A matter of science: the Massachusetts Institute of Technology and the transformation of American management education, 1950-1964

In 1950, General Motors chairman Alfred P. Sloan, Jr. approached MIT’s leaders about establishing a business school. The result was the School of Industrial Management (SIM), founded in 1952 and renamed in 1964 the MIT Sloan School of Management. During these early years the SIM’s leaders and faculty sought to create something extraordinary: a business school housed, grounded, and inspired by an institute of engi-neering and technology. They strived to apply new scientific techniques to the nascent field of industrial management and to American industrial firms that increasingly demanded rational, analytical, rigorously trained executives. They struggled to integrate the physical and social sciences into their education and research, helping to blaze a trail that long-established peers would not follow until the 1960s. And they strained to balance relevance with independence, colliding repeatedly with Sloan and other external advisors over a proper understanding of academic research, institutions, and cooperation with industry. By 1964 these efforts had developed a school at the forefront of business education’s “new look.” But as the extensive archival records demonstrate, it was never inevitable that they would succeed. Only by ongoing experimentation and agile diplomacy did the School become (in the words of the 1951 Deed of Gift) “a great center of research and education in the field of industrial management.” And although they helped transform management education through integrated, scientifically based study and teaching, the SIM’s deans, faculty, and leaders never found complete consensus on the extent to which industrial management was, in Alfred Sloan’s words, “a matter of science.”2018-06-22T00:00:00

Stimulation of the A2B adenosine receptor subtype enhances connexin26 hemichannel activity in small airway epithelial cells

Background/Aims: Adenosine release and connexin (Cx) hemichannel activity are enhanced in the respiratory epithelium during pathophysiological events such as inflammation. We analysed the interplay between Cx channels and adenosine signalling in human respiratory airway epithelium using the Calu-3 cell line as a model. Methods: The Cx hemichannel activity in Calu-3 cells was evaluated by dye uptake assays. The expressed Cx isoforms and adenosine receptor subtypes were identified by PCR and western blot analysis. Pharmacological and molecular biological experiments were performed to analyse the involvement of the different adenosine receptor subtypes, the induced signalling pathways and the contribution of specific Cx isoforms to the hemichannel activity. Results: The adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased the dye uptake rate in Calu-3 cells. The pannexon and Cx hemichannel inhibitor carbenoxolone (CBX) did not supress the dye uptake at pannexin-specific concentrations (100 µM). High CBX concentrations or the inhibitor La3+, both effective on Cx hemichannels, were needed to inhibit the dye uptake. The NECA-related increase of dye uptake depended on enhanced cAMP synthesis and subsequent activation of the protein kinase A (PKA) as shown by quantification of cAMP levels and pharmacological inhibition of the adenylyl cyclase and the PKA. Further pharmacological inhibition as well as knockdown experiments with specific siRNA showed that the A2B adenosine receptor was the subtype mainly responsible for the increased dye uptake. The NECA-related increase of the dye uptake rate correlated with a decrease of Cx43 mRNA and an increase of Cx26 mRNA content in the cells as well as Cx26 protein synthesis and was inhibited by Cx26 knockdown using Cx26 siRNA. Of note, a siRNA-induced knockdown of Cx43 increased the content of Cx26 mRNA and correspondingly the dye uptake rate. Conclusion: The Calu-3 cell model shows that stimulation of the A2B adenosine receptor subtype activates synthesis of cAMP. cAMP activates PKA and induces thereby an increase in Cx26 and a decrease in Cx43 mRNA levels. As a result, the synthesis of Cx26 is reinforced, leading to an enhanced Cx hemichannel activity. The report identifies a mechanism that integrates adenosine release and Cx hemichannel activity and shows how adenosine signalling and Cx channels may act together to promote persistent inflammation, which is observed in several chronic diseases of the respiratory airway

Parameters for Optoperforation-Induced Killing of Cancer Cells Using Gold Nanoparticles Functionalized With the C-terminal Fragment of Clostridium Perfringens Enterotoxin

Recently, we used a recombinant produced C-terminus (D194-F319) of the Clostridium perfringens enterotoxin (C-CPE) to functionalize gold nanoparticles (AuNPs) for a subsequent specific killing of claudin expressing tumor cells using the gold nanoparticle-mediated laser perforation (GNOME-LP) technique. For a future in vivo application, it will be crucial to know the physical parameters and the biological mechanisms inducing cell death for a rational adaptation of the system to real time situation. Regarding the AuNP functionalization, we observed that a relationship of 2.5 × 10−11 AuNP/mL to 20 µg/mL C-CPE maximized the killing efficiency. Regardingphysical parameters, a laser fluence up to 30 mJ/cm2 increased the killing efficiency. Independent from the applied laser fluence, the maximal killing efficiency was achieved at a scanning velocity of 5 mm/s. In 3D matrigel culture system, the GNOME-LP/C-CPE-AuNP completely destroyed spheroids composed of Caco-2 cells and reduced OE-33 cell spheroid formation. At the biology level, GNOME-LP/C-CPE-AuNP-treated cells bound annexin V and showed reduced mitochondria activity. However, an increased caspase-3/7 activity in the cells was not found. Similarly, DNA analysis revealed no apoptosis-related DNA ladder. The results suggest that the GNOME-LP/C-CPE-AuNP treatment induced necrotic than apoptotic reaction in tumor cells

Medical Malpractice of Vestibular Schwannoma: A 40-Year Review of the United States Legal Databases.

