Martingale Posterior Neural Processes

A Neural Process (NP) estimates a stochastic process implicitly defined with neural networks given a stream of data, rather than pre-specifying priors already known, such as Gaussian processes. An ideal NP would learn everything from data without any inductive biases, but in practice, we often restrict the class of stochastic processes for the ease of estimation. One such restriction is the use of a finite-dimensional latent variable accounting for the uncertainty in the functions drawn from NPs. Some recent works show that this can be improved with more "data-driven" source of uncertainty such as bootstrapping. In this work, we take a different approach based on the martingale posterior, a recently developed alternative to Bayesian inference. For the martingale posterior, instead of specifying prior-likelihood pairs, a predictive distribution for future data is specified. Under specific conditions on the predictive distribution, it can be shown that the uncertainty in the generated future data actually corresponds to the uncertainty of the implicitly defined Bayesian posteriors. Based on this result, instead of assuming any form of the latent variables, we equip a NP with a predictive distribution implicitly defined with neural networks and use the corresponding martingale posteriors as the source of uncertainty. The resulting model, which we name as Martingale Posterior Neural Process (MPNP), is demonstrated to outperform baselines on various tasks.Comment: ICLR 202

Toxicity assessments of chalcone and some synthetic chalcone analogues in a zebrafish model

[[abstract]]The aim of this study was to investigate the in vivo toxicities of some novel synthetic chalcones. Chalcone and four chalcone analogues 1a–d were evaluated using zebrafish embryos following antibody staining to visualize their morphological changes and muscle fiber alignment. Results showed that embryos treated with 3'-hydroxychalcone (compound 1b) displayed a high percentage of muscle defects (96.6%), especially myofibril misalignment. Ultrastructural analysis revealed that compound 1b-treated embryos displayed many muscle defect phenotypes, including breakage and collapse of myofibrils, reduced cell numbers, and disorganized thick (myosin) and thin (actin) filaments. Taken together, our results provide in vivo evidence of the myotoxic effects of the synthesized chalcone analogues on developing zebrafish embryos.[[incitationindex]]SCI[[booktype]]電子

Interstitial pulmonary fibrosis in a Malaysian captive Asian elephant (Elephas maximus)

A 14-year-old female captive Asian elephant in a Malaysian z oo with a history of positive sero-reactivity to Elephant TB STAT-PAK assay was humanely euthanized due to chronic weight loss and poor response to treatment. Postmortem revealed generalized congestion and emphysematous lungs. Microscopically, there were severe pulmonary emphysema, eosinophilic hyaline membrane and infiltration of mature fibrocytes in the alveolar walls. Based on the histopathological findings interstitial pulmonary fibrosis was diagnosed. The possible cause of which although not completely known, is most likely due to hypersensitivity. The allergic reaction could have been caused by exposure to antigens of avian origin or the Mycobacterium gilvum, an non-tuberculous mycobacterium (NTM), isolated from the lung. This is the second case reported in elephants globally, thought it has been well studied in humans and reported in horses. Providing good husbandry for elephants in captivity is important to reduce the occurrence of such condition

Tuberculosis in captive Asian elephants (Elephas maximus) in Peninsular Malaysia

A cross-sectional study was conducted from 10 January to 9 April 2012, to determine the seroprevalence of tuberculosis (TB) of all captive Asian elephants and their handlers in six locations in Peninsular Malaysia. In addition, trunk-wash samples were examined for tubercle bacillus by culture and polymerase chain reaction (PCR). For 63 elephants and 149 elephant handlers, TB seroprevalence was estimated at 20·4% and 24·8%, respectively. From 151 trunk-wash samples, 24 acid-fast isolates were obtained, 23 of which were identified by hsp65-based sequencing as non-tuberculous mycobacteria. The Mycobacterium tuberculosis-specific PCR was positive in the trunk-wash samples from three elephants which were also seropositive. Conversely, the trunk wash from seven seropositive elephants were PCR negative. Hence, there was evidence of active and latent TB in the elephants and the high seroprevalence in the elephants and their handlers suggests frequent, close contact, two-way transmission between animals and humans within confined workplaces

Therapeutic and Tumor-specific Immunity Induced by Combination of Dendritic Cells and Oncolytic Adenovirus Expressing IL-12 and 4-1BBL

Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic

Evidence and potential risk factors of tuberculosis among captive Asian elephants and wildlife staff in Peninsular Malaysia

