Modeling the Construction of Polymeric Adsorbent Media: Effects of Counter-Ions on Ligand Immobilization and Pore Structure

Molecular dynamics modeling and simulations are employed to study the effects of counter-ions on the dynamic spatial density distribution and total loading of immobilized ligands as well as on the pore structure of the resultant ion exchange chromatography adsorbent media. The results show that the porous adsorbent media formed by polymeric chain molecules involve transport mechanisms and steric resistances which cause the charged ligands and counter-ions not to follow stoichiometric distributions so that (i) a gradient in the local nonelectroneutrality occurs, (ii) non-uniform spatial density distributions of immobilized ligands and counter-ions are formed, and (iii) clouds of counter-ions outside the porous structure could be formed. The magnitude of these counter-ion effects depends on several characteristics associated with the size, structure, and valence of the counter-ions. Small spherical counter-ions with large valence encounter the least resistance to enter a porous structure and their effects result in the formation of small gradients in the local nonelectroneutrality, higher ligand loadings, and more uniform spatial density distributions of immobilized ligands, while the formation of exterior counter-ion clouds by these types of counter-ions is minimized. Counter-ions with lower valence charges, significantly larger sizes, and elongated shapes, encounter substantially greater steric resistances in entering a porous structure and lead to the formation of larger gradients in the local nonelectroneutrality, lower ligand loadings, and less uniform spatial density distributions of immobilized ligands, as well as substantial in size exterior counter-ion clouds. The effects of lower counter-ion valence on pore structure, local nonelectroneutrality, spatial ligand density distribution, and exterior counter-ion cloud formation are further enhanced by the increased size and structure of the counter-ion. Thus, the design, construction, and functionality of polymeric porous adsorbent media will significantly depend, for a given desirable ligand to be immobilized and represent the adsorption active sites, on the type of counter-ion that is used during the ligand immobilization process. Therefore, the molecular dynamics modeling and simulation approach presented in this work could contribute positively by representing an engineering science methodology to the design and construction of polymeric porous adsorbent media which could provide high intraparticle mass transfer and adsorption rates for the adsorbate biomolecules of interest which are desired to be separated by an adsorption process

A Molecular Dynamics Study on the Transport of a Charged Biomolecule in a Polymeric Adsorbent Medium and Its Adsorption onto a Charged Ligand

The transport of a charged adsorbate biomolecule in a porous polymeric adsorbent medium and its adsorption onto the covalently immobilized ligands have been modeled and investigated using molecular dynamics modeling and simulations as the third part of a novel fundamental methodology developed for studying ion-exchange chromatography based bioseparations. To overcome computational challenges, a novel simulation approach is devised where appropriate atomistic and coarse grain models are employed simultaneously and the transport of the adsorbate is characterized through a number of locations representative of the progress of the transport process. The adsorbate biomolecule for the system studied in this work changes shape, orientation, and lateral position in order to proceed toward the site where adsorption occurs and exhibits decreased mass transport coefficients as it approaches closer to the immobilized ligand. Furthermore, because the ligands are surrounded by counterions carrying the same type of charge as the adsorbate biomolecule, it takes the biomolecule repeated attempts to approach toward a ligand in order to displace the counterions in the proximity of the ligand and to finally become adsorbed. The formed adsorbate-ligand complex interacts with the counterions and polymeric molecules and is found to evolve slowly and continuously from one-site (monovalent) interaction to multisite (multivalent) interactions. Such a transition of the nature of adsorption reduces the overall adsorption capacity of the ligands in the adsorbent medium and results in a type of surface exclusion effect. Also, the adsorption of the biomolecule also presents certain volume exclusion effects by not only directly reducing the pore volume and the availability of the ligands in the adjacent regions, but also causing the polymeric molecules to change to more compact structures that could further shield certain ligands from being accessible to subsequent adsorbate molecules. These findings have significant practical implications to the design and construction of polymeric porous adsorbent media for effective bioseparations and to the synthesis and operation of processes employed in the separation of biomolecules. The modeling and analysis methods presented in this work could also be suitable for the study of biocatalysis where an enzyme is immobilized on the surface of the pores of a porous medium

