Detection of radio emission from the gamma-ray pulsar J1732-3131 at 327 MHz

Although originally discovered as a radio-quiet gamma-ray pulsar, J1732-3131 has exhibited intriguing detections at decameter wavelengths. We report an extensive follow-up of the pulsar at 327 MHz with the Ooty radio telescope. Using the previously observed radio characteristics, and with an effective integration time of 60 hrs, we present a detection of the pulsar at a confidence level of 99.82%. The 327 MHz mean flux density is estimated to be 0.5-0.8 mJy, which establishes the pulsar to be a steep spectrum source and one of the least-luminous pulsars known to date. We also phase-aligned the radio and gamma-ray profiles of the pulsar, and measured the phase-offset between the main peaks in the two profiles to be 0.24$\pm$0.06. We discuss the observed phase-offset in the context of various trends exhibited by the radio-loud gamma-ray pulsar population, and suggest that the gamma-ray emission from J1732-3131 is best explained by outer magnetosphere models. Details of our analysis leading to the pulsar detection, and measurements of various parameters and their implications relevant to the pulsar's emission mechanism are presented.Comment: 8 pages, 6 figures; Accepted for publication in MNRA

The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone

Bone metastases are frequent complications of malignant melanoma leading to reduced quality of life and significant morbidity. Regulation of immune cells by the gut microbiome influences cancer progression, but the role of the microbiome in tumor growth in bone is unknown. Using intracardiac or intratibial injections of B16-F10 melanoma cells into mice, we showed that gut microbiome depletion by broad-spectrum antibiotics accelerated intraosseous tumor growth and osteolysis. Microbiome depletion blunted melanoma-induced expansion of intestinal NK cells and Th1 cells and their migration from the gut to tumor-bearing bones. Demonstrating the functional relevance of immune cell trafficking from the gut to the bone marrow (BM) in bone metastasis, blockade of S1P-mediated intestinal egress of NK and Th1 cells, or inhibition of their CXCR3/CXCL9-mediated influx into the BM, prevented the expansion of BM NK and Th1 cells and accelerated tumor growth and osteolysis. Using a mouse model, this study revealed mechanisms of microbiota-mediated gut-bone crosstalk that are relevant to the immunological restraint of melanoma metastasis and tumor growth in bone. Microbiome modifications induced by antibiotics might have negative clinical consequences in patients with melanoma

NKG2A Expression Is Not per se Detrimental for the Anti-Multiple Myeloma Activity of Activated Natural Killer Cells in an In Vitro System Mimicking the Tumor Microenvironment

Natural killer (NK) cell-based immunotherapy is a promising therapy for cancer patients. Inhibitory killer immunoglobulin-like receptors (KIRs) and NKG2A are required for NK cell licensing, but can also inhibit NK cell effector function. Upon reconstitution in a stem cell transplantation setting or after ex vivo NK expansion with IL-2, NKG2A is expressed on a large percentage of NK cells. Since the functional consequences of NKG2A co-expression for activated NK cells are not well known, we compared NKG2A+ vs NKG2A− NK cell subsets in response to K562 cells, multiple myeloma (MM) cell lines and primary MM cells. NK cells were isolated from healthy donors (HLA-C1+C2+Bw4+) and activated overnight with 1,000 U/ml IL-2. NK cell degranulation in subsets expressing KIRs and/or NKG2A was assessed at 21 or 0.6% O2. Activated NKG2A+ NK cell subsets degranulated more vigorously than NKG2A− subsets both at 21 and 0.6% O2. This was irrespective of the presence of KIR and occurred in response to HLA-deficient K562 cells as well as HLA competent, lowly expressing HLA-E MM cell lines. In response to primary MM cells, no inhibitory effects of NKG2A were observed, and NKG2A blockade did not enhance degranulation of NKG2A+ subsets. KIR− NK cells expressing NKG2A degranulated less than their NKG2A− counterparts in response to MM cells having high levels of peptide-induced membrane HLA-E, suggesting that high surface HLA-E levels are required for NKG2A to inhibit activated NK cells. Addition of daratumumab, an anti-CD38 to trigger antibody-dependent cell-mediated cytotoxicity, improved the anti-MM response for all subsets and degranulation of the KIR−NKG2A− “unlicensed” subset was comparable to KIR+ or NKG2A+ licensed subsets. This demonstrates that with potent activation, all subsets can contribute to tumor clearance. Additionally, subsets expressing KIRs mismatched with the HLA ligands on the target cell had the highest level of activation in response to MM cell lines as well as against primary MM. Our current study demonstrated that if NK cells are sufficiently activated, e.g., via cytokine or antibody activation, the (co-)expression of NKG2A receptor may not necessarily be a disadvantage for NK cell-based therapy

Validation of the test need for cognition: a study in behavioral accounting

This study aimed to validate the Need for Cognition scale (NFC) in behavioral accounting. In addition, we sought to measure the possible correlations between the level of need for cognition and the existence of cognitive biases in decisions in accounting and financial information. Two validations were performed to carry out the process of full validation – criterion and construct. The analysis was done by the examination of a sample comprised by 128 graduation students. The statistical technique used for the validation of this test was a factorial analysis for it has the ability to determine the degree of influence of a particular variable in the explanation of a factor, and the processing logistic regression was used for the explanation of possible values as a function of known values or independent variables. The results of the construct of validity showed the legitimacy of the NFC as a unidimensional scale excluding three outputs of its original scale, since the criterion validity of the results confirmed the impact of the level of cognition in maximizing the occurrence of heuristics in managerial decisions

Pharmacological and Genetic Modulation of REV-ERB Activity and Expression Affects Orexigenic Gene Expression

The nuclear receptors REV-ERBα and REV-ERBβ are transcription factors that play pivotal roles in the regulation of the circadian rhythm and various metabolic processes. The circadian rhythm is an endogenous mechanism, which generates entrainable biological changes that follow a 24-hour period. It regulates a number of physiological processes, including sleep/wakeful cycles and feeding behaviors. We recently demonstrated that REV-ERB-specific small molecules affect sleep and anxiety. The orexinergic system also plays a significant role in mammalian physiology and behavior, including the regulation of sleep and food intake. Importantly, orexin genes are expressed in a circadian manner. Given these overlaps in function and circadian expression, we wanted to determine whether the REV-ERBs might regulate orexin. We found that acute in vivo modulation of REV-ERB activity, with the REV-ERB-specific synthetic ligand SR9009, affects the circadian expression of orexinergic genes in mice. Long term dosing with SR9009 also suppresses orexinergic gene expression in mice. Finally, REV-ERBβ-deficient mice present with increased orexinergic transcripts. These data suggest that the REV-ERBs may be involved in the repression of orexinergic gene expression

Real Time Vision System for Collision Detection

Collision detection is an essential feature for any Real-Time Active Vision system to safeguard it against imminent collisions. In this paper, we describe the design and implementation of a real-time (25Hz) collision detection and avoidance system. The implementation is based on a theory originally proposed in [5, 4]. A relative motion between an observer and an object induces a corresponding image velocity, which is divergent in nature when the object moves towards the camera. In this system, we detect imminent collision from the divergent image flow. The implementation is based on a combination of spatial parallelism and pipelining. We have developed a general purpose library for implementing a pipeline application. This library can be ported on to any multiprocessing machine supporting inter-process communications. To achieve real-time performance, we have developed the collision detection system using the pipe library on a network of T805 transputers. A mobile robot with a camera m..