Building Ethical Business Cultures: BRIC by BRIC

As the economies of Brazil, Russia, India, and China (BRICs) continue to grow both in size and clout, and their resident multinational corporations become major players in global markets, questions pertaining to trust and integrity, and of universally shared standards for ethical business behavior become important concerns for numerous stakeholders. Whether or not managers and employees behave ethically depends on how one defines ethical behavior and applies it to an organization’s culture. We start this article by discussing attributes of ethical business behavior and cultures in each of the four BRICs countries, and then present results of our recent large scale survey-based studies, comparing managers’ and employees’ perceptions of ethical cultures in BRICs and in economically developed Western economies

Wolfram Syndrome protein, Miner1, regulates sulphydryl redox status, the unfolded protein response, and Ca2+ homeostasis.

Miner1 is a redox-active 2Fe2S cluster protein. Mutations in Miner1 result in Wolfram Syndrome, a metabolic disease associated with diabetes, blindness, deafness, and a shortened lifespan. Embryonic fibroblasts from Miner1(-/-) mice displayed ER stress and showed hallmarks of the unfolded protein response. In addition, loss of Miner1 caused a depletion of ER Ca(2+) stores, a dramatic increase in mitochondrial Ca(2+) load, increased reactive oxygen and nitrogen species, an increase in the GSSG/GSH and NAD(+)/NADH ratios, and an increase in the ADP/ATP ratio consistent with enhanced ATP utilization. Furthermore, mitochondria in fibroblasts lacking Miner1 displayed ultrastructural alterations, such as increased cristae density and punctate morphology, and an increase in O2 consumption. Treatment with the sulphydryl anti-oxidant N-acetylcysteine reversed the abnormalities in the Miner1 deficient cells, suggesting that sulphydryl reducing agents should be explored as a treatment for this rare genetic disease

Inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 2 perturbs 26S proteasome-addicted neoplastic progression

Dependence on the 26S proteasome is an Achilles' heel for triple-negative breast cancer (TNBC) and multiple myeloma (MM). The therapeutic proteasome inhibitor, bortezomib, successfully targets MM but often leads to drug-resistant disease relapse and fails in breast cancer. Here we show that a 26S proteasome-regulating kinase, DYRK2, is a therapeutic target for both MM and TNBC. Genome editing or small-molecule mediated inhibition of DYRK2 significantly reduces 26S proteasome activity, bypasses bortezomib resistance, and dramatically delays in vivo tumor growth in MM and TNBC thereby promoting survival. We further characterized the ability of LDN192960, a potent and selective DYRK2-inhibitor, to alleviate tumor burden in vivo. The drug docks into the active site of DYRK2 and partially inhibits all 3 core peptidase activities of the proteasome. Our results suggest that targeting 26S proteasome regulators will pave the way for therapeutic strategies in MM and TNBC

Comment on "How green is blue hydrogen?"

This paper is written in response to the paper “How green is blue hydrogen?” by R. W. Howarth and M. Z. Jacobson. It aims at highlighting and discussing the method and assumptions of that paper, and thereby providing a more balanced perspective on blue hydrogen, which is in line with current best available practices and future plant specifications aiming at low CO2 emissions. More specifically, in this paper, we show that: (i) the simplified method that Howarth and Jacobson used to compute the energy balance of blue hydrogen plants leads to significant overestimation of CO2 emissions and natural gas (NG) consumption and (ii) the assumed methane leakage rate is at the high end of the estimated emissions from current NG production in the United States and cannot be considered representative of all-NG and blue hydrogen value chains globally. By starting from the detailed and rigorously calculated mass and energy balances of two blue hydrogen plants in the literature, we show the impact that methane leakage rate has on the equivalent CO2 emissions of blue hydrogen. On the basis of our analysis, we show that it is possible for blue hydrogen to have significantly lower equivalent CO2 emissions than the direct use of NG, provided that hydrogen production processes and CO2 capture technologies are implemented that ensure a high CO2 capture rate, preferably above 90%, and a low-emission NG supply chain

