Effects of weaning and inactivated Lactobacillus helveticus supplementation on dairy calf behavioral and physiological indicators of affective state.

The objectives of this study were to determine if weaning would induce behavioral and physiological indicators of a negative affective state, and if supplementation of inactivated Lactobacillus helveticus (ILH) to dairy calves would reduce those indicators of negative affect during weaning. Male Holstein calves (n = 23) were enrolled in the study on d 1 of life. The calves were housed in individual pens in 1 of 4 rooms for the 42 d study. Calves began a stepdown weaning from 9 L/d of milk replacer (MR), at 150 g of MR powder/L, on d 35 and received 6 L/d on d 35 - 36, 3 L/d on d 37 - 38, and 0.4 L/d on d 39 - 42. The MR was divided between 3 meals/d until the last 0.4 L/d phase which was divided between 2 meals/d. Calves had ad libitum water access throughout the study and calf starter from d 28 onwards. Within room, calves were assigned to 1 of 2 treatments: 1) control (CON; n = 11) and 2) 5 g of ILH/d split over and mixed into the 0800 h and 2000 h milk feedings from d 3-42 (ILH; n = 12). Lying behavior was recorded using HOBO data loggers from d 21-41. On d 33, 37 and 41, infrared eye images were taken to determine maximum eye temperature (MET), saliva samples were collected to determine cortisol concentration, and play assessments were conducted to quantify play behavior. On d 34, 38, and 42, blood samples were collected to determine blood serotonin concentration, whereas on d 38 and 39, calves were tested with a cognitive task. A subset of calves (n = 5/treatment) were euthanized to collect gut and brain tissue samples for serotonin concentration on d 43. Weaning resulted in fewer (d 37-41, tendency: d 36), but longer (d 38-41, tendency: d 37), lying bouts and reduced play (d 41), although no changes in lying time, MET, saliva cortisol, nor blood serotonin were detected with initiation of weaning. Supplementation of ILH was associated with lower lying time throughout the study, and reduced play duration and higher salivary cortisol and MET during weaning. No differences in lying bouts, play count, blood and tissue (colon, ileum, prefrontal cortex and brain stem) serotonin concentration, and time to complete the cognitive task were detected between the treatments. Overall, weaning induced behavioral changes indicative of negative affective state, and some behavioral differences were observed with ILH supplementation both before and during weaning, with some physiological changes observed during weaning.

Sub-wavelength effects in a free electron laser oscillator.

Previous simulation studies of cavity based free electron lasers (FELs) have utilised models which average the optical field in the FEL interaction over an integer number of radiation wavelengths. In this paper, two unaveraged simulation codes, OPC and Puffin, are combined to enable modelling, for the first time, of a cavity based FEL at the sub-wavelength scale. This enables modelling of effects such as coherent spontaneous emission from the electron beam and sub-wavelength cavity length detuning. A cavity FEL operating in the mid-infrared is modelled and it is shown that, for small sub-wavelength cavity detunings, the FEL can preferentially lase at the third harmonic of the fundamental FEL wavelength. This novel result suggests other modes of operation may be possible and opens up cavity-based FEL operation to investigation of further, potentially useful, modes of operation.

Effects of Echinacea purpurea supplementation on markers of immunity, health, intake, and growth of dairy calves.

