Implementing the Lean Sigma Framework in an Indian SME: a case study

Lean and Six Sigma are two widely acknowledged business process improvement strategies available to organisations today for achieving dramatic results in cost, quality and time by focusing on process performance. Lately, Lean and Six Sigma practitioners are integrating the two strategies into a more powerful and effective hybrid, addressing many of the weaknesses and retaining most of the strengths of each strategy. Lean Sigma combines the variability reduction tools and techniques from Six Sigma with the waste and non-value added elimination tools and techniques from Lean Manufacturing, to generate savings to the bottom-line of an organisation. This paper proposes a Lean Sigma framework to reduce the defect occurring in the final product (automobile accessories) manufactured by a die-casting process. The proposed framework integrates Lean tools (current state map, 5S System, and Total Productive Maintenance (TPM)) within Six Sigma DMAIC methodology to enhance the bottom-line results and win customer loyalty. Implementation of the proposed framework shows dramatic improvement in the key metrics (defect per unit (DPU), process capability index, mean and standard deviation of casting density, yield, and overall equipment effectiveness (OEE)) and a substantial financial savings is generated by the organisation

The CAPCI Network: A CAncer Prostate Consortium of India for Conducting Next-Generation Genomic Sequencing Studies

The CAncer Prostate Consortium of India (CAPCI) was established in September 2020 by a group of researchers and clinicians interested in identifying inherited and somatic risk factors that are related to theonset of prostate cancer (PCa). The consortium aims to improve the patient care and treatment in India byexploring and expanding the utility of genomic repositories associated with PCa. These aims are reached by advancing discovery in genome science particular to Indian phenotypes, translating scientific discoveries to improved standard of care. One of the impending goals of the consortium is to combine the data from the west and other sub-population ancestries, and identify common and exclusive risk profiles associated with PCa in Indian scenarios. These findings would additionally allow us to validate in experimental settings to explore the molecular mechanisms underlying pathogenesis of PCa besides understanding new personalized therapeutic regimens

Monoclonal Antibodies Recognizing the Non-Tandem Repeat Regions of the Human Mucin MUC4 in Pancreatic Cancer

The MUC4 mucin is a high molecular weight, membrane-bound, and highly glycosylated protein. It is a multi-domain protein that is putatively cleaved into a large mucin-like subunit (MUC4α) and a C-terminal growth-factor like subunit (MUC4β). MUC4 plays critical roles in physiological and pathological conditions and is aberrantly overexpressed in several cancers, including those of the pancreas, cervix, breast and lung. It is also a potential biomarker for the diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays diverse functional roles in cancer initiation and progression as evident from its involvement in oncogenic transformation, proliferation, inhibition of apoptosis, motility and invasion, and resistance to chemotherapy in human cancer cells. We have previously generated a monoclonal antibody 8G7, which is directed against the TR region of MUC4, and has been extensively used to study the expression of MUC4 in several malignancies. Here, we describe the generation of anti-MUC4 antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S-transferase (GST)-fused MUC4α fragments, both upstream (MUC4α-N-Ter) and downstream (MUC4α-C-Ter) of the TR domain, were used as immunogens to immunize BALB/c mice. Following cell fusion, hybridomas were screened using the aforementioned recombinant proteins ad lysates from human pancreatic cell lines. Three anti MUC4α-N-Ter and one anti-MUC4α-C-Ter antibodies were characterized by several inmmunoassays including enzyme-linked immunosorbent assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The antibodies also reacted with the MUC4 in human pancreatic tumor sections in immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will serve as important reagents to study the structure-function relationship of MUC4 domains and for the development of MUC4-based diagnostics and therapeutics

Potentials of Plasma NGAL and MIC-1 as Biomarker(s) in the Diagnosis of Lethal Pancreatic Cancer

Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91) and compared it with those in healthy control (HC) individuals (n = 24) and patients with chronic pancreatitis (CP, n = 23). The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD) plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2), 219.2 U/mL (7.8) and 4.5 ng/mL (4.1), respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81%) but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively). For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively). CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2) pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml). Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029). Overall, MIC-1 in combination with CA19-9 improved the diagnostic accuracy of differentiating PC from CP and HCs

Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux by the Plasmodium falciparum Chloroquine Resistance Transporter

Plasmodium falciparum multidrug resistance constitutes a major obstacle to the global malaria elimination campaign. Specific mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) mediate resistance to the 4-aminoquinoline drug chloroquine and impact parasite susceptibility to several partner agents used in current artemisinin-based combination therapies, including amodiaquine. By examining gene-edited parasites, we report that the ability of the wide-spread Dd2 PfCRT isoform to mediate chloroquine and amodiaquine resistance is substantially reduced by the addition of the PfCRT L272F mutation, which arose under blasticidin selection. We also provide evidence that L272F confers a significant fitness cost to asexual blood stage parasites. Studies with amino acid-restricted media identify this mutant as a methionine auxotroph. Metabolomic analysis also reveals an accumulation of short, hemoglobin-derived peptides in the Dd2 + L272F and Dd2 isoforms, compared with parasites expressing wild-type PfCRT. Physiologic studies with the ionophores monensin and nigericin support an impact of PfCRT isoforms on Ca2+ release, with substantially reduced Ca2+ levels observed in Dd2 + L272F parasites. Our data reveal a central role for PfCRT in regulating hemoglobin catabolism, amino acid availability, and ionic balance in P. falciparum, in addition to its role in determining parasite susceptibility to heme-binding 4-aminoquinoline drugs

Synthesis and characterisation of triethanolaminates of titanium and zirconium

568-572Equimolar reactions of Ti(OPr-i)4 or Zr(OPr-i)4.i-PrOH with triethanolamine (teaH3) in benzene yield the derivatives [(i-PrO)M {(OCH2CH2)3N}] (M = Ti or Zr). The reactions of these compounds with a variety of chelating compounds (LLH) such as alkoxyethanols, N-methylaminoalcohol and acetylacetone yield new homometallic complexes of the general formula [(L-L)M(tea)]. All of these products have been characterized by elemental analyses, molecular weight determinations and spectroscopic (IR, NMR) studies

Preparation and properties of novel heterobimetallic glycolate derivatives of titanium and zirconium

236-240Reaction in 1:3 molar ratio of titanium and zirconium isopropoxides with glycols (2,5-dimethyl hexane- 2,5-diol/2,3-dimethyl butane-2,3-diol) in benzene under refluxing conditions afford soluble aggregates of the composition [M(O-G-O)(O-G-OH)2] (M=Ti, Zr; G = (CH3)2CCH2CH2C(CH3)2 or (CH3)2CC(CH3 )2) These on treatment with isopropoxides of other metals (eg; Al, Ti, Nb and Ta) yield heterobimetallic isopropoxide-glycolate derivatives which have been characterized by elemental analyses, spectroscopic (IR, NMR (1H, 13C, 27AL)) data and molecular weight measurements