Irreversible inhibition of plasma membrane (Ca2+ + Mg2+)-ATPase and Ca2+ transport by 4-OH-2,3-trans-nonenal

4-OH-2,3-trans-nonenal (HNE), a major aldehydic lipid peroxidation product, has been shown to cause cellular toxicities and has been linked to a number of pathophysiological processes including atherogenesis. Specifically, in vitro exposure of erythrocyte plasma membrane preparations to HNE resulted in the inhibition of membrane transport function and integrity. To characterize the nature of the inhibitory effects of HNE on plasma membrane regulatory mechanisms, we investigated its effects on substrate and calmodulin (CaM) stimulation on erythrocyte Ca2+ transport and (Ca2+ + Mg2+)-ATPase activities. Concentration-effect relationship analysis in erythrocyte membrane "ghosts" and inside-out vesicles (IOVs) yielded purely noncompetitive kinetics for Ca2+, ATP, and CaM activation of (Ca2+ + Mg2+)-ATPase and Ca2+ transport. Reductions of Vmax from direct addition of 0.1 mM HNE to the assay incubation mixtures ranged from 23 to 41%. Similarly, pretreatment with HNE of both membrane ghosts and IOVs resulted in a concentration-dependent inactivation of ATPase and transport activities without changes in affinity for Ca2+, ATP, or CaM. Conversely, pretreatment of CaM itself did not impair its ability to stimulate (Ca2+ + Mg2+)-ATPase activity threefold. Moreover, HNE-pretreated membranes exhibited unaltered acetylcholinesterase activity compared to sham-pretreated membranes. Together, these results suggest that HNE may structurally, and thus irreversibly, modify one or more functionally important sites on the transport protein itself.     

Industrial Cogeneration?Insights and Observations

Industrial cogeneration competes for funds with new industrial manufacturing facilities. New manufacturing capacity or production modernization programs have historically received investment priorities over utility systems. Due to rising energy costs and higher percentages of energy-content in overall manufacturing costs, new interests are being directed to the potential for reducing costs and improving company earnings by having well-designed industrial co-generation systems. Methods and techniques for achieving the highest available returns-on-investment are presented. Equations are proivded for steam turbine topping industrial cogeneration systems which are formulated with the objective of achieving the best selection of system design parameters which have the highest possible returns-on-investment.     

Quantification of mast cells and microflora in the vaginal cul-de-sac of the brushtail possum (Trichosurus vulpecula)

Mast cells are typically associated with biological responses to intracellular parasitic or bacterial invasion in gut and pulmonary tissues. Large numbers of these cells are present in the vaginal cul-de-sac, a component of the reproductive tract in female brushtail possums (Trichosurus vulpecula). The presence of mast cells in this area may reflect microbial presence or indicate a role for mast cells in reproductive function in this marsupial. In this study, the number and spatial location of mast cells in vaginal cul-de-sac tissues at different reproductive stages was determined, and related to the presence of microflora. Vaginal cul-de-sac tissue was collected from juvenile (n = 5), lactationally anoestrous and cyclic adult brushtail possums (n = 6 per group). Oestrous cyclicity was induced by removal of pouch young and reproductive status was confirmed by laparoscopy. Tissue was collected aseptically for microbiological procedures. The fractionator and optical disector stereological methods were used to quantify mast cell populations. In all groups, microflora populations were low (< 5 x 10(5) organisms g(-1)). Mast cell density in epithelial tissue was highest in lactationally anoestrous and luteal phase brushtail possums and lowest in follicular phase animals. No correlation between the numbers of bacteria isolated and mast cell density was apparent. Gram stained tissue showed no evidence of bacterial invasion. Mast cell density was significantly lower in epithelial tissue from follicular phase animals, corroborating previous studies in which an increase in mast cell degranulation coincided with high oestrogen concentrations.     

The power of process [software processes]

Some people in the software development community think “process” is a four letter word. They think software processes are rigid, restrictive, and inefficient. They hold that the best way to run a project is to hire the best people you can, give them all the resources they ask for, and turn them loose to do what they do best. Sure, they say, there will be some amount of unproductive work is (also known as “thrashing”). After all, developers will make mistakes. But they will also be able to quickly and efficiently correct these mistakes at a cost that is less overall than the cost of processes. This point of view has intuitive appeal. At the beginning of a project, a focus on process certainly does take time away from productive work. If that trend were to continue throughout the project, it wouldn't make sense to spend much time on process. Software industry experience, however, has found that for projects that don't pay attention to establishing effective processes early are forced to slap them together late, when slapping them together takes more time and does less good. The article points out the problems caused by inattention to process, explains what happens when a project thrashes, and discusses the use of process versus creativity     

Why you should use routines...routinely

As an undergraduate computer science student, the author thought that the main reason to create new routines, instead of leaving all the code in one big routine, was to avoid duplicate code. This is undoubtedly the most popular reason for creating a routine, and it's a good one. Similar code in two routines is a warning sign. David Parnas says that if you use copy and paste while you're coding, you're probably committing a design error. Instead of copying code, move it into its own routine. Future modifications will be easier because you will need to modify the code in only one location. The code will be more reliable because you will have only one place in which to be sure that the code is correct. That is one good reason to create a routine, but it hardly makes a complete list. There are many additional reasons to create routines, and many of them are more important than avoiding duplicate code: reducing complexity; limiting effects of changes; hiding sequences; improving performance; hiding data structures; hiding global data; promoting code reuse; planning for a family of programs; improving readability; improving portability; isolating use of nonstandard language functions; and isolating complex operations     

Analysis of Immune Escape Variants from Antibody-Based Therapeutics against COVID-19: A Systematic Review

The accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID-19-convalescent plasma (CCP). While the former is mainly associated with specific single amino acid mutations at residues within the receptor-binding domain (e.g., E484K/Q, Q493R, and S494P), a few cases of immune evasion after CCP were associated with recurrent deletions within the N-terminal domain of the spike protein (e.g., ΔHV69-70, ΔLGVY141-144 and ΔAL243-244). The continuous genomic monitoring of non-responders is needed to better understand immune escape frequencies and the fitness of emerging variants.     

The cost of event-based prospective memory: Salient target events.

Evidence has begun to accumulate showing that successful performance of event-based prospective memory (PM) comes at a cost to other ongoing activities. The current study builds on previous work by examining the cost associated with PM when the target event is salient. Target salience is among the criteria for automatic retrieval of intentions according to the multiprocess view of PM. An alternative theory, the preparatory attentional and memory processes theory, argues that PM performance, including retrieval of the intent, is never automatic and successful performance always will come at a cost to other ongoing activity. The 4 experiments reported here used a salient PM target event. In addition, Experiments 3 and 4 were designed to meet the stringent criteria proposed for automatic retrieval of intentions by multiprocess theory, and, yet, in all 4 experiments, delayed intentions interfered with ongoing task performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dielectric studies of water absorption and desorption in epoxy resins: influence of cure process on behaviour

Little is known about the way in which the chemical structure of an epoxy resin influences its ability to absorb and desorb moisture. This issue is addressed in a study of dicyandiamide‐ and amine‐cured epoxy resins. The dicyandiamide‐cured material will have a significantly lower preponderance of pendant hydroxyl groups than the amine‐cured material and may exhibit different behaviour when exposed to moisture. The uptake and loss of moisture was monitored gravimetrically, using broad band dielectric, dynamic mechanical thermal analysis and thickness measurements performed as a function of time at various temperatures. A comparison of the uptake and loss profiles for the first and subsequent cycles indicated significant differences in behaviour attributed to the way in which water can plasticise the matrix. Stresses frozen into the matrix during the cure process are allowed to relax as a consequence of the water hydrating the matrix and create voids and also allow matrix densification. These processes occur during the first hydration cycle and are not reversible. Subsequent hydration and dehydration appear to be reversible after the first hydration cycle. Water in the polymer is distributed between free water which is to be found in microvoids and bound water which is attached to the polymer chain. The amine‐cured epoxy resin which contains pendant hydroxyl groups has a greater capacity for water absorption than the ether‐containing backbone of the dicyandiamide‐cured material. Copyright © 2008 Society of Chemical Industry