Varying plantain content in temperate ryegrass-white clover pastures affects urinary-nitrogen excretion of non-lactating dairy cows.

Dairy cow urine patches contain high rates of nitrogen (N; >500 kg N/ha) and represent the main source of N loss from grazed pastoral systems. Emerging research has identified plantain (Plantago lanceolata) as a key forage to potentially reduce urine N (UN) losses from dairy cows. This experiment examined the effect of increasing proportions of plantain in the diet of dairy cows on UN excretion relative to a ryegrass-white clover diet. Twenty mixed aged non-lactating dairy cows were randomly assigned to one of five treatment diets; 0 %, 20 %, 40 %, 60 % or 100 % plantain (dry matter basis), with the remainder comprised of ryegrass-white clover pasture and grass-silage. Cows were fitted with urine sensors to measure urination event N concentration, volume and frequency. Daily N intake increased with increasing proportions of plantain in the diet due to the greater N concentration of plantain. Conversely, mean UN concentration was reduced as the proportion of plantain in the diet increased. Urine-N concentration was >40 % lower for cows on 100 % plantain compared with 0 % plantain (0.46 and 0.81 % N respectively). There was no treatment effect on the total daily amount of UN excreted, indicating a dilution effect of plantain as total daily urine volumes markedly increased with increasing plantain diets. Nitrogen load per urination event was lower for cows on 100 % plantain than 0 % despite greater N intake, with no significant difference for the intermediate treatment groups. The reduced N load per event for cows on >60 % plantain could help to reduce N leaching losses at the urine patch level. This experiment suggests that a reduction in UN concentration can be achieved on low levels of plantain (20 % of the diet), but >60 % plantain diets are required to reduce N load per event.

Longitudinal tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling.

BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) is rapidly rising and has a 5-year survival rate of <20%. Beyond TNM (tumor-node-metastasis) staging, no reliable risk stratification tools exist and no large-scale studies have profiled circulating tumor DNA (ctDNA) at relapse in EAC. Here we analyze the prognostic potential of ctDNA dynamics in EAC, taking into account clonal hematopoiesis with indeterminate potential (CHIP). PATIENTS AND METHODS: A total of 245 samples from 97 patients treated with neoadjuvant chemotherapy and surgery were identified from the prospective national UK Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium data set. A pan-cancer ctDNA panel comprising 77 genes was used. Plasma and peripheral blood cell samples were sequenced to a mean depth of 7082× (range 2196-28 524) and ctDNA results correlated with survival. RESULTS: Characteristics of the 97 patients identified were as follows: 83/97 (86%) male, median age 68 years (SD 9.5 years), 100% cT3/T4, 75% cN+. EAC-specific drivers had higher variant allele fractions than passenger mutations. Using stringent quality criteria 16/79 (20%) were ctDNA positive following resection; recurrence was observed in 12/16 (75%) of these. As much as 78/97 (80%) had CHIP analyses that enabled filtering for CHIP variants, which were found in 18/78 (23%) of cases. When CHIP was excluded, 10/63 (16%) patients were ctDNA positive and 9/10 of these (90%) recurred. With correction for CHIP, median cancer-specific survival for ctDNA-positive patients was 10.0 months versus 29.9 months for ctDNA-negative patients (hazard ratio 5.55, 95% confidence interval 2.42-12.71; P = 0.0003). Similar outcomes were observed for disease-free survival. CONCLUSIONS: We demonstrate in a large, national, prospectively collected data set that ctDNA in plasma following surgery for EAC is prognostic for relapse. Inclusion of peripheral blood cell samples can reduce or eliminate false positives from CHIP. In future, post-operative ctDNA could be used to risk stratify patients into high- and low-risk groups for intensification or de-escalation of adjuvant chemotherapy.

Stretchable liquid-crystal blue-phase gels.

Liquid-crystalline polymers are materials of considerable scientific interest and technological value. An important subset of these materials exhibit rubber-like elasticity, combining the optical properties of liquid crystals with the mechanical properties of rubber. Moreover, they exhibit behaviour not seen in either type of material independently, and many of their properties depend crucially on the particular mesophase employed. Such stretchable liquid-crystalline polymers have previously been demonstrated in the nematic, chiral-nematic, and smectic mesophases. Here, we report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that remains electro-optically switchable under a moderate applied voltage, and whose optical properties can be manipulated by an applied strain. We also find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and possibilities for low-voltage electro-optic devices.

Spontaneous emission from radiative chiral nematic liquid crystals at the photonic band-gap edge: an investigation into the role of the density of photon states near resonance.

In this article, we investigate the spontaneous emission properties of radiating molecules embedded in a chiral nematic liquid crystal, under the assumption that the electronic transition frequency is close to the photonic edge mode of the structure, i.e., at resonance. We take into account the transition broadening and the decay of electromagnetic field modes supported by the so-called "mirrorless"cavity. We employ the Jaynes-Cummings Hamiltonian to describe the electron interaction with the electromagnetic field, focusing on the mode with the diffracting polarization in the chiral nematic layer. As known in these structures, the density of photon states, calculated via the Wigner method, has distinct peaks on either side of the photonic band gap, which manifests itself as a considerable modification of the emission spectrum. We demonstrate that, near resonance, there are notable differences between the behavior of the density of states and the spontaneous emission profile of these structures. In addition, we examine in some detail the case of the logarithmic peak exhibited in the density of states in two-dimensional photonic structures and obtain analytic relations for the Lamb shift and the broadening of the atomic transition in the emission spectrum. The dynamical behavior of the atom-field system is described by a system of two first-order differential equations, solved using the Green's-function method and the Fourier transform. The emission spectra are then calculated and compared with experimental data.

Density of photon states in dye-doped chiral nematic liquid crystal cells in the presence of losses and gain.

We calculate the density of photon states (DOS) of the normal modes in dye-doped chiral nematic liquid crystal (LC) cells in the presence of various loss mechanisms. Losses and gain are incorporated into the transmission characteristics through the introduction of a small imaginary part in the dielectric constant perpendicular and along the director, for which we assume no frequency dispersion. Theoretical results are presented on the DOS in the region of the photonic band gap for a range of values of the loss coefficient and different values of the optical anisotropy. The obtained values of the DOS at the photonic band gap edges predict a reversal of the dominant modes in the structure. Our results are found to be in good agreement with the experimentally obtained excitation thresholds in chiral nematic LC lasers. The behavior of the DOS is also discussed for amplifying LC cells providing additional insight to the lasing mechanism of these structures.

Blue-phase templated fabrication of three-dimensional nanostructures for photonic applications.

A promising approach to the fabrication of materials with nanoscale features is the transfer of liquid-crystalline structure to polymers. However, this has not been achieved in systems with full three-dimensional periodicity. Here we demonstrate the fabrication of self-assembled three-dimensional nanostructures by polymer templating blue phase I, a chiral liquid crystal with cubic symmetry. Blue phase I was photopolymerized and the remaining liquid crystal removed to create a porous free-standing cast, which retains the chiral three-dimensional structure of the blue phase, yet contains no chiral additive molecules. The cast may in turn be used as a hard template for the fabrication of new materials. By refilling the cast with an achiral nematic liquid crystal, we created templated blue phases that have unprecedented thermal stability in the range -125 to 125 °C, and that act as both mirrorless lasers and switchable electro-optic devices. Blue-phase templated materials will facilitate advances in device architectures for photonics applications in particular.

Thermodynamically stable blue phases.

We show theoretically that flexoelectricity stabilizes blue phases in chiral liquid crystals. Induced internal polarization reduces the elastic energy cost of splay and bend deformations surrounding singular lines in the director field. The energy of regions of double twist is unchanged. This in turn reduces the free energy of the blue phase with respect to that of the chiral nematic phase, leading to stability over a wider temperature range. The theory explains the discovery of large temperature range blue phases in highly flexoelectric "bimesogenic" and "bent-core" materials, and predicts how this range may be increased further.

Flexoelectro-optic properties of chiral nematic liquid crystals in the uniform standing helix configuration.

The flexoelectro-optic effect describes the rotation of the optic axis of a short-pitch chiral nematic liquid crystal under the application of an electric field. We investigate the effect in the uniform standing helix, or "Grandjean" configuration. An in-plane electric field is applied. The director profile is determined numerically using a static one-dimensional continuum model with strong surface anchoring. The Berreman method is used to solve for plane-wave solutions to Maxwell's equations, and predict the optical properties of the resulting structure in general cases. By using a chiral nematic with short pitch between crossed polarizers an optical switch may be generated. With no applied field the configuration is nontransmissive at normal incidence, but becomes transmissive with an applied field. For this case, numerical results using the Berreman method are supplemented with an analytic theory and found to be in good agreement. The transmitted intensity as a function of tilt, the contrast ratio, and the tilt required for full intensity modulation are presented. The angular dependence of the transmission is calculated and the isocontrast curves are plotted. For typical material and cell parameters a switching speed of 0.017 ms and contrast ratio of 1500:1 at normal incidence are predicted, at a switch-on tilt of 41.5 degrees. Experimental verification of the analytic and numerical models is provided.

Structure-flexoelastic properties of bimesogenic liquid crystals.

In this paper, we report on the flexoelastic and viscoelastic ratios for a number of bimesogens compounds with the same generic structure. Values are obtained indirectly by measuring the flexoelectro-optic response in the chiral nematic phase. By varying the molecular structure we alter the bend angle, transverse dipole moment, and length of the molecule. First, to examine the influence of the bend angle we use a homologous series whereby the only alteration in the molecular structure is the number of methylene units in the aliphatic spacer, n . Results show that the flexoelastic ratio, e/K , and the effective flexoelectric coefficient, e , both exhibit an odd-even effect with values for n=odd being greater than that for n=even . This is understood in terms of an increase in the bend angle of the molecule and an increase in the transverse dipole moment. Second, in order to investigate the impact of the dipole moment, we have altered the mesogenic units so as to vary the longitudinal dipole moment and used different linkages in the aliphatic spacer in an attempt to alter the transverse dipole moment. Qualitatively, the results demonstrate that the odd-spaced bimesogen with larger transverse dipole moments exhibit larger flexoelastic ratios.

