Di-μ-oxido-bis-[(1,4,8,11-tetra-aza-cyclo-tetra-decane-κN,N',N'',N''')dimangan-ese(III,IV)] bis-(tetra-phenyl-borate) chloride acetonitrile disolvate.

The title compound, [Mn(2)O(2)(C(10)H(24)N(4))(2)](C(24)H(20)B)(2)Cl·2CH(3)CN, is a mixed-valent Mn(III)/Mn(IV) oxide-bridged mangan-ese dimer with one chloride and two tetra-phenyl-borate counter-anions. There are two non-coordinated mol-ecules of acetonitrile in the formula unit. A center of inversion is present between the two metal atoms, and, consequently, there is no distinction between Mn(III) and Mn(IV) metal centers. In the Mn(2)O(2) core, the Mn-O distances are 1.817 (3) and 1.821 (3) Å. The cyclam ligand is in the cis configuration. The chloride counter-anion resides on a center of symmetry, whereas the tetra-phenyl-borate counter-anion is in a general position. The cyclam ligand is hydrogen bonded to the acetonitrile as well as to the chloride anion. One of the phenyl rings of the anion and the acetonitrile solvent molecule are each disordered over two sets of sites

The application of S isotopes and S/Se ratios in determining ore-forming processes of magmatic Ni–Cu–PGE sulfide deposits: a cautionary case study from the northern Bushveld Complex

The application of S/Se ratios and S isotopes in the study of magmatic Ni–Cu–PGE sulfide deposits has long been used to trace the source of S and to constrain the role of crustal contamination in triggering sulfide saturation. However, both S/Se ratios and S isotopes are subject to syn- and post-magmatic processes that may alter their initial signatures. We present in situ mineral δ34S signatures and S/Se ratios combined with bulk S/Se ratios to investigate and assess their utility in constraining ore-forming processes and the source of S within magmatic sulfide deposits. Magmatic Ni–Cu–PGE sulfide mineralization in the Grasvally Norite–Pyroxenite–Anorthosite (GNPA) member, northern Bushveld Complex was used as a case study based on well-defined constraints of sulfide paragenesis and local S isotope signatures. A crustal δ34S component is evident in the most primary sulfide assemblage regardless of footwall lithology, and is inferred that the parental magma(s) of the GNPA member was crustally contaminated and sulfide saturated at the time of emplacement. However, S/Se ratios of both the primary and in particular secondary sulfide assemblages record values within or below the mantle range, rather than high crustal S/Se ratios. In addition, there is a wide range of S/Se ratio for each sulfide mineral within individual assemblages that is not necessarily consistent with the bulk ratio. The initial crustal S/Se ratio is interpreted to have been significantly modified by syn-magmatic lowering of S/Se ratio by sulfide dissolution, and post-magmatic lowering of the S/Se ratio from hydrothermal S-loss, which also increases the PGE tenor of the sulfides. Trace element signatures and variations in Th/Yb and Nb/Th ratios support both an early pre-emplacement contamination event as seen by the S isotopes and S/Se ratios, but also a second contamination event resulting from the interaction of the GNPA magma with the local footwall country rocks at the time of emplacement; though this did not add any additional S. We are able to present an integrated emplacement and contamination model for the northern limb of the Bushveld Complex. Although the multitude of processes that affect variations in the δ34S signature and in particular S/Se ratio may be problematic in interpreting ore genesis, they can reveal a wealth of additional detail on a number of processes involved in the genetic history of a Ni–Cu–PGE deposit in addition to crustal contamination. However, a prerequisite for being able to do this is to utilize other independent petrological and mineralogical techniques that provide constraints on both the timing and effect of various ore-forming and modifying processes. Utilizing both bulk and in situ methods in concert to determine the S/Se ratio allows for the assessment of multiple sulfide populations, the partitioning behaviour of Se during sulfide liquid fractionation and also the effects of low temperature fluid alteration. In comparison, S isotopes are relatively more robust and represent a more reliable indicator of the role of crustal S contamination. The addition of trace element data to the above makes for an incredibly powerful approach in assessing the role of crustal contamination in magmatic sulfide systems

Updated estimated incidence and prevalence of serious fungal infections in Trinidad and Tobago

Objective: : To estimate the incidence and prevalence of serious fungal infections in Trinidad and Tobago (T&T), with a population of 1 394 973 million. Methods: : The medical literature was searched to obtain published data on the incidence and prevalence of fungal infections in the Caribbean. If data were unavailable, estimations were performed using the frequencies of fungal infection in populations at risk. Asthma and pulmonary tuberculosis rates were used to derive the prevalence of allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitization (SAFS), and chronic pulmonary aspergillosis (CPA). Results: : The estimated annual burden of fungal infections was 46 156 persons (3.3% of the population), including 21 455 women with recurrent vulvovaginal candidiasis, 118 persons with invasive aspergillosis, 3637 adults with ABPA, 4800 with SAFS, and 178 with CPA. Annually, we estimated 70 cases of candidemia and 14 647 cases of tinea capitis in children. Of the 11 000 persons living with HIV/AIDS, it was estimated that there were 40 cases of cryptococcal meningitis, 88 cases of disseminated histoplasmosis, and 124 cases of Pneumocystis pneumonia. Conclusion: : There seems to be an extensive burden of fungal infections in T&T. Hence, targeted interventions are required to improve clinical and laboratory diagnosis and a national surveillance system should be implemented.S

The geometry of thermodynamic control

A deeper understanding of nonequilibrium phenomena is needed to reveal the principles governing natural and synthetic molecular machines. Recent work has shown that when a thermodynamic system is driven from equilibrium then, in the linear response regime, the space of controllable parameters has a Riemannian geometry induced by a generalized friction tensor. We exploit this geometric insight to construct closed-form expressions for minimal-dissipation protocols for a particle diffusing in a one dimensional harmonic potential, where the spring constant, inverse temperature, and trap location are adjusted simultaneously. These optimal protocols are geodesics on the Riemannian manifold, and reveal that this simple model has a surprisingly rich geometry. We test these optimal protocols via a numerical implementation of the Fokker-Planck equation and demonstrate that the friction tensor arises naturally from a first order expansion in temporal derivatives of the control parameters, without appealing directly to linear response theory

Di-μ-oxido-bis­[(1,4,8,11-tetra­aza­cyclo­tetra­decane-κ4 N,N′,N′′,N′′′)dimangan­ese(III,IV)] bis­(tetra­phenyl­borate) chloride acetonitrile disolvate

The title compound, [Mn2O2(C10H24N4)2](C24H20B)2Cl·2CH3CN, is a mixed-valent MnIII/MnIV oxide-bridged mangan­ese dimer with one chloride and two tetra­phenyl­borate counter-anions. There are two non-coordinated mol­ecules of acetonitrile in the formula unit. A center of inversion is present between the two metal atoms, and, consequently, there is no distinction between MnIII and MnIV metal centers. In the Mn2O2 core, the Mn—O distances are 1.817 (3) and 1.821 (3) Å. The cyclam ligand is in the cis configuration. The chloride counter-anion resides on a center of symmetry, whereas the tetra­phenyl­borate counter-anion is in a general position. The cyclam ligand is hydrogen bonded to the acetonitrile as well as to the chloride anion. One of the phenyl rings of the anion and the acetonitrile solvent molecule are each disordered over two sets of sites

The Fundamental Plane of QSOs and the Relationship Between Host and Nucleus

We present results from an archival study of 70 medium-redshift QSOs observed with the Wide Field Planetary Camera 2 on board the Hubble Space Telescope. The QSOs have magnitudes M_V <= -23 (total nuclear plus host light) and redshifts $0.06 <= z <= 0.46$. The aim of the present study is to investigate the connections between the nuclear and host properties of QSOs, using high-resolution images and removing the central point source to reveal the host structure. We confirm that more luminous QSO nuclei are found in more luminous host galaxies. Using central black hole masses from the literature, we find that nuclear luminosity also generally increases with black hole mass, but it is not tightly correlated. Nuclear luminosities range from 2.3% to 200% of the Eddington limit. Those in elliptical hosts cover the range fairly evenly, while those in spirals are clustered near the Eddington limit. Using a principal components analysis, we find a kind of fundamental plane relating the nuclear luminosity to the size and effective surface magnitude of the bulge. Using optical nuclear luminosity, this relationship explains 96.1% of the variance in the overall sample, while another version of the relationship uses x-ray nuclear luminosity and explains 95.2% of the variance. The form of this QSO fundamental plane shows similarities to the well-studied fundamental plane of elliptical galaxies, and we examine the possible relationship between them as well as the difficulties involved in establishing this connection.Comment: 49 pages, 6 figures. Accepted by Ap

