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Two-dimensional transition metal dichalcogenides exhibit strong optical transitions with significant potential for optoelectronic devices. In particular they are suited for cavity quantum electrodynamics in which strong coupling leads to polariton formation as a root to realisation of inversionless lasing, polariton condensation and superfluidity. Demonstrations of such strongly correlated phenomena to date have often relied on cryogenic temperatures, high excitation densities and were frequently impaired by strong material disorder. At room-temperature, experiments approaching the strong coupling regime with transition metal dichalcogenides have been reported, but well resolved exciton-polaritons have yet to be achieved. Here we report a study of monolayer WS2 coupled to an open Fabry-Perot cavity at room-temperature, in which polariton eigenstates are unambiguously displayed. In-situ tunability of the cavity length results in a maximal Rabi splitting of ħΩRabi = 70 meV, exceeding the exciton linewidth. Our data are well described by a transfer matrix model appropriate for the large linewidth regime. This work provides a platform towards observing strongly correlated polariton phenomena in compact photonic devices for ambient temperature applications.

Purpose: To establish whether hypothalmic-pituitary-adrenal axis suppression is possible secondary to long-term topical ophthalmic corticosteroid use in patients who have undergone penetrating keratoplasty (PKP)., Methods: Patients who had undergone a PKP and had been using corticosteroid-based eye drops continuously for more than 6 months, with no history of concomitant steroid (oral, inhaled, or cutaneous) use, were included within the study. A low-dose short Synacthen (LDSST) test was performed in each patient followed later by a short Synacthen test (SST). The mean SST and LDSST after 30 min were calculated along with their corresponding 95% confidence intervals (CIs). Correlation between both baseline SST and baseline LDSST with duration of treatment was determined using Spearman's correlation., Results: In all, 20 patients were included within the study. The mean duration treatment was 28.2 months (range 11-96 months). All patients had normal baseline cortisol levels in both SST and LDSST tests. The mean 30 min SST was 753.8 nmol/l (95%CI: 696.6 nmol/l, 811.0 nmol/l) and no patients displayed inadequate adrenal response. The mean 30 min LDSST was 709.8 nmol/l (95%CI: 665.1 nmol/l, 754.5 nmol/l) and only one patient had an inadequate adrenal response. There was no correlation between baseline SST or LDSST and duration of treatment., Conclusions: This study found no evidence that patients using continuous long-term corticosteroid eye drops after PKP experienced inadequate adrenal response. We did not find any evidence of a negative correlation between length of treatment and SST or LDSST measurements at baseline.

Purpose: To evaluate the compression characteristics of the human lens nucleocortex in relation to its LOCSIII clinical grading., Methods: Sixteen subjects undergoing planned extracapsular cataract surgery had pre-operative slit-lamp examination and assessment of cataract LOCSIII grade followed by postoperative in vitro evaluation of the nucleus with measurement of 'linear compressibility' by a purpose-designed caliper incorporating a strain gauge, enabling the derivation of a graph of nuclear compression (D (mm) against applied force (F (N))., Results: Nuclear colour correlates with the force required to compress a lens to 75% of its original depth (F75) (R = 0.625, P = 0.017). Nuclear opalescence correlates with the force required to compress a lens to 75% of its original depth (R = 0.651, P = 0.012) and inversely with linear compressibility (DeltaD/DeltaF, the slope of the graph of nuclear compression against applied force) (R = -0.610, P = 0.014). F75 is a direct and linear compressibility is an inverse related parameter of lens nucleus 'hardness'., Conclusion: A new instrument is described which allows measurement of 'hardness'-related compression characteristics of the human cataract in vitro. There is a relationship between the LOCSIII clinical classification of nuclear cataracts and mechanical compression characteristics of the cataractous lens. LOCSIII classification may aid the preoperative planning of an appropriate surgical approach to an individual cataract.

