of ZNF652 nuclear expression were observed in 5 (100%) of VIN I, 6 (75%) of VIN II and 109 (50.2%) of the vulvar carcinomas, whereas low levels were seen in 2 (25%) VIN II, 9 (100%) of VIN III and 108 (49.8%) of the vulvar carcinomas. High levels of ZNF652 expression in the vulvar carcinomas were significantly correlated to high expression of EphA2. However, when correcting for multiple testing this correlation was lost. No association was identified between ZNF652 expression and p16, p21, p27, p53, cyclin A, D1, D3, E, EphrinA-1 and human papillomavirus. Variations in levels of ZNF652 were not related to prognosis. Low levels of ZNF652 protein were identified in the vulvar carcinoma cell line SW954. Furthermore, SW954 cells ectopically expressing ZNF652 showed reduced cell proliferation and the ability to form colonies on plastic. Conclusions: ZNF652 protein expression is reduced in 25% of VIN II, 100% of VIN III and approximately 50% of the cases of vulvar squamous cell carcinoma, and may be an early event in the pathogenesis of vulvar squamous cell carcinoma. Variations in the levels of ZNF652 were not related to patient's prognosis. [ABSTRACT FROM AUTHOR] more...

Aims: To examine the expression of EphA2 and EphrinA-1 in vulvar squamous cell carcinomas and investigate their prognostic relevance. Methods: Tumours from 224 patients with vulvar squamous cell carcinomas were investigated for expression of EphA2 and EphrinA-1 using single and double immunostaining methods. Results: High expression (strong/moderate staining intensity) of EphA2 and EphrinA-1 was observed in 114 (51%) and 126 (56%) vulvar carcinomas, respectively. In the three cases tested using the double immunostaining method, colocalisation of EphA2 and EphrinA-1 proteins was identified in the same neoplastic cells. High EphA2 expression was significantly correlated to high expression of EphrinA-1 (p<0.01) and cyclin A (p<0.01), large tumour size (p=0.03), deep invasion (p<0.01) and higher FIGO stage (p = 0.05). A correlation between high EphrinA-1 expression and high levels of cyclin A (p<0.01) and p21 (p<0.01), deep invasion (p<0.01) and higher FIGO stage (p=0.01) was also seen. In univariate analysis, high expression of EphrinA-1 was associated with poor survival (p=0.03). However, in the multivariate analysis neither EphrinA-1 nor EphA2 were significantly correlated to survival. Conclusions: EphA2 and EphrinA-1 were overexpressed in 51% and 56% of the vulvar squamous cell carcinomas, respectively, and high levels of EphA2 and EphrinA-1 proteins were associated with deep tumour invasion and high FIGO stage. However, EphA2 and EphrinA-1 were not independently associated with clinical outcome in vulvar carcinomas. [ABSTRACT FROM AUTHOR] more...

The Food Quality Protection Act (FQPA) was enacted in August 1996 and required the US Environmental Protection Agency (EPA) to reassess all existing and new crop protection active substances using a new set of health and environmental standards to further protect infants and children. The initial fear that many minor or specialty crop use registrations would be lost without adequate replacements has largely been overcome by an aggressive programme by the International Research Project no. 4 (IR-4) in partnership with the EPA and the crop protection industry to register new, safer, reduced risk products for specialty crop pest control needs. Since the FQPA, the EPA has approved over 5600 new specialty crop uses resulting from IR-4 residue programmes. This amounts to about 56% of the over 10 000 clearances received by the IR-4 programme in its 43 year history and about 50% of all new uses granted by the EPA since FQPA. The positive outcomes from these efforts have been partially negated by the lack of tolerances or Maximum Residue Levels (MRLs) in countries to which US produce is exported. This has forced some US specialty crop growers to continue to use older, less desirable products. IR-4 has been addressing this challenge by cooperating in the NAFTA (North American Free Trade Agreement) countries with Agriculture and Agri-Food Canada's Pest Management Centre and Health Canada's Pest Management Regulatory Agency to harmonize MRLs through joint projects and regulatory reviews. IR-4 has also provided leadership for the International Crop Grouping Consulting Committee to harmonize specialty/minor crop groupings and representative crops for residue studies with the long-term goal being to globally harmonize MRLs. [ABSTRACT FROM AUTHOR] more...