The Hubble Constant determined through an inverse distance ladder including quasar time delays and Type Ia supernovae

Context. The precise determination of the present-day expansion rate of the Universe, expressed through the Hubble constant $H_0$, is one of the most pressing challenges in modern cosmology. Assuming flat $\Lambda$CDM, $H_0$ inference at high redshift using cosmic-microwave-background data from Planck disagrees at the 4.4$\sigma$ level with measurements based on the local distance ladder made up of parallaxes, Cepheids and Type Ia supernovae (SNe Ia), often referred to as "Hubble tension". Independent, cosmological-model-insensitive ways to infer $H_0$ are of critical importance. Aims. We apply an inverse-distance-ladder approach, combining strong-lensing time-delay-distance measurements with SN Ia data. By themselves, SNe Ia are merely good relative distance indicators, but by anchoring them to strong gravitational lenses one can obtain an $H_0$ measurement that is relatively insensitive to other cosmological parameters. Methods. A cosmological parameter estimate is performed for different cosmological background models, both for strong-lensing data alone and for the combined lensing + SNe Ia data sets. Results. The cosmological-model dependence of strong-lensing $H_0$ measurements is significantly mitigated through the inverse distance ladder. In combination with SN Ia data, the inferred $H_0$ consistently lies around 73-74 km s$^{-1}$ Mpc$^{-1}$, regardless of the assumed cosmological background model. Our results agree nicely with those from the local distance ladder, but there is a >2$\sigma$ tension with Planck results, and a ~1.5$\sigma$ discrepancy with results from an inverse distance ladder including Planck, Baryon Acoustic Oscillations and SNe Ia. Future strong-lensing distance measurements will reduce the uncertainties in $H_0$ from our inverse distance ladder.Comment: 5 pages, 3 figures, A&A letters accepted versio

High redshift X-ray galaxy clusters. I. The impact of point sources on the cluster properties

The current generation of X-ray observatories like Chandra allows studies with very fine spatial details. It is now possible to resolve X-ray point sources projected into the cluster diffuse emission and exclude them from the analysis to estimate the ``correct'' X-ray observables. In order to verify the incidence of point sources on the cluster thermal emission and to evaluate the impact of their non-thermal emission on the determination of cluster properties, we used a sample of 18 high-z (0.25 < z < 1.01) clusters from the Chandra archive. We performed a detailed analysis of the cluster properties and compared the changes observed in the X-ray observables, like temperature and luminosity or their inter-relation, when one keeps the point sources in the analysis. The point sources projected into the cluster extended emission affect the estimates of cluster temperature or luminosity considerably (up to 13% and 17% respectively). These percentages become even larger for clusters with z > 0.7 where temperature and luminosity increase up to 24% and 22%, respectively. Thus the point sources should be removed to correctly estimate the cluster properties. However the inclusion of the point sources does not impact significantly the slope and normalization of the L-T relationship since for each cluster the correction to be applied to T and L produces a moderate shift in the L-T plane almost parallel to the best-fit of the ``correct'' L-T relation.Comment: 16 pages, 18 postscript figures. Accepted for publication in Astronomy & Astrophysic

The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing.

Transcriptional regulation in eukaryotes occurs at promoter-proximal regions wherein transcriptionally engaged RNA polymerase II (Pol II) pauses before proceeding toward productive elongation. The role of chromatin in pausing remains poorly understood. Here, we demonstrate that the histone deacetylase SIRT6 binds to Pol II and prevents the release of the negative elongation factor (NELF), thus stabilizing Pol II promoter-proximal pausing. Genetic depletion of SIRT6 or its chromatin deficiency upon glucose deprivation causes intragenic enrichment of acetylated histone H3 at lysines 9 (H3K9ac) and 56 (H3K56ac), activation of cyclin-dependent kinase 9 (CDK9)-that phosphorylates NELF and the carboxyl terminal domain of Pol II-and enrichment of the positive transcription elongation factors MYC, BRD4, PAF1, and the super elongation factors AFF4 and ELL2. These events lead to increased expression of genes involved in metabolism, protein synthesis, and embryonic development. Our results identified SIRT6 as a Pol II promoter-proximal pausing-dedicated histone deacetylase

