Long-term monitoring of the short period SU UMa-type dwarf nova, V844 Herculis

We report on time-resolved CCD photometry of four outbursts of a short-period SU UMa-type dwarf nova, V844 Herculis. We successfully determined the mean superhump periods to be 0.05584(64) days, and 0.055883(3) for the 2002 May superoutburst, and the 2006 April-May superoutburst, respectively. During the 2002 October observations, we confirmed that the outburst is a normal outburst, which is the first recorded normal outburst in V844 Her. We also examined superhump period changes during 2002 May and 2006 April-May superoutbursts, both of which showed increasing superhump period over the course of the plateau stage. In order to examine the long-term behavior of V844 Her, we analyzed archival data over the past ten years since the discovery of this binary. Although photometry is not satisfactory in some superoutbursts, we found that V844 Her showed no precursors and rebrightenings. Based on the long-term light curve, we further confirmed V844 Her has shown almost no normal outbursts despite the fact that the supercycle of the system is estimated to be about 300 days. In order to explain the long-term light curves of V844 Her, evaporation in the accretion disk may play a role in the avoidance of several normal outbursts, which does not contradict with the relatively large X-ray luminosity of V844 Her.Comment: 10 pages, 11 figures, accepted for PAS

Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells

CARシグナルを補完する遺伝子改変により *iCAR-T細胞の固形がん治療効果が改善される. 京都大学プレスリリース. 2022-12-13.Genetic modifications boosting CAR signaling improve the therapeutic efficacy of iPSC-derived CAR-T cells against solid tumors. 京都大学プレスリリース. 2022-12-13.The effectiveness of chimaeric antigen receptor (CAR) T-cell immunotherapies against solid tumours relies on the accumulation, proliferation and persistency of T cells at the tumour site. Here we show that the proliferation of CD8αβ cytotoxic CAR T cells in solid tumours can be enhanced by deriving and expanding them from a single human induced-pluripotent-stem-cell clone bearing a CAR selected for efficient differentiation. We also show that the proliferation and persistency of the effector cells in the tumours can be further enhanced by genetically knocking out diacylglycerol kinase, which inhibits antigen-receptor signalling, and by transducing the cells with genes encoding for membrane-bound interleukin-15 (IL-15) and its receptor subunit IL-15Rα. In multiple tumour-bearing animal models, the engineered hiPSC-derived CAR T cells led to therapeutic outcomes similar to those of primary CD8 T cells bearing the same CAR. The optimization of effector CAR T cells derived from pluripotent stem cells may aid the development of long-lasting antigen-specific T-cell immunotherapies for the treatment of solid tumours

Data from: Can recombinant human thrombomodulin increase survival among patients with severe septic-induced disseminated intravascular coagulation: a single-centre, open-label, randomised controlled trial

Objective: To determine whether treatment with recombinant human thrombomodulin (rhTM) increases survival among severe septic patients with sepsis-induced disseminated intravascular coagulation (DIC) Design: Single-center, open-label, randomized controlled trial Setting: Single tertiary hospital Participant: 92 severe septic patients with sepsis-induced DIC Interventions: Patients with DIC scores ≥4, as defined by the Japanese Association of Acute Medicine, were diagnosed with DIC. Randomization was performed by the envelope method. The treatment group (rhTM group, n = 47) was intravenously treated with rhTM within 24 h of admission (day 0), and the control group (n = 45) did not receive any anti-coagulants, except in cases of deep venous thrombosis and pulmonary embolism. Primary and secondary measurements: Data were collected on days 0 (admission), 1, 2, 3, 5, 7, and 10. The primary outcome was survival at 28 and 90 days. The secondary endpoints comprised changes in DIC scores, platelet counts, D-dimer, antithrombin III (ATIII), and C-reactive protein (CRP) levels, and Sequential Organ Failure Assessment (SOFA) scores. All analyses were conducted on an intent-to-treat basis. Main Results: The 28-day survival rates were 84 and 83% in the control and rhTM groups, respectively (p = 0.745, log rank test). The 90-day survival rates were 73% and 72% in the control and rhTM groups, respectively (p = 0.94, log rank test). Meanwhile, the rates of recovery from DIC (<4) were significantly higher in the rhTM group than in the control group (p = 0.001, log rank test). Relative change from baseline of D-dimer levels were significantly lower in the rhTM group than in the control group, on day 3 and 5. Conclusion: rhTM treatment decreased D-dimer levels and facilitated DIC recovery in severe septic patients with sepsis-induced DIC. However, the treatment did not improve survival in this cohort

rhTM open data

rhTM, recombinant human thrombomodulin; FDP, fibrin/fibrinogen degradation products; FDP0, FDP value ar day 0; delta, Relative change rate from baseline = ([measurement day value − day 0 value]/day 0 value); delta FDP1, ([FDP value at day 1− day 0 value]/day 0 value); PLT, platelet; Fib, fibrinogen; PT, PTINR, prothrombin time ratio, –international normalized ratio; PTperc, PT percentage; APTT, partial thromboplastin time; ATIII, antithrombin III; TM, thrombomodulin value; SIRS, Systemic inflammatory response syndrome; SOFA, sequential organ failure assessment score; SOFA PF, SOFA respiratory score; SOFA PL, SOFA coagulation score; SOFA bil, SOFA hepatic dysfunction score; SOFA CV, SOFA cardiovascular system score; SOFA GCS, SOFA Glasgow Come Scale score; SOFA Cr, SOFA renal dysfunction score

Study protocol for single-center, open-label, randomized controlled trial to clarify the preventive efficacy of electrical stimulation for muscle atrophy after trauma

Abstract Background Management of trauma involves long-term bed rest even when muscle strength in the lower extremities is preserved. Prolonged bed rest reduces muscle mass and causes muscle atrophy. A recent study reported the efficacy of rehabilitation using electrical muscle stimulation (EMS) for muscle strength maintenance in intensive care unit patients with disturbance of consciousness. However, despite the expected benefits of EMS in maintaining muscle strength, little is known about its efficacy in trauma patients. Methods/design A single-center, open-label, randomized controlled trial of 40 patients with pelvic fracture to test the effectiveness of 14 days of EMS. The primary outcome will be change in cross-sectional area of the thigh muscle between pre and post intervention, as measured on computed tomography images. We will analyze the primary endpoint by analysis of covariance (ANCOVA) and analyze the secondary endpoints in an exploratory manner. Conclusion If our hypothesis is confirmed, this study will provide evidence that the use of EMS can be effective in preventing muscle atrophy. Trial registration UMIN registration number: UMIN000030190. Registered on 1 December 2017

Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response

ヒトiPS細胞由来T細胞に遺伝子を導入すると、ヘルパーT細胞様の機能を獲得することを発見しました. 京都大学プレスリリース. 2018-06-04.CD4+ T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40Lhigh iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40Lhigh iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia