Theory of imaging a photonic crystal with transmission near-field optical microscopy

While near-field scanning optical microscopy (NSOM) can provide optical images with resolution much better than the diffraction limit, analysis and interpretation of these images is often difficult. We present a theory of imaging with transmission NSOM that includes the effects of tip field, tip/sample coupling, light propagation through the sample and light collection. We apply this theory to analyze experimental NSOM images of a nanochannel glass (NCG) array obtained in transmission mode. The NCG is a triangular array of dielectric rods in a dielectric glass matrix with a two-dimensional photonic band structure. We determine the modes for the NCG photonic crystal and simulate the observed data. The calculations show large contrast at low numerical aperture (NA) of the collection optics and detailed structure at high NA consistent with the observed images. We present calculations as a function of NA to identify how the NCG photonic modes contribute to and determine the spatial structure in these images. Calculations are presented as a function of tip/sample position, sample index contrast and geometry, and aperture size to identify the factors that determine image formation with transmission NSOM in this experiment.Comment: 28 pages of ReVTex, 14 ps figures, submitted to Phys. Rev.

Accurate state estimation from uncertain data and models: an application of data assimilation to mathematical models of human brain tumors

<p>Abstract</p> <p>Background</p> <p>Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.</p> <p>Results</p> <p>We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.</p> <p>Conclusions</p> <p>The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.</p> <p>Reviewers</p> <p>This article was reviewed by Anthony Almudevar, Tomas Radivoyevitch, and Kristin Swanson (nominated by Georg Luebeck).</p

Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

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Caenorhabditis briggsae Recombinant Inbred Line Genotypes Reveal Inter-Strain Incompatibility and the Evolution of Recombination

The nematode Caenorhabditis briggsae is an emerging model organism that allows evolutionary comparisons with C. elegans and exploration of its own unique biological attributes. To produce a high-resolution C. briggsae recombination map, recombinant inbred lines were generated from reciprocal crosses between two strains and genotyped at over 1,000 loci. A second set of recombinant inbred lines involving a third strain was also genotyped at lower resolution. The resulting recombination maps exhibit discrete domains of high and low recombination, as in C. elegans, indicating these are a general feature of Caenorhabditis species. The proportion of a chromosome's physical size occupied by the central, low-recombination domain is highly correlated between species. However, the C. briggsae intra-species comparison reveals striking variation in the distribution of recombination between domains. Hybrid lines made with the more divergent pair of strains also exhibit pervasive marker transmission ratio distortion, evidence of selection acting on hybrid genotypes. The strongest effect, on chromosome III, is explained by a developmental delay phenotype exhibited by some hybrid F2 animals. In addition, on chromosomes IV and V, cross direction-specific biases towards one parental genotype suggest the existence of cytonuclear epistatic interactions. These interactions are discussed in relation to surprising mitochondrial genome polymorphism in C. briggsae, evidence that the two strains diverged in allopatry, the potential for local adaptation, and the evolution of Dobzhansky-Muller incompatibilities. The genetic and genomic resources resulting from this work will support future efforts to understand inter-strain divergence as well as facilitate studies of gene function, natural variation, and the evolution of recombination in Caenorhabditis nematodes

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14–8.23; P < 0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19–3.77; P = 0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08–3.47; P = 0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10–5.50; P = 0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30–0.72; P = 0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01–1.04; P < 0.001) and age (OR, 1.17; 95% CI, 1.08–1.26; P < 0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54–0.69) and a specificity of 0.63 (95% CI, 0.59–0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.Supplemental Table S1. Number of dogs included from each institution and years reviewed.Supplemental Table S2. Included breeds.Supplemental Table S3. Distribution of various reasons given for performing cholecystectomy in the 179 subclinical dogs with gallbladder mucocele (GBM).Supplemental Table S4. Distribution of clinical signs associated with systemic illness in 982 dogs with gallbladder mucocele.Supplemental Table S5. Distribution of reasons for death in-hospital (i.e. euthanized and died) in 179 dogs with gallbladder mucocele that underwent cholecystectomy.http://www.elsevier.com/locate/tvjlhj2020Companion Animal Clinical Studie

Properties of the Binary Black Hole Merger GW150914

On September 14, 2015, the Laser Interferometer Gravitational-Wave Observatory (LIGO) detected a gravitational-wave transient (GW150914); we characterize the properties of the source and its parameters. The data around the time of the event were analyzed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity. GW150914 was produced by a nearly equal mass binary black hole of masses 36+5−4M⊙ and 29+4−4M⊙; for each parameter we report the median value and the range of the 90% credible interval. The dimensionless spin magnitude of the more massive black hole is bound to be <0.7 (at 90% probability). The luminosity distance to the source is 410+160−180  Mpc, corresponding to a redshift 0.09+0.03−0.04 assuming standard cosmology. The source location is constrained to an annulus section of 610  deg2, primarily in the southern hemisphere. The binary merges into a black hole of mass 62+4−4M⊙ and spin 0.67+0.05−0.07. This black hole is significantly more massive than any other inferred from electromagnetic observations in the stellar-mass regime

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival