Analysis of transient permeation fluxes into and out of membranes for adsorption measurements

A relationship between the integrated fluxes into and out of a membrane following a positive or negative step change in feed concentration was derived. This analysis allows adsorption isotherms in the transport pathways through membranes to be determined from transient permeation responses to step concentration changes in the feed without measuring the retentate response. For Fickian diffusion through a membrane with Langmuir adsorption and zero coverage at the permeate boundary, the difference between the time-integrated flux into and flux out of the membrane is shown to be three times the time-integrated difference between the steady-state flux and the flux out. For Maxwell-Stefan diffusion, this ratio of integrated flux differences is 3 at low coverages and decreases towards 2 at saturation coverage. Mass transfer resistance at the permeate boundary increases the Fickian ratio above 3, and the ratio increases with decreasing Sherwood number. The ratio of integrated flux differences is shown to be identical to the steady-state replenishment time divided by the time lag. Thus, the ratio can be calculated directly from the steady-state concentration profile and the concentration-dependent diffusion coefficient. Surface diffusion through zeolite membranes was analyzed to demonstrate the calculation of the flux relationship for specific adsorption and diffusion models, but the method developed can be applied to membrane permeation in general.     

Incorporating a Polyethyleneglycol Linker to Enhance the Hydrophilicity of Mitochondria-Targeted Triphenylphosphonium Constructs

The targeting of bioactive molecules and probes to mitochondria can be achieved by coupling to the lipophilic triphenyl phosphonium (TPP) cation, which accumulates several hundred-fold within mitochondria in response to the mitochondrial membrane potential (Δψ_m). Typically, a simple alkane links the TPP to its “cargo”, increasing overall hydrophobicity. As it would be beneficial to enhance the water solubility of mitochondria-targeted compounds we explored the effects of replacing the alkyl linker with a polyethylene glycol (PEG). We found that the use of PEG led to compounds that were readily taken up by isolated mitochondria and by mitochondria inside cells. Within mitochondria the PEG linker greatly decreased adsorption of the TPP constructs to the matrix-facing face of the mitochondrial inner membrane. These findings will allow the distribution of mitochondria-targeted TPP compounds within mitochondria to be fine-tuned.     

A graphical approach to process synthesis and its application to steam reforming

It is common practice in chemical engineering to design processes sequentially. The type of product desired determines the choice of the feed materials that are introduced into the reactor networks. These in turn lead into the separation networks. The flows of heat and work are the final part of the sequence to be considered, with the application of heat exchanger networks, and any deficiency or excess in these flows is usually compensated for with the use of utilities. Although the ongoing research into reactor, separation, and heat exchanger optimization is of indubitable value, an aspect that is often overlooked in conventional research is the question: How do changes to one of the elements in the sequence affect the others? Most process designers do not address such matters until the next optimization of the sequence begins. The result of this sequential approach to design is that processes may contain a few very efficient units, but may also have others that are highly inefficient. A graphical technique that incorporates the flows of heat and work into the design of the process at a very early stage is proposed. The technique can be used to prepare flow sheets that represent a synthesized version of the elements that make up the complete process, rendering each component highly efficient. This new design tool uses the thermodynamic properties of enthalpy (representative of process heat requirements) and Gibbs free energy (representative of process work requirements) to develop process flow sheets that operate as close to reversibly as possible, and can be used as a foundation for more detailed refinements to achieve the best possible result. A case was described in a previous paper in which the graphical technique was applied to gasification. The application of the technique to the production of syngas by the steam reforming of natural gas is detailed. We show that the steam reforming process can be operated with increased reversibility and can actually consume carbon dioxide, thus representing a process with a carbon efficiency of greater than 100%, if the way in which all the process units interact with one another is used to utmost advantage. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3714–3729, 2013     

Structure-function studies of an engineered scaffold protein derived from Stefin A. II: Development and applications of the SQT variant

Constrained binding peptides (peptide aptamers) may serve as tools to explore protein conformations and disrupt protein-protein interactions. The quality of the protein scaffold, by which the binding peptide is constrained and presented, is of crucial importance. SQT (Stefin A Quadruple Mutant-Tracy) is our most recent development in the Stefin A-derived scaffold series. Stefin A naturally uses three surfaces to interact with its targets. SQT tolerates peptide insertions at all three positions. Peptide aptamers in the SQT scaffold can be expressed in bacterial, yeast and human cells, and displayed as a fusion to truncated pIII on phage. Peptides that bind to CDK2 can show improved binding in protein microarrays when presented by the SQT scaffold. Yeast two-hybrid libraries have been screened for binders to the POZ domain of BCL-6 and to a peptide derived from PBP2', specific to methicillin-resistant Staphylococcus aureus. Presentation of the Noxa BH3 helix by SQT allows specific interaction with Mcl-1 in human cells. Together, our results show that Stefin A-derived scaffolds, including SQT, can be used for a variety of applications in cellular and molecular biology. We will henceforth refer to Stefin A-derived engineered proteins as Scannins.     

Transient measurements of adsorption and diffusion in H-ZSM-5 membranes

A transient permeation method presented here not only determines the adsorption and diffusion properties of the pores that are the transport pathways through zeolite membranes, but nondestructively estimates the effective thickness of the membrane. Transient responses of the permeate concentration to step changes in the feed were measured on two H-ZSM-5 tubular membranes and modeled assuming Maxwell-Stefan diffusion and Langmuir adsorption. The adsorption isotherms determined from these transient measurements at 298 K of N₂ and CO₂ were nearly identical to those measured by calorimetry on H-ZSM-5 powders. The CH₄ isotherm at 298 K was similar to isotherms measured by calorimetry and gravimetric techniques on Na-ZSM-5 and silicalite powders. The similarity of the isotherms indicates that transport of these light gases occurs mainly through zeolite pores. The Maxwell-Stefan diffusion coefficients D_MS depended on concentration and were higher for higher feed partial pressures. Average D_MS values for the two membranes were 7.5, 5 and 1.5×10⁻¹⁰ m²/s for N₂, CH₄, and CO₂, respectively; these are in the same range and order as diffusion coefficients measured in zeolite crystals.     

Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET) Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

Radiolabeled antibodies (mAbs) provide efficient tools for cancer therapy. The combination of low energy β⁻-emissions (500 keV_max; 130 keV_ave) along with a γ-emission for imaging makes ¹⁷⁷Lu (T_1/2 = 6.7 day) a suitable radionuclide for radioimmunotherapy (RIT) of tumor burdens possibly too large to treat with α-particle radiation. RIT with ¹⁷⁷Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts) were treated with ¹⁷⁷Lu-trastuzumab comparatively to animals treated with a non-specific control, ¹⁷⁷Lu-HuIgG, and then to prior published results obtained using ²¹²Pb-trastuzumab, an α-particle RIT agent. ¹⁷⁷Lu-trastuzumab induced cell death via DNA double strand breaks (DSB), caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein ²¹²Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. ¹⁷⁷Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β⁻- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β⁻-particle RIT for the management of intraperitoneal disease.     

Claramines: A New Class Of Broad‐Spectrum Antimicrobial Agents With Bimodal Activity

The emergence of multidrug‐resistant bacteria and pathogens has created an urgent need for the development of new antibiotics. Herein we report our investigations into the broad‐spectrum activity of an easily prepared water‐soluble polyaminosterol compound, namely claramine A1, against both drug‐sensitive and drug‐resistant Gram‐negative and Gram‐positive bacterial strains. We also report its peculiar mechanism of action, which differs from that of all the other well‐known classes of antibiotics, toward Gram‐negative and Gram‐positive bacteria. Given their low cytotoxicity, this class of compounds based on claramine A1 could constitute an effective response to combat the emergence of multidrug‐resistant bacteria and nosocomial diseases.     

Image analysis of the porous yttria-stabilized zirconia (YSZ) structure for a lanthanum ferrite-impregnated solid oxide fuel cell (SOFC) electrode

Image analysis and quantification were performed on porous scaffolds for building SOFC cathodes using the two types of YSZ powders. The two powders (U1 and U2) showed different particle size distribution and sinterability at 1300?°C. AC impedance on symmetrical cells was used to evaluate the performance of the electrode impregnated with 35-wt.% La_0.8Sr_0.2FeO₃. For example, at 700?°C, the electrode from U2 powder shows a polarization resistance (R_p) of 0.21?Ω?cm², and series resistance (R_s) of 8.5?Ω?cm² for an YSZ electrolyte of 2-mm thickness, lower than the electrode from U1 powder (0.25?Ω?cm² for R_p and 10?Ω?cm² for R_s) does. The quantitative study on image of the sintered scaffold indicates that U2 powder is better at producing architecture of high porosity or long triple phase boundary (TPB), which is attributed as the reason for the higher performance of the LSF-impregnated electrode.     

Identification of Two Sex Pheromone Components of the Potato Aphid, Macrosiphum euphorbiae (Thomas)

Females of the potato aphid Macrosiphum euphorbiae exhibit typical calling behavior, with virgin female oviparae raising their back legs off the substrate to release sex pheromone from glands on the tibia. Airborne collections from calling oviparae were analyzed by GC and GC-MS to determine if, like the majority of aphids examined to date, they produced (1R,4aS,7S,7aR)-nepetalactol (1) and (4aS,7S,7aR)-nepetalactone (2). Both components were present and produced in ratios that varied with age from 4:1 to 2:1. The relative stereochemical configurations of these components were determined by GC-coinjection of the aphid-derived sample with synthetic standards on both HP-1 and DB-Wax GC columns. The absolute stereochemical configuration of the nepetalactol (determined from approximately 15 microg of material in an air entrainment sample) was determined as (1R,4aS,7S,7aR)-1 by derivatization of the aphid sample with (S)-(+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride (Mosher's acid chloride) to generate a diastereoisomer that was compared to synthetic samples by NMR spectroscopy and GC. In bioassays in the wind tunnel, M. euphorbiae males responded to potato plants with oviparae but not to unattacked plants or those infested with parthenogenetically reproducing apterae. In no-choice laboratory bioassays, the same level of male response was observed to virgins and to the 3:1-5:1 synthetic blends of nepetalactol (1):nepetalactone (2). However, the time taken to reach the source was significantly less to virgin females than to the synthetic pheromone blends. In all cases, males walked rather than flew to the source. Males showed lower responses to a 1:1 synthetic mixture and did not respond to either of the components when presented alone. Under field conditions, few M. euphorbiae males were captured in traps baited with different ratios of the synthetic pheromone. Possible reasons for the different responses under laboratory and field conditions are discussed.     

Harvester Ants Utilize Cuticular Hydrocarbons in Nestmate Recognition

Cuticular hydrocarbons appear to play a role in ant nestmate recognition, but few studies have tested this hypothesis experimentally with purified hydrocarbon extracts. We exposed captive colonies of the harvester ant Pogonomyrmex barbatus to small glass blocks coated with whole cuticular lipid extracts and the purified hydrocarbon portion of extracts from nestmate and nonnestmate workers. As an estimate of agonistic behavior, we measured the proportion of ants in contact with blocks that flared their mandibles. Blocks coated with cuticular extracts from nonnestmates were contacted by more workers in one of two experiments and elicited higher levels of aggression in both experiments than blocks bearing extracts from nestmates. The cuticular hydrocarbon fraction of extracts alone was sufficient to elicit agonistic behavior toward nonnestmates. The results demonstrate that harvester ants can perceive differences in cuticular hydrocarbon composition, and can use those differences in nestmate recognition.