Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus

For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane and diffuse throughout the cytosol. Organelle surfaces within human B cells are reconstructed from soft X-ray tomographic images, and modeled as reflecting barriers to the molecules’ diffusion. We show that signal inactivation sharpens signals, reducing variability in the arrival time at the nuclear membrane. Inactivation can also compensate for an observed slowdown in signal propagation induced by the presence of organelle barriers, leading to arrival times at the nuclear membrane that are comparable to models in which the cytosol is treated as an open, empty region. In the limit of strong signal inactivation this is achieved by filtering out molecules that traverse non-geodesic paths.https://www.biorxiv.org/content/10.1101/2020.01.16.909333v1First author draf

The chain structure of [Ni(C4H2O4)(C12H8N2)(H2O)]n with different types of fumarate bridging

Using modified solvothermal conditions (longer cooling time), beside previously characterized dark-green crystals of [Ni(C4H2O4)(C12H8N2)] (main product), a few light-green crystals of the polymeric title compound, catena-poly[[aqua­(1,10-phenanthroline-κ2 N,N′)nickel(II)]-μ-fumarato-κ2 O:O′-[aqua­(1,10-phenanthroline-κ2 N,N′)nickel(II)]-μ-fumarato-κ4 O,O′:O′′,O′′′], [Ni(C4H2O4)(C12H8N2)(H2O)]n were isolated. Its crystal structure is made up from zigzag chains, propagating in [001], in which the Ni2+ ions are linked alternatively by μ2-fumarato and bis-chelating fumarato bridging ligands. The Ni2+ ion is coordinated in a deformed octa­hedral geometry by one chelating 1,10-phenanthroline ligand, one aqua ligand in a cis position with regard to both N-donor atoms and by two different fumarato ligands, each residing with its central C=C bond on an inversion centre, occupying the remaining coordination sites in a fac fashion. The chains thus formed are linked by O—H⋯O hydrogen bonds and π–π inter­actions between the aromatic rings of the phenanthroline ligands with a shortest ring centroid separation of 3.4787 (10) Å

Improved model for air pressure due to wind on 2D freak waves in finite depth

This paper presents an improved model for evaluating air pressure acting on 2D freak waves in a finite depth due to the presence of winds. This pressure model is developed by analysing the pressure distribution over freak waves using the QALE-FEM/StarCD approach, which combines the quasi arbitrary Lagrangian-Eulerian finite element method (QALE-FEM) with the commercial software package StarCD and has been proven to be sufficiently accurate for such cases according to our previous publication Yan and Ma (2010) [8]. In this model for air pressure, the pressure is decomposed into the components related to the local wave profiles and others. By coupling with the QALE-FEM, the accuracy of the pressure model is tested using various cases. The results show that the pressure distribution estimated using this model is close to that computed by using the QALE-FEM/StarCD approach when there is no significant vortex shedding and wave breaking. The accuracy investigation in predicting the freak wave heights and elevations demonstrates that this pressure model is much better than others in the literature so far used for modelling wind effects on freak waves in finite depth

catena-Poly[[[diaqua­(di-2-pyridylamine-κ2 N,N′)nickel(II)]-μ-fumarato-κ2 O 1:O 4] tetra­hydrate]

In the crystal structure of the title compound, {[Ni(C4H2O4)(C10H9N3)(H2O)2]·4H2O}n, zigzag chains are built up from cis-[Ni(dpya)(H2O)2]2+ cations (dpya is di-2-pyridylamine) linked by bis-monodentate coordinated bridging fumarate ligands. The NiII atom is coordinated by one chelating dpya ligand, two aqua ligands in trans positions and two monodentate fumarate ligands in cis positions in the form of a deformed octa­hedron. The water mol­ecules, O atoms of the fumarate carboxyl­ate groups and the amine group of the dpya ligand are involved in an extended network of intra- and inter­molecular O—H⋯O hydrogen bonds. Moreover, π–π inter­actions between the pyridine rings of the dpya ligand contribute to the stability of the structure. Two of the five uncoordinated water molecules are half-occupied

Patterns of antihypertensive prescribing, discontinuation and switching among a Hong Kong Chinese population from over one million prescriptions

Hypertension is an alarming public health problem among Chinese. The present study evaluated the prescribing patterns, discontinuation and switching profiles of antihypertensive agents and their associated factors in one Hong Kong Chinese population. Data were retrieved from computerized records for patients prescribed anti-hypertensive agents in government primary care clinics of Hong Kong from January, 2004 to June, 2007. A total of 1,069,836 antihypertensive drug visits, representing 67,028 patients, were analyzed. The most commonly prescribed drugs were Calcium Channel Blockers (CCBs) (49%), b-Blockers (BBs) (46%) and Angiotensin-Converting Enzyme Inhibitors (ACEIs) (19%). Thiazide diuretic prescribing was low (13%) and on the decline (14% in 2004 to 12% in 2007). Prescribing of ACEIs was rising (16% in 2004 to 23% in 2007). Patients’ age, gender, and socio-economic status were independent predictors of class of anti-hypertensive prescribed but explained less than 3.5% of the variation observed. Drug discontinuation was highest for BBs (21%) and lowest for CCBs (12%). The high rates of discontinuation in BBs remained apparent after controlling for confounding variables. Switching was less common than discontinuation and was most likely with thiazide diuretics. To summarize, prescribing of CCBs and BBs were high and that of thiazide diuretics particularly low in this Chinese population when compared with international trends. CCBs may be a particularly favorable antihypertensive treatment in Chinese, given the high discontinuation rates of BBs and international guidelines advising against the use of BBs as first-line therapy. The low use of thiazide diuretics warrants further clinical and cost effectiveness studies among Chinese