Echinacea purpurea (EP) is an herb that has demonstrated immunostimulatory and anti-inflammatory effects with the potential to improve immunity, health, and performance in animals. The objective of this study was to investigate how supplementing calves with EP affects their blood immunity marker profile, health, intake, and growth. Male Holstein calves (n = 240), sourced from local dairy farms or auction, arrived at a rearing facility between 5 and 14 d of age and were kept in individual pens in 1 of 3 rooms (80/room) for 56 d, and then put into groups for the remaining 21 d of the trial. Calves received milk replacer (MR) 2× per day for 56 d (total = 36 kg of MR) and had ab libitum water and starter access. Within room, calves were randomly assigned to 1 of 3 treatments: (1) control (n = 80), (2) 3g of dried (powder) EP extract per day split over 2 milk feedings from experiment d 14-28 (n = 80), and (3) 3 g of dried (powder) EP extract per day split over 2 milk feedings from experiment d 1-56 (E56; n = 80). The powdered EP treatments were mixed into the liquid MR. On d 1, 14, 28, and 57 rectal temperatures and blood were collected from a subset of calves (n = 117; 39 calves/treatment), and blood serum was assessed for serum total protein (d 1), haptoglobin, white blood cells, and cytokines. Failed transfer of passive immunity was defined as serum total protein <5.2 g/dL. Calves were health scored 2× per day, receiving fecal and respiratory scores until d 28 and 77, respectively. Calves were weighed on arrival and then weekly until d 77. Milk replacer and feed refusals were recorded. Supplementation of EP was associated with lower haptoglobin levels, segmented neutrophil counts, segmented neutrophil per lymphocyte ratio, respiratory scores in auction derived calves, and higher lymphocyte counts and d 28 rectal temperature. Of calves with heavier arrival body weight, E56 calves had greater postweaning weekly body weight. There was no detected effect of EP supplementation on total white blood cells, band neutrophil, monocyte, and basophil counts, IL-10, IL-6, and TNF-α levels, fecal scores, risk of receiving diarrhea and respiratory treatment, risk of bovine respiratory disease (calves were deemed at risk for bovine respiratory disease if they had at least 1 respiratory score ≥5), risk of mortality, MR and feed intake, average daily gain, and feed conversion ratio. Overall, EP supplementation to dairy calves was associated with immunomodulation and reduced inflammation, evidenced through blood markers, although only few minor health and growth improvements were observed. Benefits were observed particularly when fed across the whole milk feeding period.

Attosecond-Angstrom free-electron-laser towards the cold beam limit.

Electron beam quality is paramount for X-ray pulse production in free-electron-lasers (FELs). State-of-the-art linear accelerators (linacs) can deliver multi-GeV electron beams with sufficient quality for hard X-ray-FELs, albeit requiring km-scale setups, whereas plasma-based accelerators can produce multi-GeV electron beams on metre-scale distances, and begin to reach beam qualities sufficient for EUV FELs. Here we show, that electron beams from plasma photocathodes many orders of magnitude brighter than state-of-the-art can be generated in plasma wakefield accelerators (PWFAs), and then extracted, captured, transported and injected into undulators without significant quality loss. These ultrabright, sub-femtosecond electron beams can drive hard X-FELs near the cold beam limit to generate coherent X-ray pulses of attosecond-Angstrom class, reaching saturation after only 10 metres of undulator. This plasma-X-FEL opens pathways for advanced photon science capabilities, such as unperturbed observation of electronic motion inside atoms at their natural time and length scale, and towards higher photon energies.

X-ray pulse generation with ultra-fast flipping of its orbital angular momentum.

A method to temporally tailor the properties of X-ray radiation carrying Orbital Angular Momentum (OAM) is presented. In simulations, an electron beam is prepared with a temporally modulated micro-bunching structure which, when radiating at the second harmonic in a helical undulator, generates OAM light with a corresponding temporally modulated intensity. This method is shown to generate attosecond pulse trains of OAM light without the need for any additional external optics, making the wavelength range tunable. In addition to the OAM pulse train, the method can be adapted to generate radiation where the handedness of the OAM mode may also be temporally modulated (flipped).

Induction of leaky gut by repeated intramuscular injections of indomethacin to preweaning Holstein calves.

This study was designed to develop a protocol for repeated intramuscular indomethacin injections to replicate leaky-gut-like symptoms in male Holstein calves to model and study the detrimental effects of leaky gut on gut tissue function and inflammatory response. A generalized randomized block design was used to evaluate how repeated indomethacin intramuscular injections affected the development of leaky gut in 18 male Holstein calves. Animals were enrolled at 3 ± 1 d of life, and after 21 d of adaptation, they were randomly assigned to 1 of 3 treatments consisting of intramuscular saline or indomethacin injections every 12 h for 48 h: (1) control (CTL), saline injection, (2) low intramuscular indomethacin (INDO-L) dosed at 1.2 mg/kg of body weight (BW), and (3) high intramuscular indomethacin (INDO-H) dosed at 2.4 mg/kg of BW. During the challenge, milk intake, starter intake, fecal scores, and rectal temperature were measured daily, and BW was measured at the beginning and at the end of the challenge. Plasma samples were used to measure the recovery of markers of intestinal permeability before and after the challenge by dosing lactulose, d-mannitol, and chromium-EDTA. In addition, several cytokines were measured in plasma during the challenge. Calves were dissected at the end of the challenge to obtain tissue and digesta samples from the gastrointestinal tract and liver. No treatment differences were observed for starter and milk intakes, fecal scores, BW, and rectal temperature. The difference in marker concentrations between pre and post challenges was higher for INDO calves compared with CTL calves in the case of lactulose and chromium-EDTA. In addition, chemokine ligand 2 and 4 and IL-6 were higher for INDO-H calves compared with CTL. Both doses of indomethacin resulted in reductions in villus length and surface area in the distal jejunum and ileum and reductions in crypt depth and width in the colon. We showed that repeated indomethacin injections over a 48-h period induced leaky-gut-like symptoms in a region-specific manner, affecting mainly the distal section of the intestine. This outcome was characterized by histomorphological changes in the distal jejunum, ileum, and colon and by increased gut permeability. Interestingly, changes in liver morphology and immune function also occurred, possibly due to the increased translocation of foreign antigens breaching the epithelial cell wall. The leaky gut challenge model described here could be used to improve understanding of the pathogenesis of intestinal disorders in cattle and provide a reliable alternative for testing feed additives with intestinal health benefits.

