States Of N2 Research Articles

High-temperature magnetic susceptibility in metal-electron systems

High-temperature magnetic susceptibility is studied using the Hubbard model. The equation in the high-temperature limit is derived from the Kubo formula as the Curie law of Ns free 1/2-spins, where Ns is the average number of electrons not forming singlets. Exact results for Ns are presented for various cases and are shown to depend only on the total number of electrons Ne and available orbital states, which is the number of lattices L in the single-band case. The condition of kBT≫U, W with the onsite repulsion U and bandwidth W gives Ns=Lp(2−p)/2 with filling p=Ne/L. The numerical calculation for U=0 shows that the universal Curie law holds at temperatures above the threshold temperature T0, compatible with the Fermi temperature. The threshold temperature for U>0 is found to be lower than T0. The application of the present results to a heavy-fermion system near the Mott transition is proposed.

Patients Hospitalized for Complications of Cirrhosis may Have Benefited From Medicaid Expansion Under the Affordable Care Act

ObjectiveThe benefit of the Affordable Care Act (ACA) for patients with cirrhosis is unclear. We determined the impact of ACA expansion on outcomes in patients hospitalized for complications of cirrhosis. Patients and MethodsWe compared hospitalizations; in-hospital outcomes; and readmissions among patients with cirrhosis identified using International Classification of Diseases, Ninth Revision, and International Classification of Diseases, 10th Revision, codes in states that expanded Medicaid under ACA (expanded [E] states) and those that did not (nonexpanded [NE] states). Data from the State Inpatient Databases were obtained for 3 pairs of contiguous E and NE states with both pre-ACA expansion and post-ACA expansion data. The difference-in-difference analysis was performed to compare the pre- and post-ACA data between the E and NE states. The outcomes were admission rates, hospital complications, resource utilization, length of stay, in-hospital mortality, discharge destination, cost of initial hospitalization, and readmission characteristics. ResultsThere were 228,349 admissions (E states, 149,705; NE states, 78,644). After ACA implementation, the E states had lower rates of admission increase per 100,000 population (22.9 in E states vs 25.5 in NE states, P=.005), sepsis (relative risk, 0.884; P=.0084), and hepatic coma (relative risk, 0.763; P<.001) than the NE states. The length of stay was lower by 0.21 days (P=.00028), with a $587.40 lower cost per hospitalization (P=.00091), in the E states than in the NE states. The readmission rates within 30, 60, and 90 days decreased in the E states after ACA implementation but increased in the NE states after ACA implementation. ConclusionAmong patients hospitalized for cirrhosis, quality indicators, such as the rate of admission increase, complications, costs, and readmissions, were more favorable in the states that expanded Medicaid. Medicaid expansion under ACA may have benefited patients with cirrhosis.

The Differential Impact of Medicaid Expansion on Disparities in Outcomes Following Peripheral Vascular Intervention

