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ABSTRACT Tuberculosis is caused by the bacteriumMycobacterium tuberculosis(Mtb). While eukaryotic species employ several specialized RNA polymerases (Pols) to fulfill the RNA synthesis requirements of the cell, bacterial species use a single RNA polymerase (RNAP). To contribute to the foundational understanding of how Mtb and the related non-pathogenic mycobacterial species,Mycobacterium smegmatis(Msm), perform the essential function of RNA synthesis, we performed a series ofin vitrotranscription experiments to define the unique enzymatic properties of Mtb and Msm RNAPs. In this study, we characterize the mechanism of nucleotide addition used by these bacterial RNAPs with comparisons to previously characterized eukaryotic Pols I, II, and III. We show that Mtb RNAP and Msm RNAP demonstrate similar enzymatic properties and nucleotide addition kinetics to each other but diverge significantly from eukaryotic Pols. We also show that Mtb RNAP and Msm RNAP uniquely bind a nucleotide analog with significantly higher affinity than canonical nucleotides, in contrast to eukaryotic RNA polymerase II. This affinity for analogs may reveal a vulnerability for selective inhibition of the pathogenic bacterial enzyme.IMPORTANCETuberculosis, caused by the bacteriumMycobacterium tuberculosis(Mtb), remains a severe global health threat. The World Health Organization (WHO) has reported that tuberculosis is second only to COVID-19 as the most lethal infection worldwide, with more annual deaths than HIV and AIDS (WHO.int). The first-line treatment for tuberculosis, Rifampin (or Rifampicin), specifically targets the Mtb RNA polymerase. This drug has been used for decades, leading to increased numbers of multi-drug-resistant infections (Stephanie,et al). To effectively treat tuberculosis, there is an urgent need for new therapeutics that selectively target vulnerabilities of the bacteria and not the host. Characterization of the differences between Mtb enzymes and host enzymes is critical to inform these ongoing drug design efforts. 

Universities have developed various informal learning experiences, such as design challenges, hackathons, startup incubator competitions, and accelerator programs that engage students in real-world challenges and enable environments for creative problem-solving. However, limited studies explain the extent and nature of the impact of student innovation competitions and programs (ICPs) on participating students' innovation mindset. Current literature was analysed using network analytics techniques to discover relations among ICPs and innovation skills. Using an online instrument, 194 students from two universities categorised and ranked skills/abilities they gained as the most or least improved due to participating in ICPs and their challenges during ICPs. The collected data was analysed to gain insight into the student's experiences and perceptions. The findings of this study showed that overall, students rated technical and problem-solving skills higher than some innovation mindset skills. However, the findings also suggested that incorporating more entrepreneurial elements in ICPs may improve the innovation mindset learning outcomes of ICPs. The findings contribute to how ICPs can be better designed to foster an innovation mindset, mitigate challenges that students come across, and increase the participation of all students. 

Engineering and computing education have always embraced student Innovation Competitions and Programs (ICPs), such as design challenges, hackathons, startup competitions, and boot camps. These programs are typically organized to increase interest in STEM fields, achieve the broader objective of forming well-rounded engineers and encourage students to bring their innovative ideas into real life. In addition, all ICPs also aim to advance students' innovative thinking skills. With the increased focus on entrepreneurship and innovation in STEM programs, many higher education institutions now organize some form of ICPs. This increased popularity of ICPs bears the questions of (i) whether ICPs achieve their intended objectives, (ii) what program components are most effective, and (iii) how to design ICPs for recruiting diverse student groups. Although these questions are highly relevant to advancing the educational benefits of ICPs, the literature lacks holistic studies focusing on the best practices of ICPs. In this paper, we present the findings of a qualitative research study to investigate ICP types and attributes that make the most impact on fostering an innovation mindset. We interviewed the organizers of ICPs to understand their objectives for organizing their events and rationales for specific program elements. Besides, we asked questions about how they promote their events, the best ways to reach out to students, team selection and forming, their assessment and judging procedures, during and after competition support, and the best practices and challenges. These interview scripts were transcribed, coded, and analyzed using qualitative data analysis software. An analysis of extracted thematic concepts was performed to identify the best practices and strategies that ICP organizers utilize to increase the Impact of their programs. The paper presents the preliminary results of this thematic analysis of the codes. Overall, findings suggest that incorporating more entrepreneurial elements, innovation training in ICPs, and effective mentoring may improve the learning outcomes related to innovative thinking skills. 