Simulating Cardiac Fluid Dynamics in the Human Heart

Cardiac fluid dynamics fundamentally involves interactions between complex blood flows and the structural deformations of the muscular heart walls and the thin, flexible valve leaflets. There has been longstanding scientific, engineering, and medical interest in creating mathematical models of the heart that capture, explain, and predict these fluid-structure interactions. However, existing computational models that account for interactions among the blood, the actively contracting myocardium, and the cardiac valves are limited in their abilities to predict valve performance, resolve fine-scale flow features, or use realistic descriptions of tissue biomechanics. Here we introduce and benchmark a comprehensive mathematical model of cardiac fluid dynamics in the human heart. A unique feature of our model is that it incorporates biomechanically detailed descriptions of all major cardiac structures that are calibrated using tensile tests of human tissue specimens to reflect the heart's microstructure. Further, it is the first fluid-structure interaction model of the heart that provides anatomically and physiologically detailed representations of all four cardiac valves. We demonstrate that this integrative model generates physiologic dynamics, including realistic pressure-volume loops that automatically capture isovolumetric contraction and relaxation, and predicts fine-scale flow features. None of these outputs are prescribed; instead, they emerge from interactions within our comprehensive description of cardiac physiology. Such models can serve as tools for predicting the impacts of medical devices or clinical interventions. They also can serve as platforms for mechanistic studies of cardiac pathophysiology and dysfunction, including congenital defects, cardiomyopathies, and heart failure, that are difficult or impossible to perform in patients

Development of a Novel Cell-Permeable Protein-Protein Interaction Inhibitor for the Polo-box Domain of Polo-like Kinase 1.

Polo-like kinase 1 (PLK1) is a key regulator of mitosis and a recognized drug target for cancer therapy. Inhibiting the polo-box domain of PLK1 offers potential advantages of increased selectivity and subsequently reduced toxicity compared with targeting the kinase domain. However, many if not all existing polo-box domain inhibitors have been shown to be unsuitable for further development. In this paper, we describe a novel compound series, which inhibits the protein-protein interactions of PLK1 via the polo-box domain. We combine high throughput screening with molecular modeling and computer-aided design, synthetic chemistry, and cell biology to address some of the common problems with protein-protein interaction inhibitors, such as solubility and potency. We use molecular modeling to improve the solubility of a hit series with initially poor physicochemical properties, enabling biophysical and biochemical characterization. We isolate and characterize enantiomers to improve potency and demonstrate on-target activity in both cell-free and cell-based assays, entirely consistent with the proposed binding model. The resulting compound series represents a promising starting point for further progression along the drug discovery pipeline and a new tool compound to study kinase-independent PLK functions

Investigation of bone resorption within a cortical basic multicellular unit using a lattice-based computational model

In this paper we develop a lattice-based computational model focused on bone resorption by osteoclasts in a single cortical basic multicellular unit (BMU). Our model takes into account the interaction of osteoclasts with the bone matrix, the interaction of osteoclasts with each other, the generation of osteoclasts from a growing blood vessel, and the renewal of osteoclast nuclei by cell fusion. All these features are shown to strongly influence the geometrical properties of the developing resorption cavity including its size, shape and progression rate, and are also shown to influence the distribution, resorption pattern and trajectories of individual osteoclasts within the BMU. We demonstrate that for certain parameter combinations, resorption cavity shapes can be recovered from the computational model that closely resemble resorption cavity shapes observed from microCT imaging of human cortical bone.Comment: 17 pages, 11 figures, 1 table. Revised version: paper entirely rewritten for a more biology-oriented readership. Technical points of model description now in Appendix. Addition of two new figures (Fig. 5 and Fig. 9) and removal of former Fig.