OBJECTIVES:To analyze medical malpractice lawsuit trends pertaining to cases of vestibular schwannomas (VS). METHODS:Two major computerized legal databases (LexisNexis and WestLaw) were queried and reviewed for evaluation of all the US state and federal court records from civil trials alleging malpractice between 1976 and 2016. RESULTS:A total of 32 VS cases were identified. Allegations were divided into four categories: misdiagnosis/delayed diagnosis (47%), postoperative complications (44%), failure of informed consent or information sharing (16%), and other (3%). Postoperative complications included facial nerve paralysis, myocardial infarction, meningitis, and intracranial hemorrhage. Judgment amounts ranged from $300,000 to$2,000,000. The specialist type was specified for 24 of the 32 cases (75%): neurosurgeons (n = 9; 37%), neurotologists (n = 6; 25%), general otolaryngologists (n = 5; 21%), primary care physicians (n = 4; 17%), neurologists (n = 3; 12%), radiologists (n = 3; 12%), anesthesiologists (n = 2; 8%), radiation oncologists (n = 1; 4%), and general surgeon (n = 1; 4%). Of these 24 cases, (n = 9; 37%) two or more physicians were named as defendants in the lawsuit. CONCLUSIONS:Enhanced physician-patient communication, ensuring proper and adequate patient consent procedures, and proper documentation are good practices that may decrease the likelihood of lawsuits

Molekularbiologische Diskriminierung zwischen planktonischen, Biofilm- und „Viable but non-culturable“-Zellen

Staphylococcus aureus und Staphylococcus epidermidis sind opportunistische Erreger biofilmassoziierter Infektionen. In Biofilmen gehen sie häufig in einen nicht kultivierbaren Zustand mit erhöhter Resilienz gegenüber schädlichen Umwelteinflüssen über (VBNC). Der VBNC-Zustand lässt sich in den untersuchten Stämmen durch die Inkubation in nährstofffreier Lösung mit einem milden pH-Stress induzieren. Eine molekularbiologische Diskriminierung von Zellen im VBNC-Zustand, Zellen im Biofilmverbund, planktonischen Zellen und toten Zellen ist anhand der Expressionsrate des 16S-Gens nicht möglich

Surfactant Semiconductors as Trojan Horses in Cell-Membranes for On-Demand and Spatial Regulation of Oxidative Stress

Oxidative stress is a cause for numerous diseases and aging processes. Thus, researchers are keen to tune the level of intracellular stress and to learn from that. An unusual approach is presented here. The methodology involves multifunctional surfactants. Although their molecular design is nonbiological—a fullerenol head group attached covalently to pi-conjugated dyes—the surfactants possess superior biocompatibility. Using an intrinsic fluorescence signal as a probe, it is shown that the amphiphiles become incorporated into the Caco-2 cells. There, they are able to exhibit additional functions. The compound reduces cellular stress in dark reaction pathways. The antagonistic property is activated under irradiation, the photocatalytic production of reactive oxygen species (ROS), resulting in cell damage. The feature is activated even by near-infrared light (NIR-light) via a two-photon process. The properties as molecular semiconductors lead to a trojan horse situation and allows the programming of the spatial distribution of cytotoxicity

The Bioactive Phenolic Agents Diaryl Ether CVB2-61 and Diarylheptanoid CVB4-57 as Connexin Hemichannel Blockers

Inflammation mediators enhance the activity of connexin (Cx) hemichannels, especially in the epithelial and endothelial tissues. As potential release routes for injury signals, such as (oligo)nucleotides, Cx hemichannels may contribute to long-lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long-lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells, using dye uptake as functional assay. Moreover, the possible impacts of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (>5 µM) and Cx46 (>20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversibly inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to the stimulation of adenosine signalling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversibly block Cx hemichannels. Deciphering the mechanisms of the interactions of these agents with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for better and safer treatment of pathologies that involve Cx hemichannels

The role of frailty in geriatric cranial neurosurgery for primary central nervous system neoplasms

OBJECTIVE. Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Geriatric patients have a higher risk of frailty, higher incidence of brain cancer, and increased postoperative complication rates compared to nongeriatric patients. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. METHODS. The authors conducted a retrospective cohort study of geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Complications of interest included infection, anemia, infarction, kidney injury, CSF leak, urinary tract infection, and mortality. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. RESULTS. A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23–1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70–6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07–1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71–2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17–2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22–2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at the time of primary admission. However, no significant difference was found between frail and nonfrail patients with regard to rates of infection, thromboembolism, CSF leak, dural tear, cerebral infarction, acute kidney injury, and mortality at all readmission time points. CONCLUSIONS. Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients. Further research is warranted to understand the effects and timeline of frailty in geriatric patients