OBJECTIVES/GOALS: Immediate negative impact of the COVID pandemic on CTSA T trainees and K scholars was reported in 2020 to be lack of access to research facilities, clinics, human subjects, and team members, and a need for homeschooling. In this study we examined in more detail the perceived impact of the COVID pandemic on training and career development three years later. METHODS/STUDY POPULATION: CTSA T trainees and K scholars were surveyed in May-June 2023 to assess the impact of the COVID-19 pandemic on training and career development. Data were included from 309 T trainees and K scholars appointed in 2018-2023 at 50 institutions, with good representation from states that were heavily impacted by COVID. Respondents included 76 past and 64 current T trainees, and 56 past and 113 current K scholars. There were no significant differences in race, ethnicity, or gender between T and K respondents. Significantly more K scholars reported both being married or in a committed relationship, and having children. Survey items included the same questions asked in the 2020 survey, plus additional new questions. Results compare impact for T trainees and K scholars. RESULTS/ANTICIPATED RESULTS: K scholars were more negatively impacted for access to clinic/human subjects, home environment, child care, access to staff, increased clinical responsibilities, and other hospital service. T trainees and K scholars reported higher positive impact than in 2020, for having more time to think/write and develop new research ideas. About 2/3 of respondents reported returning to research full-time by April 2021, and the remaining by August 2021. Lasting changes in career progression or research direction were reported as both positive and negative (48%), negative (25%), or positive (10%). Most (2/3) respondents in faculty positions reported that a time extension was available for promotion and/or tenure. Additional in-depth analysis will be presented, based on qualitative analysis of open-ended questions. DISCUSSION/SIGNIFICANCE: Despite research shutdowns in response to the COVID-19 pandemic that lasted for about a year, CTSA T trainees and K scholars were remarkably resilient. They were able to continue some research activities and professional development activities, and developed strategies to maintain productivity and minimize impact on their training duration.

Background: AChR antibodies (Abs) in Myasthnia Gravis (MG) are detected in approximately 50% of ocular and 85% of generalized MG by the current gold standard radioimmunoprecipitation assay (RIPA). Recently, fixed and lived Cell-Based assays (L-CBA) are developed. We clinically validated our in-house L-CBA in detecting AChR Ab in clinically suspected MG patients. Methods: Between January 2020 and April 2022, we assayed 10167 sera for AChR Ab by RIPA. We also assayed 4349 of AChR Ab seronegative sera of the above suspected MG samples for anti-MuSK Ab by RIPA. Then 1228 sera of double seronegative and/or borderline AChR Ab was assessed by L-CBA for AChR Ab. For clinical validation, we obtained clinical information on 36 seropositive cases for AChR Ab by L-CBA. Results: We found additional eighty-four cases seropositive for AChR Ab by L-CBA. The clinical information was obtained for 36 cases and based on their final diagnosis, twenty had generalized MG, thirteen had ocular MG, 2 not yet diagnosed and 1 case was of not-MG. Conclusions: The L- CBA has demonstrated improved sensitivity and higher diagnostics performance than RIPA. The L-CBA allowed improved clinical diagnosis and increased seropositivity (by 7%) in clinically suspected MG patients who were earlier seronegative/borderline for AChR Ab by RIPA.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain ( ${\sim}2.8\,\mbox{K Jy}^{-1}$ ) low-system temperature ( ${\sim}18\,\mbox{K at }20\,\mbox{cm}$ ) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar $\mbox{J}0737{-}3039\mbox{A}$ , pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR $\mbox{J}0540{-}6919$ , and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR $\mbox{J}2241{-}5236$ exhibits a jitter limit of $<4\,\mbox{ns h}^{-1}$ whilst timing of PSR $\mbox{J}1909{-}3744$ over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.

A nonparaxial investigation for propagation characteristics of q-Gaussian laser beam in rippled density plasma is studied by considering the relativistic nonlinearity. The field distribution in the medium is expressed in terms of q parameter and beam width parameter f. Nonlinear parabolic partial differential equation governing the evolution of complex envelope in slowly varying approximation is solved in a modulated density profile. Analytical theory of self-focusing including higher order terms in the expansion of dielectric function up to fourth order is developed and the variation of beam width parameter f with the distance of propagation for different parameters is studied. One may note that increased value of density ripple, laser intensity and depth of modulation, increases self-focusing whereas a lower value of q shows strong self-focusing. A comparative study between paraxial and nonparaxial study has also conducted. This study is useful for research in high energy density physics.

We have explored the thermodynamics of compressed magnetized plasmas in laboratory experiments and we call these studies ‘magnetothermodynamics’. The experiments are carried out in the Swarthmore Spheromak eXperiment device. In this device, a magnetized plasma source is located at one end and at the other end, a closed conducting can is installed. We generate parcels of magnetized plasma and observe their compression against the end wall of the conducting cylinder. The plasma parameters such as plasma density, temperature and magnetic field are measured during compression using HeNe laser interferometry, ion Doppler spectroscopy and a linear ${\dot{B}}$ probe array, respectively. To identify the instances of ion heating during compression, a PV diagram is constructed using measured density, temperature and a proxy for the volume of the magnetized plasma. Different equations of state are analysed to evaluate the adiabatic nature of the compressed plasma. A three-dimensional resistive magnetohydrodynamic code (NIMROD) is employed to simulate the twisted Taylor states and shows stagnation against the end wall of the closed conducting can. The simulation results are consistent to what we observe in our experiments.

Human embryonic stem cells (hESCs) are known for their indefinite self-renewal ability and pluripotent nature. However, during long-term culture, normal hESCs can undergo neoplastic transformation and acquire enhanced self-renewal ability and aberrant differentiation potential. These transformed-hESCs (trans-hESCs) exhibit high expression of the pluripotent gene, LIN28A. LIN28A, an RNA binding protein, is known: for its role in self-renewal of hESCs, as a reprogramming factor for generating induced-pluripotent stem cells and as a potent oncogene in several poorly differentiated, highly malignant human cancers. Despite its multiple functions, how LIN28A contributes to neoplastic transformation of normal hESCs is poorly understood. Our preliminary data demonstrate that following LIN28A knockdown, trans-hESCs display normal hESCs morphology consisting of both pluripotent colony cells surrounded by more differentiated fibroblast-like cells. Neural precursors derived from LIN28A knockdown trans-hESCs also revert back to a state of normal cell morphology and growth. Further analyses revealed that the expression levels of stage-specific embryonic antigen (SSEA3), OCT3/4 and NANOG decreases and are comparable to that observed in normal hESCs following LIN28A downregulation. Expression of miRNA targets of LIN28A such as let7i and mir125b was increased to levels seen in normal hESCs. These preliminary results indicate that LIN28A is a major contributing factor to neoplastic transformation of hESCs and that this process can be reversed by cellular “reprogramming”. This study will enhance our understanding of role of LIN28A in the transformation process in various human cancers thus, underscoring the value of hESCs and their neoplastic-derivatives as cellular and molecular model for studying tumor progression.

Twenty crossbred lactating multiparous cows were used in a 28-day study to compare dry matter intake (DMI), milk yield, milk composition and Bacillus thuringiensis (Bt) protein concentrations in plasma when fed diets containing Bollgard II® cottonseed (BGII) or a control non-genetically modified isogenic cottonseed (CON). Bollgard II cottonseed contains the Cry1Ac and Cry2Ab insecticidal proteins that protect cotton plants from feeding damage caused by certain lepidopteran insects. Cows were assigned randomly to the BGII or CON treatments after a 2-week adjustment period. Cows consumed a concentrate containing 40% crushed cottonseed according to milk yield and green maize forage ad libitum. All cows received the same diet but with different crushed cottonseed sources. Cottonseed was included to provide approximately 2.9 kg per cow daily (dry matter basis). The ingredient composition of the concentrate was 40% crushed cottonseed, 15% groundnut cake, 20% corn, 22% wheat bran, 1% salt and 2% mineral mixture. Milk and blood plasma were analyzed for Cry1Ac and Cry2Ab proteins. DMI, BW, milk yield and milk components did not differ between cows on the BGII and CON treatments. Although milk yield and milk fat percentage were not affected by treatment, 4% fat-corrected milk (FCM) production and FCM/kg DMI for cows on the BGII treatment (14.0 kg/cow per day, 1.12 kg/kg) were significantly improved compared with cows on the CON treatment (12.1 kg/cow per day, 0.97 kg/kg). Gossypol contents in BGII cottonseed and conventional cottonseed were similar. Cry1Ac and Cry2Ab2 proteins in Bollgard II cottonseed were 5.53 and 150.8 μg/g, respectively, and were not detected in the milk or plasma samples. The findings suggested that Bollgard II cottonseed can replace conventional cottonseed in dairy cattle diets with no adverse effects on performance and milk composition.

Genetic variability in carrots is a consequence of allogamy, which leads to a high level of inbreeding depression, affecting the development of new varieties. To understand the extent of genetic variability in 40 elite indigenous breeding lines of subtropical carrots, 48 DNA markers consisting of 16 inter simple sequence repeats (ISSRs), 10 universal rice primers (URPs), 16 random amplification of polymorphic DNA (RAPD) and six simple sequence repeat (SSR) markers were used. These 48 markers amplified a total of 591 bands, of which 569 were polymorphic (0·96). Amplicon size ranged from 200 to 3500 base pairs (bp) in ISSR, RAPD and URPs markers and from 100 to 300 bp in SSR markers. The ISSR marker system was found to be most efficient with (GT)n motifs as the most abundant SSR loci in the carrot genome. The unweighted pair group method with arithmetic mean (UPGMA) analysis of the combined data set of all the DNA markers obtained by four marker systems classified 40 genotypes in two groups with 0·45 genetic similarity with high Mantel matrix correlation (r=0·92). The principal component analysis (PCA) of marker data also explained 0·55 of the variation by first three components. Molecular diversity was very high and non-structured in these open-pollinated genotypes. The study demonstrated for the first time that URPs can be used successfully in genetic diversity analysis of tropical carrots. In addition, an entirely a new set of microsatellite markers, derived from the expressed sequence tags (ESTs) sequences of carrots, has been developed and utilized successfully.

Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008