Measuring Organic Molecular Emission in Disks with Low Resolution Spitzer Spectroscopy

We explore the extent to which Spitzer IRS spectra taken at low spectral resolution can be used in quantitative studies of organic molecular emission from disks surrounding low mass young stars. We use Spitzer IRS spectra taken in both the high and low resolution modules for the same sources to investigate whether it is possible to define line indices that can measure trends in the strength of the molecular features in low resolution data. We find that trends in HCN emission strength seen in the high resolution data can be recovered in low resolution data. In examining the factors that influence the HCN emission strength, we find that the low resolution HCN flux is modestly correlated with stellar accretion rate and X-ray luminosity. Correlations of this kind are perhaps expected based on recent observational and theoretical studies of inner disk atmospheres. Our results demonstrate the potential of using the large number of low resolution disk spectra that reside in the Spitzer archive to study the factors that influence the strength of molecular emission from disks. Such studies would complement results for the much smaller number of circumstellar disks that have been observed at high resolution with IRS

Instance-specific linear relaxations of semidefinite optimization problems

We present a simple yet flexible systematic way to significantly improve linear relaxations of semidefinite optimization programs (SDPs) using instance-specific information. We get inspiration for our approach by studying the celebrated SDP relaxation for max cut (GW) due to Poljak and Rendl [1995] and analyzed by Goemans and Williamson [1995]. Using the instance at hand, we provide a pair of closely related compact linear programs that sandwich the optimal value of the GW semidefinite program. The instance specific information allows us to trivially avoid hardness of approximation results of semidefinite programs using linear ones, such as Braun et al. [2015] and Kothari et al. [2021]. We give sufficient conditions that guarantee that the optimal value of both our programs match the optimal value of the semidefinite relaxation. We use these conditions to prove that our two bounds give the same value as the GW SDP for max cut on distance-regular graphs, and in particular, strongly regular graphs such as cycles and the Petersen graph. Further, we show that the approximation of the upper bounding problem is strictly better than the eigenvalue bounds of Mohar and Poljak [1990], Alon and Sudakov [2000] for max cut. To the best of our knowledge, no previously proposed linear program proposed for max cut has this guarantee. We extensively test our methodology on synthetic and real graphs, and show how our ideas perform in practice. Even though our methodology is inspired by the SDP relaxation for max cut, we show experimentally that our ideas can be applied successfully to obtain good solutions to other computationally hard SDPs such as sparse PCA and the Lovasz Theta number

Age, Growth and Natural Mortality of Blackfin Snapper Lutjanus buccanella from the Southeastern United States and U. S. Caribbean

We determined ages of Blackfin Snapper (Lutjanus buccanella Cuvier 1828; n = 622) collected from the southeastern United States coast and U.S. Caribbean from 1979–2015 using sectioned sagittal otoliths. Opaque zones were determined to be annular, forming March – July (peaking in April–June). Blackfin Snapper ranged from 1–27 years and from 180–609 mm total length (TL). Body size relationships for Blackfin Snapper were: TL = 1.09 FL + 0.81 (n = 203, r2 = 0.99); FL = 0.91 TL + 3.38 (n = 203, r2 = 0.99); TL = 1.23 SL + 14.27 (n = 83, r2 = 0.97); FL = 1.14 SL + 10.84 (n = 83, r2 = 0.99); W = 7.79 x 10—9 TL3.09 (n = 216); and W = 9.54 x 10—9 FL3.11 (n = 228). The von Bertalanffy growth equation was: Lt = 549 (1 — e—0.20 (t +1.51)) (n = 622). Point estimate of natural mortality was M = 0.16, while age—specific estimates of M ranged from 0.65–0.21/y for ages 1–27. This study presents the first findings of life history parameters for Blackfin Snapper from the Atlantic waters off the southeastern United States and U.S. Caribbean

Nonlinear Scattering of a Bose-Einstein Condensate on a Rectangular Barrier

We consider the nonlinear scattering and transmission of an atom laser, or Bose-Einstein condensate (BEC) on a finite rectangular potential barrier. The nonlinearity inherent in this problem leads to several new physical features beyond the well-known picture from single-particle quantum mechanics. We find numerical evidence for a denumerably infinite string of bifurcations in the transmission resonances as a function of nonlinearity and chemical potential, when the potential barrier is wide compared to the wavelength of oscillations in the condensate. Near the bifurcations, we observe extended regions of near-perfect resonance, in which the barrier is effectively invisible to the BEC. Unlike in the linear case, it is mainly the barrier width, not the height, that controls the transmission behavior. We show that the potential barrier can be used to create and localize a dark soliton or dark soliton train from a phonon-like standing wave.Comment: 15 pages, 15 figures, new version includes clarification of definition of transmission coefficient in general nonlinear vs. linear cas

Evidence of Female Sex Pheromones and Characterization of the Cuticular Lipids of Unfed, Adult Male Versus Female Blacklegged Ticks, Ixodes scapularis

Copulation in I. scapularis involves physical contact between the male and female (on or off the host), male mounting the female, insertion/maintenance of the male chelicerae in the female genital pore (initiates spermatophore production), and the transfer of the spermatophore by the male into the female genital pore. Bioassays determined that male mounting behavior/chelicerae insertion required direct contact with the female likely requiring non-volatile chemical cues with no evidence of a female volatile sex pheromone to attract males. Unfed virgin adult females and replete mated adult females elicited the highest rates of male chelicerae insertion with part fed virgin adult females exhibiting a much lower response. Whole body surface hexane extracts of unfed virgin adult females and males, separately analyzed by GC-MS, identified a number of novel tick surface associated compounds: fatty alcohols (1-hexadecanol and 1-heptanol), a fatty amide (erucylamid), aromatic hydrocarbons, a short chain alkene (1 heptane), and a carboxylic acid ester (5β-androstane). These compounds are discussed in terms of their potential role in female-male communication. The two most abundant fatty esters found were butyl palmitate and butyl stearate present in ratios that were sex specific. Only 6 n-saturated hydrocarbons were identified in I. scapularis ranging from 10-18 carbons

Knowledge of Objective 'Oughts': Monotonicity and the New Miners Puzzle

In the classic Miners case, an agent subjectively ought to do what they know is objectively wrong. This case shows that the subjective and objective ‘oughts’ are somewhat independent. But there remains a powerful intuition that the guidance of objective ‘oughts’ is more authoritative—so long as we know what they tell us. We argue that this intuition must be given up in light of a monotonicity principle, which undercuts the rationale for saying that objective ‘oughts’ are an authoritative guide for agents and advisors

Critical assessment of approaches for molecular docking to elucidate associations of HLA alleles with adverse drug reactions

Adverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response. There is growing interest in searching for evidence supporting this model for other ADRs using bioinformatics techniques. In this study, in silico docking was used to assess the utility and reliability of well-known docking programs when addressing these challenging HLA-drug situations. The overall aim was to address the uncertainty of docking programs giving different results by completing a detailed comparative study of docking software, grounded in the MHC-ligand experimental structural data - for Abacavir and to a lesser extent Carbamazepine - in order to assess their performance. Four docking programs: SwissDock, ROSIE, AutoDock Vina and AutoDockFR, were used to investigate if each software could accurately dock the Abacavir back into the crystal structure for the protein arising from the known risk allele, and if they were able to distinguish between the HLA-associated and non-HLA-associated (control) alleles. The impact of using homology models on the docking performance and how using different parameters, such as including receptor flexibility, affected the docking performance were also investigated to simulate the approach where a crystal structure for a given HLA allele may be unavailable. The programs that were best able to predict the binding position of Abacavir were then used to recreate the docking seen for Carbamazepine with B*15:02 and controls alleles. It was found that the programs investigated were sometimes able to correctly predict the binding mode of Abacavir with B*57:01 but not always. Each of the software packages that were assessed could predict the binding of Abacavir and Carbamazepine within the correct sub-pocket and, with the exception of ROSIE, was able to correctly distinguish between risk and control alleles. We found that docking to homology models could produce poorer quality predictions, especially when sequence differences impact the architecture of predicted binding pockets. Caution must therefore be used as inaccurate structures may lead to erroneous docking predictions. Incorporating receptor flexibility was found to negatively affect the docking performance for the examples investigated. Taken together, our findings help characterise the potential but also the limitations of computational prediction of drug-HLA interactions. These docking techniques should therefore always be used with care and alongside other methods of investigation, in order to be able to draw strong conclusions from the given results

Informatics investigations into anti-thyroid drug induced agranulocytosis associated with multiple HLA-B alleles

INTRODUCTION:Adverse drug reactions have been linked with HLA alleles in different studies. These HLA proteins play an essential role in the adaptive immune response for the presentation of self and non-self peptides. Anti-thyroid drugs methimazole and propylthiouracil have been associated with drug induced agranulocytosis (severe lower white blood cell count) in patients with B*27:05, B*38:02 and DRB1*08:03 alleles in different populations: Taiwanese, Vietnamese, Han Chinese and Caucasian. METHODS:In this study, informatics methods were used to investigate if any sequence or structural similarities exist between the two associated HLA-B alleles, compared with a set of "control" alleles assumed not be associated, which could help explain the molecular basis of the adverse drug reaction. We demonstrated using MHC Motif Viewer and MHCcluster that the two alleles do not have a propensity to bind similar peptides, and thus at a gross level the structure of the antigen presentation region of the two alleles are not similar. We also performed multiple sequence alignment to identify polymorphisms shared by the risk but not by the control alleles and molecular docking to compare the predicted binding poses of the drug-allele combinations. RESULTS:Two residues, Cys67 and Thr80, were identified from the multiple sequence alignments to be unique to these risk alleles alone. The molecular docking showed the poses of the risk alleles to favour the F-pocket of the peptide binding groove, close to the Thr80 residue, with the control alleles generally favouring a different pocket. The data are thus suggestive that Thr80 may be a critical residue in HLA-mediated anti-thyroid drug induced agranulocytosis, and thus can guide future research and risk assessment