bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humanitarian Intervention: An Overview of the Ethical Issues
Authors: Smith Michael J. 
Published: September 2006

The capacity to focus on the issue of humanitarian intervention represents what Joel Rosenthal has noted as the maturation of the field of ethics and international affairs. If nothing else, the debate surrounding this vexed issue has demonstrated that we have left behind the so-called oxymoron problem: there is no reason now to be defensive about bracketing the terms “ethics” and “international relations.” One can hardly talk about Bosnia, Rwanda, Haiti, Somalia, or any cases of possible outside intervention, without recognizing from the very beginning that ethical dilemmas abound in the way we define our goals, our interests, and the means we use to pursue them. Even Samuel P. Huntington, not usually known to be a moralist, has asserted that “it is morally unjustifiable and politically indefensible that members of the [U.S.] armed forces should be killed to prevent Somalis from killing one another.” Whether or not one agrees with that assertion (I do not), one may note that Huntington speaks in terms of moral justification and regards his view of morality to be, in effect, self-evidently true. Thus even archrealists invoke morality in urging their preferred policies.The discussion in this essay proceeds in three unequal stages. First, I present a brief and oversimple sketch of the objective and subjective changes in the broader milieu of international relations as they relate to humanitarian intervention. Second, and more substantially, I survey and analyze the arguments justifying or opposing the notion of humanitarian intervention from realist and liberal perspectives. Finally, I offer the beginnings of my own argument and consider the enormous difficulties of undertaking humanitarian intervention with any degree of effectiveness and consistency.
Postmodern Ethical Conditions and a Critical Response
Authors: Crawford Neta C. 
Published: September 2006

Postmodern, poststructural, and critical theorists say that there are no universally valid foundations for norms. Whether or not we think that ethics exists in international life, or ought to, these theorists maintain that there are no firm grounds for any particular ethical belief. Rather, they argue, ethics is contextual.Many, perhaps most, students of international ethics believe that such approaches have little to offer considerations of international ethics. Christopher Norris says postmodernists are nihilists: “Postmodernism is merely the most extreme (or as some would say, most consistent and consequent) version of this desire to have done with all truth-claims beyond what is presently and contingenty ‘good in the way of belief.‘” Ken Booth argues: “If one scratches a committed post-modernist one will almost certainly find a comfortably well-off Western urban liberal. Those who live against the wall, or who have emancipated themselves from such a position, do not hold these views.… The reason for this is obvious, and relates to the fact that post-modernism—certainly that of a doctrinaire variety—does not deliver an ethics for the emancipation of victims across the world.”
Acting on Belief: Christian Perspectives on Suffering and Violence
Authors: Lynch Cecelia 
Published: August 2006

What type of ethics should guide our behavior in contemporary conflicts? Religious groups working in many parts of the world are deeply involved in providing practical and theological answers to that question. This article examines two types of Judeo-Christian perspectives that stress the imperative to act to relieve suffering and transcend violence: liberation theology and the “religious humanitarian perspective.” Both perspectives draw linkages between ethical guidelines and action, and both have influenced broader political debates. The essay poses the following questions:What are the ethical bases of action for contemporary activists and theologians in these traditions, and have these changed with political circumstances?; andAre there ethical and practical connections between contemporary religious humanitarianism and liberation theology, and can they provide us with a coherent ethic of action to relieve suffering and reduce violence in the world?These questions are analyzed in light of current theological conceptions of evil, religious pluralism, and the uneasy boundaries between violence and nonviolence.
Atrophy and hypertrophy of skeletal muscles: structural and functional aspects
Authors: Boonyarom O. , Inui K. 
Published: September 2006

