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"Meagher, Michael"
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American Presidential Elections
American Politics, often prone to the passions of democratic governance, continues to be subject to those passions in the twenty-first century. Traditionally assigning majority party status to one of the two major parties, this has provided the engine through which change has occurred over the nation’s history. Able to set the agenda of the nation’s business and carry out its program, public frustration was muted given the ability of the political system to address concerns. However, that previous practice of having a majority party is now gone. American politics now takes place within a framework of readjustment: the two major parties are evenly balanced, making it challenging to address the nation’s ills. With the system straining to address public concerns, the public’s frustration level has increased. This essay argues that while change can occur absent a majority party, the lack of a majority party prevents the change from being long-term and systemic over decades. FDR’s New Deal was a system-level change that provided American politics with a public philosophy for decades. At present, rather than realigning, the nation has readjusted.
Journal Article
Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1
Eight infants with SCID-X1 had multilineage immune reconstitution after autologous hematopoietic stem-cell transplantation of marrow stem cells transfected with a lentiviral vector containing
IL2RG
cDNA after busulfan conditioning. Previous infections cleared and functional T cells developed in all eight infants, IgM levels normalized in seven, and three had a response to vaccines.
Journal Article
U.S. PRESIDENTIAL LEADERSHIP STYLES AND MEDIA: A HISTORICAL PERSPECTIVE
U.S. presidential leadership styles speak to us today as we seek to understand the dynamics of the current political universe. The stances adopted by especially twentieth-century U.S. presidents point to certain norms being upheld by the nation's chief executives. Some were more talented in exercising the rhetorical presidency, while others were more successful in achieving policy goals. These presidents operated under the technological mechanisms of their time. In the twenty-first century, new social media technologies are emerging that challenge previous orthodoxies. The presidency of Donald J. Trump differed significantly from previous presidencies. Identity politics that predated the twitter presidency shaped the Trump years. Does the Trump model represent the future of presidential communication? This essay concludes that future U.S. presidents will face new challenges as a result of the fractured social contract, a legacy of identity politics.
Journal Article
Development of a cGMP-compliant process to manufacture donor-derived, CD45RA-depleted memory CD19-CAR T cells
Autologous chimeric antigen receptor (CAR) T cells targeting the CD19 antigen have demonstrated a high complete response rate in relapsed/refractory B-cell malignancies. However, autologous CAR T cell therapy is not an option for all patients. Here we optimized conditions for clinical-grade manufacturing of allogeneic CD19-CAR T cells using CD45RA-depleted donor memory T cells (Tm) for a planned clinical trial. Tm were activated using the MACS GMP T Cell TransAct reagent and transduced in the presence of LentiBOOST with a clinical-grade lentiviral vector that encodes a 2nd generation CD19-CAR with a 41BB.zeta endodomain. Transduced T cells were transferred to a G-Rex cell culture device for expansion and harvested on day 7 or 8 for cryopreservation. The resulting CD19-CAR(Mem) T cells expanded on average 34.2-fold, and mean CAR expression was 45.5%. The majority of T cells were CD4+ and had a central memory or effector memory phenotype, and retained viral specificity. CD19-CAR(Mem) T cells recognized and killed CD19-positive target cells in vitro and had potent antitumor activity in an ALL xenograft model. Thus we have successfully developed a current good manufacturing practice-compliant process to manufacture donor-derived CD19-CAR(Mem) T cells. Our manufacturing process could be readily adapted for CAR(Mem) T cells targeting other antigens.
Journal Article
The Challenge of Distance Learning
This essay explores the sudden shift from residential higher education to remote learning in the United States, a consequence of the novel coronavirus. It is a personal account of experiences as a professor at a Midwestern university. Many instructors had no training in online teaching. For university faculty, Covid-19 meant having to transform courses from in-person instruction to a remote platform practically overnight. Among the student comments I received were that I managed the online transition well. Over the next academic year, 2020-21, universities face challenges in resuming on-campus teaching, and the possibility that a new outbreak of the virus might bring a repeat of the Spring 2020 semester. Although that possibility sounds dire, there is hope that the shift to remote learning may offer a silver lining in the form of expanding course offerings beyond geographic areas and reaching a wider audience. For liberal arts institutions that are struggling financially, a rise in the use of remote learning and online education may offer a new beginning, and for public universities, potential new revenue given declining state support, a silver lining.
Journal Article
Challenging preservice secondary mathematics teachers’ conceptions of function
Preservice mathematics teachers, like all learners, have well documented difficulties with the concept of function. We designed an applet-based task to challenge these known difficulties with the aim of improving preservice secondary mathematics teachers’ (PSMTs) conceptions of function. This cross-institutional study of 47 PSMTs examined the ways in which this task elicited and improved PSMTs’ conceptions of function. The results of the study show a measurable increase in the participants’ level of abstraction in their definition of function, and an increase in their attention to the univalence condition. In particular, the interaction with the specially designed applet was effective in initiating a series of dilemmas in their conception of function that resulted in the majority of the participants changing their conception of function in a positive direction.
Journal Article
DEMOCRACY IN CRISIS: JOHN F. KENNEDY'S POLITICAL THOUGHT
A remarkable political figure, John F. Kennedy contributed also to political theory focusing on community, sacrifice, and effective national leadership. Coming of age in the build-up to World War II, Kennedy's early views were framed by the inability of Western democracies to meet totalitarian challenges. As his political career developed, JFK maintained a stance favorable to strong national leadership as a way of overcoming the individualism and self-centered aspects of modern life. A keen believer in se,'vice, community, and sacrifice, his famous \"Ask not\" moment of his 1961 Inaugural Address was informed by a concern with renewing American democracy. With a weakening of the social contract and increased political dysfunctionality in the twenty-first century, the political thought of the thirty- fifth president still speaks to us with its emphasis on courage, leadership, civil society, and the quest for national unity.
Journal Article
Fed-batch fermentation of GM-CSF-producing glycoengineered Pichia pastoris under controlled specific growth rate
Background
Yeast expression systems with altered N-glycosylation are now available to produce glycoproteins with homogenous, defined N-glycans. However, data on the behaviour of these strains in high cell density cultivation are scarce.
Results
Here, we report on cultivations under controlled specific growth rate of a GlycoSwitch-Man5
Pichia pastoris
strain producing Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) at high levels (hundreds of milligrams per liter). We demonstrate that homogenous Man
5
GlcNAc
2
N-glycosylation of the secreted proteins is achieved at all specific growth rates tested.
Conclusions
Together, these data illustrate that the GlycoSwitch-Man5
P. pastoris
is a robust production strain for homogenously N-glycosylated proteins.
Journal Article
The U.S. Presidential Campaign, 2016
This essay explores the 2016 election using 1964 for comparison. The central theme is that 1964 set the context for subsequent presidential elections. Issues and public policy revolved around the standards set by the 1964 converting election. Both race and religion played a role in the 1964 converting election that redefined the Democratic Party as the liberal political party for the nation, and the Republican as its conservative counterpart. This established a political regime that endures until the present day, but its endurance has had deleterious consequences for the discussion of new proposals. Change happens slowly and piecemeal. Both parties maintain high levels of spending as politics has been reduced to administration, a technocracy rather than representative democracy. The resulting pressures and frustrations manifest themselves with increasing frequency in the political system. The tumultuous 2016 campaign is the latest manifestation of this dissatisfaction among voters. Given the peculiarities of 2016, are we on the verge of a historic realignment, one that may set a similar standard for a generation?
Journal Article