Missing Dark Matter in the Local Universe

A sample of 11 thousand galaxies with radial velocities V_ LG < 3500 km/s is used to study the features of the local distribution of luminous (stellar) and dark matter within a sphere of radius of around 50 Mpc around us. The average density of matter in this volume, Omega_m,loc=0.08+-0.02, turns out to be much lower than the global cosmic density Omega_m,glob=0.28+-0.03. We discuss three possible explanations of this paradox: 1) galaxy groups and clusters are surrounded by extended dark halos, the major part of the mass of which is located outside their virial radii; 2) the considered local volume of the Universe is not representative, being situated inside a giant void; and 3) the bulk of matter in the Universe is not related to clusters and groups, but is rather distributed between them in the form of massive dark clumps. Some arguments in favor of the latter assumption are presented. Besides the two well-known inconsistencies of modern cosmological models with the observational data: the problem of missing satellites of normal galaxies and the problem of missing baryons, there arises another one - the issue of missing dark matter.Comment: 19 pages, 7 figures, 1 table (accepted

Surface Morphological and Nanomechanical Properties of PLD-Derived ZnO Thin Films

This study reports the surface roughness and nanomechanical characteristics of ZnO thin films deposited on the various substrates, obtained by means of atomic force microscopy (AFM), nanoindentation and nanoscratch techniques. ZnO thin films are deposited on (a- and c-axis) sapphires and (0001) 6H-SiC substrates by using the pulsed-laser depositions (PLD) system. Continuous stiffness measurements (CSM) technique is used in the nanoindentation tests to determine the hardness and Young’s modulus of ZnO thin films. The importance of the ratio (H/Efilm) of elastic to plastic deformation during nanoindentation of ZnO thin films on their behaviors in contact-induced damage during fabrication of ZnO-based devices is considered. In addition, the friction coefficient of ZnO thin films is also presented here

Disturbed isolated galaxies: indicators of a dark galaxy population?

We report the results of our search for disturbed (interacting) objects among very isolated galaxies. The inspections of 1050 northern isolated galaxies from KIG and 500 nearby, very isolated galaxies situated in the Local Supercluster yielded five and four strongly disturbed galaxies, respectively. We suggest that the existence of "dark" galaxies explains the observed signs of interaction. This assumption leads to a cosmic abundance of dark galaxies (with the typical masses for luminous galaxies) that is less than ~1/20 the population of visible galaxies.Comment: 5 pages, 1 figure. Astronomy and Astrophysics, accepte

Bone mineral content after renal transplantation

Forearm bone mineral content (BMC), as evaluated by photonabsorption densitometry, was measured in 28 cadaver kidney donor recipients who entered the study 8 weeks postoperatively and were followed up for 18 months. BMC decreased signifiantly (p<0.05) but marginally in placebo-treated patients (n=14) (initial BMC 1.09±0.25 g/cm; final BMC 1.05±0.24). Fourteen patients were prophylactically given 1,25(OH)2vitamin D3 in a dose which avoided hypercalcemia and hypercalciuria (sim0.25 µg/day); under 1,25(OH)2 vitamin D3 prophylaxis a significant decrease of forearm BMC was observed no longer (initial BMC 0.94±0.21 g/cm; final BMC 0.95±0.21), but the difference between placebo and 1,25(OH)2 vitamin D3 narrowly missed statistical significance (p=0.066). It is concluded that the decrease of forearm BMC is negligible in transplant recipients with low steroid regimens. The data suggest a trend for prophylaxis with 1,25(OH)2 vitamin D3 to slightly ameliorate forearm (cortical) BMC loss