The Cbl proto-oncogene product is tyrosine phosphorylated in response to a wide variety of stimuli. Cbl and the Abl nonreceptor tyrosine kinase both bind to SH3 domains from the SH2/SH3 adaptor Nck, and are candidate effectors for Nck function. Numerous additional SH2- and SH3-domain-mediated interactions are also possible between Cbl, Abl, and Nck. We find that these three signaling proteins associate when overexpressed in mammalian cells and can regulate each other's activity. Co-expression of wt Cbl together with c-Abl, the activity of which is normally repressed in vivo, led to extensive Abl-dependent phosphorylation of Cbl. The major proline-rich region of Cbl was required for its phosphorylation by c-Abl, but not by a constitutively activated Abl mutant, suggesting Cbl activates c-Abl by engaging its SH3 domain. Efficient phosphorylation of Cbl and its stable association with Abl required the SH2 domain of Abl, suggesting that SH2-phosphotyrosine interactions prevent dissociation of active Abl from Cbl. We also show that overexpression of Nck could repress the phosphorylation of Cbl by Abl in vivo. Studies with Nck mutants suggested that the Nck SH2 domain is responsible for inhibiting the activity of Abl toward both Cbl and Nck itself, most likely by competing with the Abl SH2 for tyrosine-phosphorylated binding sites.

Purpose: To investigate the value of eye padding following uncomplicated phacoemulsification under peribulbar anaesthesia., Methods: A prospective randomised controlled study was conducted to compare the effect of a conventional eye pad and shield with that of a clear eye shield applied without a pad in 83 patients undergoing routine phacoemulsification under peribulbar anaesthesia without lid block. The primary outcome measures were corneal fluorescein staining, discomfort, diplopia and mobility., Results: Moderate or severe corneal fluorescein staining on the first post-operative day was significantly more common in the pad and shield group (39%) than in the clear shield group (19%) (p < 0.01). There was no significant difference in post-operative pain as measured either by visual analogue scale or by categorical pain scale. Forty per cent of the clear shield group reported transient post-operative diplopia during the immediate post-operative period compared with 7% of the pad and shield group (p < 0.001). There was no significant difference in reported mobility between the two groups., Conclusions: Following phacoemulsification under peribulbar anaesthesia, the use of a gauze eye pad is associated with greater corneal fluorescein staining than a clear plastic shield without pad and offers no reduction in discomfort. A clear shield protects the globe against direct trauma, is associated with reduced moderate to severe corneal staining and facilitates vision in the early post-operative period. Transient diplopia reported by some patients given a clear shield is not disabling and would not be expected to occur in patients with one seeing eye. The use of a clear shield alone is a safe alternative to eye padding and offers important advantages in patients with one seeing eye.

Genetic redundancy means that two or more genes are performing the same function and that inactivation of one of these genes has little or no effect on the biological phenotype. Redundancy seems to be widespread in genomes of higher organisms. Examples of apparently redundant genes come from numerous studies of developmental biology, immunology, neurobiology and the cell cycle. Yet there is a problem: genes encoding functional proteins must be under selection pressure. If a gene was truly redundant then it would not be protected against the accumulation of deleterious mutations. A widespread view is therefore that such redundancy cannot be evolutionarily stable. Here we develop a simple genetic model to analyse selection pressures acting on redundant genes. We present four cases that can explain why genetic redundancy is common. In three cases, redundancy is even evolutionarily stable. Our theory provides a framework for exploring the evolution of genetic organization.

There is no theoretical reason to expect evolutionary lineages to increase in complexity with time, and no empirical evidence that they do so. Nevertheless, eukaryotic cells are more complex than prokaryotic ones, animals and plants are more complex than protists, and so on. This increase in complexity may have been achieved as a result of a series of major evolutionary transitions. These involved changes in the way information is stored and transmitted.

Ferritin is important in iron homeostasis. Its twenty-four chains of two types, H and L, assemble as a hollow shell providing an iron-storage cavity. Ferritin molecules in cells containing high levels of iron tend to be rich in L chains, and may have a long-term storage function, whereas H-rich ferritins are more active in iron metabolism. The molecular basis for the greater activity of H-rich ferritins has until now been obscure, largely because the structure of H-chain ferritin has remained unknown owing to the difficulties in obtaining crystals ordered enough for X-ray crystallographic analysis. Here we report the three-dimensional structure of a human ferritin H-chain homopolymer. By genetically engineering a change in the sequence of the intermolecular contact region, we obtained crystals isomorphous with the homologous rat L ferritin and of high enough quality for X-ray diffraction analysis. The X-ray structure of human H ferritin shows a novel metal site embedded within each of its four-helix bundles and we suggest that ferroxidase activity associated with this site accounts for its rapid uptake of iron.

Electrophoretic studies suggest that bacterial populations consist of a number of independent clones and that genetic recombination is rare in nature. But DNA sequencing reveals that individual bacterial genes have a mosaic structure that could have arisen only by recombination. How can these observations be reconciled and what is their relevance to prokaryotic evolution?

Both murine and human epidermal growth factors (EGFs) are known to cause precocious opening of the eyelids in newborn mice. Another set of peptides that are structurally and functionally homologous to murine and human EGFs are the murine and human type-alpha transforming growth factors (TGF-alpha s), TGF-alpha s have been found in many cancer cells and it has been suggested that their autocrine action may play an important part in malignant transformation. In several in vitro systems murine and human TGF-alpha s are functionally interchangeable with murine and human EGFs. However, the in vivo activity of the TGF-alpha s has not been characterized, as only small amounts of these peptides were available until recently. The cloning of the gene for human TGF-alpha and its expression in Escherichia coli now allow us to demonstrate that human TGF-alpha is as active as murine EGF in promoting eyelid opening in newborn mice. Furthermore, we show in a dose-dependent eyelid opening assay that human EGF is as potent as its murine homologue with respect to this biological property.

By the combination of energy and macronutrient balances, continuous open circuit computerized indirect calorimetry, and anthropometry, we have compared small for gestational age (SGA) and appropriate for gestational age (AGA) very low birthweight infants with respect to metabolizable energy intake (mean +/- SE: 125.9 +/- 2.5 versus 130.4 +/- 3.5 kcal/kg X day), energy expenditure (67.4 +/- 1.3 versus 62.6 +/- 0.9 kcal/kg X day), storage of energy and macronutrients and growth. Fourteen studies in six SGA infants (gestational age, 33.1 +/- 0.3 weeks; birthweight, 1120 +/- 30 g) and 22 studies in 13 AGA infants (gestational age, 29.3 +/- 0.4 weeks; birthweight, 1155 +/- 40 g) were performed. The SGA infants had a lower absorption of fat (68.7 +/- 3.2 versus 79.7 +/- 1.7%) and protein (69.1 +/- 3.2 versus 83.4 +/- 1.5%) and hence increased (P less than 0.001) energy loss in excreta (29.9 +/- 2.8 versus 18.2 +/- 1.5 kcal/kg X day). The significant hypermetabolism of SGA infants by 4.8 kcal/kg X day was associated with an increased fat oxidation. Despite lower energy storage, SGA infants were gaining weight (19.4 +/- 0.9 g/kg X day), length (1.25 +/- 0.14 cm/week), and head circumference (1.16 +/- 0.9 cm/week) at higher rates than the AGA group. The energy storage per g weight gain was lower (P less than 0.001) in the SGA group (3.0 +/- 0.14 versus 4.26 +/- 0.26 kcal) reflecting higher water, lower fat (22.2 +/- 1.8 versus 33.8 +/- 2.5%; P less than 0.001) and lower protein (7.7 +/- 0.5 versus 12.5 +/- 0.8%; P less than 0.001) contents of weight gain in the SGA group.

