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Movie theaters typically appear adjacent to discussions of new media. Although there has been work on digital cinema, we shift the focus from the digitization of the medium to the digitization of the theatrical audience and analyze the movie theater as new media. To do so, we look at the historical and contemporary strategies for digitizing the theatrical audience of a prominent theater chain. We identify common media of digitization, including credit cards, computerized point-of-sale systems, and loyalty programs. The origins of these techniques and imperatives trace back to the 1970s and 1980s, even as they take on new forms today. We then analyze the industrial logics of audience digitization and emergent communication and data collection methods. Finally, we analyze the movie theater as a platform, showing both the relevance of movie theaters and the challenges their inclusion as an object of study poses for contemporary platform studies. [ABSTRACT FROM AUTHOR]

We explore how X-ray reverberation around black holes may reveal the presence of the innermost stable circular orbit (ISCO), predicted by general relativity, and probe the dynamics of the plunging region between the ISCO and the event horizon. Being able to directly detect the presence of the ISCO and probe the dynamics of material plunging through the event horizon represents a unique test of general relativity in the strong field regime. X-ray reverberation off of the accretion disc and material in the plunging region is modelled using general relativistic ray tracing simulations. X-ray reverberation from the plunging region has a minimal effect on the time-averaged X-ray spectrum and the overall lag-energy spectrum, but is manifested in the lag in the highest frequency Fourier components, above |$0.01\, c^{3}\, (GM)^{-1}$| (scaled for the mass of the black hole) in the 2–4 keV energy band for a non-spinning black hole or the 1–2 keV energy band for a maximally spinning black hole. The plunging region is distinguished from disc emission not just by the energy shifts characteristic of plunging orbits, but by the rapid increase in ionization of material through the plunging region. Detection requires measurement of time lags to an accuracy of 20 per cent at these frequencies. Improving accuracy to 12 per cent will enable constraints to be placed on the dynamics of material in the plunging region and distinguish plunging orbits from material remaining on stable circular orbits, confirming the existence of the ISCO, a prime discovery space for future X-ray missions. [ABSTRACT FROM AUTHOR]

We explore a disc origin for the highly blueshifted, variable absorption lines seen in the X-ray spectrum of the narrow-line Seyfert 1 galaxy IRAS 13224−3809. The blueshift corresponds to a velocity of ∼0.25 c. Such features in other active galactic nuclei are often interpreted as ultrafast outflows. The velocity is of course present in the orbital motions of the inner disc. The absorption lines in IRAS 13224−3809 are best seen when the flux is low and the reflection component of the disc is strong relative to the power-law continuum. The spectra are consistent with a model in which the reflection component passes through a thin, highly ionized absorbing layer at the surface of the inner disc, the blueshifted side of which dominates the flux due to relativistic aberration (the disc inclination is about 70°). No fast outflow need occurs beyond the disc. [ABSTRACT FROM AUTHOR]

SUMMARY: Aims/Objectives: To describe the impact of additional testing on the England blood supply. Background: The blood service for England, NHS Blood and Transplant, applies a system of deferral and testing to donors with potential exposure to Chagas disease, malaria and West Nile virus; however, testing costs must be justified. Here, we describe the donations and donors gained by testing. Methods: Donation testing results and demographic data on donors in England where additional testing was applied were analysed in 2012–2016. The total number and proportion of donations tested, reactive and confirmed positive were calculated. Proportions of donors requiring additional tests were calculated by ethnic group for first‐time and repeat donors. Results: Additional testing for travel was applied to 3·5% of NHSBT blood donations between 2012 and 2016. Over 98% of these tests were non‐reactive. Only malaria tests were confirmed positive, in 1·7% of donations tested. In first‐time donors, 45 and 40% of Asian and Black donors required an additional test, respectively, mainly for malaria. Testing for West Nile virus increased from 1·5% in 2012 to 2·2% of donations in 2016. Conclusion: The majority of additional tests were screened negative, allowing approximately 64 000 donations to be released for issue annually. Donors most affected by malaria testing were more likely to have rare blood groups and be targeted for recruitment, whereas those given West Nile virus testing were mainly regular donors required for continuity of supply. These data show differences in the characteristics of donors by test and can be used to inform decisions about additional testing and deferrals. [ABSTRACT FROM AUTHOR]

Youth have astute observations about site-specific personal and environmental factors that contribute to littering and marine debris, and they have a strong potential to act as change agents in communities. Interactions with youth in Pinellas County Florida add insights into a growing body of research on environmental education and marine debris prevention. This study assessed perceptions of marine debris and littering behaviors through group discussions with middle school and high school students (N = ∼44), evaluations at summer camp programs (N = ∼31) and pre- and post-assessments of environmental field trips (pre-assessment N = ∼120; post-assessment N = ∼140). Youth showed high initial awareness of the effects of marine debris on the environment but showed less understanding about the role of watersheds and biodegradation in marine litter issues. A majority of youth attributed others' littering behavior to dispositional factors, like laziness, while attributing their own littering to situational factors, like poorly placed bins. Student observations of educators and parents also influenced littering behaviors and willingness to act. To reduce littering, education and outreach programs need to (1) provide opportunities for ongoing assessment of complex marine debris topics, (2) align visual and written or verbal messages, (3) reduce actor/observer bias related to littering behaviors, and (4) support adult role models. [ABSTRACT FROM AUTHOR]

Aims/Objectives: Here, we describe the annual review of the UK blood services' infection surveillance schemes for 2017 (www.gov.uk/government/publications/safe‐supplies‐annual‐review). Background: The joint NHS Blood and Transplant/Public Health England Epidemiology Unit was set up in 1995 to ensure that blood and tissue safety is maintained, inform donor selection and testing policy and add to public health knowledge. Methods: Several surveillance schemes for blood, tissues and bacterial screening collect the numbers of donations tested, reactive and confirmed positive in order to monitor trends in infection rates in donors and calculate residual risk of infection. Investigations of potential transfusion transmissions in recipients are also monitored. Results: In the UK in 2017, the risk of testing not detecting a potentially infectious hepatitis B virus or hepatitis C virus or HIV donation was estimated as less than one in two million donations. One hepatitis A virus and one hepatitis E virus transmission incidents were proven to be transfusion‐transmitted by unscreened donations. Conclusions: The Safe Supplies annual review provides a clear picture of the very low risk associated with blood and tissues in the UK nowadays. In November 2017, the blood services for England, Wales and Scotland implemented recommendations to reduce the deferrals for higher risk sexual behaviour from 12 to 3 months. The surveillance schemes are adapted to remain fit for purpose as testing and donor selection change. [ABSTRACT FROM AUTHOR]

GaN whiskers with nanoscale dimensions have been fabricated by photoelectrochemical (PEC) etching in dilute H3PO4 electrolyte. Etching in lower concentration H3PO4 electrolyte for 1 h or for a short time of 5 min at a higher concentration results in individual whiskers with a density of ∼2×109cm-2 and diameters to 15nm. It is observed that ∼10% of them have formed nearly perfect hexagonal plates on the top of the whiskers, which appear to evolve into flowerlike features upon extended etching to 12 min. Such hexagonal plates have not been reported previously in the PEC etching of GaN. The presence of a dislocation along the central axis of the needles is clearly demonstrated, and the etch pattern is suggested to be related to the growth mechanism for GaN on sapphire. When etched for times >30 min, these whiskers are typically arranged in clusters with a density of 2–5×107cm-2 and have ten or more whiskers contributing to the central top of the cluster. [ABSTRACT FROM AUTHOR]

Focuses on a study which investigated the sidegating characteristics of aluminum gallium arsenide/gallium arsenide heterostructure field-effect transistors (HFET), fabricated on molecular-beam epitaxially grown layers. Discussion on HFET; Methodology of the study; Results and discussion.

Background and Objectives The rate of confirmed hepatitis C virus (HCV) cases, in first-time donors, is much lower in 2015 than 20 years ago. We investigate reasons for the decline. Materials and Methods HCV rates were analysed by gender and birth cohort for 1996 to 2015 and ethnic group for 2006 to 2015. Variables for confirmed positive cases were compared for two ten-year periods (1996 to 2005 and 2006 to 2015) including genotyping data for 2006 to 2015. Results There were 2007 confirmed HCV cases identified between 1996 and 2015. The rate per 100 000 donations fell from 78·6 in 1996 to 26·9 by 2015. By birth cohort, HCV rates were highest in donors born in the 1950s and 1960s who contributed a decreasing proportion of first-time donors. Between 2006 and 2015, there was no significant decline in HCV rate. The HCV-positive donor profile has changed in the last 10 years with increased proportions of younger donors, donors born abroad and decreased reported injecting drug use. Genotype 1a remains predominate, but genotype 1b has increased associated with this change in birth cohort and ethnicity. Conclusion The decline in number and rate of confirmed HCV-positive first-time donors is mainly due to a decrease in first-time donors born before 1970, with the highest rate of HCV. However, the decline has slowed and the profile of HCV-positive first-time donors is changing. A better understanding of behaviour and sources of HCV in younger and ethnic minority donors are needed. [ABSTRACT FROM AUTHOR]

We present the deepest Chandra observation to date of the galaxy M84 in the Virgo Cluster, with over 840 ks of data provided by legacy observations and a recent 730 ks campaign. The increased signal-to-noise ratio allows us to study the origins of the accretion flow feeding the supermassive black hole in the centre of M84 from the kiloparsec scales of the X-ray halo to the Bondi radius, R B. Temperature, metallicity, and deprojected density profiles are obtained in four sectors about M84's active galactic nucleus (AGN), extending into the Bondi radius. Rather than being dictated by the potential of the black hole, the accretion flow is strongly influenced by the AGN's bipolar radio jets. Along the jet axis, the density profile is consistent with n e ∝  r −1; however, the profiles flatten perpendicular to the jet. Radio jets produce a significant asymmetry in the flow, violating a key assumption of Bondi accretion. Temperature in the inner kiloparsec is approximately constant, with only a slight increase from 0.6 to 0.7 keV approaching R B, and there is no evidence for a temperature rise imposed by the black hole. The Bondi accretion rate |$\dot{M}_{\rm B}$| exceeds the rate inferred from AGN luminosity and jet power by over four orders of magnitude. In sectors perpendicular to the jet, |$\dot{M}_{\rm B}$| measurements agree; however, the accretion rate is >4σ lower in the North sector along the jet, likely due to cavities in the X-ray gas. Our measurements provide unique insight into the fuelling of AGN responsible for radio mode feedback in galaxy clusters. [ABSTRACT FROM AUTHOR]

Background Exposure to respirable crystalline silica (RCS) causes emphysema, airflow limitation and chronic obstructive pulmonary disease (COPD). Slate miners are exposed to slate dust containing RCS but their COPD risk has not previously been studied. Aims To study the cumulative effect of mining on lung function and risk of COPD in a cohort of Welsh slate miners and whether these were independent of smoking and pneumoconiosis. Methods The study was based on a secondary analysis of Medical Research Council (MRC) survey data. COPD was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7. We created multivariable models to assess the association between mining and lung function after adjusting for age and smoking status. We used linear regression models for FEV1 and FVC and logistic regression for COPD. Results In the original MRC study, 1255 men participated (726 slate miners, 529 unexposed non-miners). COPD was significantly more common in miners (n = 213, 33%) than non-miners (n = 120, 26%), P < 0.05. There was no statistically significant difference in risk of COPD between miners and non-miners when analysis was limited to non-smokers or those without radiographic evidence of pneumoconiosis. After adjustment for smoking, slate mining was associated with a reduction in%predicted FEV1 [β coefficient = -3.97, 95% confidence interval (CI) -6.65, -1.29] and FVC (β coefficient = -2.32, 95% CI -4.31, -0.33) and increased risk of COPD (odds ratio: 1.38, 95% CI 1.06, 1.81). Conclusions Slate mining may reduce lung function and increase the incidence of COPD independently of smoking and pneumoconiosis. [ABSTRACT FROM AUTHOR]

Interest is growing in developing integrated postabsorptive metabolism models for dairy cattle. An integral part of linking a multi-organ postabsorptive model is the prediction of nutrient fluxes between organs, and thus blood flow. The purpose of this paper was to use a multivariate meta-analysis approach to model portal blood flow (PORBF) and hepatic venous blood flow (HEPBF) simultaneously, with evaluation of hepatic arterial blood flow (ARTBF; ARTBF = HEPBF - PORBF) and PORBF/HEPBF (%) as calculated values. The database used to develop equations consisted of 296 individual animal observations (lactating and dry dairy cows and beef cattle) and 55 treatments from 17 studies, and a separate evaluation database consisted of 34 treatment means (lactating dairy cows and beef cattle) from 9 studies obtained from the literature. Both databases had information on dry matter intake (DMI), metabolizable energy intake (MEI), body weight, and a basic description of the diet including crude protein intake and forage proportion of the diet (FP; %). Blood flow (L/h or L/kg of BW0.75/h) and either DMI or MEI (g or MJ/d or g or MJ/kg of BW0.75/d) were examined with linear and quadratic fits. Equations were developed using cow within experiment and experiment as random effects, and blood flow location as a repeated effect. Upon evaluation with the evaluation database, equations based on DMI typically resulted in lower root mean square prediction errors, expressed as a % of the observed mean (rMSPE%) and higher concordance correlation coefficient (CCC) values than equations based on MEI. Quadratic equation terms were frequently nonsignificant, and the quadratic equations did not outperform their linear counterparts. The best performing blood flow equations were PORBF (L/h) = 202 (± 45.6) + 83.6 (± 3.11) × DMI (kg/d) and HEPBF (L/h) = 186 (± 45.4) + 103.8 (± 3.10) × DMI (kg/d), with rMSPE% values of 17.5 and 16.6 and CCC values of 0.93 and 0.94, respectively. The residuals (predicted - observed) for PORBF/HEPBF were significantly related to the forage % of the diet, and thus equations for PORBF and HEPBF based on forage and concentrate DMI were developed: PORBF (L/h) = 210 (± 51.0) + 82.9 (± 6.43) × forage (kg of DM/d) + 82.9 (± 6.04) × concentrate (kg of DM/d), and HEPBF (L/h) = 184 (± 50.6) + 92.6 (± 6.28) × forage (kg of DM/d) + 114.2 (± 5.88) × concentrate (kg of DM/d), where rMSPE% values were 17.5 and 17.6 and CCC values were 0.93 and 0.94, respectively. Division of DMI into forage and concentrate fractions improved the joint Bayesian information criterion value for PORBF and HEPBF (Bayesian information criterion = 6,512 vs. 7,303), as well as slightly improved the rMSPE and CCC for ARTBF and PORBF/HEPBF. This was despite minimal changes in PORBF and HEPBF predictions. Developed equations predicted blood flow well and can easily be used within a postabsorptive model of nutrient metabolism. Results also suggest different sensitivity of PORBF and HEPBF to the composition of DMI, and accounting for this difference resulted in improved ARTBF predictions. [ABSTRACT FROM AUTHOR]

Future extreme climate scenarios may harbour flows that have notably different intrinsic uncertainty from those of the present day. Here, ensemble perturbation analysis is used to explore this possibility for tropospheric flow on weather time-scales for a climate scenario from the National Center for Atmospheric Research (NCAR) Community Climate Modeling System version 4 (CCSM4). Statistically significant changes are found in terms of basic uncertainty metrics including ensemble-average perturbation total energy, ensemble variance, and the growth rate of perturbation total energy and ensemble variance. Strong seasonal, geographic, and vertical variation in the changes are observed. For the winter season, the poles and the jet levels are regions that exhibit notable increases in ensemble uncertainty under the extreme scenario. These increases are accompanied in some cases by substantially larger peak growth rates. For the summer season, there are prominent increases in uncertainty under the extreme scenario in terms of moist metrics. Meanwhile, there are noteworthy reductions in uncertainty for many synoptic variables. These changes in uncertainty properties are accompanied by significant changes in measures of both baroclinic and convective flow stability. Collectively, the results suggest the changes in intrinsic uncertainty under the extreme climate scenario have a fairly nuanced character. Since the CCSM4 exhibits one of the lowest climate sensitivities of available climate models, the results define a conservative estimate of the changes to intrinsic uncertainty that might be expected from extreme climate change. [ABSTRACT FROM AUTHOR]

Presents a study which examined the control of forward voltage of heterostructure transistors by varying the thickness of the undoped gallium arsenide layer beneath the gate or by low energy ion implantation of a surface layer. Information on related studies on the formation of Schottky barriers; Description of how the selectively doped heterostructure wafers were grown; Discussion of results.

Focuses on the magnitude of carrier depletion at the interface between molecular beam epitaxial gallium arsenide and its substrate. Exposure to ultraviolet ozone radiation; Relationship between ozone exposure time and interfacial carbon concentration; Range of the measured oxide desorption temperatures; Carrier concentration profiles for wafers subjected to ultraviolet ozone radiation.

SUMMARY Background/Objectives: When NHS Blood and Transplant ( NHSBT) confirms a blood donation to have markers of infection, the donor is contacted by letter to arrange a discussion about the test results and onward care. A survey was carried out to assess the level of satisfaction with this process. Materials/Methods: A questionnaire was sent to 335 donors who had been notified by NHSBT in 2008 and 2009 that they had tested positive for hepatitis B virus ( HBV), hepatitis C virus ( HCV), human immunodeficiency virus ( HIV) or human T-cell lymphotropic virus ( HTLV). Ratings were made using Likert scales, where the respondent indicated the level of agreement or satisfaction with statements about the initial notification letter and the subsequent post-test discussion (PTD) with the NHSBT clinician. Results: There was an overall 47·5% (159/335) response rate. Fifty-eight percent (91/157) agreed that they were satisfied with the letter, but 30% (46/152) disagreed that it was easy to stay calm (average score 3·2). Scores for the letter were significantly lower in HIV and HTLV than in hepatitis for several questions. Scores for the discussion were in general higher than the initial letter, with 90% (114/127) satisfied overall, although 2 of 19 HIV positive donors remained dissatisfied. Conclusion: Overall, most donors were satisfied with the notification process, although scores were slightly lower for HTLV and HIV. Further audit is planned; in particular to remeasure the satisfaction with, and understanding of, the notification letter for HTLV positive donors and the telephone PTD. [ABSTRACT FROM AUTHOR]

SUMMARY Objective To design and pilot a survey of UK blood donors to assess, on a large scale, their understanding of and compliance with the donor selection guidelines ( DSG). Background Compliance with the DSG is important for maintaining blood safety, however, little is currently known about the extent of this among UK donors. Materials and methods The online, unlinked survey was based on the donor health check form with a focus on behaviours associated with blood borne infections, sexual contact, drug use and travel. The survey materials were reviewed by a donor focus group and the survey was piloted among 2982 UK donors. Percentage responses were calculated, complaints monitored and answers to questions reviewed. The survey went live in 2013; 225 091 donors were invited via email to participate followed by two reminders. Results The survey was well received by the focus group, with little concern about the sensitive and personal questions. Their feedback led to important refinement in the survey materials. In the pilots, 21·0% (627/2982) responded, a reminder was necessary to achieve this. Among responders, there was evidence of non-compliance and test seeking behaviour, and no evidence that intention to donate again was affected. In the live survey, 29% (65 439) responded; responders were generally representative of donors overall. Conclusion A large scale survey of donor compliances is feasible, acceptable and effective in ascertaining appropriate information; involving donors and the blood services in the development stages through a focus group and pilots was important to achieve this. [ABSTRACT FROM AUTHOR]

Treatment resistance in T-cell acute lymphoblastic leukemia (T-ALL) is associated with phosphatase and tensin homolog (PTEN) deletions and resultant phosphatidylinositol 3′-kinase (PI3K)-AKT pathway activation, as well as MYC overexpression, and these pathways repress mitochondrial apoptosis in established T-lymphoblasts through poorly defined mechanisms. Normal T-cell progenitors are hypersensitive to mitochondrial apoptosis, a phenotype that is dependent on the expression of proapoptotic BIM. In a conditional zebrafish model, MYC downregulation induced BIM expression in T-lymphoblasts, an effect that was blunted by expression of constitutively active AKT. In human T-ALL cell lines and treatment-resistant patient samples, treatment with MYC or PI3K-AKT pathway inhibitors each induced BIM upregulation and apoptosis, indicating that BIM is repressed downstream of MYC and PI3K-AKT in high-risk T-ALL. Restoring BIM function in human T-ALL cells using a stapled peptide mimetic of the BIM BH3 domain had therapeutic activity, indicating that BIM repression is required for T-ALL viability. In the zebrafish model, where MYC downregulation induces T-ALL regression via mitochondrial apoptosis, T-ALL persisted despite MYC downregulation in 10% of bim wild-type zebrafish, 18% of bim heterozygotes and in 33% of bim homozygous mutants (P=0.017). We conclude that downregulation of BIM represents a key survival signal downstream of oncogenic MYC and PI3K-AKT signaling in treatment-resistant T-ALL. [ABSTRACT FROM AUTHOR]

Background:Although the negative consequences on health of being obese are well known, most adults gain weight across the lifespan. The general increase in body mass index (BMI) is mainly considered to originate from behavioral and environmental changes; however, few studies have evaluated the influence of these factors on change in BMI in the presence of genetic risk. We aimed to study the influence of multifactorial causes of change in BMI, over 65 years.Methods and Findings:Totally, 6130 participants from TwinGene, who had up to five assessments, and 536 from the Swedish Adoption/Twin Study of Aging, who had up to 12 assessments, ranging over 65 years were included. The influence of lifestyle factors, birth cohort, cardiometabolic diseases and an individual obesity genetic risk score (OGRS) based on 32 single nucleotide polymorphisms on change in BMI was evaluated with a growth model. For both sexes, BMI increased from early adulthood to age of 65 years, after which the increase leveled off; BMI declined after age of 80 years. A higher OGRS, birth after 1925 and cardiometabolic diseases were associated with higher average BMI and a steeper increase in BMI prior to 65 years of age. Among men, few factors were identified that influence BMI trajectories in late life, whereas for women type 2 diabetes mellitus and dementia were associated with a steeper decrease in BMI after the age of 65 years.Conclusions:There are two turning points in BMI in late adulthood, one at the age of 65 years and one at the age 80 years. Factors associated with an increase in BMI in midlife were not associated with an increase in BMI after the age of 65 years. These findings indicate that the causes and consequences of change in BMI differ across the lifespan. Current health recommendations need to be adjusted accordingly. [ABSTRACT FROM AUTHOR]

The objective was to measure effects of 3-nitrooxypropanol (3NP) on methane production of lactating dairy cows and any associated changes in digestion and energy and N metabolism. Six Holstein-Friesian dairy cows in mid-lactation were fed twice daily a total mixed ration with maize silage as the primary forage source. Cows received 1 of 3 treatments using an experimental design based on two 3 x 3 Latin squares with 5-wk periods. Treatments were a control placebo or 500 or 2,500 mg/d of 3NP delivered directly into the rumen, via the rumen fistula, in equal doses before each feeding. Measurements of methane production and energy and N balance were obtained during wk 5 of each period using respiration calorimeters and digestion trials. Measurements of rumen pH (48 h) and postprandial volatile fatty acid and ammonia concentrations were made at the end of wk 4. Daily methane production was reduced by 3NP, but the effects were not dose dependent (reductions of 6.6 and 9.8% for 500 and 2,500 mg/d, respectively). Dosing 3NP had a transitory inhibitory effect on methane production, which may have been due to the product leaving the rumen in liquid outflow or through absorption or metabolism. Changes in rumen concentrations of volatile fatty acids indicated that the pattern of rumen fermentation was affected by both doses of the product, with a decrease in acetate:propionate ratio observed, but that acetate production was inhibited by the higher dose. Dry matter, organic matter, acid detergent fiber, N, and energy digestibility were reduced at the higher dose of the product. The decrease in digestible energy supply was not completely countered by the decrease in methane excretion such that metabolizable energy supply, metabolizable energy concentration of the diet, and net energy balance (milk plus tissue energy) were reduced by the highest dose of 3NP. Similarly, the decrease in N digestibility at the higher dose of the product was associated with a decrease in body N balance that was not observed for the lower dose. Milk yield and milk fat concentration and fatty acid composition were not affected but milk protein concentration was greater for the higher dose of 3NP. Twice-daily rumen dosing of 3NP reduced methane production by lactating dairy cows, but the dose of 2,500 mg/d reduced rumen acetate concentration, diet digestibility, and energy supply. Further research is warranted to determine the optimal dose and delivery method of the product. [ABSTRACT FROM AUTHOR]

Maternal undernutrition (UN) is associated with the development of obesity and metabolic complications in adult offspring. This study investigated the impact of preweaning growth hormone (GH) treatment on adipocyte functionality in adult male offspring. Sprague-Dawley rats were assigned either standard (C) or undernourished (UN) diet (50% ad libitum) throughout gestation. Postnatal day 3-21, male C/UN pups received either saline (CS, UNS) or GH (2.5 µg/g/d; CGH, UNGH) by subcutaneous injection. Primary adipocytes were isolated following the collagenase digestion of adipose tissue. Primary adipocytes from UN offspring had significantly increased the secretion of pro-inflammatory cytokines accompanied by increased cytokine/cytokine receptor expression. This correlated with increased TLR4/NF-κB signaling. While increased inflammatory potential was not observed in adipocytes derived from UNGH offspring, there was a clear alteration in the expression of genes relating to carbohydrate and lipid metabolism along with nutrient transporters. Overall, preweaning GH treatment alters detrimental patterns of development, which predispose UN offspring to obesity and insulin resistance. [ABSTRACT FROM AUTHOR]

Physiological dormancy in weed species has significant implications for weed management, as viable seeds may persist in soil seedbanks for many years. The major stimulatory compound in smoke, karrikinolide ( KAR1), promotes germination in a range of physiologically dormant weed species allowing targeted eradication methods to be employed. Control of Chrysanthemoides monilifera ssp. monilifera (boneseed), a Weed of National Significance in Australia, may benefit from adopting such an approach. In this study, we hypothesised that seeds of C. monilifera ssp. monilifera exhibit physiological dormancy, germinate more rapidly as dormancy is alleviated, show fluctuations in sensitivity to KAR1 and form a persistent soil seedbank. Seeds responded to 1 μM KAR1 (40-60% germination) even during months (i.e. March, April, July, August) when seeds were observed to be more deeply dormant (control germination: 7-20%). Seeds germinated readily over a range of cooler temperatures (i.e. 10, 15, 20, 20/10 and 25/15°C) and were responsive to KAR2 (~50% germination) as well. Eradication efforts for C. monilifera ssp. monilifera may benefit from use of karrikins to achieve synchronised germination from soil seedbanks, even at times of the year when C. monilifera ssp. monilifera seeds would be less likely to germinate, allowing more rapid depletion of the soil seedbank and targeted control of young plants. [ABSTRACT FROM AUTHOR]

ABSTRACT We examine how location-based tax incentives affect quality of life and business environment through changes in property values and equilibrium wages. Using the federal Empowerment Zone program, we determine whether offering tax incentives to firms improves the welfare of the citizens and attractiveness to firms. We demonstrate that quality of life methodologies can be applied using small geographically aggregated data, such as census block groups. We find that the tax incentives offered by the program notably enhances the quality of business environment for firms in the area while modestly improving the quality of life for the individuals living in the area. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hospitalization of student's household members lowers educational attainment. [•] Hospitalization reduces HS completion, college attendance and BA completion. [•] Negative hospitalization effects disproportionately experienced by oldest children. [•] Negative hospitalization effects disproportionately experienced by male children. [ABSTRACT FROM AUTHOR]

Timing techniques are powerful tools to study dynamical astrophysical phenomena. In the X-ray band, they offer the potential of probing accretion physics down to the event horizon. Recent work has used frequency- and energy-dependent time lags as tools for studying relativistic reverberation around the black holes in several Seyfert galaxies. This was achieved due to the evenly sampled light curves obtained using XMM-Newton. Continuously sampled data are, however, not always available and standard Fourier techniques are not applicable. Here, building on the work of Miller et al., we discuss and use a maximum likelihood method to obtain frequency-dependent lags that takes into account light curve gaps. Instead of calculating the lag directly, the method estimates the most likely lag values at a particular frequency given two observed light curves. We use Monte Carlo simulations to assess the method's applicability and use it to obtain lag-energy spectra from Suzaku data for two objects, NGC 4151 and MCG-5-23-16, that had previously shown signatures of iron K reverberation. The lags obtained are consistent with those calculated using standard methods using XMM-Newton data. [ABSTRACT FROM AUTHOR]

