Variation in temperature of peak trait performance constrains adaptation of arthropod populations to climatic warming.

The capacity of arthropod populations to adapt to long-term climatic warming is currently uncertain. Here we combine theory and extensive data to show that the rate of their thermal adaptation to climatic warming will be constrained in two fundamental ways. First, the rate of thermal adaptation of an arthropod population is predicted to be limited by changes in the temperatures at which the performance of four key life-history traits can peak, in a specific order of declining importance: juvenile development, adult fecundity, juvenile mortality and adult mortality. Second, directional thermal adaptation is constrained due to differences in the temperature of the peak performance of these four traits, with these differences expected to persist because of energetic allocation and life-history trade-offs. We compile a new global dataset of 61 diverse arthropod species which provides strong empirical evidence to support these predictions, demonstrating that contemporary populations have indeed evolved under these constraints. Our results provide a basis for using relatively feasible trait measurements to predict the adaptive capacity of diverse arthropod populations to geographic temperature gradients, as well as ongoing and future climatic warming.

The Role of Vector Trait Variation in Vector-Borne Disease Dynamics.

Many important endemic and emerging diseases are transmitted by vectors that are biting arthropods. The functional traits of vectors can affect pathogen transmission rates directly and also through their effect on vector population dynamics. Increasing empirical evidence shows that vector traits vary significantly across individuals, populations, and environmental conditions, and at time scales relevant to disease transmission dynamics. Here, we review empirical evidence for variation in vector traits and how this trait variation is currently incorporated into mathematical models of vector-borne disease transmission. We argue that mechanistically incorporating trait variation into these models, by explicitly capturing its effects on vector fitness and abundance, can improve the reliability of their predictions in a changing world. We provide a conceptual framework for incorporating trait variation into vector-borne disease transmission models, and highlight key empirical and theoretical challenges. This framework provides a means to conceptualize how traits can be incorporated in vector borne disease systems, and identifies key areas in which trait variation can be explored. Determining when and to what extent it is important to incorporate trait variation into vector borne disease models remains an important, outstanding question.

Reducing the Dispersion of Periodic Structures with Twist and Polar Glide Symmetries.

In this article, a number of guiding structures are proposed which take advantage of higher symmetries to vastly reduce the dispersion. These higher symmetries are obtained by executing additional geometrical operations to introduce more than one period into the unit cell of a periodic structure. The specific symmetry operations employed here are a combination of p-fold twist and polar glide. Our dispersion analysis shows that a mode in a structure possessing higher symmetries is less dispersive than in a conventional structure. It is also demonstrated that, similar to the previously studied Cartesian glide-symmetric structures, polar glide-symmetric structures also exhibit a frequency independent response. Promising applications of these structures are leaky-wave antennas which utilize the low frequency dependence.

Omnidirectional surface wave cloak using an isotropic homogeneous dielectric coating.

The field of transformation optics owes a lot of its fame to the concept of cloaking. While some experimental progress has been made towards free-space cloaking in three dimensions, the material properties required are inherently extremely difficult to achieve. The approximations that then have to be made to allow fabrication produce unsatisfactory device performance. In contrast, when surface wave systems are the focus, it has been shown that a route distinct from those used to design free-space cloaks can be taken. This results in very simple solutions that take advantage of the ability to incorporate surface curvature. Here, we provide a demonstration in the microwave regime of cloaking a bump in a surface. The distortion of the shape of the surface wave fronts due to the curvature is corrected with a suitable refractive index profile. The surface wave cloak is fabricated from a metallic backed homogeneous dielectric waveguide of varying thickness, and exhibits omnidirectional operation.

Lenses on curved surfaces.

This Letter presents a theory that allows graded index lenses to be mapped onto arbitrary rotationally symmetric curved surfaces. Examples of the Luneburg and Maxwell fish-eye lens are given, for numerous surfaces, always resulting in isotropic permittivity requirements. The performance of these lenses is initially illustrated with full-wave simulations utilizing a waveguide structure. A transformation of the refractive index profiles is then performed to design surface-wave lenses, where the dielectric layer is not only isotropic but also homogenous, demonstrating the applicability and ease of fabrication.