Peripheral artery disease (PAD) disproportionately affects nonwhite, Hispanic/Latino, and low socioeconomic status patients, who are less likely to have insurance and routine healthcare visits. Medicaid expansion (ME) has improved insurance rates and access to care, potentially benefitting these patients. We sought to assess the impact of ME on disparities in outcomes after peripheral vascular intervention (PVI) for PAD. A retrospective analysis of prospectively-collected Vascular Quality Initiative PVI procedures between 2011 and 2019 was conducted. The sample was restricted to first-record procedures in adults under the age 65 in states that expanded Medicaid on January 1, 2014 (ME group) or had not expanded before January 1, 2019 (non-expansion [NE] group). ME and NE groups were compared between pre-expansion (2011-2013) and post-expansion (2014- 2019) time periods to assess baseline demographic and operative differences. We used difference-in-differences multivariable logistic regression adjusted for patient factors and clinical center and year fixed effects. Our primary outcome was 1-year major amputation. Secondary outcomes included trends in presentation, 30-day mortality, 1-year mortality, and 1-year primary and secondary patency. Outcomes were stratified by race and ethnicity. We examined 34,313 PVI procedures, including 20,378 with follow-up data. Rates of Medicaid insurance increased post-expansion in ME and NE states (ME 16.7% to 23.0%, P<0.001; NE 10.0% to 11.9%, P=0.013) while rates of self-pay decreased in ME states only (ME 4.6% to 1.8%, P<0.001; NE 8.1% to 8.4%, P=0.620). Adjusted difference-in-differences analysis revealed lower odds of urgent/emergent PVI among all patients and all nonwhite patients in ME states post-expansion compared to NE states (all: odds ratio [OR] 0.53 [95% confidence interval 0.33-0.87], P=0.011; nonwhite: OR 0.41 [0.19-0.88], P=0.023). No differences were observed for 1-year major amputation (OR 0.70 [0.43-1.14], P=0.152), primary patency (OR 0.93 [0.63-1.38], P=0.726), or secondary patency (OR 1.29 [0.69-2.41], P=0.431). Odds of 1-year mortality were higher in ME states post-expansion compared to NE states (OR 2.50 [1.07-5.87], P=0.035), although 30-day mortality was not different (OR 2.04 [0.60-6.90], P=0.253). Notably, odds of 1-year major amputation among Hispanic/Latino patients decreased in ME states post-expansion compared to NE states (OR 0.11 [0.01-0.86], P=0.036). ME was associated with lower odds of 1-year major amputation among Hispanic/Latino patients who underwent PVI for PAD. ME was also associated with lower odds of urgent/emergent procedures among patients overall and nonwhite patients specifically. However, 1-year mortality increased in the overall cohort. Further study is needed to corroborate our findings that ME may have benefits for certain underserved populations with PAD.

Characterization of aEEG During Sleep and Wakefulness in Healthy Children.

IntroductionInterpretation of amplitude-integrated EEG (aEEG) is hindered by lacking knowledge on physiological background patterns in children. The aim of this study was to find out whether aEEG differs between wakefulness and sleep in children.MethodsForty continuous full-channel EEGs (cEEG) recorded during the afternoon and overnight in patients <18 years of age without pathologies or only solitary interictal epileptiform discharges were converted into aEEGs. Upper and lower amplitudes of the C3–C4, P3–P4, C3–P3, C4–P4, and Fp1–Fp2 channels were measured during wakefulness and sleep by two investigators and bandwidths (BW) calculated. Sleep states were assessed according to the American Academy of Sleep Medicine. Median and interquartile ranges (IQR) were calculated to compare the values of amplitudes and bandwidth between wakefulness and sleep.ResultsMedian age was 9.9 years (IQR 6.1–14.7). All patients displayed continuous background patterns. Amplitudes and BW differed between wakefulness and sleep with median amplitude values of the C3–C4 channel 35 μV (IQR: 27–49) for the upper and 13 μV (10–19) for the lower amplitude. The BW was 29 μV (21–34). During sleep, episodes with high amplitudes [upper: 99 μV (71–125), lower: 35 μV (25–44), BW 63 μV (44–81)] corresponded to sleep states N2–N3. High amplitude-sections were interrupted by low amplitude-sections, which became the longer toward the morning [upper amplitude: 39 μV (30–51), lower: 16 μV (11–20), BW 23 μV (19–31)]. Low amplitude-sections were associated with sleep states REM, N1, and N2. With increasing age, amplitudes and bandwidths declined.ConclusionaEEGs in non-critically ill children displayed a wide range of amplitudes and bandwidths. Amplitudes were low during wakefulness and light sleep and high during deep sleep. Interpretation of pediatric aEEG background patterns must take into account the state of wakefulness in in clinical practice and research.

Information Sources Utilization among Potato Farmers in North East India

Information technology has transformed many other aspects of human endeavor and has helped create systems for responding to a wide range of societal needs. The benefits of pertinent farm related information in empowering farmer are significant and remain to be exploited. Potato is one of the most important crops grown successfully in North East India but farmers have limited access to the updated information. A research study was undertaken in four major potato growing states of NE including Assam, Meghalaya, Nagaland and Tripura with a sample of 480 farmers. It was found that potato farmers preferred to utilize informal information sources more than formal as well as the mass media sources with respect to using inputs and taking pertinent decisions with respect to sustainable potato cultivation. Farmers urgently require timely and reliable sources of information for taking important farm management decisions. Therefore, it is recommended to popularize the strategic use of mass media including user friendly ICT tools for better and faster outreach to the target farmers.

