We present the results of a dust reverberation survey for 17 nearby Seyfert 1 galaxies, which provides the largest homogeneous data collection for the radius of the innermost dust torus. A delayed ...response of the K-band light curve after the V-band light curve was found for all targets, and 49 measurements of lag times between the flux variation of the dust emission in the K band and that of the optical continuum emission in the V band were obtained by the cross-correlation function analysis and also by an alternative method for estimating the maximum likelihood lag. We discuss the possible origins of the intrinsic scatter of the dust lag-luminosity correlation, which was estimated to be approximately 0.13 dex, and we find that the difference of internal extinction and delayed response of changes in lag times to the flux variations could have partly contributed to intrinsic scatter.
We present the results of a dust-reverberation survey of quasars at redshifts z < 0.6. We found a delayed response of the K-band flux variation after the optical flux variation in 25 out of 31 ...targets, and obtained the lag time between them for 22 targets. Combined with the results for nearby Seyfert galaxies, we provide the largest homogeneous collection of K-band dust-reverberation data for 36 type 1 active galactic nuclei (AGNs). This doubles the sample and includes the most distant AGN and the largest lag so far measured. We estimated the optical luminosity of the AGN component of each target using three different methods: spectral decomposition, the flux-variation-gradient method, and image decomposition. We found a strong correlation between the reverberation radius for the innermost dust torus and the optical luminosity over a range of approximately four orders of magnitude in luminosity, as is already known for Seyfert galaxies. We estimated the luminosity distances of the AGNs based on their dust-reverberation lags, and found that the data in the redshift-distance diagram are consistent with the current standard estimates of the cosmological parameters. We also present the radius-luminosity relations for isotropic luminosity indicators such as the hard X-ray (14-195 keV), O IV 25.89 m, and mid-infrared (12 m) continuum luminosities, which are applicable to obscured AGNs.
Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro-immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and ...are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain. Although the antigen binding affinities of natural IgM antibodies are typically lower than IgG, their polyvalency allows for high avidity binding and efficient engagement of complement to induce complement-dependent cell lysis. The high avidity of IgM antibodies renders them particularly efficient at binding antigens present at low levels, and non-protein antigens, for example, carbohydrates or lipids present on microbial surfaces. Pentameric IgM antibodies also contain a joining (J) chain that stabilizes the pentameric structure and enables binding to several receptors. One such receptor, the polymeric immunoglobulin receptor (pIgR), is responsible for transcytosis from the vasculature to the mucosal surfaces of the lung and gastrointestinal tract. Several naturally occurring IgM antibodies have been explored as therapeutics in clinical trials, and a new class of molecules, engineered IgM antibodies with enhanced binding and/or additional functional properties are being evaluated in humans. Here, we review the considerable progress that has been made regarding the understanding of biology, structure, function, manufacturing, and therapeutic potential of IgM antibodies since their discovery more than 80 years ago.
The most intense monitoring observations yet made in the optical and near-infrared wave bands were carried out for Seyfert 1 galaxies NGC 5548, NGC 4051, NGC 3227, and NGC 7469 by the MAGNUM ...telescope, and clear time-delayed responses of the K-band flux variations to the V-band flux variations were found for all of these galaxies. Their H - K color temperatures of 1500-1800 K, estimated from their observed flux variation gradients, support a view that the bulk of the K flux should originate in the thermal radiation of hot dust surrounding the central engine and that the lag time should correspond to light-travel distance between them. Cross-correlation analysis measures their lag times to be 47-53 (NGC 5548), 11-18 (NGC 4051), about 20 (NGC 3227), and 65-87 (NGC 7469) days. The lag times are tightly correlated with the optical luminosities, as expected from dust reverberation (t 8 L super(0.5)), while weakly with the central virial masses, which suggests that the inner radii of the dust tori around active nuclei have one-to-one correspondences with their central luminosities. In the lag time versus central luminosity diagram, the K-band lag times place an upper boundary on the similar lag times of broad emission lines in the literature, which not only supports the unified scheme of AGNs but also implies a physical transition from the BLR out to the dust torus that encircles the BLR. Correlated short-term V-band and X-ray flux variations in NGC 5548 are also found with a delay of 1 or 2 days, indicating the thermal reprocessing of X-ray emission by the central accretion flow.