Gastric emptying following Finney pyloroplasty and vagotomy

Gastric emptying was evaluated in a series of unanesthetized dogs in the intact state, following Finney pyloroplasty, and with the addition of vagotomy. Sodium chromate labeled test meals of glucose, trisodium citrate, and trisodium citrate-fat were used. Finney pyloroplasty resulted in a trend for delayed emptying of fat from the stomach. The trisodium citrate test meal increased the levels of gastric secretion after pyloroplasty.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44373/1/10620_2005_Article_BF02239291.pd

Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain

Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the “flow index” (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation

A Semantic Web Management Model for Integrative Biomedical Informatics

Data, data everywhere. The diversity and magnitude of the data generated in the Life Sciences defies automated articulation among complementary efforts. The additional need in this field for managing property and access permissions compounds the difficulty very significantly. This is particularly the case when the integration involves multiple domains and disciplines, even more so when it includes clinical and high throughput molecular data.The emergence of Semantic Web technologies brings the promise of meaningful interoperation between data and analysis resources. In this report we identify a core model for biomedical Knowledge Engineering applications and demonstrate how this new technology can be used to weave a management model where multiple intertwined data structures can be hosted and managed by multiple authorities in a distributed management infrastructure. Specifically, the demonstration is performed by linking data sources associated with the Lung Cancer SPORE awarded to The University of Texas MD Anderson Cancer Center at Houston and the Southwestern Medical Center at Dallas. A software prototype, available with open source at www.s3db.org, was developed and its proposed design has been made publicly available as an open source instrument for shared, distributed data management.The Semantic Web technologies have the potential to addresses the need for distributed and evolvable representations that are critical for systems Biology and translational biomedical research. As this technology is incorporated into application development we can expect that both general purpose productivity software and domain specific software installed on our personal computers will become increasingly integrated with the relevant remote resources. In this scenario, the acquisition of a new dataset should automatically trigger the delegation of its analysis

Positron emission tomography imaging and clinical progression in relation to molecular pathology in the first Pittsburgh Compound B positron emission tomography patient with Alzheimer’s disease

The accumulation of β-amyloid in the brain is an early event in Alzheimer’s disease. This study presents the first patient with Alzheimer’s disease who underwent positron emission tomography imaging with the amyloid tracer, Pittsburgh Compound B to visualize fibrillar β-amyloid in the brain. Here we relate the clinical progression, amyloid and functional brain positron emission tomography imaging with molecular neuropathological alterations at autopsy to gain new insight into the relationship between β-amyloid accumulation, inflammatory processes and the cholinergic neurotransmitter system in Alzheimer’s disease brain. The patient underwent positron emission tomography studies with 18F-fluorodeoxyglucose three times (at ages 53, 56 and 58 years) and twice with Pittsburgh Compound B (at ages 56 and 58 years), prior to death at 61 years of age. The patient showed a pronounced decline in cerebral glucose metabolism and cognition during disease progression, while Pittsburgh Compound B retention remained high and stable at follow-up. Neuropathological examination of the brain at autopsy confirmed the clinical diagnosis of pure Alzheimer’s disease. A comprehensive neuropathological investigation was performed in nine brain regions to measure the regional distribution of β-amyloid, neurofibrillary tangles and the levels of binding of 3H-nicotine and 125I-α-bungarotoxin to neuronal nicotinic acetylcholine receptor subtypes, 3H-L-deprenyl to activated astrocytes and 3H-PK11195 to microglia, as well as butyrylcholinesterase activity. Regional in vivo 11C-Pittsburgh Compound B-positron emission tomography retention positively correlated with 3H-Pittsburgh Compound B binding, total insoluble β-amyloid, and β-amyloid plaque distribution, but not with the number of neurofibrillary tangles measured at autopsy. There was a negative correlation between regional fibrillar β-amyloid and levels of 3H-nicotine binding. In addition, a positive correlation was found between regional 11C-Pittsburgh Compound B positron emission tomography retention and 3H-Pittsburgh Compound B binding with the number of glial fibrillary acidic protein immunoreactive cells, but not with 3H-L-deprenyl and 3H-PK-11195 binding. In summary, high 11C-Pittsburgh Compound B positron emission tomography retention significantly correlates with both fibrillar β-amyloid and losses of neuronal nicotinic acetylcholine receptor subtypes at autopsy, suggesting a closer involvement of β-amyloid pathology with neuronal nicotinic acetylcholine receptor subtypes than with inflammatory processes