Removing singular refractive indices with sculpted surfaces.

The advent of Transformation Optics established the link between geometry and material properties, and has resulted in a degree of control over electromagnetic fields that was previously impossible. For waves confined to a surface it is known that there is a simpler, but related, geometrical equivalence between the surface shape and the refractive index, and here we demonstrate that conventional devices possessing a singularity - that is, the requirement of an infinite refractive index - can be realised for waves confined to an appropriately sculpted surface. In particular, we redesign three singular omnidirectional devices: the Eaton lens, the generalized Maxwell Fish-Eye, and the invisible sphere. Our designs perfectly reproduce the behaviour of these singular devices, and can be achieved with simple isotropic media of low refractive index contrast.

Perfect surface wave cloaks.

This Letter presents a method for making an uneven surface behave as a flat surface. This allows an object to be concealed (cloaked) under an uneven portion of the surface, without disturbing the wave propagation on the surface. The cloaks proposed in this Letter achieve perfect cloaking that only relies upon isotropic radially dependent refractive index profiles, contrary to those previously published. In addition, these cloaks are very thin, just a fraction of a wavelength in thickness, yet can conceal electrically large objects. While this paper focuses on cloaking electromagnetic surface waves, the theory is also valid for other types of surface waves. The performance of these cloaks is simulated using dielectric filled waveguide geometries, and the curvature of the surface is shown to be rendered invisible, hiding any object positioned underneath. Finally, a transformation of the required dielectric slab permittivity was performed for surface wave propagation, demonstrating the practical applicability of this technique.

Results of a two-center study comparing hepatic fibrosis progression in HCV-positive liver transplant patients receiving cyclosporine or tacrolimus.

A 2-center retrospective analysis was performed in 60 patients undergoing liver transplantation for hepatitis C virus (HCV)-related disease (cyclosporine in 20, tacrolimus in 40). Mean (±SEM) follow-up was 23.6 ± 22.5 and 22.3 ± 13.7 months in patients receiving cyclosporine or tacrolimus, respectively. Clinically indicated biopsies were performed in 15/20 cyclosporine patients (75%) and 22/40 tacrolimus patients (55%; P = .17). The Ishak fibrosis score was significantly lower in cyclosporine-treated patients versus tacrolimus-treated patients (mean 1.7 ± 0.4 vs 3.1 ± 0.4; P = .023), as was percentage of fibrosis grade Ishak ≥4 (7% vs 41%; P = .028). The mean time to moderate fibrosis (Ishak score ≥3) was 38.2 ± 15.1 months in cyclosporine patients (4/15) and 23.5 ± 12.6 months in tacrolimus patients (14/22); the difference was not statistically significant (P = .09). This retrospective study suggests that cyclosporine-based immunosuppression is associated with less severe hepatic fibrosis in HCV-positive liver transplant recipients compared with tacrolimus-based regimens, but a larger prospective comparative trial is necessary to confirm these findings.

Supernova 2007bi as a pair-instability explosion.

Stars with initial masses such that 10M[symbol: see text] or= 140M[symbol: see text] (if such exist) develop oxygen cores with masses, M(core), that exceed 50M[symbol: see text], where high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs before oxygen ignition and leads to a violent contraction which triggers a nuclear explosion that unbinds the star in a pair-instability supernova. Transitional objects with 100M[symbol: see text] < M(initial) < 140M[symbol: see text] may end up as iron-core-collapse supernovae following violent mass ejections, perhaps as a result of brief episodes of pair instability, and may already have been identified. Here we report observations of supernova SN 2007bi, a luminous, slowly evolving object located within a dwarf galaxy. We estimate the exploding core mass to be M(core) approximately 100M[symbol: see text], in which case theory unambiguously predicts a pair-instability supernova. We show that >3M[symbol: see text] of radioactive (56)Ni was synthesized during the explosion and that our observations are well fitted by models of pair-instability supernovae. This indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic stellar mass limit, which perhaps result from processes similar to those that created the first stars in the Universe.

Efficiency of converting nutrient dry matter to milk in Holstein herds.

