Predicted Number, Multiplicity, and Orbital Dynamics of TESS M Dwarf Exoplanets

We present a study of the M dwarf exoplanetary systems forthcoming from NASA's TESS mission. While the mission's footprint is too complex to be characterized by a single detection completeness, we extract an ensemble completeness function that recovers the M dwarf planet detections from previous work. We employ this completeness function, together with a dual-population planet occurrence model that includes compact multiple planetary systems, to infer anew the planet yield. We predict both the number of M dwarf planets likely from TESS and their system architectures. We report four main findings: first, that TESS will likely detect more planets orbiting M dwarfs that previously predicted. Around stars with spectral types between M1V--M4V, we predict TESS will find 990$\pm$350 planets orbiting 715$\pm$255 stars, a 1.5-fold increase over previous predictions. Secondly, TESS will find two or more transiting planets around 20% of these host stars, a number similar to the multiplicity yield of NASA's Kepler mission. Thirdly, TESS light curves in which one or more planets are detected will often contain transits of additional planets below the detection threshold of TESS. Among a typical set of 200 TESS hosts to one or more detected planets, 116$\pm$28 transiting planets will be missed. Transit follow-up efforts with the photometric sensitivity to detect an Earth or larger around a mid-M dwarf, even with very modest period completeness, will readily result in additional planet discoveries. And fourth, the strong preference of TESS for systems of compact multiples indicates that TESS planets will be dynamically cooler on average than Kepler planets, with 90% of TESS-detected planets residing in orbits with $e<0.15$.Comment: 14 pages, 11 figures, submitted to Ap

High working memory performers have efficient eye movement control systems under Reading Span Test

Controlled eye movements are critical in performing highly goal oriented behavior such as text reading. Previous studies have examined the relationship between working memory capacity and eye movement control during working memory task. However, the results were inconsistent, due to a methodological issue including the predictability of target location. In the present study, we used Japanese version of reading span test, where the position of to-be-remembered word is not predictable so that more efficient attentional control is required, and investigated how working memory capacity contributes to eye movement control during reading span test. Results based on total fixation time revealed that highworking memory performers efficiently control or shift their attention under high memory load

Effect of memory load on eye movement control: A study using the reading span test

We investigated the effect of memory load on attentional control using the Reading Span Test (RST), a task that requires working memory capacity. Previous studies have shown that a shortage of working memory resources leads to a deficit of inhibition of taskirrelevant information and that memory load affects eye movement control. Here, we recorded eye movement and integrated it with RST performance. Total fixation time and the number of regressions showed a memory load effect with the to-be-remembered word, and RST performance was also affected under high memory load. We concluded that a shortage of working memory resources caused by memory load prevents flexible eye movement control and may cause a deficit in inhibitory control based on intrusion errors

A Critical Role for the Programmed Death Ligand 1 in Fetomaternal Tolerance

Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cel

Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for efective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model

[EN] The expression of PD-L1 on tumor cells or within the tumor microenvironment has been associated with good prognosis and sustained clinical responses in immunotherapeutic regimens based on PD-L1/PD-1/CD80 immune checkpoint blockade. To look into the current controversy in cancer immunotherapy of the relative importance of PD-L1 expression on tumor cells versus non-tumor cells of the tumor microenvironment, a hematological mouse tumor model was chosen. By combining a genetic CRISPR/Cas9 and immunotherapeutic approach and using a syngeneic hematopoietic transplantable tumor model (E.G7-cOVA tumor cells), we demonstrated that dual blockade of PD-L1 interaction with PD-1 and CD80 enhanced anti-tumor immune responses that either delayed tumor growth or led to its complete eradication. PD-L1 expression on non-tumor cells of the tumor microenvironment was required for the promotion of tumor immune escape and its blockade elicited potent anti-tumor responses to PD-L1 WT and to PD-L1-defcient tumor cells. PD-L1+ tumors implanted in PDL1-defcient mice exhibited delayed tumor growth independently of PD-L1 blockade. These fndings emphasize that PD-L1 expression on non-tumor cells plays a major role in this tumor model. These observations should turn our attention to the tumor microenvironment in hematological malignancies because of its unappreciated contribution to create a conditioned niche for the tumor to grow and evade the anti-tumor immune response.SIThis work has been supported by Grant FIS PI# 1300029 (Fondo de Investigaciones Sanitarias, Ministry of Health, Spanish Government, and co-funded by European Union ERDF/ESF, “Investing in your future”), LE093U13 and Unit of Excellence Research UIC #012 (Department of Education of the Regional Government, Junta de Castilla y Leon) and Gerencia Regional de Salud (BIO/01/15) to JIRB. It was also funded by Miguel Servet National Grant (Health National Organization Research) CP12/03063, CPII17/00002 and FIS PI16/00002 (Instituto de Salud Carlos III and co-funded by European Union ERDF/ESF, “Investing in your future”), and Gerencia Regional de Salud GRS963/A/2014, GRS1142/A/2015 and GRS 1505/A/2017 to M.L.R.G. This work has been partially funded by the National Network CIBER-ONC (oncology research) CB16/12/00480