In most Western countries, saturated fatty acid (SFA) intake exceeds recommended levels, which is considered a risk factor for cardiovascular disease (CVD). As milk and dairy products are major contributors to SFA intake in many countries, recent research has focused on sustainable methods of producing milk with a lower saturated fat concentration by altering dairy cow diets. Human intervention studies have shown that CVD risk can be reduced by consuming dairy products with reduced SFA and increased cis-monounsaturated fatty acid (MUFA) concentrations. This milk fatty acid profile can be achieved by supplementing dairy cow diets with cis-MUFA-rich unsaturated oils. However, rumen exposure of unsaturated oils also leads to enhanced milk trans fatty acid (TFA) concentrations. Because of concerns about the effects of TFA consumption on CVD, feeding strategies that increase MUFA concentrations in milk without concomitant increases in TFA concentration are preferred by milk processors. In an attempt to limit TFA production and increase the replacement of SFA by cis-MUFA, a preparation of rumen-protected unsaturated oils was developed using saponification with calcium salts. Four multiparous Holstein-Friesian cows in mid-late lactation were used in a 4 x 4 Latin square design with 21-d periods to investigate the effect of incremental dietary inclusion of a calcium salt of cis-MUFA product (Ca-MUFA; 20, 40, and 60 g/kg of dry matter of a maize silage-based diet), on milk production, composition, and fatty acid concentration. Increasing Ca-MUFA inclusion reduced dry matter intake linearly, but no change was observed in estimated ME intake. No change in milk yield was noted, but milk fat and protein concentrations were linearly reduced. Supplementation with Ca-MUFA resulted in a linear reduction in total SFA (from 71 to 52 g/100 g of fatty acids for control and 60 g/kg of dry matter diets, respectively). In addition, concentrations of both cis- and trans-MUFA were increased with Ca-MUFA inclusion, and increases in other biohydrogenation intermediates in milk fat were also observed. The Ca-MUFA supplement was very effective at reducing milk SFA concentration and increasing cis-MUFA concentrations without incurring any negative effects on milk and milk component yields. However, reduced milk fat and protein concentrations, together with increases in milk TFA concentrations, suggest partial dissociation of the calcium salts in the rumen. [ABSTRACT FROM AUTHOR]

Several X-ray observations have recently revealed the presence of reverberation time delays between spectral components in active galactic nuclei. Most of the observed lags are between the power-law Comptonization component, seen directly, and the soft excess produced by reflection in the vicinity of the black hole. NGC 4151 was the first object to show these lags in the iron K band. Here, we report the discovery of reverberation lags in the Fe K band in two other sources: MCG-5-23-16 and NGC 7314. In both objects, the 6-7 keV band, where the Fe Kα line peaks, lags the bands at lower and higher energies with a time delay of ~1 ks. These lags are unlikely to be due to the narrow Fe Kα line. They are fully consistent with reverberation of the relativistically broadened iron Kα line. The measured lags, their time scale, and spectral modeling indicate that most of the radiation is emitted at ~5 and 24 gravitational radii for MCG-5-23-16 and NGC 7314, respectively. [ABSTRACT FROM AUTHOR]

Recent studies analysing immunogenetics and immune mechanisms controlling susceptibility to chronic bacterial infection in bronchiectasis implicate dysregulated immunity in conjunction with chronic bacterial infection. Bronchiectasis is a structural pathological end-point with many causes and disease associations. In about half of cases it is termed idiopathic, because it is of unknown aetiology. Bronchiectasis is proposed to result from a 'vicious cycle' of chronic bacterial infection and dysregulated inflammation. Paradoxically, both immune deficiency and excess immunity, either in the form of autoimmunity or excessive inflammatory activation, can predispose to disease. It appears to be a part of the spectrum of inflammatory, autoimmune and atopic conditions that have increased in prevalence through the 20th century, attributed variously to the hygiene hypothesis or the 'missing microbiota'. Immunogenetic studies showing a strong association with human leucocyte antigen ( HLA)- Cw*03 and HLA- C group 1 homozygosity and combinational analysis of HLA- C and killer immunoglobulin-like receptors ( KIR) genes suggests a shift towards activation of natural killer ( NK) cells leading to lung damage. The association with HLA-DR1, DQ5 implicates a role for CD4 T cells, possibly operating through influence on susceptibility to specific pathogens. We hypothesize that disruption of the lung microbial ecosystem, by infection, inflammation and/or antibiotic therapy, creates a disturbed, simplified, microbial community ('disrupted microbiota') with downstream consequences for immune function. These events, acting with excessive NK cell activation, create a highly inflammatory lung environment that, in turn, permits the further establishment and maintenance of chronic infection dominated by microbial pathogens. This review discusses the implication of these concepts for the development of therapeutic interventions. [ABSTRACT FROM AUTHOR]

We report the results of a detailed investigation thataddressesthe influence of polymer morphology and chain aggregation, as controlledby the chemical nature of the solvent, on the optical gain propertiesof the conjugated polymer poly[2-methoxy-5-(2′-ethylhexyloxy)-p-phenylene vinylene] (MEH-PPV). Using the variable stripelength technique in the picosecond regime, we have extensively studiedthe optical gain performance of asymmetric planar waveguides formedwith thin MEH-PPV films spin-cast from concentrated chlorobenzene(CB) and tetrahydrofuran (THF) solutions onto thermally oxidized siliconsubstrates. CB and THF solvents were chosen based on their known abilityto promote and effectively limit aggregate formation, respectively.Very large net gain coefficients are demonstrated, reaching valuesof 330 and 365 cm–1, respectively, when opticallypumping the waveguides with a maximum energy density of 85 μJ/cm2. Our results clearly demonstrate that polymer morphology,and hence, the chain conformation dependence of the degree of aggregationin the films as controlled by the solvent, has minimal impact on thenet gain. Moreover, the waveguides exhibit low loss coefficients of10–20 cm–1at the ASE wavelength. These resultsquestion the importance of polymer morphology and aggregate formationin polymer-based optical devices operating at high excitation densitiesin the stimulated emission regime as would be characteristic of lasersand optical amplifiers. [ABSTRACT FROM AUTHOR]

Abstract: Two-year colleges are an important part of the higher education system in the United States but there are concerns as to how attendance at these institutions affects educational attainment and labor market outcomes. This paper uses data from a nationally representative survey to examine the impact of students beginning their college career at a two-year college instead of a four-year college. Treatment effects are estimated using both standard regression techniques as well as propensity score matching. As these estimates may be contaminated because of selection on unobservable characteristics this paper will also employ a number of sensitivity analyses to consider the potential bias. The results show large negative impacts on both educational attainment and labor market outcomes for men and women who begin at a two-year college, even for those students who expect to complete a bachelor''s degree. The evidence from the sensitivity analyses suggest that to eliminate these large effects there would need to be substantial, and arguably implausible, selection on unobservable characteristics. [Copyright &y& Elsevier]

The Suzaku AGN Spin Survey is designed to determine the supermassive black hole spin in six nearby active galactic nuclei (AGNs) via deep Suzaku stares, thereby giving us our first glimpse of the local black hole spin distribution. Here, we present an analysis of the first target to be studied under the auspices of this Key Project, the Seyfert galaxy NGC 3783. Despite complexity in the spectrum arising from a multi-component warm absorber, we detect and study relativistic reflection from the inner accretion disk. Assuming that the X-ray reflection is from the surface of a flat disk around a Kerr black hole, and that no X-ray reflection occurs within the general relativistic radius of marginal stability, we determine a lower limit on the black hole spin of a ≥ 0.88 (99% confidence). We examine the robustness of this result to the assumption of the analysis and present a brief discussion of spin-related selection biases that might affect flux-limited samples of AGNs. [ABSTRACT FROM AUTHOR]

We present XMM-Newton observations of three active galactic nuclei (AGNs) taken as part of a hunt to find very heavily obscured Compton-thick AGNs. For obscuring columns greater than 1025 cm-2, AGNs are only visible at energies below 10 keV via reflected/scattered radiation, characterized by a flat power law. We therefore selected three objects (ESO 417-G006, IRAS 05218-1212, and MCG - 01-05-047) from the Swift Burst Alert Telescope (BAT) hard X-ray survey catalog with Swift X-ray Telescope (XRT) 0.5-10 keV spectra with flat power-law indices as candidate Compton-thick sources for follow-up observations with the more sensitive instruments on XMM-Newton. The XMM spectra, however, rule out reflection-dominated models based on the weakness of the observed Fe Kα lines. Instead, the spectra are well fit by a model of a power-law continuum obscured by a Compton-thin absorber plus a soft excess. This result is consistent with previous follow-up observations of two other flat-spectrum BAT-detected AGNs. Thus, out of the six AGNs in the 22 month BAT catalog with apparently flat Swift XRT spectra, all five that have had follow-up observations are not likely Compton thick. We also present new optical spectra of two of these objects, IRAS 05218-1212 and MCG -01-05-047. Interestingly, though both the AGNs have similar X-ray spectra, their optical spectra are completely different, adding evidence against the simplest form of the geometric unified model of AGNs. IRAS 05218-1212 appears in the optical as a Seyfert 1, despite the ~8.5 x 1022 cm-2 line-of-sight absorbing column indicated by its X-ray spectrum. MCG - 01-05-047's optical spectrum shows no sign of AGN activity; it appears as a normal galaxy. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]

A cause and effect relationship between glucagon-like peptide 1 (7, 36) amide (GLP-1) and cholecystokinin (CCK) and DMI regulation has not been established in ruminants. Three randomized complete block experiments were conducted to determine the effect of feeding fat or infusing GLP-1 or CCK intravenously on DMI, nutrient digestibility, and Cr rate of passage (using Cr2O3 as a marker) in wethers. A total of 18 Targhee × Hampshire wethers (36.5 ± 2.5 kg of BW) were used, and each experiment consisted of four 21-d periods (14 d for adaptation and 7 d for infusion and sampling). Wethers allotted to the control treatments served as the controls for all 3 experiments; experiments were performed simultaneously. The basal diet was 60% concentrate and 40% forage. In Exp. 1, treatments were the control (0% added fat) and addition of 4 or 6% Ca salts of palm oil fatty acids (DM basis). Treatments in Exp. 2 and 3 were the control and 3 jugular vein infusion dosages of GLP-1 (0.052, 0.103, or 0.155 μg∙kg of BW-1∙d-1) or CCK (0.069, 0.138, or 0.207 ∙g∙kg of BW-1∙d-1), respectively. Increases in plasma GLP-1 and CCK concentrations during hormone infusions were comparable with increases observed when increasing amounts of fat were fed. Feeding fat and infusion of GLP-1 tended (linear, P = 0.12; quadratic, P = 0.13) to decrease DMI. Infusion of CCK did not affect (P > 0.21) DMI. Retention time of Cr in the total gastrointestinal tract decreased (linear, P < 0.01) when fat was fed, but was not affected by GLP-1 or CCK infusion. In conclusion, jugular vein infusion produced similar plasma CCK and GLP-1 concentrations as observed when fat was fed. The effects of feeding fat on DMI may be partially regulated by plasma concentration of GLP-1, but are not likely due solely to changes in a single hormone concentration. [ABSTRACT FROM AUTHOR]

Owners' perceptions and priorities regarding quality of life (QoL) are important considerations given the unknown efficacy of many commonly administered medications, stress of hospital visits, difficulties providing home care, and personal choices including euthanasia. To describe the relative importance of quality versus quantity of life to owners of cats with heart disease. Two hundred and thirty-nine cats with heart disease. Prospective questionnaire-based clinical study. Cat owners completed a questionnaire to identify important parameters when assessing their cat's QoL, the relative importance of quality versus quantity of life, and willingness to trade survival time for QoL. Variables associated with these parameters were evaluated with multivariate analyses. Appetite, owner interaction, sleep patterns, and litterbox habits were deemed important to QoL. Concern over pet suffering was significantly greater than concern over life expectancy. Ninety-three percent of owners were willing to trade survival time for good QoL; 57% of these were willing to trade up to 6 months. On multivariate analysis, the only factor significantly ( P= .002) associated with willingness to trade 6 months was study site. Owner concern regarding stress of administering medications at home increased with number and frequency of medications. These results indicated that QoL is more important to owners of cats with heart disease than longevity. The various priorities and concerns of cat owners should be taken into account in order to provide optimal care. [ABSTRACT FROM AUTHOR]

Background: Increased serotonin (5HT) signaling has been implicated in valvular disease of humans and animals, including canine degenerative mitral valve disease (DMVD). High circulating 5HT concentration is a potential source of increased signaling, and serum 5HT concentrations have not been previously reported in dogs with DMVD. Hypothesis: Dogs with DMVD and small breed dogs predisposed to DMVD have higher serum 5HT concentrations than large breed controls. Animals: Fifty dogs affected with DMVD, 34 dogs predisposed to DMVD but without cardiac murmur or echocardiographic evidence of DMVD, and 36 healthy large breed control dogs. Methods: Prospective analysis. Serum 5HT concentration was measured by an ELISA test. Results: Median serum 5HT concentration was significantly higher in dogs with DMVD and in dogs predisposed to DMVD as compared with controls (DMVD, 765.5 ng/mL [interquartile range, 561.3–944.4]; predisposed, 774.9 ng/mL [528.3–1,026]; control, 509.8 ng/mL [320.8–708.8]; P= .0001). Subgroup analysis of predisposed dogs indicated significantly higher serum 5HT concentrations in Cavalier King Charles Spaniel (CKCS) dogs than in other breeds (CKCS, 855.0 ng/mL [635.8–1,088]; non-CKCS, 554.2 ng/mL [380.6–648.4]; P= .0023). Age, platelet count, and platelet morphology were not correlated with 5HT concentration in any group. Conclusions and Clinical Importance: Dogs with DMVD had significantly higher serum 5HT concentrations when compared with large breed control dogs. Healthy CKCS dogs had significantly higher serum 5HT concentrations than other healthy dogs predisposed to DMVD. Additional investigation into a possible role of 5HT in the pathogenesis of DMVD is warranted. [ABSTRACT FROM AUTHOR]

Escherichia coli mutants deficie'nt in 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) biosynthesis are conditionally lethal, but their phenotypes are bypassed by certain suppressor mutations or by over- expression of MsbA, the inner membrane flippase for core-lipid A. These strains grow on broth with the tetraacylated precursor lipid IVA replacing lipopolysaccharide [Meredith, T. C., et al. (2006) ACS Chem. Biol. 1, 33-42]. Deletion of kdtA, which encodes the Kdo transferase, is possible under these conditions. We now show that lipid IVA reaches the Outer surface of the outer membrane in these strains, as judged by its accessibility to the lipase PagL. On the assumption that MsbA is optimized to transport penta- or hexaacylated lipid A, we overexpressed the lauroyl- or the myristoyltransferase of lipid A biosynthesis, encoded by IpxL and ipxM, respectively, and demonstrated that kdtA deletion mutants were also viable in this setting. Although E. coli LpxL is stimulated by the presence of the Kdo disaccharide in its acceptor substrate, LpxL does slowly acylate lipid IVA. Overexpression of LpxL from a plasmid suppressed the lethality of kdtA deletions on nutrient broth at 30 or 37 °C without the need for MsbA overproduction. These strains accumulated penta- and hexaacylated free lipid A containing a secondary laurate chain or a laurate and a myristate chain, respectively. Deletion of kdtA in strains overexpressing LpxM accumulated pentaacylated lipid A with a secondary myristate moiety. None of the strains lacking kdtA grew in the presence of bile salts at any temperature or on nutrient broth at 42 °C. Our findings show that the main function of Kdo is to provide the right substrates for the acyltransferases LpxL and LpxM, resulting in the synthesis of penta- and hexaacylated lipid A, which is optimal for the MsbA flippase. [ABSTRACT FROM AUTHOR]

This paper describes the use of hyperspectral imaging microscopy (HIM) for the characterization and differentiation of live viable versus dead/non-viable bacterial endospores for two species of Bacillus. To accomplish this, endospore-forming Bacillus were cultured and differentiated into endospores. Non-viable endospores were produced using sporicidal methods representing standard decontamination procedures incorporating chlorine and peroxide. Finally, endospore samples were lyophilized to prepare them for spectral analysis. Prior to HIM, baseline spectral reflectance characterizing the endospores was measured using an ASD (400–900 nm) reflectance spectrometer. These data were used to calibrate the resulting spectral image data. HIM data comprising 32 images ranging from 400 to 720 nm (visible to near infrared) were recorded using a C-mounted VariSpec hyperspectral camera attached to an epifluorescent microscope. The images produced by the system record the reflectance and absorption features of endospores based on the structure of the outer coat. Analysis of the HIM data was performed using accepted image and spectral processing routines. Where peroxide was the sporicide, changes in the outer endospore coat contributed to structurally significant visible and near infrared signature differences between live-viable versus dead, non-viable endospores. A statistical test for divergence, a method for scoring spectral structural diversity, also showed the difference between viable and non-viable peroxide killed endospores to be statistically significant. These findings may lead to an improved optical procedure to rapidly identify viable and non-viable endospores in situations of decontamination. [ABSTRACT FROM AUTHOR]

Sixteen multiparous Holstein cows were used to determine the effects of 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi: 0 vs. 1.26 g/kg of total ration dry matter (DM) and dietary crude protein (CP) concentration [14.7% (low) vs. 16.9% (standard), DM basis] on milk yield and composition using a replicated 4 x 4 Latin square design experiment with 4-wk periods. Cows were fed ad libitum a total mixed ration with a 1:1 forage-to-concentrate ratio (DM basis), and diets provided an estimated 6.71 and 1.86% lysine and methionine, respectively, in metabolizable protein for the low-protein diet and 6.74 and 1.82% in the standard protein diet. Dry matter intake, milk yield, and composition were measured during wk 4 of each period. There were no effects on DM intake, which averaged 24.7 kg/d. There was an interaction between dietary CP and HMBi for milk yield and 3.5% fat-corrected milk (FCM). Feeding HMBi decreased milk and FCM yield when fed with the low-CP diet but did not affect milk or FCM yield when fed with the standard CP diet. Feeding HMBi increased milk protein concentration regardless of diet CP concentration and increased milk protein yield when added to the standard CP diet but not the low-CP diet. The positive effect of HMBi on milk protein yield was only observed at the standard level of dietary CP, suggesting other factors limited the response to HMBi when dietary protein supply was restricted. [ABSTRACT FROM AUTHOR]

The core-lipid A domain of Escherichia coil lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and QuiP substitutions in LptA. MB1 stops growing after 30 mm at 42°C. 32Pi and [35S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-O-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42°C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42°C, consistent with a role for LptA in shuttling LPS across the periplasm. [ABSTRACT FROM AUTHOR]

The microtubule-associated protein tau can associate with various other proteins in addition to tubulin, including the SH3 domains of Src family tyrosine kinases. Tau is well known to aggregate to form hyperphosphorylated filamentous deposits in several neurodegenerative diseases (tauopathies) including Alzheimer disease. We now report that tau can bind to SH3 domains derived from the p8Sa subunit of phosphatidylinositol 3-kinase, phospholipase Cγ1, and the N-terminal (but not the C-terminal) SH3 of Grb2 as well as to the kinases Fyn, cSrc, and, Fgr. However, the short inserts found in neuron-specific isoforms of Src prevented the binding of tau. The experimentally determined binding of tau peptides is well accounted for when modeled into the peptide binding cleft in the SH3 domain of Fyn. After phosphorylation in vitro or in transfected cells, tau showed reduced binding to SH3 domains; no binding was detected with hyperphosphorylated tau isolated from Alzheimer brain, but SH3 binding was restored by phosphatase treatment. Tau mutants with serines and threonines replaced by glutamate, to mimic phosphorylation, showed reduced SH3 binding. These results strongly suggest that tau has a potential role in cell signaling in addition to its accepted role in cytoskeletal assembly, with regulation by phosphorylation that may be disrupted in the tauopathies including Alzheimer disease. [ABSTRACT FROM AUTHOR]