Like many faculty, we have organized student innovation competitions and programs (ICPs) and coached many student teams for various competitions; therefore, we have observed first-hand how transformational the experience has been for our students. ICPs allow students to quickly test their skills and knowledge, push them beyond their comfort zones, encourage them to take risks, and provide a safe place to try and fail, as failures can be seen as a critical part of the learning process. Despite their invaluable learning benefits, existing literature lacks a theoretical body of knowledge on the influence of ICPs on the educational experience. Our goal is to explore transformations in students’ mindsets toward innovation through perspectives and data from students who formerly participated in ICPs, mentors who coach students through ICPs, and ICP organizers who create these opportunities for students. This paper will focus on the essential practices of mentors. 

Innovation Competitions and Programs (ICPs), such as design challenges, hackathons, startup incubator competitions, boot camps, customer discovery labs, and accelerator programs, are informal learning experiences that supplement the formal education of Science, Technology, Engineering, and Mathematics (STEM) students. As learning dynamics are shifting toward becoming more personalized, location-unbounded, and spontaneous, informal learning is also becoming increasingly important for achieving the broader objectives of STEM education. ICPs are important in educating the next generation of innovators, and they serve as a gateway to innovation and entrepreneurial ecosystems in many colleges. The current literature provides limited quantitative and qualitative evidence on student learning because of participation in ICPs. This paper summarizes the findings of a study to investigate the learning and experiences of students who participated in ICPs. The results showed that overall, students rated technical and problem-solving skills higher than some innovation mindset skills, such as understanding people’s needs and pains. Furthermore, the results demonstrated relationships among student backgrounds, learning experiences, and ICP types. Findings suggested that incorporating more entrepreneurial elements in ICPs may improve the innovation mindset learning outcomes of ICPs 

Innovation Competitions and Programs (ICPs), such as design challenges, hackathons, startup incubator competitions, boot camps, customer discovery labs, and accelerator programs, are informal learning experiences that supplement the formal education of Science, Technology, Engineering, and Mathematics (STEM) students. As learning dynamics are shifting toward becoming more personalized, location-unbounded, and spontaneous, informal learning is also becoming increasingly important for achieving the broader objectives of STEM education. ICPs are important in educating the next generation of innovators, and they serve as a gateway to innovation and entrepreneurial ecosystems in many colleges. The current literature provides limited quantitative and qualitative evidence on student learning because of participation in ICPs. This paper summarizes the findings of a multi-institutional study to investigate the learning and experiences of students who participated in ICPs. The results showed that overall, students rated technical and problem-solving skills higher than some innovation mindset skills, such as understanding people’s needs and pains. Furthermore, the results demonstrated relationships among student backgrounds, learning experiences, and ICP types. Findings suggested that incorporating more entrepreneurial elements in ICPs may improve the innovation mindset learning outcomes of ICPs. 

Many students in Science, Technology, Engineering, and Mathematics (STEM) fields seek to expand their technical knowledge, develop an innovative mindset, and build teamwork and communication skills. To respond to this need, many higher education institutions and foundations have broadened their co-curricular program offerings to include design challenges, hackathons, startup competitions, customer discovery labs, and pitch competitions that are designed to support and benefit student innovators. Faculty mentors are responsible for being available to students to answer questions, guide student thinking, and advise student teams to facilitate learning. For these students to gain crucial knowledge and at least be educationally successful in these programs, a mentor possessing key traits and using certain strategies is proven to be highly influential. While much research supports the importance and benefit of STEM students’ participation in these programs, literature discussing the effective strategies for mentoring students participating in these programs remains limited. Exploring the best mentoring practices will provide insight into how to support and prepare students for innovation competitions and their upcoming careers as well as catalyze their entrepreneurial minds for future success. Based on a series of interviews with experienced mentors of innovation competitions and programs, this paper presents a set of best practices for mentoring student innovation teams. 

Abstract. Earth system models are essential tools for understandingthe impacts of a warming world, particularly on the contribution of polarice sheets to sea level change. However, current models lack full couplingof the ice sheets to the ocean and are typically run at a coarse resolution(1∘ grid spacing or coarser). Coarse spatial resolution isparticularly a problem over Antarctica, where sub-grid-scale orography iswell-known to influence precipitation fields, and glacier models requirehigh-resolution atmospheric inputs. This resolution limitation has beenpartially addressed by regional climate models (RCMs), which must be forcedat their lateral and ocean surface boundaries by (usually coarser) globalatmospheric datasets, However, RCMs fail to capture the two-way couplingbetween the regional domain and the global climate system. Conversely,running high-spatial-resolution models globally is computationallyexpensive and can produce vast amounts of data. Alternatively, variable-resolution grids can retain the benefits of highresolution over a specified domain without the computational costs ofrunning at a high resolution globally. Here we evaluate a historicalsimulation of the Community Earth System Model version 2 (CESM2)implementing the spectral element (SE) numerical dynamical core (VR-CESM2)with an enhanced-horizontal-resolution (0.25∘) grid over theAntarctic Ice Sheet and the surrounding Southern Ocean; the rest of theglobal domain is on the standard 1∘ grid. We compare it to1∘ model runs of CESM2 using both the SE dynamical core and thestandard finite-volume (FV) dynamical core, both with identical physics andforcing, including prescribed sea surface temperatures (SSTs) and sea ice concentrations fromobservations. Our evaluation reveals both improvements and degradations inVR-CESM2 performance relative to the 1∘ CESM2. Surface massbalance estimates are slightly higher but within 1 standard deviation ofthe ensemble mean, except for over the Antarctic Peninsula, which isimpacted by better-resolved surface topography. Temperature and windestimates are improved over both the near surface and aloft, although theoverall correction of a cold bias (within the 1∘ CESM2 runs) hasresulted in temperatures which are too high over the interior of the icesheet. The major degradations include the enhancement of surface melt aswell as excessive cloud liquid water over the ocean, with resultant impactson the surface radiation budget. Despite these changes, VR-CESM2 is avaluable tool for the analysis of precipitation and surface mass balanceand thus constraining estimates of sea level rise associated with theAntarctic Ice Sheet. 

Cancer cells require robust ribosome biogenesis to maintain rapid cell growth during tumorigenesis. Because RNA polymerase I (Pol I) transcription of the ribosomal DNA (rDNA) is the first and rate-limiting step of ribosome biogenesis, it has emerged as a promising anti-cancer target. Over the last decade, novel cancer therapeutics targeting Pol I have progressed to clinical trials. BMH-21 is a first-in-class small molecule that inhibits Pol I transcription and represses cancer cell growth. Several recent studies have uncovered key mechanisms by which BMH-21 inhibits ribosome biosynthesis but the selectivity of BMH-21 for Pol I has not been directly measured. Here, we quantify the effects of BMH-21 on Pol I, RNA polymerase II (Pol II), and RNA polymerase III (Pol III) in vitro using purified components. We found that BMH-21 directly impairs nucleotide addition by Pol I, with no or modest effect on Pols II and III, respectively. Additionally, we found that BMH-21 does not affect the stability of any of the Pols’ elongation complexes. These data demonstrate that BMH-21 directly exploits unique vulnerabilities of Pol I.