Tobramycin Adenylyltransferase: A New AminoglycosideInactivating Enzyme from Staphylococcus epidermidis

Certain strains of Staphylococcus epidermidis resistant to the aminoglycoside antibiotics were shown to contain an enzyme that inactivates the kanamycins, neomycins, butirosins, paromomycin, gentamicin A, amikacin, and tobramycin by adenylylation. Tobramycin adenylyltransferase, as this enzyme is called, was found to be optimally active at pH 5.5. With paromomycin or neomycin Band C as substrates, however, two pH values (5.5 and 9.0) for optimal activity were observed. The enzyme requires Mg+ + for activity and is stabilized significantly by dithiothreitol. It is probable that the 4′-hydroxyl group of ring I of the antibiotics is adenylylated. Those aminoglycosides that are not substrates for the enzyme lack a hydroxyl group in the corresponding positio

Modern Constraint Programming Education: Lessons for the Future

This paper details an outlook on modern constraint programming (CP) education through the lens of a CP instructor. A general overview of current CP courses and instructional methods is presented, with a focus on online and virtually-delivered courses. This is followed by a discussion of the novel approach taken to introductory CP education for engineering students at large scale at the Georgia Institute of Technology (Georgia Tech) in Atlanta, GA, USA. The paper summarizes important takeaways from the Georgia Tech CP course and ends with a discussion on the future of CP education. Some ideas for instructional methods, promotional methods, and organizational changes are proposed to aid in the long-term growth of CP education.Comment: Paper and presentation for Workshop on Teaching of Constraint Programming (WTCP) 2023 as part of CP 2023, the 29th International Conference on Principles and Practice of Constraint Programmin

If You Let Them Build It, They Will Stay! An Empirical Study of Add-on Content and User Engagement

This study aims to uncover the effects of two \ types of add-on content –namely, user generated and developer \ generated content– on user engagement with software. Utilizing \ a novel dataset from a major online game distribution platform \ covering 7323 products between January 2015 and February \ 2016, the findings reveal that both types of add-on content \ increases the engagement with software. However, we observe \ substitutive patterns between different types of add-on content. \ Our results suggest integrating social features to the base \ product reduces these substitution effects. The results of this \ study contribute to the literatures on user engagement and \ add-on content by uncovering hitherto overlooked substitutive \ relations between user generated and developer generated add- \ on content

The Role of Religion in Online Prosocial Lending

The Internet has long been argued to have “flattened” the world. A variety of work, however, has shown that cross-border frictions continue to manifest through various individual level differences, e.g., cultural, demographic, and geographic. We extend this literature here, offering a novel consideration of religious differences as a significant barrier to online peer-to-peer transactions in the context of prosocial lending. Specifically, we propose a measure of religious distance between any given pair of countries. We then incorporate this measure into a standard gravity model of trade, which we use to explain country-to-country lending volumes between 2006 and 2017 at kiva.org. We demonstrate the negative and significant effects of religious differences on lending activity over and above other established factors. Moreover, we demonstrate that the effects of religious differences vary a great deal, being moderated by the social environment characterizing both a lender country and borrower country in a given time period. That is, we show that increases in the degree of social hostilities within a lender country amplifies the baseline (negative) effects of religious differences on lending activity. At the same time, we demonstrate that diversity of religion and greater physical distances attenuate the role of religious differences

Aqueous extracts of cigarette smoke promote the oxidation of low density lipoprotein by peroxidases

AbstractOxidation of low density lipoprotein (LDL) by cigarette smoke has been considered a potential mechanism by which smoking may promote atherosclerosis. We report in this study that cigarette smoke extract (CSE) inhibited copper-induced oxidation of LDL suggesting the presence of antioxidants in CSE. It is currently believed that peroxidases may oxidize LDL in vivo and during such oxidations antioxidants become pro-oxidants. Accordingly, when LDL was oxidized by peroxidase in the presence of CSE there was an increase in the oxidation of LDL. This is the first study suggesting that smoking may promote atherosclerosis by enhancing peroxidase-catalyzed lipid peroxidation

Irbesartan, an angiotensin type 1 receptor inhibitor, regulates markers of inflammation in patients with premature atherosclerosis

AbstractOBJECTIVESThis study assessed the role of angiotensin II type 1 (AT1) receptor antagonists on inflammatory mechanisms involved in atherogenesis. Specific inflammatory markers included solubilized tumor necrosis factor-alpha receptor II (sTNF-αRII), vascular cell adhesion molecule-1 (VCAM-1) and superoxide. In addition, the AT1receptor blocker irbesartan was evaluated for its ability to suppress these markers in individuals with atherosclerosis.BACKGROUNDMechanisms involved in the complex process of atherogenesis include alterations in the inflammatory responses. The use of compounds that suppress these responses may reduce the degree of damage seen in atherosclerosis.METHODSWith a cross-sectional study design, 33 normotensive patients with stable coronary artery disease (CAD) were treated with irbesartan for a 24-week period. These patients were compared against a control population with no known coronary atherosclerosis. Marker levels were measured by enzyme-linked immunosorbent assay technique and lucigenin chemiluminescence assay and statistically evaluated by two-way repeated measures analysis of variance.RESULTSAll patients with coronary artery disease had increased levels of inflammatory molecules over those of control patients. Treatment with irbesartan in these patients significantly reduced levels of inflammatory molecules measured. Soluble VCAM-1 levels were reduced by 36%; soluble TNF-alpha levels were reduced by 54% and superoxide level decreased by 52%. Maximal suppression of inflammatory markers by irbesartan therapy in patients with CAD was seen at 12 weeks.CONCLUSIONSThe effect of irbesartan on each inflammatory marker is significant. Our results show that use of irbesartan may retard the inflammatory process seen in premature forms of atherosclerosis