On Conflict of Human Rights

[Excerpt] “This article supports Gewirth’s view: that is, the reason why utilitarian values such as national security, public safety, public order, public health, and public morality may outweigh human rights is that they contain human rights elements. Thus, as a rule, whenever human rights clash with nonrights value considerations, we should analyze whether they contain human rights elements. If they do, they may override human rights that conflict with them. If they do not, they cannot.

Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs

BACKGROUND: The coinhibitory receptor Programmed Death-1 (PD-1) inhibits effector functions of activated T cells and prevents autoimmunity, however, cancer hijack this pathway to escape from immune attack. The costimulatory receptor glucocorticoid-induced TNFR related protein (GITR) is up-regulated on activated T cells and increases their proliferation, activation and cytokine production. We hypothesize that concomitant PD-1 blockade and GITR triggering would synergistically improve the effector functions of tumor-infiltrating T cells and increase the antitumor immunity. In present study, we evaluated the antitumor effects and mechanisms of combined PD-1 blockade and GITR triggering in a clinically highly relevant murine ID8 ovarian cancer model. METHODS: Mice with 7 days-established peritoneal ID8 ovarian cancer were treated intraperitoneally (i.p.) with either control, anti-PD-1, anti-GITR or anti-PD-1/GITR monoclonal antibody (mAb) and their survival was evaluated; the phenotype and function of tumor-associated immune cells in peritoneal cavity of treated mice was analyzed by flow cytometry, and systemic antigen-specific immune response was evaluated by ELISA and cytotoxicity assay. RESULTS: Combined anti-PD-1/GITR mAb treatment remarkably inhibited peritoneal ID8 tumor growth with 20% of mice tumor free 90 days after tumor challenge while treatment with either anti-PD-1 or anti-GITR mAb alone exhibited little antitumor effect. The durable antitumor effect was associated with a memory immune response and conferred by CD4(+) cells and CD8(+) T cells. The treatment of anti-PD-1/GITR mAb increased the frequencies of interferon-γ-producing effector T cells and decreased immunosuppressive regulatory T cells and myeloid-derived suppressor cells, shifting an immunosuppressive tumor milieu to an immunostimulatory state in peritoneal cavity. In addition, combined treatment of anti-PD-1/GITR mAb mounted an antigen-specific immune response as evidenced by antigen-specific IFN-γ production and cytolytic activity of spleen cells from treated mice. More importantly, combined treatment of anti-PD-1/GITR mAb and chemotherapeutic drugs (cisplatin or paclitaxel) further increased the antitumor efficacy with 80% of mice obtaining tumor-free long-term survival in murine ID8 ovarian cancer and 4 T1 breast cancer models. CONCLUSIONS: Combined anti-PD-1/GITR mAb treatment induces a potent antitumor immunity, which can be further promoted by chemotherapeutic drugs. A combined strategy of anti-PD-1/GITR mAb plus cisplatin or paclitaxel should be considered translation into clinic

Ultrafast Measurement of Chemical Dynamics in the Condensed Phase Using Transient Vibrational Spectroscopy.

Geminate recombination and vibrational energy relaxation of iodine in the condensed phase are investigated using picosecond transient Raman spectroscopy. The advantages of transient Raman in measuring vibrational energy relaxation and separating different reaction dynamics are demonstrated in this dissertation. Using transient Raman spectroscopy we have for the first time directly observed geminate recombination and vibrational energy relaxation of I\sb2 on both X and A\sp\prime \sp3\Pi\sb{2u} states. For the X state, energy relaxation from vibrational levels ranging from $\upsilon$ = 52 to $\upsilon$ = 1 have been observed. These levels correspond to absolute energies of 9,300 to 210 cm\sp{-1} above the zero point in the X potential. The importance of vibrational to vibrational (V-V) energy transfer pathways has been studied and the V-V transfer efficiency is found to be very solvent dependent. The results suggest that the vibrational coupling between the excited iodine oscillator and the solvent is drastically affected by the nature of the normal mode character of the solvent vibration. For the A\sp\prime state, geminate recombination rate is found to be significantly slower than the X state. Evidence is reported which suggests the possible role of iodine atom-solvent complexes in the reaction step leading from photodissociated atoms to formation of the excited state. Electronic relaxation is investigated and is found to be largely the result of the formation and decay of I\sb2\cdotSolvent exciplexes. Geminate recombination between iodine radical and iodine molecule is directly observed by dissociating iodine dimer. The geminate recombination time of I + I\sb2 in cyclohexane is measured to be 50-100 ps. The slower recombination rate of I + I\sb2 in comparison with the fast geminate recombination of I + I provides direct experimental evidence for the existence of an activation barrier for the former reaction. Recombination rates in different solvents decrease in the order n-hexane $\u3e$ neo-hexane $\ge$ deuterated cyclohexane $\approx$ cyclohexane. The lifetime of I\sb3 is determined to be greater than 500 ps

LncRNAs: the bridge linking RNA and colorectal cancer.

Long noncoding RNAs (lncRNAs) are transcribed by genomic regions (exceeding 200 nucleotides in length) that do not encode proteins. While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, lncRNAs control pleiotropic cancer phenotypes through interactions with other cellular molecules including DNA, protein, and RNA. Recent studies have demonstrated that dysregulation of lncRNAs is influential in proliferation, angiogenesis, metastasis, invasion, apoptosis, stemness, and genome instability in colorectal cancer (CRC), with consequent clinical implications. In this review, we explicate the roles of different lncRNAs in CRC, and the potential implications for their clinical application

Distributed Event-Triggered Online Learning for Multi-Agent System Control using Gaussian Process Regression

For the cooperative control of multi-agent systems with unknown dynamics, data-driven methods are commonly employed to infer models from the collected data. Due to the flexibility to model nonlinear functions and the existence of theoretical prediction error bound, Gaussian process (GP) regression is widely used in such control problems. Online learning, i.e. adding newly collected training data to the GP models, promises to improve control performance via improved predictions during the operation. In this paper, we propose a distributed event-triggered online learning algorithm for multi-agent system control. The proposed algorithm only employs locally available information from the neighbors and achieves a guaranteed overall control performance with desired tracking error bound. Moreover, the exclusion of the Zeno behavior for each agent is proved. Finally, the effectiveness of the proposed event-triggered online learning is demonstrated in simulations