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‘Obama’s Presidency of the Harvard Law Review Board and his US Presidency’
Get PDFThis paper attempts a discourse analysis of the 1990 issues of the Harvard Law Review edited by Obama as the first black President of the Law Review. Although Politico.com1 and The New York Times2 have reported on the significance of Obama’s previous presidency for his subsequent or current one, legal scholars are yet to explore what the discourse in Obama’s editorials says about his discourse as the first black president of the US. The task is made difficult because Obama did not sign any article for the Harvard Law Review during his presidency and does not dwell a lot on that period in his published memoirs. This conference presentation will therefore dwell mainly on his choice of authors for each issue of the journal, the articles that he selected along with the other editors and what they say about public issues, the article on Constitutional Physics that he was acknowledged as having helped Professor Tribe to write (Professor Tribe acknowledged his assistance and those of a few others in the paper), and possibly other unsigned articles that are attributable to him as well, starting with volume 102 when he was a freshman, continuing with volume 103 when he joined the editorial board and concluding with volume 104 which he presided over. Finally, I will try to show if there are any parallels and or contradictions between the two Obama presidencies
Targeting severe acute respiratory syndrome-coronavirus (SARS-CoV-1) with structurally diverse inhibitors: A comprehensive review
Get PDFCoronaviruses, which were discovered in 1968, can lead to some human viral disorders, like severe acute respiratory syndrome (SARS), Middle East respiratory syndrome-related (MERS), and, recently, coronavirus disease 2019 (COVID-19). The coronavirus that leads to COVID-19 is rapidly spreading all over the world and is the reason for the deaths of thousands of people. Recent research has revealed that there is about 80% sequence homology between the coronaviruses that cause SARS and COVID-19. Considering this fact, we decided to collect the maximum available information on targets, structures, and inhibitors reported so far for SARS-CoV-1 that could be useful for researchers who work on closely related COVID-19. There are vital proteases, like papain-like protease 2 (PL2pro) and 3C-like protease (3CLpro), or main protease (Mpro), that are involved in and are essential for the replication of SARS coronavirus and so are valuable targets for the treatment of patients affected by this type of virus. SARS-CoV-1 NTPase/helicase plays an important role in the release of several non-structural proteins (nsps), so it is another essential target relating to the viral life cycle. In this paper, we provide extensive information about diverse molecules with anti-SARS activity. In addition to traditional medicinal chemistry outcomes, HTS, virtual screening efforts, and structural insights for better understanding inhibitors and SARS-CoV-1 target complexes are also discussed. This study covers a wide range of anti-SARS agents, particularly SARS-CoV-1 inhibitors, and provides new insights into drug design for the deadly SARS-CoV-2 virus
A hierarchical model of perceptual multistability involving interocular grouping
No full textAmbiguous visual images can generate dynamic and stochastic switches in perceptual interpretation known as perceptual rivalry. Such dynamics have primarily been studied in the context of rivalry between two percepts, but there is growing interest in the neural mechanisms that drive rivalry between more than two percepts. In recent experiments, we showed that split images presented to each eye lead to subjects perceiving four stochastically alternating percepts (Jacot-Guillarmod et al. Vision research, 133, 37–46, 2017): two single eye images and two interocularly grouped images. Here we propose a hierarchical neural network model that exhibits dynamics consistent with our experimental observations. The model consists of two levels, with the first representing monocular activity, and the second representing activity in higher visual areas. The model produces stochastically switching solutions, whose dependence on task parameters is consistent with four generalized Levelt Propositions, and with experiments. Moreover, dynamics restricted to invariant subspaces of the model demonstrate simpler forms of bistable rivalry. Thus, our hierarchical model generalizes past, validated models of binocular rivalry. This neuromechanistic model also allows us to probe the roles of interactions between populations at the network level. Generalized Levelt’s Propositions hold as long as feedback from the higher to lower visual areas is weak, and the adaptation and mutual inhibition at the higher level is not too strong. Our results suggest constraints on the architecture of the visual system and show that complex visual stimuli can be used in perceptual rivalry experiments to develop more detailed mechanistic models of perceptual processing
A parametric study of frictional load influence in spur gear bending resistance