AbstractThis review summarizes current information on structural and functional changes that occur during muscle atrophy and hypertrophy. Most published studies consider an increase in total mass of a muscle as hypertrophy, whereas a decrease in total mass of a muscle is referred to as atrophy. In hypertrophy, the rate of synthesis is much higher than the rate of degradation of muscle contractile proteins, leading to an increase in the size or volume of an organ due to enlargement of existing cells. When a muscle remains in disuse for a long period, the rate of degradation of contractile proteins becomes greater than the rate of replacement, resulting in muscle atrophy. This defect may occur as a result of lack of nutrition, loss of nerve supply, micro‐gravity, ageing, systemic disease, prolonged immobilization or disuse. An understanding of the specific modifications that occur during muscle atrophy and hypertrophy may facilitate the development of novel techniques, as well as new therapies for affected muscles.
Adventitia‐dependent mechanical properties of brachiocephalic ovine arteries in in vivo and in vitro studies
Authors: Cabrera Fischer E. I. , Bia D. , Camus J. M. , Zócalo Y. , De Forteza E. , Armentano R. L. 
Published: September 2006

AbstractAim:  An adventitia dependent regulation of the vascular smooth muscle tone has been described. However, if the adventitia plays an active role on arterial wall biomechanical behaviour and functions remains to be established. Our aim was to characterize the influence of adventitia on arterial wall mechanical properties and the arterial conduit and buffer functions.Methods:  Ovine brachiocephalic arteries were studied in vivo (n = 8) and in vitro (with null tone) in a circulation mock (n = 8). Isobaric, isoflow and isofrequency studies were performed. In each segment, pressure and diameter waves were assessed before and after adventitia removal. From the arterial stress–strain relationship, we derived the elastic and the viscous modulus. The buffering and conduit functions were calculated using the Kelvin–Voigt's time constant and the inverse of the characteristic impedance, respectively.Results:  In in vivo studies arterial diameter decreased after adventitia removal (P < 0.05). Elastic and viscous modulus in in vivo studies were significantly higher in adventitia‐removed arteries, compared with values in intact vessels (P < 0.05). This behaviour was not observed in in vitro experiments. An impairment of buffer and conduit functions was observed in vivo after adventitia removal (P < 0.05), while both functions remain unchanged in in vitro studies (P > 0.05).Conclusions:  Arterial wall viscosity and elasticity were influenced by adventitia removal in in vivo studies, possibly by a smooth muscle‐dependent mechanism, since it was not present in in vitro experiments. Adventitia would be involved in a physiological mechanism of arterial wall viscous and elastic properties regulation, that could influence arterial buffering and conduit functions.
A New Bis-Tröger's Base: Synthesis, Spectroscopy, Crystal Structure and Isomerization
Authors: Valík Martin , Matějka Pavel , Herdtweck Eberhardt , Král Vladimír , Dolensky Bohumil 
Published: September 2006

A new bis-Tröger's base was prepared from a tetraamine precursor as a mixture of two diastereoisomers. One of the isomers has a chair-like geometry, and the other possesses a boat-like geometry, embodying molecular tweezers. A one-pot preparation of bis-TB isomers and their interconversion under acid conditions was also studied. Structures of both isomers were confirmed by single-crystal X-ray diffraction. Extensive spectroscopic data, including 1H and 13C NMR, IR and Raman spectra of the isomers, are given.
MONOTONICITY IN THE VOLATILITY OF SINGLE-BARRIER OPTION PRICES
Authors: ERIKSSON JONATAN 
Published: September 2006

We generalize earlier results on barrier options for puts and calls and log-normal stock processes to general local volatility models and convex contracts. We show that Γ ≥ 0, that Δ has a unique sign and that the option price is increasing with the volatility for convex contracts in the following cases: • If the risk-free rate of return dominates the dividend rate, then it holds for up-and-out options if the contract function is zero at the barrier and for down-and-in options in general. • If the risk-free rate of return is dominated by the dividend rate, then it holds for down-and-out options if the contract function is zero at the barrier and for up-and-in options in general. We apply our results to show that a hedger who misspecifies the volatility using a time-and-level dependent volatility will super-replicate any claim satisfying the above conditions if the misspecified volatility dominates the true (possibly stochastic) volatility almost surely.
Sequential Valproic Acid/All-trans Retinoic Acid Treatment Reprograms Differentiation in Refractory and High-Risk Acute Myeloid Leukemia
Authors: Cimino Giuseppe , Lo-Coco Francesco , Fenu Susanna , Travaglini Lorena , Finolezzi Erica , Mancini Marco , Nanni Mauro , Careddu Angela , Fazi Francesco , Padula Fabrizio , Fiorini Roberto , Aloe Spiriti Maria Antonietta , Petti Maria Concetta , Venditti Adriano , Amadori Sergio , Mandelli Franco , Pelicci Pier Giuseppe , Nervi Clara 
Published: September 2006

