A Study of the Action of Lysozymes on Some New Synthetic Substrates and Inhibitors

Hen egg white lysozyme has, in recent years been one of the most widely studied of enzymes, since its three-dimensional structure was determined by X-ray crystallography. From these studies, there have been proposed several mechanisms of action of the enzyme, at least three of which are possible. One object of this work was to determine which is the correct one. Despite the interest, only a handful of significant papers have appeared regarding the mechanism of action of the enzyme. This is because accurate kinetic investigation on the natural substrate is difficult or impossible, and all the synthetic substrates prepared prior to this work were very poor ones. The first object of this work was therefore to synthesise a good substrate whose hydrolysis could be followed easily. An obvious candidate was an aryl glycoside of NAG4, but there were considerable practical problems to overcome, since glycosides of NAG4 had not been previously prepared. The chromatographic separation, on a preparative scale, of the peracetates of NAG2 to NAG6 was achieved, and from these, some 2,4-dinitro, p-nitro, and 3,4-dinitrophenyl glycosides were synthesised. The increased specificity of the p-nitrophenyl glycosides and 3,4-dinitrophenyl glycosides on increasing the sugar chain length from NAG2 to NAG4 was observed , as expected. NAG4-beta-3,4 dinitrophenyl was a 250-fold better substrate for hen egg-white lysozyme than NAG2-beta-2,4 dinitrophenyl, the best synthetic substrate prepared prior to this work. NAG-beta-3,4-dinitrophenyl was less active than NAG6, and was used in unsuccessful attempts to detect a covalent intermediate in its hydrolysis. In an attempt to make even better substrates, the acetylated B -fluorides of NAG1, NAG2 and NAG4 were prepared. The former two were deacetylated, using a new deacetylation technique. These fluorides proved to have high spontaneous rates of hydrolysis. The NAG2-beta-fluoride proved to be a better substrate for lysozyme than NAG2-beta-2,4 dnp. The 2 methyl oxazoline derivative, formed by neighbouring group participation of the acetamido group, was shown to be present, by PMR during the methanolysis of NAG1-beta-fluoride. A series of inhibitors for the enzyme was studied, using NAG4-beta-3, 4-dinitrophenyl as substrate. These were the reducing sugars, NAG2 to NAG4, and their paranitrophenyl glycosides. Attempts were made to study the lactone inhibitors reported by Secemski. A comprehensive analysis of a full kinetic model of lysozyme reactions was carried out. The behaviour of many reactions was explained in terms of changes in non-productive complexes, and a distorted productive complex. Some important parameters for individual reactions were determined. NAG4-beta-3, 4 dinitrophenyl was also found to be a substrate for human milk, duck II and duck III lysozymes, and proved useful in the assay of hen-egg-white lysozymes

Analysis of Performance of Dynamic Multicast Routing Algorithms

In this paper, three new dynamic multicast routing algorithms based on the greedy tree technique are proposed; Source Optimised Tree, Topology Based Tree and Minimum Diameter Tree. A simulation analysis is presented showing various performance aspects of the algorithms, in which a comparison is made with the greedy and core based tree techniques. The effects of the tree source location on dynamic membership change are also examined. The simulations demonstrate that the Source Optimised Tree algorithm achieves a significant improvement in terms of delay and link usage when compared to the Core Based Tree, and greedy algorithm

Human resource management, Lean processes and outcomes for employees: towards a research agenda

Lean management or lean thinking is a process improvement technique that along with Six Sigma is used in an increasing range of workplaces. This special issue focuses on the use of Lean in developed countries. This increased usage reflects a growing propensity for managers to launch initiatives to upgrade the efficiency and productivity of the enterprises that they manage, usually in an attempt to enhance the cost- effectiveness of operations. This special issue of the IJHRM includes eight articles in addition to this one on various aspects of the connections between lean management, human resource management (HRM) and outcomes for employees. The present article reviews the context for the increasing popularity of lean ideas among managers. Drawing on research in a range of countries, the articles in the special issue provide interesting insights into the relationships between process improvement innovations and HRM, as well as raise further important questions for research, which enable us to suggest an agenda for future research. This includes asking: what are the differences in the ways that Lean is implemented, for example the differences that may reflect industry, regional and national variables

Managerialism and academic professional autonomy – power and resistance in the UK universities: the case of lecture capture policies before and during Covid-related shift to online learning

