Restless bandits are a class of sequential resource allocation problems concerned with allocating one or more resources among several alternative processes where the evolution of the processes depends on the resources allocated to them. Such models capture the fundamental trade-offs between exploration and exploitation. In 1988, Whittle developed an index heuristic for restless bandit problems which has emerged as a popular solution approach because of its simplicity and strong empirical performance. The Whittle index heuristic is applicable if the model satisfies a technical condition known as indexability. In this paper, we present two general sufficient conditions for indexability and identify simpler-to-verify refinements of these conditions. We then revisit a previously proposed algorithm called the adaptive greedy algorithm which is known to compute the Whittle index for a sub-class of restless bandits. We show that a generalization of the adaptive greedy algorithm computes the Whittle index for all indexable restless bandits. We present an efficient implementation of this algorithm which can compute the Whittle index of a restless bandit with K states in $\mathcal{O}\!\left(K^3\right)$ computations. Finally, we present a detailed numerical study which affirms the strong performance of the Whittle index heuristic.

Junglerice [Echinochloa colona (L.) Link] is increasing its prevalence in eastern Australia by adapting to Australia’s changing climatic conditions and conservation agricultural systems and by evolving resistance to glyphosate. Information is limited on the growth and seed production dynamics of E. colona when it interferes with mung bean [Vigna radiata (L). R. Wilczek], a major potential export crop for eastern Australia. This field study examined the interference of E. colona in mung bean for two summer seasons (2020 and 2021) at Gatton, QLD. Different infestation levels (0, 2, 4, 8, 16, and 32 plants m−2) of E. colona were assessed for their potential to cause yield reductions in mung bean. Seed yield of mung bean was highest in the weed-free plots (2,767 kg ha−1) and declined by 20%, 27%, 34%, and 43% at weed infestation levels of 4, 8, 16, and 32 plants m−2, respectively. Echinochloa colona biomass in mung bean varied from 11 to 137 g m−2 as weed density increased from 2 to 32 plants m−2. Based on a three-parameter hyperbolic rectangular decay model, crop yield loss was 52% and 57%, respectively, when weed density and weed biomass approached maximum. Echinochloa colona at the highest density (32 plants m−2) produced a maximum of 15,140 seeds m−2, and this seed production was reduced by 50% at a weed density of 10 plants m−2. Echinochloa colona plants retained 63% to 68% seeds at mung bean maturity, indicating a great opportunity for harvest weed seed control. This study suggests that a high infestation of E. colona in mung bean fields could cause a substantial yield loss and increase the weed seedbank.

OBJECTIVES/GOALS: Our goal is to develop a cost-effective approach for precision medicine treatment by providing computational predictions for new uses of currently available FDA approved, and experimental drugs for NSCLC. METHODS/STUDY POPULATION: Cell Lines: A549 (ATCC- CCL-185) Human epithelial Lung Carcinoma cells, H1792 (ATCC-CRL-5895) Human Lung Carcinoma cells. In Vitro Cytotoxicity Assay: A Vybrant® MTT Cell Proliferation Assay was used. Colony Formation Assay: NCI-H1792, A549 cells were seeded at a density of 500 cells/ dish, then treated with ARS-1620, Osimertinib. The Computational Analysis of Novel Drug Opportunities (CANDO):  Herein, we employed the bioanalytic docking (BANDOCK) protocol within CANDO to calculate the compound-protein interaction scores for a library of 13,218 compounds from DrugBank against a library of 5,317 protein structures from the Protein Data Bank, resulting in a proteomic interaction signature for each compound, and identified Osimertinib as the most likely EGFR/ErbB inhibitor to synergize with ARS-1620. RESULTS/ANTICIPATED RESULTS: ARS-1620 and Osimertinib in combination displays potent anti-tumor activity as evident by a decrease in cell viability with cytotoxicity assays, as well as reduced number of colonies in the colony formation assay for both A549 and H1792 cells. By using CANDO, and cross-referencing the obtained rankings with known experimental information, we have obtained drug predictions within the context of precision medicine. Our preliminary data indicates that EGFR inhibitor Osimertinib may be most structurally similar to KRAS G12C inhibitors overall, compared to other ErbB/ EGFR inhibitors. Validations with human cancer cell lines A549 and H1792 have confirmed that Osimertinib in combination with KRAS G12C inhibitor ARS-1620 may exhibit a synergistic effect in decreasing cellular proliferation and colony formation. DISCUSSION/SIGNIFICANCE: This suggests that this innovative drug combination therapy may help improve treatment outcomes for KRAS G12C(H1792) and KRASG12S(A549) mutant cancers. Cell migration and cell invasion studies in response to treatment with Osimertinib and ARS-1620 are currently ongoing.

Control of glyphosate-resistant (GR) junglerice is a challenging task in eastern Australia. There is limited information on the efficacy and reliability of alternate herbicides for GR populations of junglerice, especially when targeting large plants and when temperatures are high. A series of experiments were conducted to confirm the level of glyphosate resistance in three populations of junglerice and to evaluate the efficacy of alternate herbicides for the control of GR junglerice populations. The LD50 of glyphosate of B17/7, B17/34, and B17/35 populations was found to be 298, 2,260, and 1,715 g ae ha–1, respectively, suggesting that populations B17/34 and B17/35 were highly resistant to glyphosate. Glyphosate efficacy was reduced at high-temperature (35 C day/25 C night) compared with low-temperature conditions (25 C day/15 C night), suggesting that control of susceptible populations may also be reduced if glyphosate is sprayed under hot conditions. Preemergence herbicides dimethenamid-P (1,000 g ai ha–1) and pendimethalin (1,500 g ai ha–1) provided 100% control of GR populations (B17/34 and 17/35). Postemergence herbicides, such as clethodim (60 or 90 g ai ha–1), glufosinate (750 g ai ha–1), haloxyfop (52 or 78 g ai ha–1), and paraquat (400 or 600 g ai ha–1), applied at the four-leaf stage provided 100% control of GR populations. For larger junglerice plants (eight-leaf stage), postemergence applications of paraquat (400 or 600 g ai ha–1) provided greater weed control than clethodim, glufosinate, and haloxyfop. A mixture of either glufosinate or haloxyfop with glyphosate provided poor control of GR junglerice populations compared with application of glufosinate or haloxyfop applied alone. Efficacy of glufosinate and haloxyfop for the control of GR populations decreased when applied in the sequential spray after glyphosate application. This study identified alternative herbicide options for GR junglerice populations that can be used in herbicide rotation programs for sustainable weed management.

Maternal folic acid and vitamin B12 (B12) status during pregnancy influence fetal growth. This study elucidated the effect of altered dietary ratio of folic acid and B12 on the regulation of H19/IGF2 locus in C57BL/6 mice. Female mice were fed diets with nine combinations of folic acid and B12 for 4 weeks. They were mated and the offspring born (F1) were continued on the same diet for 6 weeks post-weaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. H19 overexpression observed under dietary deficiency of folate combined with normal B12 (B12 normal folic acid-deficient, BNFD) was associated with an increased expression of microRNA-675 (miR-675) in maternal and fetal tissues. Insulin-like growth factor 2 (IGF2) expression was decreased under folic acid-deficient conditions combined with normal, deficient or over-supplemented state of B12 (BNFD, BDFD and BOFD) in fetal tissues along with B12 deficiency combined with normal folic acid (BDFN) in the placenta. The altered expression of imprinted genes under folic acid-deficient conditions was related to decreased serum levels of folate and body weight (F1). Hypermethylation observed at the H19 differentially methylated region (DMR) (in BNFD) might be responsible for the decreased expression of IGF2 in female fetal tissues. IGF2 DMR2 was found to be hypomethylated and associated with low serum B12 levels with B12 deficiency in fetal tissues. Results suggest that the altered dietary ratio of folic acid and B12 affects the in utero development of the fetus in association with altered epigenetic regulation of H19/IGF2 locus.

Wild mustard (Sinapis arvensis L.) is a widespread weed of the southeastern cropping region of Australia. Seed germination ecology of S. arvensis populations selected from different climatic regions may differ due to adaptative traits. Experiments were conducted to evaluate the effects of temperature, light, radiant heat, soil moisture, salt concentration, and burial depth on seed germination and seedling emergence of two populations (Queensland [Qld] population: tropical region; and Victoria [Vic] population: temperate region) of S. arvensis. Both populations germinated over a wide range of day/night (12-h/12-h) temperatures (15/5 to 35/25 C), and had the highest germination at 30/20 C. Under complete darkness, the Qld population (61%) had higher germination than the Vic population (21%); however, under the light/dark regime, both populations had similar germination (78% to 86%). At 100 C pretreatment for 5 min, the Qld population (44%) had higher germination than the Vic population (13%). Germination of both populations was nil when given pretreatment at 150 and 200 C. The Vic population was found tolerant to high osmotic and salt stress compared with the Qld population. At an osmotic potential of −0.4 MPa, germination of Qld and Vic populations was reduced by 85% and 42%, respectively, compared with their respective controls. At 40, 80, and 160 mM sodium chloride, germination was lower for the Qld population than the Vic population. Averaged over the populations, seedling emergence was highest (52%) from a burial depth of 1 cm and was nil from 8-cm depth. Differential germination behaviors of both populations to temperature, light, radiant heat, water stress, and salt stress suggest that populations of S. arvensis may have undergone differential adaptation. Knowledge gained from this study will assist in developing suitable control measures for this weed species to reduce the soil seedbank.

Apricot is considered an ecologically and economically important tree species of the stone-fruit crops that is widely grown in temperate regions of the world. Very few studies on apricot genetic diversity assessment have been carried out from the regions of Kashmir and Ladakh. In this backdrop, the present study was carried out to analyse the genetic diversity and population structure of 120 apricot genotypes collected from both the regions using 21 SSR markers. A total of 52 alleles were amplified with average values of marker index (MI) = 0.7084, resolving power (RP) = 2.8690, polymorphism information content (PIC) = 0.3132, Na = 2.317, Ne = 1.720, I = 0.572, Ho = 0.284, He = 0.360 and an average polymorphism of 91.2% per assay indicating high level of genetic diversity. The neighbour-joining (NJ) dendrogram generated three main clusters among selected apricot genotypes independent of their geographical locations. Interestingly, the result of the dendrogram coincides with the results of structure analysis which showed that the 120 apricot genotypes could be assigned to three (K = 3) sub-populations and the grouping of genotypes did not follow their geographical location suggesting that they share the same genetic pool. Moreover, analysis of molecular variance showed that 73% of the variation was attributed to differences within the individuals, 25% among individuals while only 2% of the variation was observed among the populations. The present study represents the most comprehensive analysis of the genetic diversity and population structure of apricot genotypes in Kashmir and Ladakh regions of India.

Sumatran fleabane [Conyza sumatrensis (Retz.) Walker] is an emerging weed in the Australian cropping region. Populations resistant to glyphosate have evolved in Australia, creating the demand for information regarding the seed germination ecology of glyphosate-resistant (R) and glyphosate-susceptible (S) populations of C. sumatrensis. A study was conducted to examine the effects of temperature, light intensity, salt stress, osmotic stress, and burial depth on the germination and emergence of two populations (R and S) of C. sumatrensis. Both populations were able to germinate over a wide range of alternating day/night temperatures (15/5 to 35/25 C). In light/dark conditions, the R population had higher germination than the S population at 20/10 and 35/25 C. In the dark, the R population had higher germination than the S population at 25/15 C. In the dark, germination was inhibited at 30/20 C and above. Averaged over populations, seed germination of C. sumatrensis was reduced by 97% at zero light intensity (completely dark conditions) compared with full light intensity. Seed germination of C. sumatrensis was reduced by 17% and 85% at osmotic potentials of −0.4, and −0.8 MPa, respectively, compared with the control treatment. The R population had lower germination (57%) than the S population (72%) at a sodium chloride concentration of 80 mM. Seed germination was highest on the soil surface and emergence was reduced by 87% and 90% at burial depths of 0.5 and 1.0 cm, respectively. Knowledge gained from this study suggests that a shallow-tillage operation to bury weed seeds in conventional tillage systems and retention of high residue cover on the soil surface in zero-till systems may inhibit the germination of C. sumatrensis. This study also warrants that the R population may have a greater risk of invasion over a greater part of a year due to germination over a broader temperature range.