To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and ...prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients.
Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided.
Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged with MR after CHOP (P = .0004) but not after R-CHOP (P = .81) with 2-year FFS rates from second random assignment of 77%, 79%, 74%, and 45% for R-CHOP, R-CHOP + MR, CHOP + MR, and CHOP, respectively. In a secondary analysis excluding MR patients, R-CHOP alone reduced the risks of treatment failure (P = .003) and death (P = .05) compared with CHOP alone.
Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.
We have pioneered a new method for the measurement of extragalactic distances. This method uses the time lag between variations in the short wavelength and long wavelength light from an active ...galactic nucleus (AGN), based on a quantitative physical model of dust reverberation that relates the time lag to the absolute luminosity of the AGN. We use the large homogeneous data set from intensive monitoring observations in optical and near-infrared wavelength bands with the dedicated 2 m MAGNUM telescope to obtain the distances to 17 AGNs in the redshift range z = 0.0024 to z = 0.0353. These distance measurements are compared with distances measured using Cepheid variable stars, and are used to infer that H sub(0) = 73 + or - 3 (random) km s super(-1) Mpc super(-1). The systematic error in H sub(0) is examined, and the uncertainty in the size distribution of dust grains is the largest source of the systematic error, which is much reduced for a sample of AGNs for which their parameter values in the model of dust reverberation are individually measured. This AGN time lag method can be used beyond 30 Mpc, the farthest distance reached by extragalactic Cepheids, and can be extended to high-redshift quasi-stellar objects.
Luminosity functions and their integrated luminosity densities are presented for the 6-degree Field Galaxy Survey (6dFGS). This ongoing survey ultimately aims to measure around 150 000 redshifts and ...15 000 peculiar velocities over almost the entire southern sky at |b| > 10°. The main target samples are taken from the 2-Micron All-Sky Survey (2MASS) Extended Source Catalog and the SuperCOSMOS Sky Survey catalogue, and comprise 138 226 galaxies complete to (K, H, J, rF, bJ) = (12.75, 13.00, 13.75, 15.60, 16.75). These samples are comparable in size to the optically selected Sloan Digital Sky Survey and 2-degree Field Galaxy Redshift Survey (2dFGRS) samples, and improve on recent near-infrared-selected redshift surveys by more than an order of magnitude in both number and sky coverage. The partial samples used in this paper contain a little over half of the total sample in each band and are ∼90 per cent complete. Luminosity distributions are derived using the 1/Vmax, Sandage–Tammann–Yahil (STY) and step-wise maximum likelihood (SWML) estimators, and probe 1–2 absolute magnitudes fainter in the near-infrared than previous surveys. The effects of magnitude errors, redshift incompleteness and peculiar velocities have been taken into account and corrected throughout. Generally, the 6dFGS luminosity functions are in excellent agreement with those of similarly sized surveys. Our data are of sufficient quality to demonstrate that a Schechter function is not an ideal fit to the true luminosity distribution, due to its inability to simultaneously match the faint-end slope and rapid bright-end decline. Integrated luminosity densities from the 6dFGS are consistent with an old stellar population and moderately declining star formation rate.
Motion Segmentation via Generalized Curvatures Arn, Robert T.; Narayana, Pradyumna; Emerson, Tegan ...