Production of milk from feed dry matter intakes (DMI), called dairy or feed efficiency, is not commonly measured in dairy herds as is feed conversion to weight gain in swine, beef, and poultry; however, it has relevance to conversion of purchased input to salable product and proportion of dietary nutrients excreted. The purpose of this study was to identify some readily measured factors that affect dairy efficiency. Data were collected from 13 dairy herds visited 34 times over a 14-mo period. Variables measured included cool or warm season (high ambient temperature <21 degrees C or >21 degrees C, respectively), days in milk, DMI, milk yield, milk fat percent, herd size, dietary concentrations (DM basis) and kilograms of crude protein (CP), acid detergent fiber (ADF), neutral detergent fiber (NDF), and forage. Season, days in milk, CP % and forage % of diet DM, and kilograms of dietary CP affected dairy efficiency. When evaluated using a model containing the significant variables, dairy efficiency was lower in the warm season (1.31) than in the cool season (1.40). In terms of simple correlations, dairy efficiency was negatively correlated with days in milk (r = -0.529), DMI (r = -0.316), forage % (r = -0.430), NDF % (r = -0.308), and kilograms of forage (r = -0.516), NDF (r = -0.434), and ADF (r = -0.313), in the diet, respectively. Dairy efficiency was positively correlated with milk yield (r = 0.707). The same relative patterns of significance and correlation were noted for dairy efficiency calculated with 3.5% fat-corrected milk yield. Diets fed by the herds fell within such a small range of variation (mean +/- standard deviation) for CP % (16.3 +/- 0.696), NDF % (33.2 +/- 2.68), and forage % (46.9 +/- 5.56) that these would not be expected to be useful to evaluate the effect of excessive underfeeding or overfeeding of these dietary components. The negative relationships of dairy efficiency with increasing dietary fiber and forage may reflect the effect of decreased diet digestibility. The results of this study suggest that managing herd breeding programs to reduce average days in milk and providing a cooler environment for the cows may help to maximize dairy efficiency. The mechanisms for the effects of the dietary variables on dairy efficiency need to be understood and evaluated over a broader range of diets and conditions before more firm conclusions regarding their impact can be drawn.

Retinoblastoma gene expression in human non-melanoma skin cancer.

BACKGROUND: The aberrant expression of both the retinoblastoma and p53 tumor suppressor genes has been associated with more aggressive tumors, metastasis and lower survival. METHODS: We have evaluated immunohistochemically the expression of pRB in a panel of non-melanoma skin cancers containing p53 somatic mutations. RESULTS: Nuclear anti-p53 staining was detected in 18 (72%) differentiated squamous cell carcinomas, six (100%) undifferentiated squamous cell carcinomas and seven (28%) basal cell carcinomas. A correlation was observed between p53 expression and the proliferative activity of differentiated squamous cell carcinomas (P < 0.066), undifferentiated squamous cell carcinomas (P < 0.05) and basal cell carcinomas (P < 0.01). Tumors were selected for mutant p53 expression by PCR-directed DNA sequencing and pRB expression measured immunohistochemically. Anti-pRB reactivity was detected in the nuclei of basal and suprabasal layer cells of normal epidermis, and in the proliferative compartment of all the differentiated squamous cell carcinomas, and basal cell carcinomas. A correlation was observed between pRB expression and the proliferative activity of the differentiated squamous cell carcinomas (P < 0.01) and basal cell carcinomas (P < 0.025). However, anti-pRB reactivity was not detected in the six anti-p53 reactive undifferentiated squamous cell carcinomas.

The effect of calcium pump inhibitors on the response of intracellular calcium to caffeine in snail neurones.

