Isolated optical vortex knots Dennis, Mark R; Padgett, Miles J; King, Robert P ...
Nature physics,
02/2010, Letnik:
6, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Natural and artificially created light fields in three-dimensional space contain lines of zero intensity, known as optical vortices. Here, we describe a scheme to create optical beams with isolated ...optical vortex loops in the forms of knots and links using algebraic topology. The required complex fields with fibred knots and links are constructed from abstract functions with braided zeros and the knot function is then embedded in a propagating light beam. We apply a numerical optimization algorithm to increase the contrast in light intensity, enabling us to observe several optical vortex knots. These knotted nodal lines, as singularities of the wave's phase, determine the topology of the wave field in space, and should have analogues in other three-dimensional wave systems such as superfluids and Bose-Einstein condensates.
Abstract
We used existing data from the New Horizons Long-range Reconnaissance Imager (LORRI) to measure the optical-band (0.4 ≲
λ
≲ 0.9
μ
m) sky brightness within seven high–Galactic latitude ...fields. The average raw level measured while New Horizons was 42–45 au from the Sun is 33.2 ± 0.5 nW m
−2
sr
−1
. This is ∼10× as dark as the darkest sky accessible to the Hubble Space Telescope, highlighting the utility of New Horizons for detecting the cosmic optical background (COB). Isolating the COB contribution to the raw total required subtracting scattered light from bright stars and galaxies, faint stars below the photometric detection limit within the fields, and diffuse Milky Way light scattered by infrared cirrus. We removed newly identified residual zodiacal light from the IRIS 100
μ
m all-sky maps to generate two different estimates for the diffuse Galactic light. Using these yielded a highly significant detection of the COB in the range 15.9 ± 4.2 (1.8 stat., 3.7 sys.) nW m
−2
sr
−1
to 18.7 ± 3.8 (1.8 stat., 3.3 sys.) nW m
−2
sr
−1
at the LORRI pivot wavelength of 0.608
μ
m. Subtraction of the integrated light of galaxies fainter than the photometric detection limit from the total COB level left a diffuse flux component of unknown origin in the range 8.8 ± 4.9 (1.8 stat., 4.5 sys.) nW m
−2
sr
−1
to 11.9 ± 4.6 (1.8 stat., 4.2 sys.) nW m
−2
sr
−1
. Explaining it with undetected galaxies requires the assumption that the galaxy count faint-end slope steepens markedly at
V
> 24 or that existing surveys are missing half the galaxies with
V
< 30.
We show how careful control of the incident polarization of a light beam close to the Brewster angle gives a giant transverse spatial shift on reflection. This resolves the long-standing puzzle of ...why such beam shifts transverse to the incident plane (Imbert-Fedorov shifts) tend to be an order of magnitude smaller than the related Goos-Hänchen shifts in the longitudinal direction, which are largest close to critical incidence. We demonstrate that with the proper initial polarization the transverse displacements can be equally large, which we confirm experimentally near Brewster incidence. In contrast to the established understanding, these polarizations are elliptical and angle dependent. We explain the magnitude of the Imbert-Fedorov shift by an analogous change of the symmetry properties for the reflection operators as compared to the Goos-Hänchen shift.
Type II topoisomerases alter DNA topology to control DNA supercoiling and chromosome segregation and are targets of clinically important anti-infective and anticancer therapeutics. They act as ...ATP-operated clamps to trap a DNA helix and transport it through a transient break in a second DNA. Here, we present the first X-ray crystal structure solved at 2.83 Å of a closed clamp complete with trapped T-segment DNA obtained by co-crystallizing the ATPase domain of S. pneumoniae topoisomerase IV with a nonhydrolyzable ATP analogue and 14-mer duplex DNA. The ATPase dimer forms a 22 Å protein hole occupied by the kinked DNA bound asymmetrically through positively charged residues lining the hole, and whose mutagenesis impacts the DNA decatenation, DNA relaxation and DNA-dependent ATPase activities of topo IV. These results and a side-bound DNA-ParE structure help explain how the T-segment DNA is captured and transported by a type II topoisomerase, and reveal a new enzyme-DNA interface for drug discovery.
Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine ...(also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results.
We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy.
A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival.
In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00003375.).
Human immunodeficiency virus-1 (HIV-1) infection currently requires lifelong therapy with drugs that are used in combination to control viremia. The indole-3-glyoxamide 6 was discovered as an ...inhibitor of HIV-1 infectivity using a phenotypic screen and derivatives of this compound were found to interfere with the HIV-1 entry process by stabilizing a conformation of the virus gp120 protein not recognized by the host cell CD4 receptor. An extensive optimization program led to the identification of temsavir (31), which exhibited an improved antiviral and pharmacokinetic profile compared to 6 and was explored in phase 3 clinical trials as the phosphonooxymethyl derivative fostemsavir (35), a prodrug designed to address dissolution- and solubility-limited absorption issues. In this drug annotation, we summarize the structure–activity and structure–liability studies leading to the discovery of 31 and the clinical studies conducted with 35 that entailed the development of an extended release formulation suitable for phase 3 clinical trials.
Artificial intelligence is generating substantial interest in the field of medicine. One form of artificial intelligence, deep learning, has led to rapid advances in automated image analysis. In ...2017, an algorithm demonstrated the ability to diagnose certain skin cancers from clinical photographs with the accuracy of an expert dermatologist. Subsequently, deep learning has been applied to a range of dermatology applications. Although experts will never be replaced by artificial intelligence, it will certainly affect the specialty of dermatology. In this first article of a 2-part series, the basic concepts of deep learning will be reviewed with the goal of laying the groundwork for effective communication between clinicians and technical colleagues. In part 2 of the series, the clinical applications of deep learning in dermatology will be reviewed and limitations and opportunities will be considered.
Because of a convergence of the availability of large data sets, graphics-specific computer hardware, and important theoretical advancements, artificial intelligence has recently contributed to ...dramatic progress in medicine. One type of artificial intelligence known as deep learning has been particularly impactful for medical image analysis. Deep learning applications have shown promising results in dermatology and other specialties, including radiology, cardiology, and ophthalmology. The modern clinician will benefit from an understanding of the basic features of deep learning to effectively use new applications and to better gauge their utility and limitations. In this second article of a 2-part series, we review the existing and emerging clinical applications of deep learning in dermatology and discuss future opportunities and limitations. Part 1 of this series offered an introduction to the basic concepts of deep learning to facilitate effective communication between clinicians and technical experts.
While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to ...pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility.
Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity.
Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at http://cpag.oit.duke.edu and the software code at https://github.com/tbalmat/iCPAGdb .
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