Get PDFA revised Lewis bending fatigue stress capacity model for spur gears is presented and used to study the influence of mesh friction on root stress. It took the original Lewis formula and made modifications for dynamic loads, shear stress, and mesh friction in spur gear design. The study reveals that mesh friction may increase bending stress by up to 6% in enclosed cylindrical gear drives when an average mesh friction coefficient of 0.07 is assumed. A possible increase of 15% in root stress may occur in open gear drives when the mesh friction coefficient is taken as 0.15, a value considered to be representative for properly maintained open drives. To account for mesh frictional load and other factors directly influencing mesh friction, a friction load factor of 1.1 is suggested and introduced to gear service load estimation for enclosed gear drives and 1.15 for open gear drives
Histone deacetylase inhibitors as multitarget-directed epi-drugs in blocking pi3k oncogenic signaling: A polypharmacology approach
Get PDFGenetic mutations and aberrant epigenetic alterations are the triggers for carcinogenesis. The emergence of the drugs targeting epigenetic aberrations has provided a better outlook for cancer treatment. Histone deacetylases (HDACs) are epigenetic modifiers playing critical roles in numerous key biological functions. Inappropriate expression of HDACs and dysregulation of PI3K signaling pathway are common aberrations observed in human diseases, particularly in cancers. Histone deacetylase inhibitors (HDACIs) are a class of epigenetic small-molecular therapeutics exhibiting promising applications in the treatment of hematological and solid malignancies, and in non-neoplastic diseases. Although HDACIs as single agents exhibit synergy by inhibiting HDAC and the PI3K pathway, resistance to HDACIs is frequently encountered due to activation of compensatory survival pathway. Targeted simultaneous inhibition of both HDACs and PI3Ks with their respective inhibitors in combination displayed synergistic therapeutic efficacy and encouraged the development of a single HDAC-PI3K hybrid molecule via polypharmacology strategy. This review provides an overview of HDACs and the evolution of HDACs-based epigenetic therapeutic approaches targeting the PI3K pathway
Social Media as an Innovative Policy Tool: Lessons and Recommendations from the City of Austin
Get PDFSocial media brings opportunities for local governments to innovatively engage the public to enhance service delivery. Using the City of Austin, Texas as a backdrop, we assess the Austin Police Department’s utilization of social media in its communication efforts around community policing. This assessment develops a practical model to evaluate its community policing communication policies and practices by way of social media. The findings from this assessment provide several lessons and recommendations for practitioners to use in their efforts to integrate social media into public service delivery. These lessons and recommendations drawn from this case can provide an example of the potential strengths and weaknesses behind incorporating social media within public service delivery
Social Responsibility: Preparing Students for the Real World
Get PDFEthics and corporate social responsibility are widely discussed in business and in the classroom. In fact, many mission statements for Colleges of Business include ethics as a major component. As corporations become increasingly aware of their impact on the environment, sustainability and social responsibility have become significant issues for many executives.
How to “teach” ethics and social responsibility is a dilemma that has been addressed with no definitive solution. Research shows that the traditional model of teaching and/or learning is outdated. In many disciplines, instructor/lecture and student note-taking are outdated methods of teaching. To increase student engagement and to reach a new generation of students, college courses must incorporate new models that lead to active engagement.
Service learning has been defined as “a form of experimental education in which students engage in activities that address human and community needs together with structured opportunities intentionally designed to promote student learning and development” (Johnson 2013). Based on the idea of service learning and the need for students to be socially responsible on campus, students in an MBA course were assigned a field project to support a university organization, the LU Green Squad.
The Green Squad focuses on interacting with the campus and surrounding community concerning environmental and sustainability efforts. The student/instructor team guided the organization through the goal-setting and execution process. Students acted as managers and executed plans to help the organization develop a plan for achieving its goals. The experiential component of the project enabled students to determine ideas that seem perfect in theory often do not work in the real world. Applying what they learned in the classroom in a real setting anchored students’ learning and produced a high level of engagement.