The use of 13CO2 excretion to measure the oxidation of 13CO2 labeled substrates is increasing as it is both noninvasive and lacks the radiation exposure associated with the use of 14C. No standards are available for 13CO2 recovery in breath from the bicarbonate pool in the neonate. A primed constant infusion of NaH13CO3 over 4 h was used with open circuit indirect calorimetry in 15 appropriate for gestational age newborn infants (gestational age 28-39 wk; postnatal age 2-52 days), on varying amounts of intravenous feeding (37-114 kcal X kg-1 X day-1). Following a bolus of 6.9 mumol X kg-1 of NaH13CO3, a maintenance infusion of 4.6 mumol X kg-1 X h-1 was started. The 13C enrichment in breath rose rapidly to reach a plateau by 90 min with less than 5% variation of the plateau. Recovery of the tracer in breath ranged from 69.6-83.5% and was significantly correlated with 1) energy intake (37-114 kcal X kg-1 X day-1); 2) metabolic rate (34.6-56.1 kcal X kg-1 X day-1); 3) VCO2 (4.86-7.43 ml X kg X -1 X min-1). There was no correlation with the level of protein or fat intake. We provide an equation that can be used to calculate the correction factor when doing constant infusion substrate oxidation studies with a 13C label in neonates.

This study defines the relationship between heart rate and metabolic rate in newborn infants and evaluates the accuracy of prediction of metabolic rate from heart rate. Continuous measurements of oxygen uptake, CO2 production, respiratory quotient, and cumulative heart rate were performed using computerized, open-circuit indirect calorimetry and on-line electrocardiogram monitoring over periods of 1 to 24 hr (mean 4.5 hr). Metabolic rate was calculated from the individual oxygen uptake and respiratory quotient. Thirty-five studies were performed in 16 infants (birthweight 0.75 to 3.1 kg; gestational age, 26 to 42 wk; mean +/- S.D. age at study, 26.5 +/- 15.7 days; study weight, 1.78 +/- 0.5 kg). Metabolic rate (cal/kg . min) and heart rate (beats/min) were compared minute by minute (8269 measurements) and showed a close third degree polynomial relationship for heart rates of 110 to 230/min (y = -0.0000291x3 + 0.01685x2 -2.93x + 197; r = 0.99; P less than 0.001); however, at heart rates above 140 beats/min, a linear relationship was found (r = 0.997; P less than 0.001). From cumulated heart rate measurements, factors defining metabolic rate per heart beat were also determined: for each beat 51.8 +/- 6.8 microliter of oxygen/kg are consumed and 0.258 +/- 0.03 cal/kg (1.1 J/kg) are expended. Despite the wide variation in birthweight, gestational age, method of feeding, and clinical characteristics, there was a remarkable consistency in the heart rate-metabolic rate relationships. A further 10 studies were performed in a similar group of infants to assess the predictive value of the previously defined relationships and showed a mean percentage deviation of 5.7 +/- 4% from the measured value. We conclude that in the varied group of newborns studied, heart rate correlates closely with metabolic rate and that cumulative heart rate measurements enable the estimation of metabolic rate in newborn infants. This provides a method of monitoring energy expenditure and caloric requirements over long periods.

The evolutionary stability of the female-biased sex ratio observed in the wood lemming (Myopus schisticolor) is discussed. The hypothesis analysed is that the skewed sex ratio is maintained as a result of partial and/or recurrent inbreeding. Fredga et al. (1976, 1977) have suggested that an X-linked mutant gene, X, affects the male-determining action of the Y chromosome, thus converting some XY individuals into females. By a mechanism of selective non-disjunction in the foetal ovary only X-carrying eggs are produced. In particular the stability of that genetic mechanism (or the X chromosome) is analysed by considering the introduction of a "suppressing" sex-linked mutant gene Y. Several deterministic simulation models assuming father-daughter and/or brother-sister matings have been developed and analysed. It is concluded that in the case of extremely strong inbreeding, the hypothesised genetic mechanism may, as a result, be evolutionarily stable. Interpreting field observations on microtine rodents in general it is concluded that only a few species are likely to experience such extreme cases of inbreeding. The wood lemming and the related collared lemming (Dicrostonyx troquatus), another case which seems to have XY-females, are likely to exhibit sufficiently strong inbreeding.

Since the genes in any given organism have evolved together to produce an adaptive phenotype, one might expect that rearrangement by chromosomal recombination would be maladaptive and thus wiped out by natural selection. This article reviews various theories that explain why, on the contrary, recombination is almost universal.