Elephant tuberculosis (TB) caused by Mycobacterium tuberculosis is an important re-emerging zoonosis with considerable conservation and public health risk. We conducted prospective cohort and cross-sectional studies in elephants and wildlife staff respectively in order to identify potential risk factors associated with TB in captive Asian elephants and their handlers in Peninsular Malaysia. Sixty elephants in six different facilities were screened for TB longitudinally using the ElephantTB STAT-PAK and DPP VetTB assays from February 2012 to May 2014, and 149 wildlife staff were examined for tuberculosis infection using the QuantiFERON-TB Gold In-tube (QFT) assay from January to April, 2012. Information on potential risk factors associated with infection in both elephants and staff were collected using questionnaires and facility records. The overall seroprevalence of TB amongst the elephants was 23.3% (95% CI: 13.8–36.3) and the risk of seroconversion was significantly higher among elephants with assigned mahouts [p = 0.022, OR = 4.9 (95% CI: 1.3–18.2)]. The percentage of QFT responders among wildlife staff was 24.8% (95% CI: 18.3–32.7) and the risk of infection was observed to be significantly associated with being a zoo employee [p = 0.018, OR = 2.7 (95% CI: 1.2–6.3)] or elephant handler [p = 0.035, OR = 4.1 (95% CI: 1.1–15.5)]. These findings revealed a potential risk of TB infection in captive elephants and handlers in Malaysia, and emphasize the need for TB screening of newly acquired elephants, isolating sero-positive elephants and performing further diagnostic tests to determine their infection status, and screening elephant handlers for TB, pre- and post-employment

Probing the Nature of High-z Short GRB 090426 with Its Early Optical and X-ray Afterglows

GRB 090426 is a short duration burst detected by Swift ($T_{90}\sim 1.28$ s in the observer frame, and $T_{90}\sim 0.33$ s in the burst frame at $z=2.609$). Its host galaxy properties and some $\gamma$-ray related correlations are analogous to those seen in long duration GRBs, which are believed to be of a massive-star origin (so-called Type II GRBs). We present the results of its early optical observations with the 0.8-m TNT telescope at Xinglong observatory, and the 1-m LOAO telescope at Mt. Lemmon Optical Astronomy Observatory in Arizona. Our well-sampled optical afterglow lightcurve covers from $\sim 90$ seconds to $\sim 10^4$ seconds post the GRB trigger. It shows two shallow decay episodes that are likely due to energy injection, which end at $\sim 230$ seconds and $\sim 7100$ seconds, respectively. The decay slopes post the injection phases are consistent with each other ($\alpha\simeq 1.22$). The X-ray afterglow lightcurve appears to trace the optical, although the second energy injection phase was missed due to visibility constraints introduced by the {\em Swift} orbit. The X-ray spectral index is $\beta_X\sim 1.0$ without temporal evolution. Its decay slope is consistent with the prediction of the forward shock model. Both X-ray and optical emission is consistent with being in the same spectral regime above the cooling frequency ($\nu_c$). The fact that $\nu_c$ is below the optical band from the very early epoch of the observation provides a constraint on the burst environment, which is similar to that seen in classical long duration GRBs. We therefore suggest that death of a massive star is the possible progenitor of this short burst.Comment: 7 pages, 1 figures, 2 tables, revised version, MNRAS, in pres

What is the Most Promising Electromagnetic Counterpart of a Neutron Star Binary Merger?

The final inspiral of double neutron star and neutron star-black hole binaries are likely to be detected by advanced networks of ground-based gravitational wave (GW) interferometers. Maximizing the science returns from such a discovery will require the identification and localization of an electromagnetic (EM) counterpart. Here we critically evaluate and compare several possible counterparts, including short-duration gamma-ray bursts (SGRBs), "orphan" optical and radio afterglows, and ~day-long optical transients powered by the radioactive decay of heavy nuclei synthesized in the merger ejecta ("kilonovae"). We assess the promise of each counterpart in terms of four "Cardinal Virtues": detectability, high fraction, identifiability, and positional accuracy. Taking into account the search strategy for typical error regions of ~10s degs sq., we conclude that SGRBs are the most useful to confirm the cosmic origin of a few GW events, and to test the association with NS mergers. However, for the more ambitious goal of localizing and obtaining redshifts for a large sample of GW events, kilonovae are instead preferred. Off-axis optical afterglows will be detectable for at most ~10% of all events, while radio afterglows are promising only for the unique combination of energetic relativistic ejecta in a high density medium, and even then will require hundreds of hours of EVLA time per event. Our main recommendations are:(i) an all-sky gamma-ray satellite is essential for temporal coincidence detections, and for GW searches of gamma-ray triggered events; (ii) LSST should adopt a 1-day cadence follow-up strategy, ideally with ~0.5 hr per pointing to cover GW error regions (the standard 4-day cadence and depth will severely limit the probability of a unique identification); and (iii) radio searches should only focus on the relativistic case, which requires observations for a few months.Comment: 16 pages, 9 figures, 3 tables, submitted to Ap

In Vitro and In Vivo Anti-Angiogenic Activities of Panduratin A

Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy