Prostaglandin E2-bisphosphonate conjugates : potential agents for treatment of osteoporosis.

Conjugates of bisphosphonates (potential bone resorption inhibitors) and prostaglandin E2 (a bone formation enhancer) were prepared and evaluated for their ability to bind to bone and to liberate, enzymatically, free PGE2. The conjugate 3, an amide at C-1 of PGE2 proved to be too stable in vivo while conjugate 6, a thioester, was too labile. Several PGE2, C-15 ester-linked con- jugates (18, 23, 24 and 31) were prepared and conjugate 23 was found to bind effectively to bone in vitro and in vivo and to liberate PGE2 at an acceptable rate. A 4-week study in a rat model of osteoporosis showed that 23 was better tolerated and more effective as a bone growth stimulant than daily maximum tolerated doses of free PGE2

New use for succinylated sugarcane bagasse containing adsorbed Cu2+ and Ni2+ : efficient catalysts for gas-phase n-hexane and n-heptane oxidation reactions.

This study describes the use of succinylated twice-mercerized sugarcane bagasse containing adsorbed Cu2+ or Ni2+ ions from spiked aqueous solutions (2MSBA-Cu and 2MSBA-Ni) as heterogeneous catalysts for the catalytic oxidation of n-hexane and n-heptane in gas phase. To the best of our knowledge, this is the first study in which a spent adsorbent material based on lignocellulose biomass is used in the catalytic oxidation of volatile organic compounds. The adsorbent and spent adsorbent materials were characterized by FTIR, TGA and XRD. The amount of Cu2+ and Ni2+ adsorbed on 2MSBA was 0.49 and 2.49 mmol g?1, respectively. The catalysts were active for total oxidation of n-hexane and n-heptane, even at low temperatures. 2MSBA-Cu exhibited higher catalytic activity than 2MSBA-Ni and surprisingly their performances were comparable or superior to those of some catalysts reported in the literature, including noble metal-based catalysts

Condensed matter lessons about the origin of time

It is widely hoped that quantum gravity will shed light on the question of the origin of time in physics. The currently dominant approaches to a candidate quantum theory of gravity have naturally evolved from general relativity, on the one hand, and from particle physics, on the other hand. A third important branch of 20th century `fundamental' physics, condensed-matter physics, also offers an interesting perspective on quantum gravity, and thereby on the problem of time. The bottomline might sound disappointing: to understand the origin of time, much more experimental input is needed than what is available today. Moreover it is far from obvious that we will ever find out the true origin of physical time, even if we become able to directly probe physics at the Planck scale. But we might learn some interesting lessons about time and the structure of our universe in the process. A first lesson is that there are probably several characteristic scales associated with "quantum gravity" effects, rather than the single Planck scale usually considered. These can differ by several orders of magnitude, and thereby conspire to hide certain effects expected from quantum gravity, rendering them undetectable even with Planck-scale experiments. A more tentative conclusion is that the hierarchy between general relativity, special relativity and Newtonian physics, usually taken for granted, might have to be interpreted with caution.Comment: v1: 9 pages. Fourth juried prize in FQXi essay contest on "the Nature of Time" (2008). v2: 2015 update, partially rewritten and extended for Foundations of Physics. arXiv admin note: substantial text overlap with arXiv:0810.061

Adiabatic out-of-equilibrium solutions to the Boltzmann equation in warm inflation

We show that, in warm inflation, the nearly constant Hubble rate and temperature lead to an adiabatic evolution of the number density of particles interacting with the thermal bath, even if thermal equilibrium cannot be maintained. In this case, the number density is suppressed compared to the equilibrium value but the associated phase-space distribution retains approximately an equilibrium form, with a smaller amplitude and a slightly smaller effective temperature. As an application, we explicitly construct a baryogenesis mechanism during warm inflation based on the out-of-equilibrium decay of particles in such an adiabatically evolving state. We show that this generically leads to small baryon isocurvature perturbations, within the bounds set by the Planck satellite. These are correlated with the main adiabatic curvature perturbations but exhibit a distinct spectral index, which may constitute a smoking gun for baryogenesis during warm inflation. Finally, we discuss the prospects for other applications of adiabatically evolving out-of-equilibrium states.publishe

