4-(Phenylsulfonyl)-4-lithiocyclopentene as a nucleophilic 2-pentene-1,5-dial synthetic equivalent. An aziridine-based synthetic approach to (−)-alstonerine

Reaction of 4-lithio-4-(phenylsulfonyl)cyclopentene with an l-tryptophan-derived N-tosylaziridine provides an adduct. Oxidative cleavage of the cyclopentene double bond provides a dialdehyde, which enters into acid-catalysed Pictet-Spengler-type bicyclisation to give a tetracyclic aldehyde. Completely regioselective silyl dienol ether formation followed by completely stereoselective hetero-Diels-Alder reaction with monomeric formaldehyde gives a late-stage intermediate in a planned total synthesis of the macroline-related alkaloid (−)-alstonerine.     

Angstrom-to-millimeter characterization of sedimentary rock microstructure

Backscatter SEM imaging and small-angle neutron scattering (SANS) data are combined within a statistical framework to quantify the microstructure of a porous solid in terms of a continuous pore-size distribution spanning over five orders of magnitude of length scale, from 10 A to 500 microm. The method is demonstrated on a sample of natural sandstone and the results are tested against mercury porosimetry (MP) and nuclear magnetic resonance (NMR) relaxation data. The rock microstructure is fractal (D=2.47) in the pore-size range 10 A-50 microm and Euclidean for larger length scales. The pore-size distribution is consistent with that determined by MP. The NMR data show a bimodal distribution of proton T(2) relaxation times, which is interpreted quantitatively using a model of relaxation in fractal pores. Pore-length scales derived from the NMR data are consistent with the geometrical parameters derived from both the SEM/SANS and MP data. The combined SANS/BSEM method furnishes new microstructural information that should facilitate the study of capillary phenomena in hydrocarbon reservoir rocks and other porous solids exhibiting broad pore-size distributions.     

Vapor-liquid equilibrium predictions of refrigerant mixtures from a cubic equation of state with a G-EoS mixing rule

A modified excess Gibbs energy model which is based on the local composition concept and assigns a single energy parameter per pair of components, is incorporated into the G^E—EoS thermodynamic formalism for vapor-liquid equilibrium (VLE) calculations of simple and complex refrigerant mixtures. One temperature set of data close to 273 K is used to obtain the model's parameters, which are used to extrapolate the VLE at other temperatures and pressures. A one-parameter form of the model based on the Wong-Sandler mixing rule is presented for several simple systems. The physical significance of the model's energy parameter is connected to the preference of the mixture for like to unlike interactions. The model is applied for VLE predictions of the ternary system R14-R23-R13, and the results are compared to calculations using the 3PWS model [H. Orbey. S.I. Sandler, Ind. Eng. Chem. Res. 34 (1995) 2520–2525] and the van der Waals mixing rule. Modelling of a few complex systems with only three data points given at each temperature is shown with a two parameter version of our model on the basis of the Huron-Vidal mixing rule.     

Stimuli-Responsive Hydrogel Microcapsules Harnessing the COVID-19 Immune Response for Cancer Therapeutics

The combination of gene therapy and immunotherapy concepts, along recent advances in DNA nanotechnology, have the potential to provide important tools for cancer therapies. We present the development of stimuli-responsive microcapsules, loaded with a viral immunogenetic agent, harnessing the immune response against the Coronavirus Disease 2019, COVID-19, to selectively attack liver cancer cells (hepatoma) or recognize breast cancer or hepatoma, by expression of green fluorescence protein, GFP. The pH-responsive microcapsules, modified with DNA-tetrahedra nanostructures, increased hepatoma permeation by 50 %. Incorporation of a GFP-encoding lentivirus vector inside the tumor-targeting pH-stimulated miRNA-triggered and Alpha-fetoprotein-dictated microcapsules enables the demonstration of neoplasm selectivity, with approximately 5,000-, 8,000- and 50,000-fold more expression in the cancerous cells, respectively. The incorporation of the SARS-CoV-2 spike protein in the gene vector promotes specific recognition of the immune-evading hepatoma by the COVID-19-analogous immune response, which leads to cytotoxic and inflammatory activity, mediated by serum components taken from vaccinated or recovered COVID-19 patients, resulting in effective elimination of the hepatoma (>85 % yield).     

Manufacturing of agarose-based chromatographic adsorbents--effect of ionic strength and cooling conditions on particle structure and mechanical strength

The effect of ionic strength of agarose solution and quenching temperature of the emulsion on the structure and mechanical strength of agarose-based chromatographic adsorbents was investigated. Solutions of agarose containing different amounts of NaCl were emulsified at elevated temperature in mineral oil using a high-shear mixer. The hot emulsion was quenched at different temperatures leading to the gelation of agarose and formation of soft particles. Analysis of Atomic Force Microscopy (AFM) images of particle surfaces shows that pore size of particles increases with ionic strength and/or high quenching temperature. Additionally it has been found that the compressive strength of particles measured by micromanipulation also increases with ionic strength of the emulsion and/or high quenching temperature but these two parameters have no significant effect on the resulting particle size and particle size distribution. Results from both characterization methods were compared with Sepharose 4B, a commercial agarose-based adsorbent. This is the first report examining the effect of ionic strength and cooling conditions on the microstructure of micron-sized agarose beads for bioseparation.     

Conformational changes of the S2YZ* intermediate of the S2 to S3 transition in photosystem II

The paper extends earlier studies on the S(2)Y(Z)* intermediate that is trapped by illumination in the temperature range 77 K to 190 K of untreated samples poised in the S(2)...Q(A) state. X-band EPR experiments on untreated and glycerol (50% v/v) treated samples at 10 K indicate that the intermediate consists of two components. A wide one with a splitting of ca 170 G, and a narrow one characterized by a splitting of ca 120 G (untreated), or 124 G (glycerol-treated samples). Lower temperatures of illumination in the above temperature range favor the wide component, which at 10 K decays faster than the narrow one. Re-illumination at 10 K after decay of the signal trapped at 77-190 K induces only the narrow component. Rapid scan experiments in the temperature range 77-190 K reveal high resolution spectra of the isolated tyz Z* radical and no evidence of alternative radicals. The two split signals are accordingly assigned to different conformations of the S(2)Y(Z)* intermediate A point-dipole simulation of the spectra yields "effective distances" between the spin densities of Y(Z)* and the Mn(4)Ca center of 5.7 ? for the wide and 6.4 ? for the narrow component. The results are discussed on the basis of a molecular model assuming two sequential proton transfers during oxidation of tyr Z. The wide component is assigned to a transient S(2)Y(Z)* conformation, that forms during the primary proton transfer.     

Information security trade-offs and optimal patching policies

We develop and simulate a basic mathematical model of the costly deployment of software patches in the presence of trade-offs between confidentiality and availability. The model incorporates representations of the key aspects of the system architecture, the managers’ preferences, and the stochastic nature of the threat environment. Using the model, we compute the optimal frequencies for regular and irregular patching, for both networks and clients, for two example types of organization, military and financial. Such examples are characterized by their constellations of parameters. Military organizations, being relatively less cost-sensitive, tend to apply network patches upon their arrival. The relatively high cost of applying irregular client patches leads both types of organization to avoid deployment upon arrival.     

Lateral-torsional buckling of simply supported beams under uniform bending and axial tensile force

In this paper, the effect of a centrally applied external axial tensile load on the lateral-torsional buckling resistance of simply supported I-beams under uniform bending acting in the plane of maximum rigidity is studied. A linear and a nonlinear analysis are performed. Following the linear analysis, an expression for the critical moment of lateral-torsional buckling is presented in which the influence of the axial tensile force is included. There is an upper limit of this force over which the equilibrium in the deformed state is not possible. In the nonlinear analysis, the nature of the critical state is studied, considering the initial part of the post-buckling path. It is concluded that this critical state is associated with a stable symmetrical bifurcation point. Nevertheless, the post-buckling path is very shallow; therefore, the beam cannot exhibit practically post-buckling strength. The paper is supplemented by a representative example.     

Linear and Non-Linear Inserts for Genuinely Wideband Continuous Frequency Tunable Coaxial Gyrotron Cavities

We consider two continuous frequency tunable CW coaxial gyrotron oscillators, one 330 GHz with 3 GHz bandwidth and output power 50 – 400 W for scientific applications and one 30 GHz with 0.4 GHz bandwidth and output power 40 – 140 kW for industrial applications. The continuous tuning of both gyrotrons is achieved by moving the linearly tapered inner conductor in the axial direction in combination with the proper adjustment of the operating magnetic field. We consider also a non-linear tapering, which makes it possible to reduce the length of the insert and to improve efficiency of the device.