Abstract
Epigenetic alterations of chromatin due to aberrant histone deacetylase (HDAC) activity and transcriptional silencing of all-trans retinoic acid (ATRA) pathway are events linked to the pathogenesis of acute myeloid leukemia (AML) that can be targeted by specific treatments. A pilot study was carried out in eight refractory or high-risk AML patients not eligible for intensive therapy to assess the biological and therapeutic activities of the HDAC inhibitor valproic acid (VPA) used to remodel chromatin, followed by the addition of ATRA, to activate gene transcription and differentiation in leukemic cells. Hyperacetylation of histones H3 and H4 was detectable at therapeutic VPA serum levels (≥50 μg/mL) in blood mononuclear cells from seven of eight patients. This correlated with myelomonocytic differentiation of leukemic cells as revealed by morphologic, cytochemical, immunophenotypic, and gene expression analyses. Differentiation of the leukemic clone was proven by fluorescence in situ hybridization analysis showing the cytogenetic lesion +8 or 7q− in differentiating cells. Hematologic improvement, according to established criteria for myelodysplastic syndromes, was observed in two cases. Stable disease and disease progression were observed in five and one cases, respectively. In conclusion, VPA-ATRA treatment is well tolerated and induces phenotypic changes of AML blasts through chromatin remodeling. Further studies are needed to evaluate whether VPA-ATRA treatment by reprogramming differentiation of the leukemic clone might improve the response to chemotherapy in leukemia patients. (Cancer Res 2006; 66(17): 8903-11)
Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells
Authors: Li Min , Cortez Shirley , Nakamachi Tomoya , Batuman Vecihi , Arimura Akira 
Published: September 2006

AbstractMultiple myeloma represents a malignant proliferation of plasma cells in the bone marrow, which often overproduces immunoglobulin light chains. We have shown previously that pituitary adenylate cyclase-activating polypeptide (PACAP) markedly suppresses the release of proinflammatory cytokines from light chain-stimulated human renal proximal tubule epithelial cells and prevents the resulting tubule cell injury. In this study, we have shown that PACAP suppresses the proliferation of human κ and λ light chain-secreting multiple myeloma–derived cells. The addition of PACAP suppressed light chain-producing myeloma cell–stimulated interleukin 6 (IL-6) secretion by the bone marrow stromal cells (BMSCs). A specific antagonist to either the human PACAP-specific receptor or the vasoactive intestinal peptide receptor attenuated the suppressive effect of PACAP on IL-6 production in the adhesion of human multiple myeloma cells to BMSCs. The secretion of IL-6 by BMSCs was completely inhibited by 10−9 mol/L PACAP, which also attenuated the phosphorylation of both p42/44 and p38 mitogen-activated protein kinases (MAPK) as well as nuclear factor-κB (NF-κB) activation in response to the adhesion of multiple myeloma cells to BMSCs, whereas the inhibition of p42/44 MAPK signaling attenuated PACAP action. The signaling cascades involved in the inhibitory effect of PACAP on IL-6-mediated paracrine stimulation of light chain-secreting myeloma cell growth was mediated through the suppression of p38 MAPK as well as modulation of activation of transcription factor NF-κB. These findings suggest that PACAP may be a new antitumor agent that directly suppresses light chain-secreting myeloma cell growth and indirectly affects tumor cell growth by modifying the bone marrow milieu of the multiple myeloma. (Cancer Res 2006; 66(17): 8796-803)
Interaction of Deleted in Liver Cancer 1 with Tensin2 in Caveolae and Implications in Tumor Suppression
Authors: Yam Judy Wai Ping , Ko Frankie Chi Fat , Chan Chung-Yiu , Jin Dong-Yan , Ng Irene Oi-Lin 
Published: September 2006