D-optimal design and the desirability function were applied to optimize a self-microemulsifying drug delivery system (SMEDDS). The optimized key parameters were the following: 1) particle size of the dispersed emulsion, 2) solubility of the drug in the vehicle, and 3) the vehicle compatibility with the hard gelatin capsule. Three formulation variables, PEG200, a surfactant mixture, and an oil mixture, were included in the experimental design. The results of the mathematical analysis of the data demonstrated significant interactions among the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the explored system. [ABSTRACT FROM AUTHOR] more...

High-reflectance group III-nitride distributed Bragg reflectors (DBRs) were deposited by metal-organic chemical-vapor deposition on Si(111) substrates. A reflectance greater than 96% was demonstrated for an AlN/GaN DBR with a stop band centered in the blue-green range of the visible spectrum. Crack-free GaN cap layers were grown on the DBR structures to demonstrate the opportunity to build III-nitride optoelectronic devices in this material. The DBR structure was under significant strain due to growth on a mismatched substrate, although the GaN cap layer was shown to be strain-free. [ABSTRACT FROM AUTHOR] more...

The heteroepitaxial growth of gallium nitride (GaN) films using three distinct growth steps is investigated in terms of improving the electrical properties of the layer. The first step involves the deposition of a fixed quality aluminum nitride (AlN) layer on an a-plane sapphire substrate. The second step is aimed at maximizing the GaN grain size initially grown on the AlN. The third step is aimed at optimizing the surface morphology of the GaN layer. The means of transitioning the growth between steps is investigated and an optimum transition method is reported. Growth parameters investigated include pressure, trimethylgallium molar flow rate, and ratio of group V to group III precursor molar flows. Carrier statistics show a lower level of compensation in films grown at a slower growth rate in the second step and a moderate rate in the third step. [ABSTRACT FROM AUTHOR] more...

Aims: To examine the prognostic relevance of the expression of the Bcl-2, BcI-xL, and Bax proteins in stage lB squamous cervical carcinoma (SCC). Methods: In total, 220 patients who underwent radical hysterectomy and bilateral lymphadenectomy at the Norwegian Radium Hospital for stage lB SCC between 1987 and 1993 were studied. lmmunohistochemistry using monoclonal antibodies against Bcl-2, Bcl-xL, and Bax was used to examine protein expression. Ten patients who underwent hysterectomy for uterine prolapse served as controls. Results: Cytoplasmic expression of Bcl-2, Bcl-xL, and Bax was low (< 5% positive cells) in 159 of 220 (73%), 193 of 220(87%), and 39 of 220 (18%) tumours, respectively, and high (⩾ 5% positive cells) in 61 of 220 (27%), 27 of 220 (13%), and 181 of 220 (82%) lumours, respectively, in univariate analysis, all classic clinicopathological parameters but none of the investigated proteins were associated with prognosis. In multivariate analysis, only deep stromal invasion was independently related to survival. Conclusion: Bcl-2, BCI-XL, and Bax were not independently associated with prognosis in stage IB SCC. [ABSTRACT FROM AUTHOR] more...

The prevention of injuriesin all sports calls for a structured plan. The plan consists, as earlier described, of four steps. We have previously presented studies incorporating all four steps. The studies have shown that it is possible to prevent most injuries in young female players in European handball by applying a training programme combining the use of an ankle disc with functional strength training. In the previous studies we were not able to discriminate whether the preventive effect was due to the functional strength training or the training with the ankle disc. The aim of this study was to compare a programme with ankle disc and functional strength training with a programme with functional strength training only. Twenty handball teams were asked to participate, and 16 of 20 handball teams agreed to participate. The teams were cluster randomised to either the programme with or without an ankle disc. The group using the programme without the ankle disc had a significantly higher number of traumatic injuries (16 vs. 6). The incidences of traumatic injuries in the ankle disc group were 2.4 (95% CI 0.7; 6.2) injuries per 1000 h of match and 0.2 (95% CI 0.02; 0.7) injuries per 1000 h of practice. In the group without ankle disc the incidences were 6.9 (95% CI 3.3; 12.7) injuries per 1000 h of match and 0.6 (95% CI 0.2; 1.3) injuries per 1000 h of practice. A significantly higher multivariate odds ratio (4.8) was found in the group not using the ankle disc. In addition the group using the ankle disc had significantly fewer moderate and major injuries. By adding ankle disc training to a training programme with functional strength training, it is possible to reduce the number of injuries significantly, especially the number of moderate and major injuries. [ABSTRACT FROM AUTHOR] more...