IEEE transactions on pattern analysis and machine intelligence,
2019-Dec.-1, 2019-12-00, 2019-12-1, 20191201, Letnik:
41, Številka:
12
Journal Article
Recenzirano
New depth sensors, like the Microsoft Kinect, produce streams of human pose data. These discrete pose streams can be viewed as noisy samples of an underlying continuous ideal curve that describes a ...trajectory through high-dimensional pose space. This paper introduces a technique for generalized curvature analysis (GCA) that determines features along the trajectory which can be used to characterize change and segment motion. Tools are developed for approximating generalized curvatures at mean points along a curve in terms of the singular values of local mean-centered data balls. The features of the GCA algorithm are illustrated on both synthetic and real examples, including data collected from a Kinect II sensor. We also applied GCA to the Carnegie Mellon University Motion Capture (MoCaP) database. Given that GCA scales linearly with the length of the time series we are able to analyze large data sets without down sampling. It is demonstrated that the generalized curvature approximations can be used to segment pose streams into motions and transitions between motions. The GCA algorithm can identify 94.2 percent of the transitions between motions without knowing the set of possible motions in advance, even though the subjects do not stop or pause between motions.
Background
Sub‐Saharan Africa is simultaneously facing a rising incidence of cancer and a dearth of medical professionals because of insufficient training numbers and emigration, creating a growing ...shortage of cancer care. To combat this, Massachusetts General Hospital and Beth Israel Deaconess Medical Center partnered with institutions in South Africa, Tanzania, and Rwanda to develop a fellowship exchange program to supplement the training of African oncologists practicing in their home countries.
Methods
In its initial year, 2018, the Program for Enhanced Training in Cancer (POETIC) hosted a pilot cohort of seven fellows for 3‐week observerships in their areas of interest. Researchers distributed questionnaires for program evaluation to participants prior to arrival and upon departure; additionally, three participated in semistructured interviews.
Results
Five themes emerged from the qualitative data: expectations of POETIC, differences between oncology in the U.S. and in sub‐Saharan Africa, positive elements of the program, areas for improvement, and potential impact. Fellows identified several elements of Western health care that will inform their practice: patient‐centered care; clinical trials; and collaboration among medical, radiation, and surgical oncologists. From the quantitative data, feedback was primarily around logistical areas for improvement.
Conclusion
POETIC was found to be feasible and valuable. The results from the pilot year justify the program's continuation in hopes of strengthening global health partnerships to support oncology training in Africa. One weakness is the small number of fellows, which will limit the impact of the study and the relevance of its conclusions. Future research will report on the expansion of the program and follow‐up with former participants.
Implications for Practice
This work presents a novel model for fellowship exchange between lower‐ and higher‐resourced areas. The program is a short‐term observership with tumor boards and didactic teaching sessions incorporated. By attracting oncologists who aim to practice in their home countries, it facilitates international collaboration without contributing to the preexisting lack of medical professionals in low‐ and middle‐income countries.
This brief communication presents case reports for two patients with metastatic melanoma treated with empiric BRAF and MEK inhibitors.
Death receptor 5 (DR5) is an attractive target for cancer therapy due to its broad upregulated expression in multiple cancers and ability to directly induce apoptosis. Though anti-DR5 IgG antibodies ...have been evaluated in clinical trials, limited efficacy has been attributed to insufficient receptor crosslinking. IGM-8444 is an engineered, multivalent agonistic IgM antibody with 10 binding sites to DR5 that induces cancer cell apoptosis through efficient DR5 multimerization. IGM-8444 bound to DR5 with high avidity and was substantially more potent than an IgG with the same binding domains. IGM-8444 induced cytotoxicity in a broad panel of solid and hematologic cancer cell lines but did not kill primary human hepatocytes
, a potential toxicity of DR5 agonists. In multiple xenograft tumor models, IGM-8444 monotherapy inhibited tumor growth, with strong and sustained tumor regression observed in a gastric PDX model. When combined with chemotherapy or the BCL-2 inhibitor ABT-199, IGM-8444 exhibited synergistic
tumor cytotoxicity and enhanced
efficacy, without augmenting
hepatotoxicity. These results support the clinical development of IGM-8444 in solid and hematologic malignancies as a monotherapy and in combination with chemotherapy or BCL-2 inhibition.
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