The possibility of North Eastern States to lead the growth story of India: A viability study

In recent years, growing concern has been noticed among Indian leaders and policy makers regarding the North East’s potentialities of growth. They have said that NE states can lead the growth story of India. Though, rich in natural resources, NE states have failed to take place among the developed states of the country. This paper deals with the question of possibility of NE states leading the growth story of India. It is based on secondary data collected from reports of the government and international organisations.

Smokeless tobacco use among women in northeastern states, India: A study of spatial clustering and its determinants using National Family Health Survey-4 data

BackgroundUse of tobacco, especially smokeless tobacco have characterised as highly prevalent among women, and also the mode of using smokeless tobacco varies based on geographic location, ingredient availability, cultural/societal norms, and personal preferences. Therefore, this study examines the prevalence and social determinants of use of smokeless tobacco among women in NE India. Further, it also identifies the cluster and district hotspots of smokeless tobacco prevalence. MethodsWe analysed a nationally representative data of NFHS-4, covering 93,409 eligible women aged 15–49 years from a survey of representative households from NE states, India. Descriptive statistics, chi-square, binary logistic and log-binomial regression were employed to analyse the data by using STATA software 13.1. Spatial clustering analysis and hotspot analysis were carried out using R-library. FindingsThe prevalence of SLT use among women in NE states, India is 23%. Mizoram (47.8 ± 1.2) shows the highest prevalence of SLT use, followed by Manipur (46.1 ± 0.7). It increases concomitantly with age among women. Social determinants like marital status (divorced/widowed), low educational level and residence (urban) were observed to be associated with smokeless tobacco use. Out of the 4032 clusters used in the analysis, 949 clusters were showed as hotspots. ConclusionThe existing implementation of tobacco control programs and policies in the NE states needs to be evaluated. Owing to the geographical barriers and cultural differences, there is a need to explore the influences unique to these regions, which can further strengthen tobacco control measures. Targeted and tailored intervention within the identified hotspots can be beneficial.

SEROPREVALENCE OF INFECTIOUS BOVINE RHINOTRACHEITIS (IBR) IN NORTH EASTERN (NE) STATES OF INDIA

Infectious bovine rhinotracheitis (IBR) is an infectious disease caused by BoHV-1 and belongs to the Herpesviridae family. IBR is endemic in India including north eastern states of the country. Hence the study was undertaken to understand the seroprevalence of IBR in north eastern parts of the country. A total of 3125 cattle (Holstein Friesian crossbred) serum samples from 35 districts of five north eastern states (Assam, Manipur, Meghalaya, Mizoram, and Sikkim) of India were screened for infectious bovine rhinotracheitis (IBR) virus antibodies using Avidin biotin ELISA. A two-stage random sampling methodology was followed for the collection of samples. Results from the present study revealed that the overall seropositivity was reported around 29.50% while the highest and lowest seropositivity of 43.39% and 16.66% were reported in the states of Sikkim and Assam respectively, followed by Mizoram (42.16%), Manipur (29.86%) and Meghalaya (27.40%). Cattle of higher age groups showed the highest seropositivity compared to younger ones. A higher percent of IBR antibodies in cattle of NE states is a cause of concern and a detailed study on IBR prevalence comprising of a large number of the bovine population need to be undertaken.

Candidates for the 5α condensed state in 20Ne

We conducted the coincidence measurement of α particles inelastically scattered from 20Ne at 0° and decay charged particles in order to search for the alpha-particle condensed state. We compared the measured excitation-energy spectrum and decay branching ratio with the statistical-decay-model calculations, and found that the newly observed states at Ex=23.6, 21.8, and 21.2 MeV in 20Ne are strongly coupled to a candidate for the 4α condensed state in 16O. This result presents the first strong evidence that these states are the candidates for the 5α condensed state.

An improved rovibrational linelist of formaldehyde, H[formula omitted]C[formula omitted

Published high-resolution rotation-vibration transitions of H212C16O, the principal isotopologue of methanal, are analyzed using the MARVEL (Measured Active Rotation-Vibration Energy Levels) procedure. The literature results are augmented by new, high-accuracy measurements of pure rotational transitions within the ground, ν3,ν4, and ν6 vibrational states. Of the 16 596 non-redundant transitions processed, which come from 43 sources including the present work, 16 403 could be validated, providing 5029 empirical energy levels of H212C16O with statistically well-defined uncertainties. All the empirical rotational-vibrational energy levels determined are used to improve the accuracy of ExoMol’s AYTY line list for hot formaldehyde. The complete list of collated experimental transitions, the empirical energy levels determined, as well as the extended and improved line list are provided as Supplementary Material.