The lipid A residues of certain Gram-negative bacteria, including most strains of Salmonella and Pseudomonas, are esterified with one or two secondary S-2-hydroxyacyl chains. The S-2 hydroxylation process is O2-dependent in vivo, but the relevant enzymatic pathways have not been fully characterized because in vitro assays have not been developed. We previously reported that expression of the Salmonella lpxO gene confers upon Escherichia coli K-12 the ability to synthesize 2-hydroxymyristate modified lipid A (J. Biol. Chem. (2000) 275, 32940-32949). We now demonstrate that inactivation of lpxO, which encodes a putative Fe2+/O2/α-ketoglutarate-dependent dioxygenase, abolishes S-2-hydroxymyristate formation in S. typhimurium. Membranes of E. coli strains expressing lpxO are able to hydroxylate Kdo2-[4'-32P]-lipid A in vitro in the presence of Fe2+, O2, α-ketoglutarate, ascorbate, and Triton X-100. The Fe2+ chelator 2,2'-bipyridyl inhibits the reaction. The product generated in vitro is a monohydroxylated Kdo2-lipid A derivative. The [4'-32P]-lipid A released by mild acid hydrolysis from the in vitro product migrates with authentic S-2-hydroxlyated lipid A isolated from 32P-labeled S. typhimurium cells. Electrospray ionization mass spectrometry and gas chromatography/mass spectrometry of the in vitro product are consistent with the 2-hydroxylation of the 3'-secondary myristoyl chain of Kdo2-lipid A. LpxO contains two predicted trans-membrane helices (one at each end of the protein), and its active site likely faces the cytoplasm. LpxO is an unusual example of an integral membrane protein that is a member of the Fe2+/O2/α- ketoglutarate-dependent dioxygenase family. [ABSTRACT FROM AUTHOR]

Diet digestibility and rate of passage, eating and rumination behavior, dry matter intake (DMI), and lactation performance were compared in 6 Jersey and 6 Holstein multiparous cows. Cows were fed gestation diets according to body weight (BW) beginning 7 wk before expected calving and ad libitum amounts of a lactation diet postpartum. Diet digestibility and rate of passage were measured in 5-d periods at wk 5 prepartum and wk 6 and 14 of lactation. Eating and ruminating behavior was measured over 5-d periods at wk 5 and 2 prepartum and wk 2, 6, 10, and 14 of lactation. Milk yield and DMI were higher in Holsteins, but milk energy output per kilogram of metabolic BW (BW0.75) and intake capacity (DMI/kg of BW) did not differ between breeds. Holsteins spent longer ruminating per day compared with Jerseys, but daily eating time did not differ between breeds. Jerseys spent more time eating and ruminating per unit of ingested feed. The duration and number of meals consumed did not differ between breeds, but the meals consumed by Jerseys were distributed more evenly throughout each 24-h period, providing a more regular supply of feed to the rumen. Feed passed through the digestive tract more quickly in Jerseys compared with Holsteins, suggesting particle breakdown and rumen outflow were faster in Jerseys, but this may also reflect the relative size of their digestive tract. Neutral detergent fiber digestibility was greater in Jerseys, despite the shorter rumen retention time, but digestibility of dry matter, organic matter, starch, and N did not differ between breeds. Utilization of digested N for tissue retention was higher at wk 5 prepartum and lower at wk 14 of lactation in Jerseys. In contrast to numerous published studies, intake capacity of Jerseys was not higher than that of Holsteins, but in the present study, cows were selected on the basis of equal expected milk energy yield per kilogram of metabolic BW. Digestibility of neutral detergent fiber and rate of digesta passage were higher in Jerseys, probably as a consequence of increased mastication per unit of feed consumed in Jerseys and their smaller size. [ABSTRACT FROM AUTHOR]

Adaptive observing guidance products for Atlantic tropical cyclones are compared using composite techniques that allow one to quantitatively examine differences in the spatial structures of the guidance maps and relate these differences to the constraints and approximations of the respective techniques. The guidance maps are produced using the ensemble transform Kalman filter (ETKF) based on ensembles from the National Centers for Environmental Prediction and the European Centre for Medium-Range Weather Forecasts (ECMWF), and total-energy singular vectors (TESVs) produced by ECMWF and the Naval Research Laboratory. Systematic structural differences in the guidance products are linked to the fact that TESVs consider the dynamics of perturbation growth only, while the ETKF combines information on perturbation evolution with error statistics from an ensemble-based data assimilation scheme. The impact of constraining the SVs using different estimates of analysis error variance instead of a total-energy norm, in effect bringing the two methods closer together, is also assessed. When the targets are close to the storm, the TESV products are a maximum in an annulus around the storm, whereas the ETKF products are a maximum at the storm location itself. When the targets are remote from the storm, the TESVs almost always indicate targets northwest of the storm, whereas the ETKF targets are more scattered relative to the storm location and often occur over the northern North Atlantic. The ETKF guidance often coincides with locations in which the ensemble-based analysis error variance is large. As the TESV method is not designed to consider spatial differences in the likely analysis errors, it will produce targets over well-observed regions, such as the continental United States. Constraining the SV calculation using analysis error variance values from an operational 3D variational data assimilation system (with stationary, quasi-isotropic background error statistics) results in a modest modulation of the target areas away from the well-observed regions, and a modest reduction of perturbation growth. Constraining the SVs using the ETKF estimate of analysis error variance produces SV targets similar to ETKF targets and results in a significant reduction in perturbation growth, due to the highly localized nature of the analysis error variance estimates. These results illustrate the strong sensitivity of SVs to the norm (and to the analysis error variance estimate used to define it) and confirm that discrepancies between target areas computed using different methods reflect the mathematical and physical differences between the methods themselves. [ABSTRACT FROM AUTHOR]

The lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most gram-negative bacteria. Escherichia coli lipid A is synthesized on the cytoplasmic surface of the inner membrane by a conserved pathway of nine constitutive enzymes. Following attachment of the core oligosaccharide, nascent core-lipid A is flipped to the outer surface of the inner membrane by the ABC transporter MsbA, where the O-antigen polymer is attached. Diverse covalent modifications of the lipid A moiety may occur during its transit from the outer surface of the inner membrane to the outer membrane. Lipid A modification enzymes are reporters for lipopolysaccharide trafficking within the bacterial envelope. Modification systems are variable and often regulated by environmental conditions. Although not required for growth, the modification enzymes modulate virulence of some gram-negative pathogens. Heterologous expression of lipid A modification enzymes may enable the development of new vaccines. [ABSTRACT FROM AUTHOR]

Our objective was to determine the effect of feeding rumen-inert fats differing in their degree of saturation on dry matter intake (DMI), milk production, and plasma concentrations of insulin, glucagon-like peptide 1 (7-36) amide (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK) in lactating dairy cows. Four midlactation, primiparous Holstein cows were used in a 4 x 4 Latin square experiment with 2-wk periods. Cows were fed a control mixed ration ad libitum, and treatments were the dietary addition (3.5% of ration dry matter) of 3 rumen-inert fats as sources of mostly saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), or polyunsaturated fatty acids (PUFA). Daily DMI, milk yield, and composition were measured on the last 4 d of each period. Jugular vein blood was collected every 30 min over a 7-h period on d 12 and 14 of each period for analysis of plasma concentrations of hormones, glucose, and nonesterified fatty acids. Feeding fat decreased DMI, and the decrease tended to be greater for MUFA and PUFA compared with SFA. Plasma concentration of GLP-1 increased when fat was fed and was greater for MUFA and PUFA. Feeding fat increased plasma glucose-dependent insulinotropic polypeptide and CCK concentrations and decreased plasma insulin concentration. Plasma CCK concentration was greater for MUFA and PUFA than for SFA and was greater for MUFA than PUFA. Decreases in DMI in cows fed fat were associated with increased plasma concentrations of GLP-1 and CCK and a decreased insulin concentration. The role of these peptides in regulating DMI in cattle fed fat requires further investigation. [ABSTRACT FROM AUTHOR]