Quantum heat current under non-perturbative and non-Markovian conditions: Applications to heat machines

We consider a quantum system strongly coupled to multiple heat baths at different temperatures. Quantum heat transport phenomena in this system are investigated using two definitions of the heat current: one in terms of the system energy and the other in terms of the bath energy. When we consider correlations among system-bath interactions (CASBIs) - which have a purely quantum mechanical origin - the definition in terms of the bath energy becomes different. We found that CASBIs are necessary to maintain the consistency of the heat current with thermodynamic laws in the case of strong system-bath coupling. However, within the context of the quantum master equation approach, both of these definitions are identical. Through a numerical investigation, we demonstrate this point for a non-equilibrium spin-boson model and a three-level heat engine model using the reduced hierarchal equations of motion approach under the strongly coupled and non-Markovian conditions. We observe the cyclic behavior of the heat currents and the work performed by the heat engine, and we find that their phases depend on the system-bath coupling strength. Through consideration of the bath heat current, we show that the efficiency of the heat engine decreases as the strength of the system-bath coupling increases, due to the CASBI contribution. In the case of a large system-bath coupling, the efficiency decreases further if the bath temperature is increased, even if the ratio of the bath temperatures is fixed, due to the discretized nature of energy eigenstates. This is also considered to be a unique feature of quantum heat engines

非摂動・非マルコフ環境下における量子熱輸送の解析：階層型運動方程式によるアプローチ

京都大学0048新制・課程博士博士(理学)甲第20194号理博第4279号新制||理||1615(附属図書館)京都大学大学院理学研究科化学専攻(主査)教授 谷村 吉隆, 教授 林 重彦, 教授 松本 吉泰学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDGA

Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable antitumor immunity in a mouse glioma model.

BackgroundToca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector encoding an optimized yeast cytosine deaminase (CD). Tumor-selective expression of CD converts the prodrug, 5-fluorocytosine (5-FC), into the active chemotherapeutic, 5-fluorouracil (5-FU). This therapeutic approach is being tested in a randomized phase II/III trial in recurrent glioblastoma and anaplastic astrocytoma (NCT0241416). The aim of this study was to identify the immune cell subsets contributing to antitumor immune responses following treatment with 5-FC in Toca 511-expressing gliomas in a syngeneic mouse model.MethodsFlow cytometry was utilized to monitor and characterize the immune cell infiltrate in subcutaneous Tu-2449 gliomas in B6C3F1 mice treated with Toca 511 and 5-FC.ResultsTumor-bearing animals treated with Toca 511 and 5-FC display alterations in immune cell populations within the tumor that result in antitumor immune protection. Attenuated immune subsets were exclusive to immunosuppressive cells of myeloid origin. Depletion of immunosuppressive cells temporally preceded a second event which included expansion of T cells which were polarized away from Th2 and Th17 in the CD4+ T cell compartment with concomitant expansion of interferon gamma-expressing CD8+ T cells. Immune alterations correlated with clearance of Tu-2449 subcutaneous tumors and T cell-dependent protection from future tumor challenge.ConclusionsTreatment with Toca 511 and 5-FC has a concentrated effect at the site of the tumor which causes direct tumor cell death and alterations in immune cell infiltrate, resulting in a tumor microenvironment that is more permissive to establishment of a T cell mediated antitumor immune response

Taiwan‘s Human Rights Policies as a Substitute for an Establishment of a Constitution

departmental bulletin pape

Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity.

BackgroundProdrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.MethodsHere we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor models, employing both human glioma xenografts in immunodeficient hosts and syngeneic murine gliomas in immunocompetent hosts.ResultsIn both models, a single injection of replicating vector followed by prodrug administration achieved long-term survival benefit. In the immunodeficient model, tumors recurred repeatedly, but bioluminescence imaging of tumors enabled tailored scheduling of multicycle prodrug administration, continued control of disease burden, and long-term survival. In the immunocompetent model, complete loss of tumor signal was observed after only 1-2 cycles of prodrug, followed by long-term survival without recurrence for >300 days despite discontinuation of prodrug. Long-term survivors rejected challenge with uninfected glioma cells, indicating immunological responses against native tumor antigens, and immune cell depletion showed a critical role for CD4+ T cells.ConclusionThese results support dual mechanisms of action contributing to the efficacy of RRV-mediated prodrug-activator gene therapy: long-term tumor control by prodrug conversion-mediated cytoreduction, and induction of antitumor immunity

Very Low-pressure Hydrocephalus: A New Clinical Entity and Issues of Treatment

Secondary normal pressure hydrocephalus (NPH) frequently occurs after severe head injury and cerebrovascular disease. This condition is usually treated by surgically implanting a cerebrospinal fluid (CSF) shunt with a pressure-setting valve or programmable valve. However, some patients do not respond to the shunt operation. Among these non-responders, we found 7 patients whose pressure-setting shunts were mechanically patent, but were not functioning due to very low intracranial pressure (ICP). In these 7 cases, continuous ICP monitoring indicated low pressure with occasional negative pressure, and the patients\u27 consciousness improved during negative-pressure CSF drainage. We performed shunt revisions with zero setting on-off valves, which raised the mean functional independence measure (FIM) scores from 26 to 62. Four patients in a persistent vegetative state (PVS) regained their ability to communicate and recovered to the level of severely disabled (SD). We propose very low-pressure hydrocephalus (VLPH) as a new clinical entity, and describe the process of diagnosis and treatment

Effect of SHED-CM on DPN

Aims/Introduction: Transplantation of stem cells promotes axonal regeneration and angiogenesis in a paracrine manner. In the present study, we examined whether the secreted factors in conditioned medium of stem cells from human exfoliated deciduous teeth (SHED‐CM) had beneficial effects on diabetic polyneuropathy in mice. Materials and Methods: Conditioned medium of stem cells from human exfoliated deciduous teeth was collected 48 h after culturing in serum‐free Dulbecco's modified Eagle's medium (DMEM), and separated into four fractions according to molecular weight. Dorsal root ganglion neurons from C57BL/6J mice were cultured with SHED‐CM or DMEM to evaluate the effect on neurite outgrowth. Streptozotocin‐induced diabetic mice were injected with 100 μL of SHED‐CM or DMEM into the unilateral hindlimb muscles twice a week over a period of 4 weeks. Peripheral nerve functions were evaluated by the plantar test, and motor and sensory nerve conduction velocities. Intraepidermal nerve fiber densities, capillary number‐to‐muscle fiber ratio, capillary blood flow and morphometry of sural nerves were also evaluated. Results: Conditioned medium of stem cells from human exfoliated deciduous teeth significantly promoted neurite outgrowth of dorsal root ganglion neurons compared with DMEM. Among four fractions of SHED‐CM, the only fraction of <6 kDa promoted the neurite outgrowth of dorsal root ganglion neurons. In addition, SHED‐CM significantly prevented decline in sensory nerve conduction velocities compared with DMEM in diabetic mice. Although SHED‐CM did not improve intraepidermal nerve fiber densities or morphometry of sural nerves, SHED‐CM ameliorated the capillary number‐to‐muscle fiber ratio and capillary blood flow. Conclusions: These results suggested that SHED‐CM might have a therapeutic effect on diabetic polyneuropathy through promoting neurite outgrowth, and the increase in capillaries might contribute to the improvement of neural function