Modulation of the enzymatic activity of papain by interdomain residues remote from the active site

The two main catalytic residues Cys25 and Hisl59 of the monomericcysteine protease papain are located on different walls of acleft formed by two domains. This topology suggests a possiblerelationship between relative domain organization and catalyticmechanism. The effect on enzymatic parameters of structuralmodifications at various locations of the twodomain interfaceof papain was examined by individual or double replacementsby Ala of pairs of interacting residues. Most modificationshad no effect on enzyme activity. However, the enzyme's substrateturnover (k_cat) decreased following simultaneous alterationof the two most conserved residues, forming an apolar contactlocated 15 Å away from the active site. The pH activityprofile of the double mutant was unchanged, indicating a conservedionization state of the active site thiolate-imidazolium ionpair. This state is strongly dependent on the distance separatingthe two residues, thus suggesting that the active site geometryhas not been significantly altered. Efficient enzymatic activityin papain requires more than a correct active site geometryand is influenced by domain packing properties in a region remotefrom the active site.     

European medical schools and tobacco

Following a survey in 19 European countries of the habits, attitudes and knowledge of medical students regarding tobacco, World Health Organisation European Office and the International Union against Tuberculosis and Lung Disease jointly circulated to the Deans of all European medical schools a summary of the results, including figures for mortality for smoking-related diseases in their countries and a brief questionnaire concerning faculty action on the tobacco problem. The response rate was just over 50%, higher in Northern Europe (66%) than in Southern (35%) or Eastern (38%). Only 8% of faculties had a specific teaching module on tobacco. In most it was either systematically (35%) or unsystematically (55%) integrated in other teaching. Teaching hospitals, teaching areas and faculty meetings were said to be smokefree by over 90%; figures were lower for other areas. Seventy-seven per cent of Deans intended to discuss our approach with their teaching staff; 72% gave the name of a staff member with a particular tobacco interest.     

The problem of correction for ohmic potential drop in linear potential sweep experiments and the derivation of s0 values for electrode surface processes

Rate constants or exchange current densities of electrode surface processes involving adatom arrays are conveniently evaluated by determining that sweep rate, s₀ (the reversibility parameter), in a linear potential sweep (LPS) experiment, below which the process just remains kinetically reversible, ie its overpotential is sensibly zero. Transition to irreversibility is characterized by peak potentials, E_p, becoming linear in the log of the sweep rate, s, following a region of independence of s for < s₀. A suitable extrapolation procedure enables s₀ to be evaluated. However, if s₀ is large and/or the resistivity of the solution is appreciable, the IR_u drop associated with uncompensated resistance in the measurement system can be comparable with the increase of E_p with log s, when s > s₀, rendering evaluation of s₀ inaccurate. While compensation or empirical correction for this may be made, it is desirable that the nature of the IR_u effect of the LPS I vs E profiles be understood in a more fundamental way. It is the purpose of this communication to provide such a treatment of this effect through evaluation of the actual time-dependent potential that becomes applied to the electrode, and to propose criteria based on the product of s₀, R_u and the reaction pseudocapacitance, C_φ for indicating the anticipated extent of the IR_u effect in the evaluation of s₀. While the transition in the E_p vs log s plot may be due to IR_u effects as well as to kinetic irreversibility, when the former are appreciable, it is shown that the corresponding transition in the value of C_φ with increasing log s can usually allow spurious IR_u and significant irreversibility effects to be distinguished.     

Ontology-based feature mapping and verification between CAD systems

Data interoperability between computer-aided design (CAD) systems remains a major obstacle in the information integration and exchange in a collaborative engineering environment. The use of CAD data exchange standards causes the loss of design intent such as construction history, features, parameters, and constraints, whereas existing research on feature-based data exchange only focuses on class-level feature definitions and does not support instance-level verification, which causes ambiguity in data exchange. In this paper, a hybrid ontology approach is proposed to allow for the full exchange of both feature definition semantics and geometric construction data. A shared base ontology is used to convey the most fundamental elements of CAD systems for geometry and topology, which is to both maximize flexibility and minimize information loss. A three-branch hybrid CAD feature model that includes feature operation information at the boundary representation level is constructed. Instance-level feature information in the form of the base ontology is then translated to local ontologies of individual CAD systems during the rule-based mapping and verification process. A combination of the Ontology Web Language (OWL) and Semantic Web Rule Language (SWRL) is used to represent feature classes and properties and automatically classify them by a reasoner in the target system, which requires no knowledge about the source system.     

Behavior of Boron in Molten Aluminum and its Grain Refinement Mechanism

The mechanism of heterogeneous grain refining of aluminum by ultrafine elemental boron particles was investigated. In order to facilitate the observation of the boron-aluminum interface, a boron filament was introduced in a melt at 1013 K (740 °C) containing different levels of Ti. The Al/B interface was studied using transmission electron microscopy and different phases were identified using the electron diffraction method. The experimental results showed that boron is dissolved in pure aluminum while its dissolution is inhibited in presence of titanium solute. A thin layer of TiB₂ formed at the surface of boron thickens with residence time in the melt. The mechanisms by which aluminum is crystallized on boron are discussed.     

Oligosaccharide model of the vascular endothelial glycocalyx in physiological flow

Experiments have consistently revealed the pivotal role of the endothelial glycocalyx layer in vasoregulation and the layer’s contribution to mechanotransduction pathways. However, the exact mechanism by which the glycocalyx mediates fluid shear stress remains elusive. This study employs atomic-scale molecular simulations with the aim of investigating the conformational and orientation properties of highly flexible oligosaccharide components of the glycocalyx and their suitability as transduction molecules under hydrodynamic loading. Fluid flow was shown to have nearly no effect on the conformation populations explored by the oligosaccharide, in comparison with static (diffusion) conditions. However, the glycan exhibited a significant orientation change, when compared to simple diffusion, aligning itself with the flow direction. It is the tethered end of the glycan, an asparagine amino acid, which experienced conformational changes as a result of this flow-induced bias. Our results suggest that shear flow through the layer can have an impact on the conformational properties of saccharide-decorated transmembrane proteins, thus acting as a mechanosensor.     

Role of end-groups and catalyst in polyester cyclodepolymerization and cycle-chain equilibria

The influence of polyesters end-groups on cyclic oligoester formation is investigated using a series of hydroxy-, carboxy- and methylester-terminated aliphatic polyesters, in the presence of various ester interchange catalysts. The presence of hydroxy end-groups is the preponderant factor on cyclodepolymerization kinetics. This indicates that the main reaction is the intramolecular hydroxy–ester interchange reaction between hydroxy end-groups and ester functions in the chain. Carboxy-ester and ester–ester interchanges play a minor role, as the cycle-chain equilibrium is reached only very slowly when carboxy- or ester-terminated polyesters are reacted. High temperature and the presence of tin catalysts are also favorable factors, while, as expected, dilution shifts the equilibrium toward the formation of high yields of cyclic oligoesters. A mechanism is proposed, based on the reverse of the “coordination-insertion” mechanism established for the ring-opening polymerization of lactones.     

Detection and analysis of the microdistribution of uranium in the gills of freshwater Corbicula fluminea by SIMS technique

The microdistribution of uranium in the gills of freshwater bivalve Corbicula fluminea following chronic direct exposure to this radioelement has been investigated using the SIMS technique. Different exposure levels and exposure durations have been studied. The SIMS mass spectra and ²³⁸U⁺ ion images produced with a SIMS CAMECA 4F-E7 show an U accumulation with the lower aqueous U concentration (20 μg/L) and the influence of the exposure levels on the bioaccumulation capacities. Furthermore, the ionic images display a heterogeneous distribution of uranium within the gill structure whatever the exposure conditions are. This study, in keeping with the ENVIRHOM French research program, was led to the conclusion that ion microscopy is an appropriate analytical method for trace elements and can give elemental cartography in a biological tissue section.     

Experimental investigation and biomechanical analysis of lower limb movements for clutch pedal operation

Lower limb movements for clutch-pedal operations were investigated and the influence of four parameters (seat height, pedal travel, pedal travel inclination, pedal resistance) was studied using a multi-adjustable experimental seat. Fifteen subjects participated in the experiment: five short females, five average height males and five tall males. A biomechanical model has been proposed to explain how pedal force direction could be controlled. The experimental observations show that the lower limb movement of clutch pedal operation is mainly guided by the geometric constraints imposed by the task and its environment, especially during the depression phase. The results support the hypothesis that movements obey the principle of minimum work and minimum discomfort. Furthermore, it seems that a functional segmentation exists between the distal joint (ankle) and the proximal joints (knee and hip), thus simplifying the control problem, which is due to the redundancy of the human body. It appears that the depression movement is controlled by proprioceptive feedback related to foot displacement and pedal force, from the fact that the deceleration duration during the depression phase increases with the pedal resistance and pedal travel. The minimum pedal resistance and pedal travel are discussed.     

Mesure de Stress Psychologique (MSP): Se sentir stressé-e.

Studied the development and validity of an instrument designed to measure stress by evaluating subjective feelings of stress without referring to "stress" or "stressors." Human subjects: 696 male and female Canadian adults, divided into 6 groups. Group I (15 Ss) were asked to provide a list of stress indicators for themselves, their spouses, and others. These indicators were used to establish the content validity of the Mesure de Stress Psychologique (MSP) ("Psychological State of Stress Measure"). Group II (98 university students) Ss were given a 95-item stress questionnaire; the results were analyzed statistically and used to select 74 items for the MSP. Group III (97 university students) Ss were given the 74-item MSP to determine the internal consistency of the instrument. Group IV (188 married couples with a primary school child) Ss were asked to answer the MSP for themselves and for their spouses. These results were analyzed statistically according to sex, family structure, and socioeconomic variables. Group V (66 adults aged 20–60 yrs) and Group VI (44 dental students) Ss were given a 53-item MSP on 2 to 4 occasions to evaluate test–retest and hypothetical-deductive validity. The results were evaluated using a multivariate analysis of variance (MANOVA). (PsycINFO Database Record (c) 2010 APA, all rights reserved)