Emission characteristics of a homologous series of bimesogenic liquid-crystal lasers.

In this study we have fabricated eight different liquid-crystal lasers using the same gain medium but different homologues from the bimesogenic series alpha-(2',4-difluorobiphenyl-4'-yloxy)-omega-(4-cyanobiphenyl-4'-yloxy)alkanes, whereby the number of methylene units in the spacer chain varied from n=5 to n=12. To quantify the performance of these lasers, the threshold energy and the slope efficiency were extracted from the input-output characteristics of each laser. A clear odd-even effect was observed when both the excitation threshold and the slope efficiency were plotted as a function of the number of methylene units in the spacer chain. In all cases, the bimesogen lasers for which n is even exhibit lower threshold energies and higher slope efficiencies than those for which n is odd. These results are then interpreted in terms of the macroscopic physical properties of the liquid-crystalline compounds. In accordance with a previous study [S. M. Morris, A. D. Ford, M. N. Pivnenko, O. Hadeler, and H. J. Coles, Phys. Rev. E. 74, 061709 (2006)], a combination of a large birefringence and high order parameters are found, in the most part, to correlate with low-threshold energy and high slope efficiency. This indicates that the threshold and slope efficiency are dominated by the host macroscopic properties as opposed to intermolecular interactions between the dye and the liquid crystal. However, certain differences in the slope efficiency could not be explained by the birefringence and order parameter values alone. Instead, we find that the slope efficiency is further increased by increasing the elastic constants of the liquid-crystal host so as to decrease the scattering losses incurred by local distortions in the director field under high-energy optical excitation.

Correlations between the performance characteristics of a liquid crystal laser and the macroscopic material properties.

In order to understand how the performance of a liquid-crystal laser depends on the physical properties of the low molar mass nematic host, we have studied the energy threshold and slope efficiency of ten optically pumped liquid-crystal lasers based on different hosts. Specifically, this leads to a variation in the birefringence, the orientational order parameter, and the order parameter of the transition dipole moment of the dye. It is found that low threshold energies and high slope efficiencies correlate with high order parameters and large birefringences. To a first approximation this can be understood by considering analytical expressions for the threshold and slope efficiency, which are derived from the space-independent rate equations for a two-level system, in terms of the macroscopic liquid crystal properties.

Optical manifestations of planar chirality.

We report that planar chiral structures affect the polarization state of light in a manner similar to three-dimensional chiral (optical active) media. In experiments with artificial metal-on-silicon chiral planar gratings of 442 wallpaper group symmetry, containing millions of chiral elements per square centimeter, we observed rotation of the polarization azimuth in excess of 30 degrees of light diffracted from it. The rotation was found to change its sign for two enantiomeric forms of the media and to have components associated with both the structural arrangement and the chirality of individual structural elements.

Constitutive expression of the machinery for programmed cell death.

In the presence of cycloheximide (CHX) to inhibit protein synthesis, a high concentration of staurosporine (STS) induces almost all cells in explant cultures of 8/8 types of newborn mouse organs and 3/3 types of adult mouse organs to die with the characteristic features of apoptosis. Eggs and blastomeres also die in this way when treated with STS and CHX, although they are less sensitive to this treatment than trophectoderm or inner cell mass cells whose sensitivity resembles that of other developing cells. Human red blood cells are exceptional in being completely resistant to treatment with STS and CHX. As (STS plus CHX)-induced cell deaths have been shown to display the characteristic features of programmed cell death (PCD), we conclude that all mammalian nucleated cells are capable of undergoing PCD and constitutively express all the proteins required to do so. It seems that the machinery for PCD is in place and ready to run, even though its activation often depends on new RNA and protein synthesis.

2-Chlorodeoxyadenosine in the treatment of hairy cell leukaemia: differences in response in patients with and without abdominal lymphadenopathy.

We treated 26 patients with hairy cell leukaemia (HCL) with 2-chlorodeoxyadenosine, including nine with abdominal lymphadenopathy and of whom two had HCL-variant; 18 were previously treated. The overall response in 23 evaluable HCL patients was 100% with 87% complete remission (CR). The CR rate was 57% in patients with abdominal lymphadenopathy. Neither of the patients with HCL-variant achieved CR. Of four patients who had become refractory to 2'-deoxycoformycin, two achieved CR and one partial remission (PR). The lower response in HCL with abdominal lymphadenopathy supports the view that this represents a more resistant form of the disease.

Programmed cell death and the control of cell survival.

We draw the following tentative conclusions from our studies on programmed cell death (PCD): (i) the amount of normal cell death in mammalian development is still underestimated; (ii) most mammalian cells constitutively express the proteins required to undergo PCD; (iii) the death programme operates by default when a mammalian cell is deprived of signals from other cells; (iv) many normal cell deaths may occur because cells fail to obtain the extracellular signals they need to suppress the death programme; and (v) neither the nucleus nor mitochondrial respiration is required for PCD (or Bcl-2 protection from PCD), raising the possibility that the death programme, like mitosis, is orchestrated by a cytosolic regulator that acts on multiple organelles in parallel.