Aim: Increased proliferation of tumour cells has prognostic value in human invasive breast carcinomas (IBCs), and high histology grade and cyclin A expression, which may reflect high proliferation rate, are associated with poor prognosis. Expression of HsMCM2 is related to cell proliferation. This study evaluates the correlation between the expression of cyclins A, D1, D3, and E, Ki-67, proliferating cell nuclear antigen (PCNA), histology grade, and HsMCM2 expression, in addition to the independent prognostic value of HsMCM2 expression in human IBCs. Methods: Immunohistochemistry to evaluate HsMCM2, Ki-67, and PCNA expression in tumours from 147 patients with IBC. Results: Nuclear staining for HsMCM2 was seen in 10-30% of the tumour cells in 30 samples, in 30-70% in 40 samples, in >70% in 44 samples, and in <10% in 33 samples. One way ANOVA showed a significant association between expression of HsMCM2 and cyclin A, D3, E, histology grade, and Ki-67. A borderline correlation was seen between HsMCM2 and PCNA. In multivariate analysis, the only association was with cyclin A, in addition to a borderline association with histology grade. In a Cox regression hazards model, expression of HsMCM2 was associated with poor patient survival, although it lost its independent prognostic value when cyclin A expression was included. Ki-67 and PCNA expression were not associated with patient survival. Conclusion: Cyclin A expression is independently associated with HsMCM2 expression, histology grade, and Ki-67. HsMCM2 expression is associated with poor patient survival, although it loses prognostic value when adjusted for cyclin A. [ABSTRACT FROM AUTHOR] more...

Differential Ki67 and bcl-2 immunoexpression in solid–glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin Aims: Synovial sarcoma is a malignant soft tissue of uncertain histogenesis that may show a biphasic (spindle and solid/glandular components) or a monophasic histological appearance. In previous studies, we demonstrated that the solid/glandular component possesses higher proliferation rates than the spindle cell component of biphasic synovial sarcomas and that the spindle cell component may exhibit a progressive transition from or to the solid-glandular component in biphasic synovial sarcoma. To evaluate this hypothesis further, we designed a novel approach to correlate immunoexpression of Ki67, bcl-2 and bax in the spindle cell and in the solid-glandular component of biphasic synovial sarcomas. We also performed a double-immunohistochemical assessment of the Ki67 proliferative indices and the immunoexpression of anti-apoptotic protein bcl-2 in neoplastic cells expressing either vimentin or cytokeratin. Methods and results: Immunohistochemistry for vimentin (10 cases), bcl-2 (10 cases), Ki67(10 cases), cytokeratin (10 cases), and bax (eight cases), and double-immunostaining for vimentin/Ki67 (10 cases), vimentin/bcl-2 (nine cases), cytokeratin/Ki67 (10 cases), and cytokeratin/bcl-2 (10 cases) assays were performed in 10 cases of primary biphasic synovial sarcoma. Semiquantitative assessment was adopted for each case in both components. Statistical analysis was performed using Fisher's exact test or χ2 test. On conventional immunohistochemistry, the solid/glandular component revealed more expression of Ki67, bax and cytokeratin than the spindle cell component (P =0.0004, P =0.082, and P < 0.0001, respectively); on the other hand, the latter showed higher expression of bcl-2 and vimentin than the former (P =0.0281 and P =0.059, respectively). Double... [ABSTRACT FROM AUTHOR] more...