Frequency modulated free electron laser.

It is shown that the output frequency of a free electron laser may be modulated to generate a series of modes that span a bandwidth of at least an order of magnitude greater than the normal FEL bandwidth. This new method of frequency modulated FEL operation has close analogies to frequency modulation in conventional cavity lasers. The FM-FEL is analysed and described in the linear regime by a summation over the exponentially amplified frequency modes. Simulations using a 3D, broad bandwidth, numerical code also demonstrate FM-FEL operation for parameters typical of FEL facilities currently under construction. Harmonic bunching methods are used to seed the FM-FEL modes to generate a temporally correlated frequency modulated output over a large bandwidth. This new, FM-FEL mode of operation scales well for X-ray generation, offering users a significantly new form of high-power, short wavelength FEL output.

Centennial-scale reductions in nitrogen availability in temperate forests of the United States.

Forests cover 30% of the terrestrial Earth surface and are a major component of the global carbon (C) cycle. Humans have doubled the amount of global reactive nitrogen (N), increasing deposition of N onto forests worldwide. However, other global changes-especially climate change and elevated atmospheric carbon dioxide concentrations-are increasing demand for N, the element limiting primary productivity in temperate forests, which could be reducing N availability. To determine the long-term, integrated effects of global changes on forest N cycling, we measured stable N isotopes in wood, a proxy for N supply relative to demand, on large spatial and temporal scales across the continental U.S.A. Here, we show that forest N availability has generally declined across much of the U.S. since at least 1850 C.E. with cool, wet forests demonstrating the greatest declines. Across sites, recent trajectories of N availability were independent of recent atmospheric N deposition rates, implying a minor role for modern N deposition on the trajectory of N status of North American forests. Our results demonstrate that current trends of global changes are likely to be consistent with forest oligotrophication into the foreseeable future, further constraining forest C fixation and potentially storage.

Relationship of thyroid transcription factor 1 to EGFR status in non-small-cell lung cancer.

BACKGROUND: Activating mutations of the epidermal growth factor receptor (EGFR) gene are known to drive a proportion of non-small-cell lung cancers. Identification of lung cancers harbouring such mutations can lead to effective treatment using one of the agents that targets and blocks egfr-mediated signalling. METHODS: All specimens received at the BC Cancer Agency (Vancouver) for EGFR testing were prospectively identified and catalogued, together with clinical information and EGFR status, over a 14-month period. RESULTS: Specimens from 586 patients were received for EGFR testing, and EGFR status was reported for 509 patients. No relationship between specimen type or site of origin and EGFR test failure rate was identified. Concurrent immunohistochemical (ihc) status for thyroid transcription factor 1 (ttf1) was available for 309 patients. The negative predictive value of ttf1-negative status by ihc was 94.2% for predicting negative EGFR status. CONCLUSIONS: In patients with limited tissue available for testing, a surrogate for EGFR status would aid in timely management. Immunohistochemistry for ttf1 is readily available and correlates highly with EGFR status. In conjunction with genetic assays, ttf1 could be used to optimize an EGFR testing strategy.

Investigating the feasibility of mid infrared spectroscopy for monitoring an industrial de-racemization biotransformation process.

Biotransformation processes have become industrially important in recent years as routes to the manufacture of high value chemical intermediates. However, measurements of key process features and analyte concentrations during these processes are still typically carried out using off-line analysis methods. Vibrational spectroscopic techniques have been extensively utilised for the monitoring and control of a variety of industrial processes. Despite the techniques success with a range of challenging biological matrices, including fermentation and cell culture systems, application of this approach to biotransformation systems has been limited. In the present study the potential of mid infrared spectroscopy to monitor an industrially relevant de-racemization biotransformation process has been investigated. This process presents a number of difficulties due to the optically challenging sample media, close structural similarities and stoichiometric relationship between the key analytes of interest. A PLS model based on the mid infrared spectra obtained during three replicates of the biotransformation process was constructed. In order to ensure that co-linearity within the system had been adequately addressed the spectral contributors to the model were examined. External validation of the constructed model was achieved by challenging the model with two previously unseen replicates of the process. The constructed model was able to predict the concentrations of two key analytes in various samples from these unseen replicates without the requirement for any time consuming sample pre-treatment stages, thus demonstrating the feasibility of near real-time mid infrared monitoring of such an industrial de-racemization biotransformation process.

Transform-limited x-ray pulse generation from a high-brightness self-amplified spontaneous-emission free-electron laser.

A method to achieve high-brightness self-amplified spontaneous emission (HB-SASE) in the free-electron laser (FEL) is described. The method uses repeated nonequal electron beam delays to delocalize the collective FEL interaction and break the radiation coherence length dependence on the FEL cooperation length. The method requires no external seeding or photon optics and so is applicable at any wavelength or repetition rate. It is demonstrated, using linear theory and numerical simulations, that the radiation coherence length can be increased by approximately 2 orders of magnitude over SASE with a corresponding increase in spectral brightness. Examples are shown of HB-SASE generating transform-limited FEL pulses in the soft x-ray and near transform-limited pulses in the hard x-ray. Such pulses may greatly benefit existing applications and may also open up new areas of scientific research.

Few-cycle pulse generation in an x-ray free-electron laser.

A method is proposed to generate trains of few-cycle x-ray pulses from a free-electron laser (FEL) amplifier via a compact "afterburner" extension consisting of several few-period undulator sections separated by electron chicane delays. Simulations show that in the hard x ray (wavelength ~0.1 nm; photon energy ~10 keV) and with peak powers approaching normal FEL saturation (GW) levels, root mean square pulse durations of 700 zs may be obtained. This is approximately two orders of magnitude shorter than that possible for normal FEL amplifier operation. The spectrum is discretely multichromatic with a bandwidth envelope increased by approximately 2 orders of magnitude over unseeded FEL amplifier operation. Such a source would significantly enhance research opportunity in atomic dynamics and push capability toward nuclear dynamics.

Oxidative stress in fungal fermentation processes: the roles of alternative respiration.

Filamentous fungi are arguably the most industrially important group of microorganisms. Production processes involving these simple eukaryotes are often highly aerobic in nature, which implies these cultures are routinely subject to oxidative stress. Despite this, little is known about how filamentous fungi cope with high levels of oxidative stress as experienced in fermenter systems. More surprisingly, much of our knowledge of oxidative stress responses in fungi comes from environmental or medical studies. Here, the current understanding of oxidative stress effects and cellular responses in filamentous fungi is critically discussed. In particular the role of alternative respiration is evaluated, and the contributions of the alternative oxidase and alternative dehydrogenases in defence against oxidative stress, and their profound influence on fungal metabolism is critically examined. Finally, the importance of further research which would underpin a less empirical approach to optimising fungal strains for the fermenter environment is emphasised.

Mode locking in a free-electron laser amplifier.

A technique is proposed to generate attosecond pulse trains of radiation from a free-electron laser amplifier. The optics-free technique synthesizes a comb of longitudinal modes by applying a series of spatiotemporal shifts between the copropagating radiation and electron bunch in the free-electron laser. The modes may be phase locked by modulating the electron beam energy at the mode spacing frequency. Three-dimensional simulations demonstrate the generation of a train of 400 as pulses at gigawatt power levels evenly spaced by 2.5 fs at a wavelength of 124 angstroms. In the x-ray at wavelength 1.5 angstroms, trains of 23 as pulses evenly spaced by 150 as and of peak power up to 6 GW are predicted.

Diversity of thermophilic populations during thermophilic aerobic digestion of potato peel slurry.

AIMS: To study the diversity of thermophiles during thermophilic aerobic digestion (TAD) of agro-food waste slurries under conditions similar to full-scale processes. METHODS AND RESULTS: Population diversity and development in TAD were studied by standard microbiological techniques and the processes monitored by standard fermentation procedures. Facultative thermophiles were identified as Bacillus coagulans and B. licheniformis, while obligate thermophiles were identified as B. stearothermophilus. They developed rapidly to peaks of 10(7) to 10(8) in

Linamarase activities in Bacillus spp. responsible for thermophilic aerobic digestion of agricultural wastes for animal nutrition.