Sub-threshold states in Ne19 relevant to F18(p,α)O15

Classical novae result from thermonuclear explosions producing several $\gamma$-ray emitters which are prime targets for satellites observing in the MeV range. The early 511 keV gamma-ray emission depends critically on the $^{18}$F(p,$\alpha$)$^{15}$O reaction rate which, despite many experimental and theoretical efforts, still remains uncertain. One of the main uncertainties in the $^{18}$F(p,$\alpha$)$^{15}$O reaction rate is the contribution in the Gamow window of interference between sub-threshold $^{19}$Ne states and known broad states at higher energies. Therefore the goal of this work is to clarify the existence and the nature of these sub-threshold states. States in the $^{19}$Ne compound nucleus were studied at the Tandem-ALTO facility using the $^{19}$F($^3$He,t)$^{19}$Ne charge exchange reaction. Tritons were detected with an Enge Split-pole spectrometer while decaying protons or $\alpha$-particles from unbound $^{19}$Ne states were collected, in coincidence, with a double-sided silicon strip detector array. Angular correlations were extracted and constraints on the spin and parity of decaying states established. The coincidence yield at $E_x$ = 6.29 MeV was observed to be high spin, supporting the conclusion that it is indeed a doublet consisting of high spin and low spin components. Evidence for a broad, low spin state was observed around 6 MeV. Branching ratios were extracted for several states above the proton threshold and were found to be consistent with the literature. R-matrix calculations show the relative contribution of sub-threshold states to the astrophysically important energy region above the proton threshold. The levels schemes of $^{19}$Ne and $^{19}$F are still not sufficiently well known and further studies of the analogue assignments are needed. The tentative broad state at 6 MeV may only play a role if the reduced proton width is large.

Experimental measurement of state-selective charge exchange and test of astrophysics soft X-ray emission model

Charge exchange, or electron capture, between highly charged ions and atoms and molecules has been considered as one of important mechanisms controlling soft X-ray emissions in many astrophysical objects and environments. However, to model charge exchange soft X-ray emission, astrophysicists commonly use principal quantum number &lt;i&gt;n&lt;/i&gt; and angular momentum quantum number&lt;i&gt;l&lt;/i&gt; resolved state-selective capture cross section data, which are usually obtained by empirical and semi-classical theory calculations. The accuracy of the theoretical model is the key to constructing an accurate X-ray spectrum. With a newly-built cold target recoil ion momentum spectroscopy apparatus, we perform a series of precise state-selective cross section measurements on Ne&lt;sup&gt;8+&lt;/sup&gt; ions’ single electron capture with He targets, with the projectile energy ranging from 1.4 to 20 keV/u. The experimentally measured Q value spectrum shows that the process of electron captured to state of Ne&lt;sup&gt;7+&lt;/sup&gt; with &lt;i&gt;n&lt;/i&gt; = 4 is the main reaction channel, and that with &lt;i&gt;n&lt;/i&gt; = 3 and 5 are the small reaction channels. Using Gaussian curve to fit the area of each channel on the Q value spectrum and normalizing the area of all channels, we obtain the &lt;i&gt;n&lt;/i&gt;-resolved relative state-selective cross section. By comparing the measured relative cross sections with the results calculated by the multichannel Landau-Zener method and molecular Coulomb over-barrier model, significant difference among the strengths of small reaction channels is found. Specifically, the multichannel Landau-Zener method overestimates the contribution of &lt;i&gt;n&lt;/i&gt; = 2 channel and &lt;i&gt;n&lt;/i&gt; = 3 channel, and underestimates the contribution of &lt;i&gt;n&lt;/i&gt; = 5 channel. The molecular Coulomb over-barrier model overestimates the contribution of &lt;i&gt;n&lt;/i&gt; = 5 channel and underestimates the contribution of &lt;i&gt;n&lt;/i&gt; = 3 channel. The significant difference between the theoretical model calculation and experimental measurement is due to the limitations of semiclassical theoretical method and classical theoretical method. Furthermore, with &lt;i&gt;l&lt;/i&gt; distribution models commonly used in the astrophysical literature, including the statistical model, separable model, Landau-Zener-I model, Landau-Zener-II model and even model, we calculate the soft X-ray emissions in the charge exchange between 1.6 and 2.4 keV/u Ne&lt;sup&gt;8+&lt;/sup&gt; and He. It is found that the calculated intensities of X-ray spectra significantly deviate from the existing measurements, and only the separable model can partly match the laboratory simulated solar wind charge exchange X-ray measurement. Furthermore, we find that the intensity of the charge exchange X-ray emission spectrum measured experimentally is dependent on the collision energy, while the emission spectrum calculated based on the model seems to be unchanged with the increase of the collision energy. These results indicate that if the classical and semi-classical models are applied to the astrophysical plasma for studying diffusive soft X-ray background, the obtained parameters of the astrophysical plasma will be inaccurate.