Leptogenesis from loop effects in curved spacetime

We describe a new mechanism -- radiatively-induced gravitational leptogenesis -- for generating the matter-antimatter asymmetry of the Universe. We show how quantum loop effects in C and CP violating theories cause matter and antimatter to propagate differently in the presence of gravity, and prove this is forbidden in flat space by CPT and translation symmetry. This generates a curvature-dependent chemical potential for leptons, allowing a matter-antimatter asymmetry to be generated in thermal equilibrium in the early Universe. The time-dependent dynamics necessary for leptogenesis is provided by the interaction of the virtual self-energy cloud of the leptons with the expanding curved spacetime background, which violates the strong equivalence principle and allows a distinction between matter and antimatter. We show here how this mechanism is realised in a particular BSM theory, the see-saw model, where the quantum loops involve the heavy sterile neutrinos responsible for light neutrino masses. We demonstrate by explicit computation of the relevant two-loop Feynman diagrams how the size of the radiative corrections relevant for leptogenesis becomes enhanced by increasing the mass hierarchy of the sterile neutrinos, and show that for realistic phenomenological parameters this mechanism can generate the observed baryon-to-photon ratio of the Universe

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Optimization of cellulose and sugarcane bagasse oxidation : application for adsorptive removal of crystal violet and auramine-O from aqueous solution.

Cellulose (Cel) and sugarcane bagasse (SB) were oxidized with an H3PO4-NaNO2 mixture to obtain adsorbent materials with high contents of carboxylic groups. The oxidation reactions of Cel and SB were optimized using design of experiments (DOE) and response surface methodology (RSM). The optimized synthesis conditions yielded Cox and SBox with 4.8 mmol/g and 4.5 mmol/g of carboxylic acid groups, respectively. Cox and SBox were characterized by FTIR, TGA, PZC and solid-state 13C NMR. The adsorption of the model cationic dyes crystal violet (CV) and auramine-O (AO) on Cox and SBox in aqueous solution was investigated as a function of the solution pH, the contact time and the initial dye concentration. The adsorption of CV and AO on Cox was described by the Elovich equation and the pseudo-first-order kinetic model respectively, while the adsorption of CV and AO on SBox was described by the pseudo-secondorder kinetic model. Adsorption isotherms were well fitted by the Langmuir and Konda models, with maximum adsorption capacities (Qmax) of 1117.8 mg/g of CV and 1223.3 mg/g of AO on Cox and 1018.2 mg/g of CV and 682.8 mg/g of AO on SBox. Desorption efficiencies were in the range of 50?52% and re-adsorption capacities varied from 65 to 81%, showing the possibility of reuse of both adsorbent materials

Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

BackgroundChemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival.MethodsIn this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and cell lines derived from them were also analyzed.ResultsOur results show that the melanoma cell lines do not express or express in a low degree the chemokine receptors on their cell surface. However, melanoma cell lines show intracellular expression of all the aforementioned receptors and most of their respective ligands. When analyzing the xenografts and the cell lines obtained from them we found variations in the intracellular expression of chemokines and chemokine receptors that differed between the primary and metastatic cell lines. However, as well as in the original cell lines, minute or no expression of the chemokine receptors was observed at the cell surface.ConclusionsCoexpression of chemokine receptors and their ligands was found in human melanoma cell lines. However, this expression is intracellular and receptors are not found at the cell membrane nor chemokines are secreted to the cell medium. The levels of expressed chemokine receptors and their ligands show dynamic variations after xenotransplantation that differ depending on the origin of the cell line (from primary tumor or from metastasis)

British societies guideline on the management of emergencies in implantable left ventricular assist device recipients in transplant centres

\ua9 The Author(s) 2024.An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs