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Development of a diverse activity-based probe library for studying serine proteases
No full textSerine proteases are ubiquitous enzymes that are involved in a variety of physiological processes ranging from digestion to immune system responses. While the functions of several serine proteases are well-characterized, many of these enzymes in the human body still lack functional annotation. Activity-based protein profiling (ABPP) technology has provided a strategy for studying these enzymes, particularly those with no known substrates. The use of a small-molecule probe that binds selectively to the active, but not the inactive, protein can enable enzyme detection, functional elucidation, and inhibitor discovery. While several activity-based probes, most notably fluorophosphonates, have been developed for serine proteases, we have found that a subset of serine proteases, including several rhomboid intramembrane proteases (RIPs), are not readily engaged by these probes. We therefore designed and synthesized a library of alkyne-functionalized structures, including phosphonates, β-lactams, and succinimides, to improve coverage of this enzyme class. We studied the ability of these structures to engage the well-studied serine protease trypsin as well as the bacterial RIP GlpG. Probe labeling was visualized by performing the azide-alkyne Huisgen cycloaddition reaction on probe-treated protein using an azide-functionalized rhodamine. These experiments have demonstrated that several of these structures react with the serine protease targets in an activity-dependent manner and have also revealed differential patterns in activity-dependent labeling between the two proteases. The chemical structures generated as part of these efforts hold promise as alternative activity-based probes for studying serine proteases that have so far eluded characterization
Introduction to the Special Issue on Early Evolution and the Last Common Ancestor
No full textThe early evolution of life spans an extensive period preceding the emergence of the first eukaryotic cell. This epoch, which transpired from 4.5 to 2.5 billion years ago, marked the advent of many fundamental cellular attributes and witnessed the existence of the Last Common Ancestor (LCA) of all life forms. Uncovering and reconstructing this elusive LCA\u27s characteristics and genetic makeup represents a formidable challenge and a pivotal pursuit in early evolution. While most scientific accounts concur that the LCA resembles contemporary prokaryotes, its precise definition, genome composition, metabolic capabilities, and ecological niche remain subjects of contentious debate
Beyond Babel: East India Company Genre and Colonial Romanticism in an Indo-Persian Diary - Erratum
No full textJewish Question, Imperial Question: Antisemitism and Colonial Anxiety in French Algeria, 1870-1900
No full textMy research project covers the rise of antisemitic ideology, targeted toward indigenous Algerian Jews, among settlers of French Algeria between 1870 and 1900. In 1870, Algerian Jews were made French citizens after a long assimilation effort, sparking backlash among French settlers who wished to keep their political rights exclusive. In the late 1890s, the Dreyfus Affair, a legal scandal and eruption of antisemitism in metropolitan France, reverberated in Algeria into what scholars call an anti-Jewish crisis that saw the worst antisemitic violence in the Francophone world at the time. My research seeks to answer the questions: why did antisemitism find such success in French Algeria? How did the conditions of settler-colonial society impact French-Algerian antisemitic ideology? I argue that antisemitism developed so strongly in Algeria because Jews, as indigenous targets of a metropole-led assimilation effort, made perfect scapegoats for colonial anxieties over settlers\u27 relationships both to the metropole and to the indigenous. Furthermore, settler antisemitic ideology was able to quickly set roots not only thanks to simultaneous antisemitism in the metropole but also, paradoxically, thanks to the preexisting philo-Semitic colonial discourse that isolated Algerian Jews as intermediaries of colonial inequality
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No full textChanging Culture through Pro-Environmental Messagibg Delivered on Digital Signs: A Longitudinal Study
No full textDelivering effective messages is critical to creating a more sustainable and resilient culture. The explosion of social media has enhanced information access but has often reinforced and polarized pre-existing viewpoints and norms. In contrast, digital signs are an in your face in your space technology that have the potential to deliver common content to a diverse local audience. Environmental Dashboard (ED) is a communications platform and set of content applications that combines information on current environmental conditions, real-time resource consumption, positive actions being taken by community members, and a community calendar. We conducted a longitudinal study to assess whether ED content delivered via digital signs in public locations would result in desirable psychological changes within a community. Participants completed surveys in six designated signage locations prior to installation (N = 174) and following two years of continuous exposure (N = 133). We observed increases in pro-environmental social norms among people of color (a demographic emphasized); enhanced awareness of and sense of connection with the local community and ecology; increased self-reported electricity conservation; and increased perception of youth engagement (another demographic emphasized). Changes were mediated by exposure to digital signage. These findings support the hypothesis that content delivered through digital signs can strengthen pro-environmental and pro-social culture within communities
Beyond Babel: East India Company Genre and Colonial Romanticism in an Indo-Persian Diary
No full textScholarship largely holds that the Persianate world -a transregional sphere of cultural exchange mediated by an Indian Ocean lingua franca-was put paid to by a colonizing English East India Company. Against that historiography, this article reveals how colonial and Indo-Persian modern textual trends were coproduced. Reading a first-person account of the hajj pilgrimage to Mecca, written in 1815-17 by a prince from a Mughal successor state under Company rule, the article argues that the travelogue\u27s unprecedented form of a diary, and its uncharacteristically affective contents for Indo-Persian prose, drew on emerging genres and Romantic ideologies in British India. But while this resulted in a new kind of Indo-Persian ego-document, this text of Indian Ocean travel remained, however, anchored in Mughal concepts of moods and manners. As such it betrayed transitional tensions that compel a reconsideration of how colonialism led ultimately to the passing of a precolonial Persianate Babel
Quantal Time Evolution in the Simple Harmonic Oscillator and the Constant-force Potentials: Analytic Solutions
No full textThis paper presents analytic solutions to quantal time-evolution problems in the simple harmonic oscillator and constant-force potential. We prove that in the simple harmonic oscillator potential, the only family of wave packets with rigidly moving probability density is the spatially translated energy eigenfunctions. In addition, we completely solve the time evolution of Gauss-Hermite waveforms, namely spatially translated and stretched energy eigenfunctions.
We also completely solve the time-evolution problem of an initially Gaussian wave packet in the constant-force potential. This solution involves using a convolutional integral transform over basis functions {Ai[( − )] ∶ ∈ R} ( ≠ 0 and ∈ R), and we prove that the integral transform is invertible and satisfies the Parseval-Plancherel identity over the Schwartz space (ℝ; ℂ). We suggest future work on generalizing the transformation to admit piece-wise continuous functions and (tempered) distributions, which can be used to solve time-evolution problems in the 1D Stark potentials, that is, 1D finite rectangular well with constant force field.
This paper also presents an overview of asymptotic methods in mathematical physics. We present asymptotic methods on Laplace-type integrals ranging from Laplace’s method to the saddle point method. Large- asymptotic expressions for the Airy function Ai() are derived explicitly using the saddle point method
