Creating a Fit Between BPR and IT Infrastructure: A Proposed Framework for Effective Implementation

As business imperatives change and new high-capability information technologies (IT) appear, organizations recognize the need to remain at the forefront of change by reengineering their business processes and implementing enabling responsive IT infrastructures. However, experience in this context indicates a lack of comprehension of essential elements and their mutual relationships that can contribute to the success of business-process change-implementation efforts. This article proposes a framework for managing IT for effective business-process redesign (BPR) implementation. After establishing BPR principles, components, and the relationship of BPR to some organizational and technological approaches, it presents the role and benefits of IT in BPR. The article then discusses in detail the core elements of the framework. Its theme is that an IT infrastructure that covers issues of BPR strategy development, IT strategic alignment, IT infrastructure development, IT sourcing, legacy systems reengineering, IS integration, and IS function competence is essential and critical for effective implementation.     

Avian epidermis contains ATPase- and Ia-positive Langerhans-like cells

Summary The occurrence of cells resembling mammalian Langerhans cells in the avian epidermis was studied by ATPase histochemistry, Ia immunoreactivity and electron microscopy. The existence of MHC class II antigen-(Ia) expressing, ATPase-positive dendritic cells, which are ultrastructurally similar to mammalian Langerhans cells except for the absence of Birbeck granules, was demonstrated. These cells may be a basic component of the immune system of birds.     

Continuation of contraception following menstrual regulation--a Bangladesh experience

The study compares the 3 years of birth control practice of 1172 women who underwent early menstrual regulation (MR) and 499 others who accepted contraceptives only (nonMR) from an urban clinic in Bangladesh. About 60% of the women in the sample were followed-up and their all-method continuation rate was analyzed by life-table technique. The 3-year overall continuation rate in the MR group (64%) did not differ from that of the nonMR group (62%). In the age groups 25 and over, the continuation rate was higher in the MR group. Among the women who did not desire any more children, the continuation rate in the MR group was significantly higher than that of the nonMR group (80% versus 68%, P0.05). Of women with parity greater than 2, the MR group had significantly higher continuation rates than the nonMR group. The MR group had higher extended use-effectiveness for IUDs, conventional contraceptives (condom and foam), injectables, and oral contraceptives than the nonMR group. These findings indicated effective contraceptive practice following MR for this urban population. Easy availability of a multimethod service after MR seemed to be important in promoting effective contraception.     

The Importance of Tryptophan B28 in H2 Relaxin for RXFP2 Binding and Activation

H2 relaxin (relaxin) is a member of the insulin–relaxin superfamily and exhibits several non-reproductive functions in addition to its well-known properties as a pregnancy hormone. Over the years, the therapeutic potential of relaxin has been examined for a number of conditions. It is currently in phase III clinical trials for the treatment of acute heart failure. The 53 amino acid peptide hormone consists of two polypeptide chains (A and B) which are cross-linked by two inter-chains and one intra-A chain disulfide bridge. Although its cognate receptor is relaxin family peptide receptor (RXFP) 1, relaxin is also able to cross-react with RXFP2, for which the native ligand is INSL3. The “RXXXRXXI” motif in the B-chain of H2 relaxin is responsible for primary binding to LRR of the RXFP1 receptor (Büllesbach and Schwabe, J Biol Chem 280:14051–14056, 2005). Previous RXFP2 receptor mutation and molecular modelling studies strongly suggest that, in addition to this motif, the Trp-B28 residue in the B-chain is responsible for H2–RXFP2 interaction. To confirm this finding, here we have mutated H2 relaxin in which Trp-B28 was replaced with alanine. The synthetic relaxin analogue was then tested on cells expressing either RXFP1 or 2 to determine the affinity and potency for the respective receptors. Our results confirm that Trp-B28 in the B-chain is crucial for binding and activating RXFP2, but not for RXFP1.     

Preliminary Structure–Function Relationship Studies on Insulin-Like Peptide 5 (INSL5)

