An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints

In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the hard coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio

Fanconi anemia and vaginal squamous cell carcinoma

Fanconi Anemia (FA) is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies. We describe here a 28 year-old female with FA and vaginal squamous cell carcinoma treated by radiation therapy alone. The patient developed arm phlebitis, pulmonary fungal infection, and severe rectal bleeding, followed by hypocalcaemia, hypokalemia, vaginal bacterial and fungal infection, with subsequent leg and arm phlebitis, perineal abscess, and sepsis. The patient died 12 weeks later

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

Direct Heme Transfer Reactions in the Group A Streptococcus Heme Acquisition Pathway

The heme acquisition machinery in Group A Streptococcus (GAS) consists of the surface proteins Shr and Shp and ATP-binding cassette transporter HtsABC. Shp cannot directly acquire heme from methemoglobin (metHb) but directly transfers its heme to HtsA. It has not been previously determined whether Shr directly relays heme from metHb to Shp. Thus, the complete pathway for heme acquisition from metHb by the GAS heme acquisition machinery has remained unclear. In this study, the metHb-to-Shr and Shr-to-Shp heme transfer reactions were characterized by spectroscopy, kinetics and protein-protein interaction analyses. Heme is efficiently transferred from the β and α subunits of metHb to Shr with rates that are 7 and 60 times greater than those of the passive heme release from metHb, indicating that Shr directly acquires heme from metHb. The rapid heme transfer from Shr to Shp involves an initial heme donor/acceptor complex and a spectrally and kinetically detectable transfer intermediate, implying that heme is directly channeled from Shr to Shp. The present results show that Shr speeds up heme transfer from metHb to Shp, whereas Shp speeds up heme transfer from Shr to HtsA. Furthermore, the findings demonstrate that Shr can interact with metHb and Shp but not HtsA. Taken together with our published results on the Shp/HtsA reaction, these findings establish a model of the heme acquisition pathway in GAS in which Shr directly extracts heme from metHb and Shp relays it from Shr to HtsA

Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries

The article reviews the current status of a theoretical approach to the problem of the emission of gravitational waves by isolated systems in the context of general relativity. Part A of the article deals with general post-Newtonian sources. The exterior field of the source is investigated by means of a combination of analytic post-Minkowskian and multipolar approximations. The physical observables in the far-zone of the source are described by a specific set of radiative multipole moments. By matching the exterior solution to the metric of the post-Newtonian source in the near-zone we obtain the explicit expressions of the source multipole moments. The relationships between the radiative and source moments involve many non-linear multipole interactions, among them those associated with the tails (and tails-of-tails) of gravitational waves. Part B of the article is devoted to the application to compact binary systems. We present the equations of binary motion, and the associated Lagrangian and Hamiltonian, at the third post-Newtonian (3PN) order beyond the Newtonian acceleration. The gravitational-wave energy flux, taking consistently into account the relativistic corrections in the binary moments as well as the various tail effects, is derived through 3.5PN order with respect to the quadrupole formalism. The binary's orbital phase, whose prior knowledge is crucial for searching and analyzing the signals from inspiralling compact binaries, is deduced from an energy balance argument.Comment: 109 pages, 1 figure; this version is an update of the Living Review article originally published in 2002; available on-line at http://www.livingreviews.org

EFFECTS OF PRIMING WITH OR WITHOUTH DRYING ON Pterogyne nitens TUL. SEEDS UNDER STRESS

Pterogyne nitens Tul. \ue9 conhecida popularmente como amendoim do campo,\ue9 uma esp\ue9cie arb\uf3rea, heli\uf3fita, secund\ue1ria inicial que se regenera intensamente em \ue1reas abertas e pastagens. Pode ser empregada como esp\ue9cie ornamental e na reposi\ue7\ue3o de mata ciliar, em l\ub0Cais sujeitos a inunda\ue7\uf5es peri\uf3dicas, em s\uedtios arenosos e degradados. O condicionamento \ue9 uma t\ue9cnica p\uf3s-colheita usada com o objetivo de aumentar a vel\ub0Cidade de germina\ue7\ue3o, emerg\ueancia, bem como ampliar a toler\ue2ncia a v\ue1rios tipos de estresse. O objetivo deste trabalho foi avaliar a efici\ueancia do condicionamento com ou sem secagem posterior em aumentar a resist\ueancia a diferentes tipos de estresse. As sementes selecionadas foram escarificadas com \ue1cido sulf\ufarico durante 15 min. e depois condicionadas em \ue1gua destilada e solu\ue7\uf5es de manitol -0,5 e -1,0 MPa durante 24h a 10\ub0C. Para cada solu\ue7\ue3o de condicionamento, o lote de sementes foi dividido em dois grupos, um dos quais foi seco at\ue9 atingir o teor de umidade apresentado antes do condicionamento, e o segundo foi imediatamente usado nos testes. Os diferentes grupos de sementes foram expostos ao envelhecimento acelerado (100% U.R. sob 35 e 40\ub0C), ao estresse t\ue9rmico (24h a 60 e 70\ub0C) e o teste de exaust\ue3o (24h submersos a 10 e 27\ub0C). Para todos os testes foram utilizadas quatro repeti\ue7\uf5es de 25 unidades e os dados de porcentagem e vel\ub0Cidade de germina\ue7\ue3o foram submetidos \ue0 an\ue1lise de vari\ue2ncia e ao teste de Tukey. Com o aumento da intensidade do estresse houve diminui\ue7\ue3o na germina\ue7\ue3o e no vigor das sementes, que as diferentes formas de condicionamento n\ue3o reverteram. Em geral, o condicionamento com o uso manitol a -1,0 MPa diminuiu a qualidade fisiol\uf3gica das sementes e, solu\ue7\uf5es a -0,5 MPa ou \ue1gua destilada aumentaram a porcentagem e/ou vel\ub0Cidade de germina\ue7\ue3o de sementes submetidas aos diferentes tipos de estresse.Pterogyne nitens Tul. is a arboreal species, with highlight requirements, growing in gaps, grass land and sandy soils . It could be used in streets, to recovery degradated areas with periodical floods. Priming is a post harvest technique, used to improve germination rate, seedling field emergence and stress tolerance. The aim of this work is to contrast, under stress conditions, different ways to the priming. The seeds with 12% of moisture content were selected, scarified with sulfuric acid during 15 min. Distilled water and mannitol solutions (-0.5 MPa and -1.0 MPa) were used to seeds pre imbibition, during 24h at 10\ub0C. A half part of the premed seeds was drying until reach the initial moisture content, and the other part is immediately used in the tests. The accelerated aging was carried out at 100% of R.U. at 35 and 40\ub0C; thermal stress at 60 and 70\ub0C during 24h, and in last test, the seeds were immersed in distilled water at 10 on 27\ub0C. All the tests were conducted with fours replicates of 20 seeds and the data registered were submitted to variance analysis and Tukey test. Seed viability and vigor decreased when stress intensity increased. The priming did not reversed this effect, but in general, mannitol solutions (-1.0 MPa) decreased the seed vigor. The primed seeds in distilled water or mannitol (-0.5 MPa) present an increase in the rate and germination percentage under stress condition