Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease

The HIV-1 transframe region (TFR) is between the structural and functional domains of the Gag-Pol polyprotein, flanked by the nucleocapsid and the protease domains at its N and C termini, respectively. Transframe octapeptide (TFP) Phe-Leu-Arg-Glu-Asp-Leu-Ala-Phe, the N terminus of TFR, and its analogues are competitive inhibitors of the action of the mature HIV-1 protease. The smallest, most potent analogues are tripeptides: Glu-Asp-Leu and Glu-Asp-Phe with Ki values of approximately 50 and approximately 20 microM, respectively. Substitution of the acidic amino acids in the TFP by neutral amino acids and d or retro-d configurations of Glu-Asp-Leu results in an >40-fold increase in Ki. Protease inhibition by Glu-Asp-Leu is dependent on a protonated form of a group with a pKa of 3.8; unlike other inhibitors of HIV-1 protease which are highly hydrophobic, Glu-Asp-Leu is extremely soluble in water, and its binding affinity decreases with increasing NaCl concentration. However, Glu-Asp-Leu is a poor inhibitor (Ki approximately 7.5 mM) of the mammalian aspartic acid protease pepsin. X-ray crystallographic studies at pH 4.2 show that the interactions of Glu at P2 and Leu at P1 of Glu-Asp-Leu with residues of the active site of HIV-1 protease are similar to those of other product-enzyme complexes. It was not feasible to understand the interaction of intact TFP with HIV-1 protease under conditions of crystal growth due to its hydrolysis giving rise to two products. The sequence-specific, selective inhibition of the HIV-1 protease by the viral TFP suggests a role for TFP in regulating protease function during HIV-1 replication.     

Caring for dying children: nurses' experiences

Interviews with 25 nurses in this grounded theory study show that when nurses recognized that a child's death was inevitable, they struggled with both grief distress and moral distress. Their distress occurred within the context of the nurse-patient relationship. Nurses employed a range of strategies to manage their distress. Several conditions facilitated or constrained nurses' strategies, and resulted in far-reaching implications both professionally and personally.     

Annexin 1 Is a Component of eATP-Induced Cytosolic Calcium Elevation in Arabidopsis thaliana Roots

Extracellular ATP (eATP) has long been established in animals as an important signalling molecule but this is less understood in plants. The identification of Arabidopsis thaliana DORN1 (Does Not Respond to Nucleotides) as the first plant eATP receptor has shown that it is fundamental to the elevation of cytosolic free Ca²⁺ ([Ca²⁺]_cyt) as a possible second messenger. eATP causes other downstream responses such as increase in reactive oxygen species (ROS) and nitric oxide, plus changes in gene expression. The plasma membrane Ca²⁺ influx channels involved in eATP-induced [Ca²⁺]_cyt increase remain unknown at the genetic level. Arabidopsis thaliana Annexin 1 has been found to mediate ROS-activated Ca²⁺ influx in root epidermis, consistent with its operating as a transport pathway. In this study, the loss of function Annexin 1 mutant was found to have impaired [Ca²⁺]_cyt elevation in roots in response to eATP or eADP. Additionally, this annexin was implicated in modulating eATP-induced intracellular ROS accumulation in roots as well as expression of eATP-responsive genes.     

On The Measurement of Temperature in Material Removal Processes

Because it is key to understanding the performance of material removal processes and resultant workpiece quality, the measurement of temperature during material removal is done extensively. We review several widely used temperature measurement methods and show how they can be applied to temperature monitoring during material removal. Since there is little documentation on measurement uncertainties as relates to material removal, this paper outlines the physics of each method, detailing the sources and evaluation of uncertainty. Finally, using criteria critical in measuring material removal, methods are compared, and the results presented in guide-format for participants in this field of work.     

The effect of protein binding on ibuprofen adsorption to activated carbons

The potential of a range of polymer-based activated carbons to remove a non-steroidal anti-inflammatory drug ibuprofen from protein containing and protein-free solutions was studied. The adsorption capacity of five activated carbons produced from phenol-formaldehyde resin precursors (MAST Carbon Ltd) was compared to a cellulose coated activated carbon Norit RBX used in a commercial Adsorba^®300C haemoperfusion column (Gambro).Ibuprofen adsorption was studied in batch experiments over 24 h at pH=7.6 and 25 °C and adsorption equilibrium data were correlated with the Langmuir and Freundlich equations.Results showed that uncoated mesoporous MAST carbons can remove ibuprofen from model solutions both in the presence and absence of serum albumin. Ibuprofen is a highly protein-bound drug and the presence of serum albumin significantly affects the adsorption of ibuprofen by cellulose-coated microporous carbon used in Adsorba^®300C column.     

Factors influencing the photofading of commercial anthraquinone dyes in solution

The photofading of two anthraquinone dyes has been studied in aqueous solution using ultraviolet-visible absorption spectroscopy and flash photolysis. The influence of alcohol concentration, pH, atmosphere, photosensitisers and stabilisers have been examined and these lead to some important conclusions on the mechanism of dye fading. Essentially, the results indicate the photoexcited triplet state of the dye undergoes a process of either electron or hydrogen-atom abstraction depending on the nature of the environment. Other factors such as aggregation and singlet oxygen also appear to play an important role in solution photofading. The relevance of these results to photofading in a polymeric phase is discussed.     

The structure and content of programming knowledge: Disentangling training and language effects in theories of skill development

This article reviews the extensive literature emerging from studies concerned with skill acquisition and the development of knowledge representation in programming. In particular, it focuses upon theories of program comprehension that suggest programming knowledge can be described in terms of stereotypical knowledge structures that can in some way capture programming expertise independently of the programming language used and in isolation from a programmer's specific training experience. An attempt is made to demonstrate why existing views are inappropriate. On the one hand, programs are represented in terms of a variety of formal notations ranging from the quasi‐mathematical to the near textual. It is argued that different languages may lead to different forms of knowledge representation, perhaps emphasizing certain structures at the expense of others or facilitating particular strategies. On the other hand, programmers are typically taught problem‐solving techniques that suggest a strict approach to problem decomposition. Hence, it seems likely that another factor that may mediate the development of knowledge representation, and that has not received significant attention elsewhere, is related to the training experience that programmers typically encounter. In this article, recent empirical studies that have addressed these issues are reviewed, and the implications of these studies for theories of skill acquisition and for knowledge representation are discussed. In conclusion, a more extensive account of knowledge representation in programming is presented that emphasizes training effects and the role played by specific language features in the development of knowledge representation within the programming domain.     

Development and field demonstration of a hardware-compressive fiber-optic true-time-delay steering system for phased-array antennas

We describe the design, fabrication, testing, and antenna-range demonstration of a photonic wavelengthmultiplexed true-time-delay steering system for use with broadband phased-array antennas. The prototype system is based on a unique hardware-compressive architecture and can drive 16 antenna elements over the 0.35-2.1-GHz band with 6-bit angular resolution over a ±45° scan angle.