Junglerice and feather fingergrass are major problematic weeds in the summer sorghum cropping areas of Australia. This study aimed to investigate the growth and seed production of junglerice and feather fingergrass in crop-free (fallow) conditions and under competition with sorghum planted in 50-cm and 100-cm row spacings at three sorghum planting and weed emergence timings. Results revealed that junglerice and feather fingergrass had greater biomass in early planting (November 11) compared to late planting times (January 11). Under fallow conditions, seed production of junglerice ranged from 12,380 to 20,280 seeds plant–1, with the highest seed production for the December 11 and lowest for the January 11 planting. Seed production of feather fingergrass under fallow conditions ranged from 90,030 to 143,180 seeds plant–1. Seed production of feather fingergrass under crop-free (fallow) conditions was similar for November 11 and December 11 planting times, but higher for the January 11 planting. Sorghum crop competition at both row spacings reduced the seed production of junglerice and feather fingergrass >75% compared to non-crop fallow. Narrow row spacing (50 cm) in early and mid-planted sorghum (November 11 and December 11) reduced the biomass of junglerice to a greater extent (88% to 92% over fallow-grown plants) compared to wider row spacing (100 cm). Narrow row spacing was found superior in reducing biomass of feather fingergrass compared to wider row spacing. Our results demonstrate that sorghum crops can substantially reduce biomass and seed production of junglerice and feather fingergrass through crop competition compared with growth in fallow conditions. Narrow row spacing (50 cm) was found superior to wider row spacing (100 cm) in terms of weed suppression. These results suggest that narrow row spacing and late planting time of sorghum crops can strengthen an integrated weed management program against these weeds by reducing weed growth and seed production.

The 2019 Global Health Security Index (GHS Index) assessed the US and the UK as the two countries best prepared to address a catastrophic pandemic. The preparedness rankings of this index have had little correlation with the actual experiences of COVID-19 in various countries. In explaining this disrepancy, the paper argues that better indicators and more data would not have fixed the problem. Rather, the prevailing paradigm of global health security that informs instruments such as the GHS Index needs to be interrogated. This dominant paradigm narrowly conceptualises global health security in terms of the availability of a technical infrastructure to detect emerging infectious diseases and prevent their contagion, but profoundly undertheorises the broader social and political determinants of public health. The neglect of social and political features is amplified in instruments such as the GHS Index that privilege universalised templates presumed to apply across countries but that prove to be inadequate in assessing how individual societies draw on their unique histories to craft public health responses.

Herbicide resistance is an increasing issue in many weed species, including rigid ryegrass (Lolium rigidum Gaudin); a major weed of winter cropping systems in southern Australia. Recently, this weed has also been found in summer crops in the southeastern region of Australia. Effective control of this herbicide-resistant weed across southeastern Australia requires alternative management strategies. These strategies can be informed by analyses on the interaction of germinable seeds with their regional environments and by identifying the differences between populations of varying herbicide-resistance levels. In this study, we explore how various environmental factors differentially affect the seed germination and seedling emergence of three L. rigidum populations, including one glyphosate-resistant population (GR), one glyphosate-susceptible population (GS), and one population of unknown resistance status (CC04). Germination was greater than 90% for all populations at each temperature regime, except 15/5 C. Populations germinated at a lower rate under 15/5 C, ranging from 74% to 87% germination. Salt stress had a similar effect on the germination of all populations, with 0% germination occurring at 250 mM salt stress. Population GS had greater tolerance to osmotic stress, with 65% germination at −0.4 MPa compared with 47% and 43% germination for CC04 and GR, respectively; however, germination was inhibited at −0.8 and −1.6 MPa for all populations. All populations had lower germination when placed in complete darkness as opposed to alternating light/dark. Germination in darkness was lower for CC04 (69%) than GR (83%) and GS (83%). Seedling emergence declined with increasing burial depth with the lowest emergence occuring at 8 cm (37%) when averaged over the populations. These results indicate that L. rigidum can survive under a range of environmental variables and that the extent of survival differs based on population; however, there was no difference based on herbicide-resistance status.

The total coronavirus disease (COVID-19) cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have reached 139 million worldwide and nearing 3 million deaths on April 16, 2021. The availability of accurate data is crucial as it makes it possible to analyze correctly the infection trends and make better forecasts. The reported recovered cases for many US states are surprisingly low. This could be due to difficulties in keeping track of recoveries, which resulted in higher numbers for the reported active cases than the actual numbers on the ground. In this work, based on the typical range of recovery rate for COVID-19, we estimate the active data from the total cases and death cases and bring out a correction for the data for all the US states reported on Worldometer.