THE PLACE OF HUMAN CONTESTABILITY IN POSITIVE MANAGEMENT

The present paper purports at analysing the place of human contestability in the field of positive management. The rationale for this paper is five-fold. First is to bestow a theoretical scaffolding of the phenomenon of ‘human contestability’ so that it can be meaningfully conceptualised and coherently understood. The scientific foundations of human contestability are explored wherein an innate human instinct ‘to compete and win’ encourages the expansion of human potential and its ultimate utilisation so that individuals, overtly or covertly, compete against each other in positive and constructive manner for gains and rewards in a highly competitive environment at work and in life. The second motivation is to emphasize that the many-sided human contestability approach is comprehensive in comparison to the traditional human-centred approaches such as human resource development, human capital, human development, capability approach, system of profound knowledge, knowledge management, and system of profound consciousness. The third motivation is to bequeath and construct the theoretical-analytical schema of multidimensionality of human contestability. The fourth motivation is to develop a conceptual model of multifarious relationships among different interconnected critical dimensions of human contestability namely bio-psycho-socioeconomic system, body capital, cognitive capital, emotional capital and resource capital. All these critical human contestability factors jointly and simultaneously contribute to the enhancement or curtailment of human contestability. The last motivation is to evaluate the place of human contestability approach in the science of positive management. The idea of human contestability is new in management science. The power of positive management, to a greater extent, is determined by the level of human contestability in an organisation. The growing rich management insights pinpoint that the applicability of human contestability principles at workplaces are good for positive management environment as well as for the satisfaction, optimism, wellbeing, engagement and happiness of employees and management. Putting an emphasis on human contestability in organisations is thus reinforcing the view that individuals are the ultimate source of value and value generation depends less on tangible resources, but rather on intangible ones, particularly body capital, cognitive intelligence, emotional wellbeing and resource capital. This paper explores the mechanisms for linking human contestability with positive management and hence creating physical attributes and abilities, creative minds, passionate hearts, and individual empowerment.

Mapping Opportunities to Increase Productivity in Coastal Bangladesh

The Ganges Basin Development Challenge (GBDC) Program of the CGIAR Challenge Program for Water and Food is focusing on improving livelihoods and increasing productivity sustainably in the coastal polder zone, and has developed and tested innovative cropping systems and water management practices suited to the local conditions.Before a new cropping system can be recommended, it is important to identify its “extrapolation domain,” which determines where it could be successful

Sequence Characterisation and Genotyping of Allelic Variants of Beta Casein Gene Establishes Native Cattle of Ladakh to be a Natural Resource for A2 Milk

Bovine milk is regarded as nature's perfect food due to presence of vital nutrients. However some peptides are generated after proteolytic digestion of β-casein that have opioid properties and may increase the risk of chronic diseases. There are 13 genetic variants of bovine beta-casein; out of these A1 and A2 are the most common in dairy cattle breeds. The A1 and A2 variants differ only at position 67, which is histidine in A1 or proline in A2 milk. Earlier published reports have indicated that A1 β casein could be responsible for several health disorders like diabetes, coronary heart disease etc. while A2 β-casein is generally considered safe for human consumption. In the present study, an effort was made to sequence characterize β casein gene and identify allelic distribution of A1A2 alleles in native cattle of Ladakh region adapted to high altitude and low oxygen condition. The data showed 2 non-synonymous variations in coding region, while 5’UTR was completely conserved. The 3’UTR showed 2 more variations in Ladakhi samples. Further, the genotyping in 85 Ladakhi cattle for A1A2 alleles revealed that in Ladakhi cattle, A2 allele is predominantly present as reported for some of the other Indian breeds. The frequency of A2 allele was 0.90 and frequency of A2A2 genotype was found to be 0.79 in Ladakhi cattle. The present data strongly indicate that local cattle of Ladakh with higher frequency of A2 allele and A2A2 genotype is natural resource for A2 milk.  Systematic efforts should be made for long term conservation and genetic improvement of this invaluable genetic resource of Ladakh

Identification of a novel quinoxaline-isoselenourea targeting the STAT3 pathway as a potential melanoma therapeutic

The prognosis for patients with metastatic melanoma remains very poor. Constitutive signal transducer and activator of transcription 3 (STAT3) activation has been correlated to metastasis, poor patient survival, larger tumor size, and acquired resistance against vemurafenib (PLX-4032), suggesting its potential as a molecular target. We recently designed a series of isoseleno- and isothio-urea derivatives of several biologically active heterocyclic scaffolds. The cytotoxic effects of lead isoseleno- and isothio-urea derivatives (compounds 1 and 3) were studied in a panel of five melanoma cell lines, including B-RAFV600E-mutant and wild-type (WT) cells. Compound 1 (IC50 range 0.8–3.8 µM) showed lower IC50 values than compound 3 (IC50 range 8.1–38.7 µM) and the mutant B-RAF specific inhibitor PLX-4032 (IC50 ranging from 0.4 to >50 µM), especially at a short treatment time (24 h). These effects were long-lasting, since melanoma cells did not recover their proliferative potential after 14 days of treatment. In addition, we confirmed that compound 1 induced cell death by apoptosis using Live-and-Dead, Annexin V, and Caspase3/7 apoptosis assays. Furthermore, compound 1 reduced the protein levels of STAT3 and its phosphorylation, as well as decreased the expression of STAT3-regulated genes involved in metastasis and survival, such as survivin and c-myc. Compound 1 also upregulated the cell cycle inhibitor p21. Docking studies further revealed the favorable binding of compound 1 with the SH2 domain of STAT3, suggesting it acts through STAT3 inhibition. Taken together, our results suggest that compound 1 induces apoptosis by means of the inhibition of the STAT3 pathway, non-specifically targeting both B-RAF-mutant and WT melanoma cells, with much higher cytotoxicity than the current therapeutic drug PLX-4032

Mucosa-associated lymphoid tissue lymphoma and concurrent adenocarcinoma of the prostate

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is a rare disease that characteristically follows an indolent course. It is believed that infection or chronic inflammation may be triggers for malignant transformation in the prostate, but it is of unknown etiology. Reports of MALT lymphomas of the prostate with other concurrent primary prostate cancers are even more limited. We present the unique case of a 67-year-old male with concurrent adenocarcinoma of the prostate and primary MALT lymphoma of the prostate. The patient was treated with standard therapy for prostate adenocarcinoma, which would also treat a primary MALT lymphoma. He has been disease-free for over one year for both his primary malignancies. This case confirms that MALT lymphoma can arise concurrently with adenocarcinoma of the prostate

Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation

According to their distinct biological functions, membrane-active peptides are generally classified as antimicrobial (AMP), cell-penetrating (CPP), or fusion peptides (FP). The former two classes are known to have some structural and physicochemical similarities, but fusogenic peptides tend to have rather different features and sequences. Nevertheless, we found that many CPPs and some AMPs exhibit a pronounced fusogenic activity, as measured by a lipid mixing assay with vesicles composed of typical eukaryotic lipids. Compared to the HIV fusion peptide (FP23) as a representative standard, all designer-made peptides showed much higher lipid-mixing activities (MSI-103, MAP, transportan, penetratin, Pep1). Native sequences, on the other hand, were less fusogenic (magainin 2, PGLa, gramicidin S), and pre-aggregated ones were inactive (alamethicin, SAP). The peptide structures were characterized by circular dichroism before and after interacting with the lipid vesicles. A striking correlation between the extent of conformational change and the respective fusion activities was found for the series of peptides investigated here. At the same time, the CD data show that lipid mixing can be triggered by any type of conformation acquired upon binding, whether α-helical, β-stranded, or other. These observations suggest that lipid vesicle fusion can simply be driven by the energy released upon membrane binding, peptide folding, and possibly further aggregation. This comparative study of AMPs, CPPs, and FPs emphasizes the multifunctional aspects of membrane-active peptides, and it suggests that the origin of a peptide (native sequence or designer-made) may be more relevant to define its functional range than any given name

Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings In 2021, there were 529 million (95% uncertainty interval [UI] 500–564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8–6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7–9·9]) and, at the regional level, in Oceania (12·3% [11·5–13·0]). Nationally, Qatar had the world’s highest age-specific prevalence of diabetes, at 76·1% (73·1–79·5) in individuals aged 75–79 years. Total diabetes prevalence—especially among older adults—primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1–96·8) of diabetes cases and 95·4% (94·9–95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5–71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5–30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22–1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1–17·6) in north Africa and the Middle East and 11·3% (10·8–11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%.Peer ReviewedPostprint (published version

Solution and molecular modeling studies on some bivalent metal complexes of higher analogues of biologically active 1,3-diaryl-4, 5, 6-pyrimidinetrione- 2-thioxo-5-oxime

1076-1081Thermodynamic proton-ligand stability constants of 1,3-diethylphenyl-4,5,6- pyrimidinetrione-2-thioxo-5-oxime (and the thermodynamic metal ligand stability constants) with some bivalent metal ions were determined by potentiometric measurements in 75% (v/v) aqueous-dioxan medium at different temperatures ranging from 25° C to 35° C. The acidity and stability constants vary according to the kind of substitution at the 1- and 3- positions of the pyrimidine ring. The order of stability constants is UO22+> Cu2+>Ni2+>Co2+ >Zn2+ >Cd2+ >Mn2+ >Mg2+. The values of Smin (χ2) have also been calculated. The thermodynamic functions for the stepwise complexation processes are calculated at 25±0.5oC. Molecular modeling studies have also been carried out on the ligand and complexes, the results of which corroborate the experimental findings