This paper reviews the learning experience of MBA students, studies the impact of the project on the client organization, and discusses the results of the project
Development and validation of ultra-high-performance liquid chromatography–mass spectrometry method for the determination of raloxifene and its phase II metabolites in plasma: Application to pharmacokinetic studies in rats
No full textThe aim of this study is to establish a reliable liquid chromatography–mass spectrometry method to simultaneously quantitate raloxifene, and its major metabolites, raloxifene-6-glucuronide, raloxifene-4′-glucuronide, and raloxifene-6-sulfate in rat plasma samples for pharmacokinetic studies. The separation of the analytes was achieved on a Waters BEH C18 column. Water (0.1% formic acid) and acetonitrile were used as the mobile phases for elution. A one-step protein precipitation using a mixture solvent was applied for plasma sample preparation. The method was validated following the FDA guidance. The results showed that the linear range were 1.95–1000 nM for raloxifene-6-glucuronide, and raloxifene-4′-glucuronide, 0.195–100 nM for raloxifene-6-sulfate, and 0.195–200 nM for raloxifene, respectively. The lower limit of quantification was 1.95, 1.95, 0.195, and 0.195 nM for raloxifene-6-glucuronide, raloxifene-4′-glucuronide, raloxifene-6-sulfate, and raloxifene, respectively. Only 20 µl of plasma sample was required since the method is sensitive. The intra- and interday variance is \u3c15% and the accuracy is within 85–115%. The variance of matrix effect and recovery were \u3c15%. The method was successfully applied in a pharmacokinetic study in rats with oral administration of raloxifene
Bioanalytical assay development and validation for the pharmacokinetic study of gmc1, a novel fkbp52 co-chaperone inhibitor for castration resistant prostate cancer
No full textBackground: GMC1 (2-(1H-benzimidazol-2-ylsulfanyl)-N-[(Z)-(4-methoxyphenyl) methylideneamino] acetamide) effectively inhibits androgen receptor function by binding directly to FKBP52. This is a novel mechanism for the treatment of castration resistant prostate cancer (CRPC). Methods: an LC-MS/MS method was developed and validated to quantify GMC1 in plasma and urine from pharmacokinetics studies in rats. An ultra-high-performance liquid chromatography (UHPLC) system equipped with a Waters XTerra MS C18 column was used for chromatographic separation by gradient elution with 0.1% (v/v) formic acid in water and methanol. A Sciex 4000 QTRAP® mass spectrometer was used for analysis by multiple reaction monitoring (MRM) in positive mode; the specific ions [M+H]+ m/z 340.995 → m/z 191.000 and [M+H]+ m/z 266.013 → m/z 234.000 were monitored for GMC1 and internal standard (albendazole), respectively. Results: GMC1 and albendazole had retention times of 1.68 and 1.66 min, respectively. The calibration curves for the determination of GMC1 in rat plasma and urine were linear from 1–1000 ng/mL. The LC-MS/MS method was validated with intra-and inter-day accuracy and precision within the 15% acceptance limit. The extraction recovery values of GMC1 from rat plasma and urine were greater than 95.0 ± 2.1% and 97.6 ± 4.6%, respectively, with no significant interfering matrix effect. GMC1 is stable under expected sample handling, storage, preparation and LC-MS/MS analysis conditions. Conclusions: Pharmacokinetic evaluation of GMC1 revealed that the molecule has a biexponential disposition in rats, is distributed rapidly and extensively, has a long elimination half-life, and appears to be eliminated primarily by first order kinetics
Design sizing of cylindrical worm gearsets
Get PDFA method for the design sizing task of cylindrical worm gearsets is presented that gives an estimate of the initial value of the normal module. Expressions are derived for the worm pitch diameter of integral and shell worms as well as for the active facewidth of the gear and the threaded length of the worm. An attempt is made to predict the contact strength of bronze materials against scoring resistance. Four Examples of design sizing tasks of cylindrical worm gears are carried out using the approach presented and the results are compared with previous solutions from other methods. The results for first three examples show excellent comparisons with previous solutions of American Gear Manufacturers Association (AGMA) method. The results of the fourth example are slightly more conservative than those of DIN3999 but are practically similar. Therefore, it appears that a systematic, reliable and more scientifically based method for cylindrical worm drive design sizing has been developed