We have measured intracellular free calcium ([Ca(2+)]i) using Fura-2 or Ca(2+)-sensitive microelectrodes in voltage-clamped neurones of the snail, Helix aspersa. Caffeine-induced transient increases in [Ca(2+)]i were normally followed by a brief fall of [Ca(2+)]i below its pre-caffeine level. We investigated the cause of this undershoot by raising [Ca(2+)]i; and by inhibiting the plasma membrane or endoplasmic reticulum Ca ATPases (PMCA or SERCA respectively). When the cell membrane potential was decreased from -60 to -25mV, steady-state [Ca(2+)]i increased. The caffeine-induced transients were smaller while the undershoots were larger than in control conditions. When the PMCA was inhibited by high pH the steady-state [Ca(2+)]i increased by 100-400nM. The caffeine-induced [Ca(2+)]i increase and the subsequent undershoot both became larger. Injection of orthovanadate, which inhibits the PMCA and increases [Ca(2+)]i, did not block either effect of caffeine. But when the SERCA was inhibited by cyclopiazonic acid the undershoot disappeared. The phosphodiesterase inhibitor IBMX did not influence the undershoot. These results suggest that the undershoot is generated by the Ca(2+)] ATPase of the stores rather than that of the plasma membrane. Since the undershoot increased as [Ca(2+)]i increased, we conclude that at higher levels of [Ca(2+)]i the stores refill more rapidly.

Protein phosphatase type 1-dependent dephosphorylation of the retinoblastoma tumor suppressor protein in ultraviolet-irradiated human skin and keratinocytes.

This study provides evidence for the involvement of a type 1 protein serine/threonine phosphatase in the ultraviolet radiation-induced dephosphorylation of retinoblastoma tumor suppressor protein in human skin and cultured keratinocytes. The retinoblastoma gene product was localized to the nuclei and nucleoli of keratinocytes, and to the nuclei of basal and spinous layer cells of normal human epidermis. Western blot analysis of the retinoblastoma tumor suppressor protein antigen from keratinocytes and skin established the presence of the hypophosphorylated and hyperphosphorylated forms of retinoblastoma tumor suppressor protein. The exposure of keratinocytes and human skin to 200 J per cm2 of ultraviolet radiation, resulted in a rapid depletion in hyperphosphorylated retinoblastoma tumor suppressor protein, and the accumulation of growth inhibitory hypophosphorylated retinoblastoma tumor suppressor protein(105). In unirradiated and ultraviolet-irradiated keratinocytes retinoblastoma tumor suppressor protein was localized to the spindles of M-phase cells. In contrast, the exposure of keratinocytes to ultraviolet in the presence of 5 mM okadaic acid, resulted in an inhibition of retinoblastoma tumor suppressor protein translocation to the mitotic spindles of M-phase keratinocytes. In addition, the ultraviolet radiation-induced depletion in hyperphosphorylated retinoblastoma tumor suppressor protein, and accumulation of hypophosphorylated retinoblastoma tumor suppressor protein(105) was inhibited by 5 mM okadaic acid. Okadaic acid (0.5 nM), however, did not affect the ultraviolet radiation-induced dephosphorylation and depletion of hyperphosphorylation of the retinoblastoma tumor suppressor protein. Western blot analysis of ultraviolet-irradiated keratinocytes demonstrated that the hypophosphorylated growth inhibitory 105 kDa form of retinoblastoma tumor suppressor protein coimmunoprecipitated with the 38 kDa catalytic subunit of a type 1 protein serine/threonine phosphatase.

Effects of a 1% hydrocortisone conditioner on hematologic and biochemical parameters, adrenal function testing, and cutaneous reactivity to histamine in normal and pruritic dogs.