Abstract
Deleted in liver cancer 1 (DLC1) is a recently identified tumor suppressor gene frequently underexpressed in hepatocellular carcinoma (HCC). DLC1 encodes a Rho GTPase-activating protein domain that exhibits growth-suppressive activity in HCC cell lines. Our recent finding has revealed that inhibition of Rho-mediated actin stress fiber formation by DLC1 is associated with its growth inhibitory activity. In the present study, we identified tensin2 as the novel binding partner of DLC1. Tensin2 belongs to a new family of focal adhesion proteins that play key roles in cytoskeleton organization and signal transduction. Dysregulation of tensin proteins has previously been implicated in human cancers. Tensin2 is highly expressed in human liver. Introduction of tensin2 into HCC cell lines with low expression of tensin2 caused significant growth inhibition and induction of apoptosis. Tensin2 directly interacted with DLC1 in vitro and in vivo. Both proteins localized to punctate structures in the cytoplasm. Sequence analysis of DLC1 and tensin2 identified caveolin-1 binding motif in both proteins. In vivo immunoprecipitation study confirmed that both proteins indeed interacted with endogenous caveolin-1, which is the major structural component of caveolae. Our findings presented here suggest a new model for the action of DLC1 in hepatocytes, whereby DLC1-tensin2 complex interacts with Rho GTPases in caveolae to effect cytoskeletal reorganization. (Cancer Res 2006; 66(17): 8367-72)
Silencing of p29 Affects DNA Damage Responses with UV Irradiation
Authors: Chu Po-Chen , Yang Yuh-Cheng , Lu Yen-Ta , Chen Hsiang-Ting , Yu Lung-Chih , Chang Mau-Sun 
Published: September 2006

Abstract
Human p29 is a newly identified nuclear protein whose function is largely undetermined. We found that p29 associated with chromatin, interacted with MCM3, and localized with proliferating cell nuclear antigen foci in the S phase. Silencing of p29 using small interfering RNA duplexes reduced DNA synthesis and increased the expression of p107, a member of the RB family, and of cyclin-dependent kinase inhibitor p21, accompanied with a decreased expression of DNA polymerase α. Lethal events consisting of premature chromatin condensation with a reduced Chk1 phosphorylation were observed in p29-depleted cells in response to UV irradiation. Intriguingly, the phosphorylation of ataxia telangectasia-mutated kinases at S1981 was suppressed in p29-depleted HeLa cells with UV irradiation, but not in hydroxyurea- and ionizing radiation-treated cells. Taken together, these results reveal a novel function of p29 in the regulation of DNA replication checkpoint responses. (Cancer Res 2006; 66(17): 8484-91)
Induction of Potent Antitumor Immunity by Intratumoral Injection of Interleukin 23–Transduced Dendritic Cells
Authors: Hu Jinwei , Yuan Xiangpeng , Belladonna Maria L. , Ong John M. , Wachsmann-Hogiu Sebastian , Farkas Daniel L. , Black Keith L. , Yu John S. 
Published: September 2006

