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

Molecular and Metabolic Regulation of Immunosuppression in Metastatic Pancreatic Ductal Adenocarcinoma

Immunosuppression is a hallmark of pancreatic ductal adenocarcinoma (PDAC), contributing to early metastasis and poor patient survival. Compared to the localized tumors, current standard-of-care therapies have failed to improve the survival of patients with metastatic PDAC, that necessecitates exploration of novel therapeutic approaches. While immunotherapies such as immune checkpoint blockade (ICB) and therapeutic vaccines have emerged as promising treatment modalities in certain cancers, limited responses have been achieved in PDAC. Therefore, specific mechanisms regulating the poor response to immunotherapy must be explored. The immunosuppressive microenvironment driven by oncogenic mutations, tumor secretome, non-coding RNAs, and tumor microbiome persists throughout PDAC progression, allowing neoplastic cells to grow locally and metastasize distantly. The metastatic cells escaping the host immune surveillance are unique in molecular, immunological, and metabolic characteristics. Following chemokine and exosomal guidance, these cells metastasize to the organ-specific pre-metastatic niches (PMNs) constituted by local resident cells, stromal fibroblasts, and suppressive immune cells, such as the metastasis-associated macrophages, neutrophils, and myeloid-derived suppressor cells. The metastatic immune microenvironment differs from primary tumors in stromal and immune cell composition, functionality, and metabolism. Thus far, multiple molecular and metabolic pathways, distinct from primary tumors, have been identified that dampen immune effector functions, confounding the immunotherapy response in metastatic PDAC. This review describes major immunoregulatory pathways that contribute to the metastatic progression and limit immunotherapy outcomes in PDAC. Overall, we highlight the therapeutic vulnerabilities attributable to immunosuppressive factors and discuss whether targeting these molecular and immunological hot spots could improve the outcomes of PDAC immunotherapies

In vitro and in vivo anti-snake venom (Daboia russelli) studies on various leaf extracts of Acalypha indica Linn

The study aims to examine the Daboia russelli venom neutralization potential of the various leaf extracts of Acalypha indica (Euphorbiaceae) by in vitro and in vivo antisnake venom studies. In vitro HRBC membrane stabilization properties of these extracts at concentrations ranging from 2-400 μg/ml revealed inhibition of haemolysis induced by Russell’s viper venom, in a concentration dependent manner. The neutralizing potency of different leaf extracts viz., petroleum ether, benzene, chloroform and acetone extracts of Acalypha indica prepared by successive solvent extraction at intraperitoneal dose levels of 250, 500 and 750 mg/kg revealed that the acetone extract possessed the most significant activity on venom-induced lethality.Keywords: Acalypha indica; Daboia russelli; anti-snake venom; mic

Contemporary spatial association of genetic diversity determinants in Asian Dipterocarps: a systematic review

Considering the research gaps and areas to be prioritized specifically in the forestry research sector with stress given on conservation genetics and tree improvement, we make an effort to understand the spatial patterns and identify the key determinants, which produce major effects on genetic diversity of Asian Dipterocarps. This review focuses on identifying patterns and establishing relationships between genecological parameters derived on the basis of molecular markers with factors, such as geographical range, vertical profile and IUCN categories along with recognizing research gaps pertaining to operational forestry and terrestrial ecosystems. Corresponding to 47 research papers, meta-analysis of 50 species under subfamily Dipterocarpoideae revealed significant differences in genetic parameters, namely expected heterozygosity (HE) and number of alleles per locus (NA), for most genera and factors. These parameters showed significant correlations with vertical strata (rk=-0.241; p<0.05) and altitude (rs=0.283; p<0.01). However, on the basis of co-dominant and dominant markers, the parameters exhibited contrasting results for the species’ characteristics. Further, pollen exchange and seed dispersal predominantly explained the genetic variations among the contributing factors, generally believed to be correlated with vertical strata and geographical range of the species. Conclusively, two major clusters were formed through principal component analysis (PCA), where HE and NA were the main deciding factors. Anthropogenic interferences, viz. forest fragmentation and deforestation found to be subsidising major impacts, which increase inbreeding and genetic drift, causing the loss of rare alleles and consequently, decreasing genetic variation. The study emphasizes the importance of genecological conservation and access to diverse genetic resources information, which will ensure global forest conservation and climate change mitigation network for sustainable development

Quantifying Serum miRNA using DNA-Gold Nanoparticles: A Modern Approach to Diagnosing Pancreatic Cancer

Pancreatic Cancer (PC) is the third leading cause of cancer-related mortality in America with nearly 50,000 deaths annually. Furthermore, PC’s low 5-year survival rate, 11% overall, is highly dependent on the stage during which it is diagnosed and treated. When confined to the pancreas, the 5-year survival rate has been shown to reach as high as 42%, a nearly four-fold increase. Due to significant mortality differences dependent on PC stage, there is an utmost clinical need to diagnose PC as early as possible to maximize the chance of favorable patient outcomes. Most PC diagnostic methods currently involve imaging techniques including x-rays, CT, MRI, US, PET, ERCP. Issues with these techniques include levels of discomfort for the patient and higher costs and commitment to diagnose PC. For this reason, noninvasive diagnostic tests, such as CA 19-9 and CEA antigen blood tests are widely used to better inform patient outcomes. Current blood tests struggle to show appropriate specificity or sensitivity to reliably diagnose PC, including the limited ability to discriminate between benign and malignant tumors. Lacking validity may lead to patients over or under-investing in PC treatment. In comparison to blood antigens, microRNA (miRNA) is a biomarker that can be much more capable of diagnosing PC. The miRNAs consist of strands of around 20 base pairs in length that are transcribed in the body for gene regulation, controlling the expression of over half of our total genes. Aberrant expression of miRNAs are associated with PC. Current diagnostic tests that utilize miRNA biomarkers (e.g., microarray, qPCR) lack the sensitivity and limit of detection (LOD) required to assay normal versus aberrant miRNA levels since they are designed to detect longer nucleotide chains. Current methods are also cumbersome to use as they require extreme precaution and resources to collect data and avoid contamination. We propose new nanoparticle-based DNA-AuNP technology that will run a real time in situ assay of a patient’s serum sample to more reliably inform PC diagnosis early on.https://digitalcommons.unmc.edu/surp2022/1010/thumbnail.jp

Emerging trends for radioimmunotherapy in solid tumors.

Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of minimal residual and micrometastatic disease. As a result several modalities for localized therapy and models of minimal disease have been developed for preclinical evaluation. This review provides a brief update on the recent efforts toward improving the efficacy of RIT for solid tumors, and development of RIT strategies for minimal disease associated with solid tumors. Further, some of promising approaches to improve tumor targeting, which showed promise in the past, but have now been ignored are also discussed