Objective To identify, in a retrospective study, possible molecular markers predictive of radioresponsiveness in patients with transitional cell carcinoma (TCC) of the bladder. Patients and methods Patients with T2–T4a TCC treated with preoperative radiotherapy and cystectomy were included in the study if their cystectomy specimen was pT3b (in 42) or pT0 (in 17). Because treatment schedules changed over time, radiotherapy was given either as 2 Gy × 23 over 4–5 weeks with cystectomy 4–5 weeks later (in 23), or as 4 Gy × 5 during 1 week with cystectomy in the following week (in 36 patients). Protein expression of p53, mdm2 and p21 (CDKN1 A/WAF1/CIP1/SDI1) was assessed immunohistochemically in biopsies taken before radiotherapy. Results There was no difference in protein expression when comparing all patients with pT0 and pT3b. However, for patients receiving 46 Gy, increased p53 expression (but not p21 or mdm2) predicted the absence of residual tumour (P = 0.005): six of seven patients with > 50% p53 expression had pT0 in the cystectomy specimen, whereas 10 of 12 patients with <= 5% expression had pT3b. Over-expression of p53 correlated with longer overall (P = 0.045) and cancer-specific survival (P = 0.020). Conclusion The expression of mdm2 or p21 did not predict radioresponsiveness in patients with TCC of the bladder. The role of p53 remains unclear; the view that p53 over-expression confers radioresistance in bladder cancer is not supported. [ABSTRACT FROM AUTHOR] more...

Reduced expression of p21WAF1 is an indicator of malignant behaviour in anal carcinomas Aims: p21 and p27 protein expression were examined in a comparatively large series of patients with squamous cell carcinoma of the anal canal and compared with clinical and histopathological data (tumour stage, nodal status and differentiation). Methods and results: We analysed the expression of p21 and p27 protein in 94 anal carcinomas by immunohistochemistry. Nuclear p21 and p27 staining were detected in 71% (67/94) and 75% (71/94) of the cases, respectively. There was no significant association between p27 staining and tumour stage, nodal status or overall survival. We observed that negative p21 immunoreactivity was significantly associated with poorly differentiated anal carcinomas. Furthermore, a shorter overall survival for patients with no p21 protein expression was seen. Conclusions: Our data indicate that p21 levels, but not p27 expression, may be a useful predictor of survival in patients with anal carcinomas. [ABSTRACT FROM AUTHOR] more...

The search for better prognostic indicators and new treatment modalities in node-negative breast carcinoma patients is important. The aim of this study was to determine the immunohistochemical expression of central cell regulator proteins in relation to hormone receptor status, tumour-cell differentiation and prognosis. We investigated the immunoreactivity of p27, p21, cdk4, cyclin D1 and p53 in 77 node-negative breast carcinomas, with long-term follow-up (mean 163 months; range 20-227). Nuclear staining for p27 was seen in 87% of the carcinomas, for cdk4 in 92%, for p21 in 68%, for cyclin D1 in 58% and for p53 in 18%. Oestrogen receptor (ER) and progesterone receptor (PgR) nuclear staining was seen in 69% and 65% of the tumours, respectively. No correlation between the levels of p21 and p53 was observed. p21 overexpression was, however, associated with positive ER status. Elevated levels of p27 and cyclin D1 correlated with positive hormone status (both ER and PgR). We did find a significant correlation between p27 and cyclin D1 and histological grade of the tumours, with extensive positive immunostaining of p27 and cyclin D1 in well-differentiated carcinomas. The only significant prognostic factor in our series was histological grading. Ten-year relapse-free survival was significantly prolonged in patients with histological grade I tumours versus histological grade II and III tumours. Our results suggest that the expression of p27 and cyclin D1 is closely linked to hormone receptor status in breast carcinomas and to tumour differentiation, a finding that may be of importance in the treatment of hormone-dependent tumours. [ABSTRACT FROM AUTHOR] more...

The organometallic vapor phase epitaxial growth of GaAs double-drift Read impact ionization avalanche transit time diodes where the p-type layers were doped with carbon is described. Ka-band oscillation testing yielded average performance of 3.5 W with 16% efficiency for pulse lengths >1 µs and 10.5 W with 13% efficiency for pulse lengths <1 µs; these RF performances are similar to conventionally grown vapor phase epitaxy IMPATTs where the p-type dopant was zinc. Photoreflectance spectra obtained from diode structures were found to be dominated by the electric field in the avalanche region and hence are sensitive to the amount of charge in the doping spikes that determine the electric field in that region. [ABSTRACT FROM AUTHOR] more...