Research aims New Public Management (NPM) and marketisation have dramatically changed UK higher education (HE). Academic roles have been re-shaped (MacFarlane, 2012), workloads increased (Jacobs, 2004; Tight, 2010; Zucas & Malcolm, 2017) performance management has increased surveillance, with diminished professional autonomy, academic freedom and professional discretion. Institutional power has shifted from academics to managers (Deem & Brehony, 2005). New technologies contribute to this. Since the COVID-19 pandemic, lecture capture (LC) technologies although enabled teaching to go on during lockdowns, have also increased the rift between managerial and professional perspectives often at the expense of academics’ job satisfaction and job security. The aim of this research project was to explore how managerial and professional powers are negotiated during lecture capture policy development and implementation as well as the shift to online teaching. How these negotiation dynamics and wider institutional, social and economic inform and shape academic responses to changes (through compliance, adaptation or resistance), and how individual and collective responses mediate academic agency. This report focuses on reporting negotiation patterns across institutions and processes of academic resistance. Methodology A mixed-method approach was engaged in this study. In the first stage, survey data were collected from 40 University and College Union (UCU) Branch Officials, in the second stage 61 semi-structured interviews across seven institutional cases were conducted. For each institutional case, at least one UCU Branch official and at least 4 academics were interviewed. In the majority of cases, the sample included a Head of Department or Deputy. Our goal was to explore how tensions between the divergent interests of managers and academic staff become apparent, contestable, and negotiable in the context of disruptive change. Scholars have long been aware that institutional policies are mediated, implemented, and resisted by local actors (Fanghanel, 2007). The introduction of lecture capture policies, now very common across UK institutions (Ibrahim et al, 2020), and the pandemic-dictated shift to online teaching in the academic year 2020-2021 presented an opportunity to explore the dynamics of managerial and academic power dynamics. We focused on the processes of academic responses and resistance in particular at individual and collective levels. Findings and Conclusions Survey • The survey results indicated that pre-92 institutions have more stringent regulations of teaching recordings through opt-out or compulsory policies (80%) as opposed to their post-92 counterparts (36%). • The survey results highlighted that the majority of UCU Branch Officials (63%) had concerns about the LC policies as they were initially proposed, but only 40% of the Branches were able to take part in meaningful negotiations. More than 65% of the policies in the sample were either opt-out or mandatory, removing academic discretion over the recording of teaching. The stringency of the opt-out clause varied across institutions with no appanrent differences between pre and post-92 institutions. • 70% of the Branches solicited their members' views about LC policy negotiations, 13% of the Branches have registered a formal failure to agree with senior management, 5% have threatened industrial action and a third of respondents, 2.5% (1 branch only) has registered a trade dispute with management. 11% have observed processes of opposition amongst academic staff in their institution outside the union channels. The level of resistance through the union was similar across pre and post-92 universities. • A third of the institutions in the sample indicated an intent to review their existing LC policy in response to the pandemic-related changes, whilst 45% of the Branches were actively seeking changes in the existing policies since the start of the pandemic. Case studies via semi-structured interviews • Academics and union concerns with regards to LC policy and practice alongside the transition to online teaching covered areas of professional autonomy with regards to the decision to record, usage of recordings alongside Intellectual Property Rights (IP Rights), Performer’s rights (PR), Moral Rights (MR) and GDRP right as well as pedagogical concerns. Concerns were more severe in the institutions with opt-out policies and during the pandemic. These concerns were present in equal measure pre and post-92 institutions. • Data analysis identified three broad patterns of managerial and professional power relations in three categories: 1. Strong union with good union-management relations; 2. Weak or strong union branches but with poor management – union relationships. 3. Ambivalent cases: mixed union-management history with mixed managerial practices. The patterns cut across pre and post-92 institutional types. • The general patterns of power relations, previous history, and the context of the pandemic were found to shape academic responses and resistance in particular to LC policies and the changes introduced during the pandemic-related transition to online teaching. • Findings discuss processes of collectivisation of individual acts of resistance and the development of a resistance subject in one institutional context

New development: 4P recommendations for implementing change, from research in hospitals

How are hospital staff involved in process improvement initiatives such as Lean? What can we learn from Lean implementation experiences about the sustainability of such initiatives? The authors considered such questions in a study of workplace change in Australia and Canada. They found that Lean is more likely to be sustained when leaders adopted the 4P recommendations presented in this article

Implementing lean management/Six Sigma in hospitals: beyond empowerment or work intensification?

This article analyses a process improvement project based on Lean Six Sigma (LSS) techniques in the emergency department (ED) of a large Australian hospital. We consider perspectives of the clinical and managerial staff involved in the project implementation, its implications for empowerment and work intensification. We find that the project appeared to improve patient flow from the ED to the wards and to have positive implications for some staff. However, these achievements tended to be the result of senior staff using the project to leverage resources and create desirable outcomes, rather than the result of the use of LSS, in particular. We found some evidence of work intensification, but this was attributable to wider systemic issues and budget constraints, rather than being a direct consequence of the use of LSS. We argue that translating LSS from a manufacturing context into the politicised and professionalised context of healthcare changes the usual questions about empowerment or work intensification to questions about the influences of powerful stakeholders

Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate

Hen egg-white lysozyme (HEWL) was the first enzyme to have its three-dimensional structure determined by X-ray diffraction techniques(1). A catalytic mechanism, featuring a long-lived oxo-carbenium-ion intermediate, was proposed on the basis of model-building studies(2). The `Phillips' mechanism is widely held as the paradigm for the catalytic mechanism of beta -glycosidases that cleave glycosidic linkages with net retention of configuration of the anomeric centre. Studies with other retaining beta -glycosidases, however, provide strong evidence pointing to a common mechanism for these enzymes that involves a covalent glycosyl-enzyme intermediate, as previously postulated(3). Here we show, in three different cases using electrospray ionization mass spectrometry, a catalytically competent covalent glycosyl-enzyme intermediate during the catalytic cycle of HEWL. We also show the three-dimensional structure of this intermediate as determined by Xray diffraction. We formulate a general catalytic mechanism for all retaining beta -glycosidases that includes substrate distortion, formation of a covalent intermediate, and the electrophilic migration of C1 along the reaction coordinate

Engaging professionals in sustainable workplace innovation: Medical doctors and institutional Work

This paper investigates the role of medical professionals in the success and longevity of the implementation of workplace innovation and organizational change in the Accident and Emergency (A&E) Departments of two large public hospitals, in Australia and Canada, during the introduction of process improvement using Lean Management (LM) methodologies. We ask why and how doctors resist, influence or enable LM initiatives in healthcare. Using a qualitative methodology, we contribute to institutional work theory by unpacking the complex forms of boundary and practice work undertaken by key actors who effectively use their professional status and power to enable practice changes to be embedded. Our findings lend support to the importance of the involvement and ownership of senior doctors in the design, introduction and implementation of successful workplace innovation and organizational change. Senior doctors use their professional expertise, positional and political power at the industry, organization and workplace levels to influence strategically the use of resources designated for workplace innovation to improve efficiencies, quality of patient care and maintain their dominance. The significant organizational change achieved reflected the ownership and leadership of the workplace innovation by senior doctors in ‘hybrid roles’ who captured the rhetoric and minimized adversarialism among key stakeholders

Process redesign for time-based emergency admission targets

Purpose: Hospitals have used process redesign to increase the efficiency of the emergency department (ED) to cope with increasing demand. While there are published studies suggesting a positive outcome, recent reviews have reported that it is difficult to conclude that these approaches are effective as a result of substandard research methodology. The purpose of this paper is to explore the perceptions of hospital staff on the impact of a process redesign initiative on quality of care. Design/methodology/approach: A retrospective qualitative case study examining a Lean Six Sigma (LSS) initiative in a large metropolitan hospital from 2009 to 2010. Non-probability sampling identified interview subjects who, through their participation in the redesign initiative, had a detailed understanding of the implementation and outcomes of the initiative. Between April 2012 and January 2013 26 in-depth semi-structured interviews were conducted and analysed with thematic content analysis. Findings: There were four important findings. First, when asked to comment on the impact of the LSS implementation, without prompting the staff spoke of quality of care. Second, there was little agreement among the participants as to whether the project had been successful. Third, despite the recognition of the need for a coordinated effort across the hospital to improve ED access, the redesign process was not successful in reducing existing divides among clinicians and among managers and clinicians. Finally, staff expressed tension between production processes to move patients more quickly and their duty of care to their patients as individuals. Originality/value: One of the first studies to explore the impact of process redesign through in-depth interviews with participating staff, this study adds further evidence that organisation implementing process redesign must ensure the supporting management practices are in place

The improvement of renal survival with steroid pulse therapy in IgA nephropathy

Background. The benefits of steroid therapy in immunoglobulin A nephropathy (IgAN) have not been established