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Replication Protein A (RPA) is single-strand DNA binding protein that plays a key role in the replication and repair of DNA. RPA is a heterotrimer made of 3 subunits – RPA1, RPA2, and RPA3. Germline pathogenic variants affectingRPA1were recently described in patients with Telomere Biology Disorders (TBD), also known as dyskeratosis congenita or short telomere syndrome. Premature telomere shortening is a hallmark of TBD and results in bone marrow failure and predisposition to hematologic malignancies. Building on the finding that somatic mutations in RPA subunit genes occur in ~1% of cancers, we hypothesized that germline RPA alterations might be enriched in human cancers. Because germlineRPA1mutations are linked to early onset TBD with predisposition to myelodysplastic syndromes, we interrogated pediatric cancer cohorts to define the prevalence and spectrum of rare/novel and putative damaging germlineRPA1,RPA2, andRPA3variants. In this study of 5,993 children with cancer, 75 (1.25%) harbored heterozygous rare (non-cancer population allele frequency (AF) < 0.1%) variants in the RPA heterotrimer genes, of which 51 cases (0.85%) had ultra-rare (AF < 0.005%) or novel variants. Compared with Genome Aggregation Database (gnomAD) non-cancer controls, there was significant enrichment of ultra-rare and novelRPA1, but notRPA2orRPA3, germline variants in our cohort (adjusted p-value < 0.05). Taken together, these findings suggest that germline putative damaging variants affectingRPA1are found in excess in children with cancer, warranting further investigation into the functional role of these variants in oncogenesis.

 

Eight semesters of qualitative data, collected over four academic years, are presented from a project that resulted in the development of a student professional learning community of high-achieving, low-income engineering and engineering technology student veterans. In the context of this project, student veterans received academic, professional, and financial support that helped them to be successful in school and to prepare them for a career in the STEM workforce. As adult learners, students in this learning community were a vital part of the curriculum development which resulted in increasing the students’ interest and buy-in. Typically, adult learners have lower levels of engagement than tradition-age students due to their non-traditional status. However, by engaging students in the development of a seminar course which served as the foundation for the student learning community, the course curriculum addressed student needs while being built on faculty expertise. Focus groups were conducted at the end of each semester to determine if students perceived the course as an effective professional development intervention. The course was comprised of various guest speaker who addressed different topics related to engineering, and the course also addressed other topics of professional development. In addition to hearing from various guest speakers, students also learned critical professional skills including how to search for an internship and/or permanent position; how to develop a cover letter, resume, and follow-up letter; how to prepare for and respond to questions during interviews; how to present themselves, how to dress, eat and hold a professional conversation at a formal meal during an interview; and how to network and follow-up after meeting people professionally. The guest speakers, veterans themselves, were excited to present to these highly motivated student veterans and to share their stories, and in the process, they inspired this next generation of engineers and engineering technologists. 

The ionospheric density displays hemispheric asymmetries in the polar region due to various hemispheric differences, for example, in the offset between geographic and geomagnetic poles and in the geomagnetic field strength. Using ground‐based ionospheric measurements from Vertical Incidence Pulsed Ionospheric Radar with Dynasonde analysis at Jang Bogo Station (JBS), Antarctica and from EISCAT Svalbard Radar (ESR) where both sites are located mostly in the polar cap, we investigate the hemispheric differences in the ionospheric density between the northern and southern hemispheres for geomagnetically quiet and solar minimum condition. The results are also compared with Thermosphere Ionosphere Electrodynamic Global Circulation Model (TIEGCM) simulations. The observations show larger density and stronger diurnal and seasonal variations at JBS in the southern hemisphere than at Svalbard in the northern hemisphere. The diurnal variations of the density peak height are also observed to be much larger at JBS. In both hemispheres, the ionospheric density is significantly reduced in winter due to the limited solar production at high geographic latitudes, but TIEGCM considerably overestimates winter density, which is even larger than summer density, especially in the northern hemisphere. Also existed are the differences in the equinoctial asymmetry between the observations and the simulations: the daytime F‐region density is observed to be larger in fall than in spring in both hemispheres, but TIEGCM shows the opposite. In general, most of the observed asymmetrical density are much weaker in the model simulation, which may result from lack of proper magnetospheric forcings and neutral dynamics in the model.

 

Abstract Indistinguishability of particles is a fundamental principle of quantum mechanics 1 . For all elementary and quasiparticles observed to date—including fermions, bosons and Abelian anyons—this principle guarantees that the braiding of identical particles leaves the system unchanged 2,3 . However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions 4–8 . Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well-developed mathematical description of non-Abelian anyons and numerous theoretical proposals 9–22 , the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. Whereas efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasiparticles, superconducting quantum processors allow for directly manipulating the many-body wavefunction by means of unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons 9,10 , we implement a generalized stabilizer code and unitary protocol 23 to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of using the anyons for quantum computation and use braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and, through the future inclusion of error correction to achieve topological protection, could open a path towards fault-tolerant quantum computing. 

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue in vitro , therefore providing a route to a predictive in vitro model. However, OOC technologies are often created at the expense of throughput, industry-standard form factors, and compatibility with state-of-the-art data collection tools. Here we present an OOC platform with advanced culture capabilities supporting a variety of human tissue models including liver, vascular, gastrointestinal, and kidney. The platform has 96 devices per industry standard plate and compatibility with contemporary high-throughput data collection tools. Specifically, we demonstrate programmable flow control over two physiologically relevant flow regimes: perfusion flow that enhances hepatic tissue function and high-shear stress flow that aligns endothelial monolayers. In addition, we integrate electrical sensors, demonstrating quantification of barrier function of primary gut colon tissue in real-time. We utilize optical access to the tissues to directly quantify renal active transport and oxygen consumption via integrated oxygen sensors. Finally, we leverage the compatibility and throughput of the platform to screen all 96 devices using high content screening (HCS) and evaluate gene expression using RNA sequencing (RNA-seq). By combining these capabilities in one platform, physiologically-relevant tissues can be generated and measured, accelerating optimization of an in vitro model, and ultimately increasing predictive accuracy of in vitro drug screening. 

Lemur catta is the most reported illegal captive lemur. We document 286 L. catta that were held in illegal captive conditions in Madagascar. Coastal tourist destinations are “hot spots” for sightings. Many of the L. catta reported were in businesses (49%) and were perceived to be held captive for the purpose of generating income (41%). Infant/juvenile L. catta were overwhelmingly observed annually in December (41%) and may suffer high mortality rates given that they are not weaned during this month of the year. Population growth modeling suggests that known capture rates may be sustainable in all but small populations of 500 individuals and when infants/juveniles are targeted. However, of the seven remaining populations of L. catta with more than 100 individuals, only one is known to contain more than 500 animals, and we present evidence here that infants/juveniles are targeted. Moreover L. catta face significant other threats including habitat loss, bushmeat hunting, and climate change. Several actions could reduce the illegal capture and ownership of L. catta in Madagascar such as tourist behavior change initiatives, enforcement of laws, and alternative livelihoods for local people. These interventions are urgently needed and could be adapted to protect other exploited wildlife in the future. 

High magnetic fields suppress cuprate superconductivity to reveal an unusual density wave (DW) state coexisting with unexplained quantum oscillations. Although routinely labeled a charge density wave (CDW), this DW state could actually be an electron-pair density wave (PDW). To search for evidence of a field-induced PDW, we visualized modulations in the density of electronic states N ( r ) within the halo surrounding Bi 2 Sr 2 CaCu 2 O 8 vortex cores. We detected numerous phenomena predicted for a field-induced PDW, including two sets of particle-hole symmetric N ( r ) modulations with wave vectors Q P and 2 Q P , with the latter decaying twice as rapidly from the core as the former. These data imply that the primary field-induced state in underdoped superconducting cuprates is a PDW, with approximately eight CuO 2 unit-cell periodicity and coexisting with its secondary CDWs.