Optimization of N2+ lasing by waveform-controlled polarization-skewed pulses.

Optical ionization of N2 and subsequent population redistribution among the ground and excited states of N2+ in an intense laser field are commonly accepted to be fundamentally responsible for the generation of N2+ lasing. By finely controlling this two-step process, the optimization of N2+ lasing is possibly achieved. Here, we design a waveform-controlled polarization-skewed (PS) pumping pulse, in which the leading and falling edges are orthogonally polarized, and their relative field strength and phase can be well controlled. We demonstrate that precise manipulation of the N2+ lasing at 391 nm and 428 nm emissions can be achieved by modulating both the relative phase and amplitudes of the two orthogonally polarized components of the pumping PS pulse. We find that the optimization of N2+ lasing depends not only on the competitive balance between the ionization and post-ionization coupling that varies in different pumping energies but also on the phase with the maximum intensity appearing at the phase of nπ. Orders of magnitude enhancement in the N2+ lasing intensity is observed as the phase changes from (n+1/2)π to nπ. The PS pulse with a controllable spatiotemporal waveform provides us a robust and straightforward tool to efficiently enhance the N2+ lasing emission.

Isospin triplet A=14: search for states with enhanced radii

This article is devoted to study of isobar-analogue states 1− in triplet A=14: 14C-14N-14O. Previously signs of neutron halo in the 1−, 6.09 MeV state of 14C were obtained by two independent groups. In this article we propose to study neighbouring nuclei 14N and 14O using the Modified diffraction model (MDM) method and the method of Asymptotic normalization coefficients (ANC). Methods were applied to experimental differential cross sections of 14C(α,α)14C scattering and reactions 13C(3He,d)14N and 14N(3He,t)14O. MDM and ANC gave practically similar within errors radii for the studied 1− states: the 6.09 MeV state in 14C – 2.7±0.1 fm, the 8.06 MeV state in 14N – 2.7 ± 0.1 fm, the 5.17 MeV state in 14O – 2.6 ± 0.2 fm. Moreover, the signs of proton halo in the 1− state of 14N were obtained for the first time.

Neutral and Excited Molecules and Atoms Densities in the Positive Column of Flowing N2 DC Discharges

We investigated flowing N2 DC discharges both experimentally and theoretically. The discharge gas and N2(X1Σ+g) vibrational temperatures, electron density (ne), reduced electric field (E/N), and radiative state densities were measured by optical emission spectrometry (OES) and Langmuir double probes. We formulated a discharge kinetic numerical model to calculate the densities of nitrogen species as functions of the gas residence time. We combine the experimental parameters measured in the discharge with the kinetic model to analyze different discharge conditions where E/N varies significantly. First, we analyzed the measured and calculated radiative states densities and N2(X1Σ+g) vibrational distributions at the end of the positive column. Results show good agreement between calculated and measured parameters. Then, we studied the excited molecular species densities, and neutral and excited atoms densities as functions of the discharge gas residence time. This work presents for the first time the temporal densities of excited molecular and atomic states from 10−9 to 10−1 s discharge residence times, calculated for experimental conditions where ne presents a low variation and E/N varies from high (94 Td) to relatively low values (48 Td). The discharge experimental conditions are discharge current of 60 mA, gas pressure of 230–530 Pa, and gas flow rate of 0.9 Slm−1.