The purpose of this double-blind study was to examine the effects of a 1% hydrocortisone, leave-on conditioner on hematologic and biochemical parameters, adrenal function tests, and cutaneous reaction to serial dilutions of histamine phosphate in healthy dogs and those with pruritic dermatitis. Groups 1 and 2 each consisted of eight healthy dogs. Seven pruritic dogs comprised Group 3. All dogs were bathed twice weekly for 6 weeks. Groups 1 and 3 had 1% hydrocortisone conditioner applied after each bath. Group 2 had vehicle from the conditioner applied after each bath. The amount of 1% hydrocortisone applied to the treated dogs ranged from 278 to 416 mg/m2. Hematologic and biochemical analysis and adrenocorticotrophic hormone (ACTH) stimulation tests were performed on all dogs on days 0,14, 28, and 42. Mean values for all blood and serum parameters remained within normal limits during the study. Post-ACTH cortisol levels were definitely lower in Group 3 than in Groups 1 and 2 on day 42 (P < 0.05) and when averaged over all days of the study (P < 0.05 and P < 0.01, respectively). Serum alkaline phosphatase levels were significantly lower in Group 3 on day 0 than on days 14 (P < 0.05), 28 (P < 0.01), and 42 (P = 0.05). All dogs received intradermal injections of buffered saline and five serial dilutions of histamine phosphate on days 0, 14, 28, and 42. No significant differences were apparent among the groups in subjective and objective evaluation of intradermally injected dilutions of histamine. In this study, the use of a 1% hydrocortisone, leave-on conditioner did not result in clinically evident adverse effects, and only minor changes in blood parameters were detected. Although mean values in all groups remained within reference ranges throughout the study, the finding of statistically significant lower post-ACTH cortisol concentrations in the pruritic dogs (Group 3) suggests that absorption of hydrocortisone may have occurred. The results of this study also show that this product does not significantly suppress cutaneous reactivity to histamine in normal and pruritic dogs.

A role for Na+/H+ exchange in pH regulation in Helix neurones.

We have used the pH-sensitive fluorescent dye 8-hydroxypyrene-1,3,6-trisulphonic acid (HPTS) to reexamine the mechanisms that extrude acid from voltage-clamped Helix aspersa neurones. Intracellular acid loads were imposed by three different methods: application of weak acid, depolarization and removal of extracellular sodium. In nominally CO2/HCO3-free Ringer the rate of recovery from acid loads was significantly slowed by the potent Na+/H+ exchange inhibitor 5-[N-ethyl-N-isopropyl]-amiloride (EIPA, 50 microM). Following depolarization-induced acidifications the rate of intracellular pH (pHi) recovery was significantly reduced from 0.41 +/- 0.13 pH units.h-1 in controls to 0.12 +/- 0.09 pH units.h-1 after treatment with EIPA at pHi approximately equal to 7.3 (n = 7). The amiloride analogue also reduced the rate of acid loading seen during extracellular sodium removal both in the presence and absence of the Na(+)-dependent Cl-/HCO3- exchange inhibitor 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonic acid (SITS, 50 microM). This is consistent with EIPA inhibiting reverse-mode Na+/H+ exchange. In 2.5% CO2/20 mM HCO3-buffered Ringer pHi recovery was significantly inhibited by SITS, but unaffected by EIPA. Our results indicate that there are two separate Na(+)-dependent mechanisms involved in the maintenance of pHi in Helix neurones: Na(+)-dependent Cl-/HCO3- exchange and Na+/H+ exchange. Acid extrusion from Helix neurones is predominantly dependent upon the activity of Na(+)-dependent Cl-/HCO3- exchange with a lesser role for Na+/H+ exchange. This adds further weight to the belief that the Na+/H+ exchanger is ubiquitous.

Synthesis and structure-activity relationships of the (alkylamino)piperidine-containing BHAP class of non-nucleoside reverse transcriptase inhibitors: effect of 3-alkylpyridine ring substitution.

Development of resistance to currently approved HIV therapies has continued to fuel research efforts to improve the metabolic stability and spectrum of activity of the (alkylamino)piperidine-containing bis(heteroaryl)piperazine (AAP-BHAP) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis of analogues in which the usual 3-alkylamino substituent on the pyridine ring is replaced by a 3-alkyl substituent led to compounds which retained activity against recombinant P236L and wild-type (WT) reverse transcriptase (RT), while inhibition of the Y181C mutant RT was reduced relative to the activity of the 3-alkylamino-substituted congeners. Testing of representative analogues in an in vitro liver microsome assay indicated that the alkyl substituent would not appreciably improve the metabolic stability of the AAP-BHAP template. In vivo pharmacokinetic evaluation of three compounds confirmed these results in that high systemic clearances were observed. Nevertheless, one compound (13), PNU-103657, possessed oral bioavailability in rats approaching that of the structurally related NNRTI drug delavirdine which is currently on the market for the treatment of HIV infection.