Thermophilic Bacillus spp. isolated from thermophilic aerobic digestion (TAD) of model agricultural slurry were screened for ability to secret linamarase activity and degrade linamarin, a cyanogenic glycoside toxin abundant in cassava. Screening was performed by both linamarin - picrate assay and by p-nitrophenyl beta-D-glucoside (PNPG) degradation, and results of both assays were related. Linamarase positive isolates were identified as Bacillus coagulans, Bacillus licheniformis and Bacillus stearothermophilus. Enzyme production was growth related and peak production was reached in 48 h in B. coagulans and 36 h in B. stearothermophilus. B. coagulans produced over 40 times greater activity than B. stearothermophilus. Enzyme productivity in shake flask was not strictly related to screening assay result. Crude enzyme of B. coagulans was optimally active at 75 degrees C while that of B. stearothermophilus was optimally active at 80 degrees C and both had optimum activity at pH 8.0. The thermophilic and neutrophilic- to marginally alkaline activity of the crude enzymes could be very useful in the detoxification and reprocessing of cyanogens containing cassava wastes by TAD for use in animal nutrition.

Harmonic lasing in a free-electron-laser amplifier.

A method is demonstrated that allows a planar wiggler high-gain Free-Electron-Laser (FEL) amplifier to lase so that the interaction with an odd harmonic of the radiation field dominates that of the fundamental. This harmonic lasing of the FEL is achieved by disrupting the electron interaction with the usually dominant fundamental while allowing that of a harmonic interaction to evolve unhindered. The disruption is achieved by a series of relative phase changes between the electrons and the ponderomotive potentials of both the fundamental and harmonic fields. Such phase changes are relatively easy to implement and some current FEL designs would require little or no structural modification to test the scheme.

Four-wave mixing with self-phase matching due to collective atomic recoil.

We describe a method for nondegenerate four-wave-mixing in a cold sample of four-level atoms. An integral part of the four-wave-mixing process is a collective instability which spontaneously generates a periodic density modulation in the cold atomic sample with a period equal to half of the wavelength of the generated high-frequency optical field. Because of the generation of this density modulation, phase matching between the pump and scattered fields is not a necessary initial condition for this wave-mixing process to occur; rather the density modulation acts to "self-phase match" the fields during the course of the wave-mixing process. We describe a one-dimensional model of this process, and suggest a proof-of-principle experiment which would involve pumping a sample of cold Cs atoms with three infrared pump fields to produce blue light.

Effect of digestion temperature and pH on treatment efficiency and evolution of volatile fatty acids during thermophilic aerobic digestion of model high strength agricultural waste.

Thermophilic aerobic digestion (TAD) of a model agricultural waste, potato peel slurry, at soluble chemical oxygen demand (COD) load equivalent to approximately 8.0 gl(-1), was carried out under batch conditions at 0.5 vvm aeration rate. Digestions were carried out at temperatures of 45, 50, 55, 60 and 65 degrees C (or left unregulated) without pH control to study the effect of digestion temperatures on TAD. The effects of digestion pH on the process were studied at pH 6.0, 7.0, 8.0, 9.0 and 9.5 (and in unregulated control) all at 55 degrees C. Except for digestion at 65 degrees C, which was inoculated extraneously using culture of Bacillus strearothermophilus all reactions were carried out using the populations indigenous to the waste. During digestion at different temperatures, the removal of soluble COD increased with temperature to reach a peak at 60 degrees C before declining slightly, removal of soluble solid (SS) followed similar pattern and reached peak at 65 degrees C being the highest temperature studied, while the degradation of TSS and TS (TSS + TS) decreased with an increase in temperature. Digestion at pH 7.0 was more efficient than at other pH values. Acetate was the predominant volatile fatty acid (VFA) in all the reactions and accounted for up to 90% of the total. Digestion at 60 degrees C led to the greatest accumulation of acetate, and this coincided with the period of highest oxygen uptake, and rapid consumption of soluble carbohydrate. Iso-valerate was also produced at all pH values. Digestion at 55 degrees C and also at pH 7.0 led to rapid and efficient processes with least accumulation of VFA and should be of interest in full-scale processes whenever it is practicable to regulate the digestion pH and temperature. The result of digestion at unregulated pH indicates that gradual adaptation may be used to achieve efficient treatment at elevated pH values. This would be of interest in full-scale processes where it is not practicable to tightly regulate digestion pH, and where the waste is produced at a pH value much higher than neutral.