Impact of urbanization on land use and land cover change in Guwahati city, India and its implication on declining groundwater level

Urban environment continues to expand at an unprecedented rate to meet the demand of increasing population and economic development. The resulting changes to landscapes have increased stress to hydrological cycles, biogeochemical processes, and environmental sustainability of natural resources. This study evaluated spatio-temporal changes of land use and land cover (LULC) between 1990 and 2020 in Guwahati city, India. Time-series Landsat satellite images were analyzed using supervised classification schemes followed by quantification of LULC change over time. Five broad LULC classes were identified on the basis of spectral reflectance signature. Confusion matrix determined high classification accuracy with Kappa Coefficient >0.81 in all cases. The results showed that the urban built environment has doubled in area in 30 years (1990–2020). The urban environments have increased at the expense of vegetation, fallow land, and open areas and to some extent wetlands. Notably, the expansions of urban areas have taken place from city center to the south, to the south-east, and along the east-west National Highway 37 connecting other NE States of India. There is no clear indication of change in the amount of precipitation in response to urbanization. However, analysis of long-term groundwater level data suggests a steady decline in the depth to groundwater level. The declining trend is attributed to urbanization and population growth. The increase in impervious surface coverage due to urbanization have extensively reduced the areas of high potential groundwater recharge zones and thereby dropping the level of groundwater in the wells.

MicroRNA determinants of neuroendocrine differentiation in metastatic castration-resistant prostate cancer.

Therapy-induced neuroendocrine prostate cancer (NEPC), an extremely aggressive variant of castration-resistant prostate cancer (CRPC), is increasing in incidence with the widespread use of highly potent androgen receptor (AR)-pathway inhibitors (APIs) such as Enzalutamide (ENZ) and Abiraterone and arises via a reversible trans-differentiation process, referred to as neuroendocrine differentiation (NED). The molecular basis of NED is not completely understood leading to a lack of effective molecular markers for its diagnosis. Here, we demonstrate for the first time, that lineage switching to NE states is accompanied by key miRNA alterations including downregulation of miR-106a~363 cluster and upregulation of miR-301a and miR-375. To systematically investigate the key miRNAs alterations driving therapy induced NED, we performed small RNA-NGS in a retrospective cohort of human metastatic CRPC clinical samples + PDX models with adenocarcinoma features (CRPC-adeno) vs those with neuroendocrine features (CRPC-NE). Further, with the application of machine learning algorithms to sequencing data, we trained a ‘miRNA classifier’ that could robustly classify ‘CRPC-NE’ from ‘CRPC-Adeno’ cases. The performance of classifier was validated in an additional cohort of mCRPC patients and publicly available PCa cohorts. Importantly, we demonstrate that miR-106a~363 cluster pleiotropically regulate cardinal nodal proteins instrumental in driving NEPC including Aurora Kinase A, N-Myc, E2F1 and STAT3. Our study has important clinical implications and transformative potential as our ‘miRNA classifier’ can be used as a molecular tool to stratify mCRPC patients into those with/without NED and guide treatment decisions. Further, we identify novel miRNA NED drivers that can be exploited for NEPC therapeutic targeting.

Search for Signs of Neutron and Proton Halos in the Excited Isobaric Analog States of A = 14 Nuclei

The isobaric analog states with isospin T = 1 in triplet of the A = 14 nuclei: 14C, 14N, and 14O, are studied. Signs of neutron halo in the 1− (6.09 MeV) state of 14C have been revealed earlier by two groups. We confirm this result and study isobaric analog 1− states of neighboring 14N and 14O nuclei. The differential cross sections of the 14C(α, α)14C* (6.09 MeV, 1−) inelastic scattering, the 13C(3He, d)14N* (8.06 MeV, 1−), and the 14N(3He, t)14O* (5.17 MeV, 1−) reactions are analyzed by two methods: the modified diffraction method and the method of asymptotic normalization coefficients. The rms radii for all three mirror nuclei in the studied 1− states are found almost the same: 2.7 ± 0.1 fm for 14C, 2.67± 0.07 fm for 14N, and 2.6 ± 0.2 fm for 14O. The signs of proton halo in the 1− state of 14N are identified for the first time.