Critical Role of the Programmed Death-1 (PD-1) Pathway in Regulation of Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is mediated by autoantigen-specific T cells dependent on critical costimulatory signals for their full activation and regulation. We report that the programmed death-1 (PD-1) costimulatory pathway plays a critical role in regulating peripheral tolerance in murine EAE and appears to be a major contributor to the resistance of disease induction in CD28-deficient mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) there was a progressive increase in expression of PD-1 and its ligand PD-L1 but not PD-L2 within the central nervous system (CNS) of mice with EAE, peaking after 3 wk. In both wild-type (WT) and CD28-deficient mice, PD-1 blockade resulted in accelerated and more severe disease with increased CNS lymphocyte infiltration. Worsening of disease after PD-1 blockade was associated with a heightened autoimmune response to MOG, manifested by increased frequency of interferon γ–producing T cells, increased delayed-type hypersensitivity responses, and higher serum levels of anti-MOG antibody. In vivo blockade of PD-1 resulted in increased antigen-specific T cell expansion, activation, and cytokine production. Interestingly, PD-L2 but not PD-L1 blockade in WT animals also resulted in disease augmentation. Our data are the first demonstration that the PD-1 pathway plays a critical role in regulating EAE

Insulin-induced remission in new-onset NOD mice is maintained by the PD-1–PD-L1 pathway

The past decade has seen a significant increase in the number of potentially tolerogenic therapies for treatment of new-onset diabetes. However, most treatments are antigen nonspecific, and the mechanism for the maintenance of long-term tolerance remains unclear. In this study, we developed an antigen-specific therapy, insulin-coupled antigen-presenting cells, to treat diabetes in nonobese diabetic mice after disease onset. Using this approach, we demonstrate disease remission, inhibition of pathogenic T cell proliferation, decreased cytokine production, and induction of anergy. Moreover, we show that robust long-term tolerance depends on the programmed death 1 (PD-1)–programmed death ligand (PD-L)1 pathway, not the distinct cytotoxic T lymphocyte–associated antigen 4 pathway. Anti–PD-1 and anti–PD-L1, but not anti–PD-L2, reversed tolerance weeks after tolerogenic therapy by promoting antigen-specific T cell proliferation and inflammatory cytokine production directly in infiltrated tissues. PD-1–PD-L1 blockade did not limit T regulatory cell activity, suggesting direct effects on pathogenic T cells. Finally, we describe a critical role for PD-1–PD-L1 in another powerful immunotherapy model using anti-CD3, suggesting that PD-1–PD-L1 interactions form part of a common pathway to selectively maintain tolerance within the target tissues

Th2 Responses to Helminth Parasites Can Be Therapeutically Enhanced by, but Are Not Dependent upon, GITR–GITR Ligand Costimulation In Vivo

The immune suppression that characterizes human helminth infections can hinder the development of protective immunity or help reduce pathogenic inflammation. Signaling through the T cell co-stimulator GITR counteracts immune down-regulation by augmenting effector T cell responses and abrogating suppression by Foxp3(+) regulatory T cells. Thus, super-physiological antibody-mediated GITR co-stimulation represents a novel therapy for promoting protective immunity towards parasitic helminths, whilst blocking physiological GITR-GITRL interactions may provide a mechanism for dampening pathogenic Th2 inflammation. We investigated the super-physiological and physiological role of the GITR-GITRL pathway in the development of protective and pathogenic Th2 responses in murine infection models of filariasis (Litomosoides sigmodontis) and schistosomiasis (Schistosoma mansoni). Providing super-physiological GITR co-stimulation using an agonistic anti-GITR mAb over the first 12 days of L. sigmodontis infection initially increased the quantity of Th2 cells as well as their ability to produce Th2 cytokines. However, as infection progressed the Th2 responses reverted to normal infection levels and parasite killing remained unaffected. Despite the Th2 promoting role of super-physiological GITR co-stimulation, antibody-mediated blockade of the GITR-GITRL pathway did not affect Th2 cell priming or maintenance during L. sigmodontis infection. Blockade of GITR-GITRL interactions during the acute egg-phase of S. mansoni infection resulted in reduced Th2 responses, but this effect was confined to the spleen and did not lead to changes in liver pathology. Thus, although super-physiological GITR co-stimulation can therapeutically enhance Th2 responses, physiological GITR-GITRL interactions are not required for the development of Th2-mediated resistance or pathology in murine models of filariasis and schistosomiasis