Insulin-like peptide 5 (INSL5) is a two-chain, three-disulfide bonded member of insulin/relaxin superfamily of peptides that includes insulin, insulin-like growth factor I and II (IGFI and IGFII), insulin-like peptide 3, 4, 5 and 6 (INSL3, 4, 5 and 6), relaxin-1 (H1 relaxin), -2 (H2 relaxin) and -3 (H3 relaxin). Although it is expressed in relatively high levels in the gut, its biological function remains unclear. However, recent reports suggest a significant orexigenic action and a role in the regulation of insulin secretion and β-cell homeostasis, which implies that both agonists and antagonists of the peptide may have significant therapeutic applications. Modern solid phase synthesis techniques together with regioselective disulfide bond formation were employed for a preliminary structure–function relationship study of mouse INSL5. Two point mutated analogues, mouse INSL5 A-B(R24A, W25A) and mouse INSL5 A-B(K6A, R14A, Y18A) were chemically prepared, where the residues in the B-chain that may be involved in receptor activation and affinity binding, were respectively mutated. Synthetic mouse INSL5 A-B(R24A, W25A) analogue was inactive on RXFP4, the native receptor for INSL5, suggesting Arg^B24 and Trp^B25 are probably directly involved in INSL5 receptor activation. Mouse INSL5 A-B(K6A, R14A, Y18A) analogue had both decreased affinity and potency on RXFP4 (pIC₅₀ 7.7 ± 0.2, pEC₅₀ 7.87 ± 0.18) which indicated that one or more of these residues are critical for the binding to the receptor.     

Computational prediction and experimental validation of the activator function of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone on pancreatic and hepatic hexokinase

Abstract

This study identifies and validates hexokinase type 4 (HK4), an isozyme of hexokinase in the liver and pancreas, as an important target of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (βdGT), a xanthone glucoside suggested to have antidiabetic property. In the study, we applied the computational pipeline of molecular docking followed by the molecular dynamics simulations to shortlist potential βdGT protein targets. The analysis of protein dynamics and the binding free energy (ΔG) led us to the identification of HK4 as a key βdGT target, whereby the binding mode and domain dynamics suggested the activator function of βdGT. βdGT bound to the allosteric site of the isozyme ～13?Å away from the substrate (glucose)-binding site. The binding free energy of the ligand-protein complex was energetically feasible (ΔG, –41.61?kcal/mol) and the cleft angle deviation between the two (small and large) domains of HK4 revealed differential HK4 dynamics in response to βdGT binding. 3D structure analysis of the isozyme-ligand complex highlighted the role of Arg63, Glu67 and Lys458 in ligand stabilization and hydrophobic interactions mediated by Tyr214 and Met235. Experimental validation of the results of computational analysis confirmed the activator function of βdGT on HK4. The study has implication in diabetes as βdGT may be used to lower the blood glucose level by activating hepatic and pancreatic hexokinase without the risk of hypoglycemia.

Communicated by Ramaswamy H. Sarma     

In vitro nemato-toxic potential of some leaf extracts on Juvenile mortality of Meloidogyne incognita race-3

Abstract

Aqueous leaf extracts of four commonly growing weeds namely Ageratum conyzoides, Elephantopus scaber, Lantana camara and Xanthium strumarium were used to evaluate their nematicidal activity on second stage juvenile of Meloidogyne incognita race-3. The juveniles were exposed to various concentration of leaf extract namely 250, 500, 1000 and 2000?ppm for 12, 24 and 48?h, respectively. All leaf extracts showed the nematicidal property in concentration and time-dependent manner. The maximum juvenile mortality was recorded in E. scaber throughout the incubation period followed by X. strumarium, L. camara and A. conyzoides. The regression and correlation of regression revealed the best concentration-dependent effect of aqueous leaf extracts on nematode mortality in E. scaber (R²?=?.751) followed by X. strumarium (R²?=?.749), A. conyzoides (R²?=?.687) and L. camara (R²?=?.756). Aqueous leaves extracts of these aforementioned weeds showed nematicidal properties, therefore, may be used as a key component of integrated disease management programme.     

Laser Doppler Flare Imaging and Quantitative Thermal Thresholds Testing Performance in Small and Mixed Fiber Neuropathies

IntroductionSmall fiber neuropathy might be a part of typical mixed small and large fiber neuropathy, or a distinct entity, affecting exclusively small nerve fibers.ObjectivesExplore the utility of small nerve fiber testing in patients with clinical presentation suggesting small fiber neuropathy, with and without evidence for concomitant large fiber neuropathy.MethodsPatients attending the neuromuscular clinic from 2012 to 2015 with a clinical presentation suggesting small nerve fiber impairment, who had Laser Doppler flare imaging (LDI_Flare) and quantitative thermal testing (QTT) were evaluated for this study. Patients with clinical or electrophysiological evidence for concomitant large fiber neuropathy were not excluded.ResultsThe sensitivities of LDI_Flare, cooling and heat threshold testing were 64%, 36%, and 0% respectively for clinically highly suggestive small fiber neuropathy, 64%, 56%, and 19% respectively for mixed fiber neuropathy, and 86%, 79%, and 29% respectively for diabetic mixed fiber neuropathy.DiscussionLDI_Flare and cooling thresholds testing are non-invasive small nerve fiber testing modalities, with moderate performance in patients with small and mixed fiber neuropathy, and excellent performance in diabetic mixed fiber neuropathy.