Different Dynamics of CH3 and Cl Fragments from Photodissociation of CH3Cl in Clusters.

We investigate the photodissociation of CH3Cl at 193.3 nm using the velocity map imaging technique in (CH3Cl)n clusters in comparison with isolated molecules. Our results for the isolated molecules are in excellent agreement with the previous study of Cl fragments, and we extend it by detecting also the CH3(ν = 0) fragments. For the clusters, the Cl (and Cl*) and CH3 fragment images are dominated by intense central isotropic features. The corresponding kinetic energy distributions (KEDs) reveal significant differences in the CH3 and Cl fragment dynamics. While the CH3 fragments exhibit a very narrow near-zero kinetic energy peak, pointing to almost complete caging of CH3 fragments, the Cl (and Cl*) fragments show more structured KEDs extending all the way to the maximum available kinetic energy. The Cl KED spectra have a bimodal character with two broad peaks close to zero and around 0.6 eV. We observe a higher ICH3(ν=0)/ICl signal ratio from the clusters compared to the monomers. This is attributed to an efficient quenching of the higher vibrationally excited ν2 states of the CH3 fragments generated in the photodissociation. Collisional quenching of these excited states in clusters enhances the detected CH3(ν = 0) state. Finally, we determine the [Cl*]/[Cl] branching ratio for the photodissociation pathways in the clusters as ≈0.55 ± 0.15 compared to 0.86 for the isolated molecules, which is also attributed to the collisional quenching of the excited state in the clusters. The clusters and photofragment dynamics are discussed.

Abstract 1404: MicroRNA-mediated induction of neuroendocrine differentiation states in metastatic castration-resistant prostate cancer

Abstract While the widespread use of androgen receptor pathway inhibitors (APIs) such as enzalutamide has led to transformative impact in the management of metastatic castration-resistant prostate cancer (CRPC) patients, resistance is near-universal leading to significantly increased incidences of highly aggressive, therapy-induced neuroendocrine differentiation (NED). It has been realized that therapy-induced NED represents a continuum of treatment-induced changes at phenotypic and molecular level that involves a series of alterations at genetic, epigenetic, post-transcriptional, post-translational levels and changes in microenvironment. Though several recent studies identified key genomic and epigenomic alterations driving therapy-induced NED, the molecular pathogenesis is still not completely understood contributing to late diagnosis of the disease, poor prognosis and lack of effective therapies. The focused objective of our study was to systematically investigate the key microRNA (miRNAs) alterations that drive therapy-induced NED in PCa. We hypothesized that this lineage switch is associated with significant alterations to the miRNAome, that in turn, drives change in cellular gene expression patterns towards NE states. We tested our hypothesis by performing small RNA-NGS in a clinical cohort of patient samples, patient-derived xenograft and cellular models. We identify for the first time that a characteristic set of miRNA alterations promote plasticity of prostate tumors to NE states. Importantly, we identify downregulation of miR-363 as a prominent molecular alteration underlying PCa NED. To examine the functional role of miR-363, we knocked down its expression in CRPC cell lines C42B and LNCaP followed by functional assays. Decreased miR-363 expression resulted in increased clonogenicity potential and invasiveness of PCa cell lines as compared to control suggesting that miR-363 loss contributes to increased aggressiveness. Importantly, we found that miR-363 directly represses Aurora kinase A (AURKA), a prototypical kinase frequently amplified in NED. Correlation analyses in TCGA database of prostate adenocarcinomas (n=494) showed a significant inverse correlation between miR-363 expression and AURKA mRNA levels. In conclusion, our study identifies crucial molecular determinants of NED with potential clinical and transformative potential. Since AURKA inhibition is currently being examined as a therapeutic modality for NEPC, we propose augmentation of miR-363 levels to repress AURKA as a novel treatment option for therapy-induced NEPC. Citation Format: Divya Bhagirath, Michael Liston, Byron Lui, Dat My To, Thao Ly Yang, Laura Z. Tabatabai, Nikhil Patel, Roni Bollag, Adam Olshen, Sharanjot Saini. MicroRNA-mediated induction of neuroendocrine differentiation states in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1404.