AbstractDendritic cells (DCs) are potent antigen-presenting cells that play a critical role in priming immune responses to tumor. Interleukin (IL)-23 can act directly on DC to promote immunogenic presentation of tumor peptide in vitro. Here, we evaluated the combination of bone marrow–derived DC and IL-23 on the induction of antitumor immunity in a mouse intracranial glioma model. DCs can be transduced by an adenoviral vector coding single-chain mouse IL-23 to express high levels of bioactive IL-23. Intratumoral implantation of IL-23–expressing DCs produced a protective effect on intracranial tumor–bearing mice. The mice consequently gained systemic immunity against the same tumor rechallenge. The protective effect of IL-23–expressing DCs was comparable with or even better than that of IL-12-expressing DCs. IL-23–transduced DC (DC-IL-23) treatment resulted in robust intratumoral CD8+ and CD4+ T-cell infiltration and induced a specific TH1-type response to the tumor in regional lymph nodes and spleen at levels greater than those of nontransduced DCs. Moreover, splenocytes from animals treated with DC-IL-23 showed heightened levels of specific CTL activity. In vivo lymphocyte depletion experiments showed that the antitumor immunity induced by DC-IL-23 was mainly dependent on CD8+ T cells and that CD4+ T cells and natural killer cells were also involved. In summary, i.t. injection of DC-IL-23 resulted in significant and effective systemic antitumor immunity in intracranial tumor–bearing mice. These findings suggest a new approach to induce potent tumor-specific immunity to intracranial tumors. This approach may have therapeutic potential for treating human glioma. (Cancer Res 2006; 66(17): 8887-96)
Mechanism of Action of Sulforaphane: Inhibition of p38 Mitogen-Activated Protein Kinase Isoforms Contributing to the Induction of Antioxidant Response Element–Mediated Heme Oxygenase-1 in Human Hepatoma HepG2 Cells
Authors: Keum Young-Sam , Yu Siwang , Chang Peter Pil-Jae , Yuan Xiaoling , Kim Jung-Hwan , Xu Changjiang , Han Jiahuai , Agarwal Anupam , Kong Ah-Ng Tony 
Published: September 2006

Abstract
Exposure of sulforaphane to HepG2 cells increased heme oxygenase-1 (HO-1) expression by activating antioxidant response element (ARE) through induction of Nrf2 and suppression of Kelch-like ECH-associated protein 1 (Keap1). Using human HO-1 promoter reporter plasmids and ChIP assay, we have identified that sulforaphane transcriptionally activated the upstream ARE-rich enhancer region, located at −9.0 kb upstream human HO-1 promoter. Induction of HO-1 by sulforaphane was attenuated by overexpression of mutant Nrf2 plasmid in HepG2 cells and totally abolished in Nrf2 knockout mouse embryonic keratinocytes and fibroblasts. Overexpression of individual p38 mitogen-activated protein (MAP) kinase (MAPK) isoforms also suppressed constitutive as well as sulforaphane- or Nrf2-induced ARE-dependent gene expression. Among the upstream kinases, although MKK3 was not involved in suppression of ARE by any of p38 MAPK isoforms, MKK6 selectively suppressed ARE by p38γ or p38δ, but not by p38α or p38β. Importantly, sulforaphane not only activated MAP/extracellular signal-regulated kinase (ERK) kinases 1/2 and ERK1/2, but also strongly suppressed anisomycin-induced activation of p38 MAPK isoforms by blocking phosphorylation of upstream kinases, MKK3/6. Finally, we found that stimulation of p38 MAPK isoforms phosphorylated purified Nrf2 protein and caused an increase in the interaction between Nrf2 and Keap1 in vitro and the suppression of Nrf2 translocation into the nucleus. Collectively, our results indicate that transcriptional activation of Nrf2/ARE is critical in sulforaphane-mediated induction of HO-1, which can be modulated in part by the blockade of p38 MAPK signaling pathway. In addition, our study shows that p38 MAPK can phosphorylate Nrf2 and promotes the association between Nrf2 and Keap1 proteins, thereby potentially inhibiting nuclear translocation of Nrf2. (Cancer Res 2006; 66(17): 8804-13)
Antiangiogenic Effect of TW37, a Small-Molecule Inhibitor of Bcl-2
Authors: Zeitlin Benjamin D. , Joo Esther , Dong Zhihong , Warner Kristy , Wang Guoping , Nikolovska-Coleska Zaneta , Wang Shaomeng , Nör Jacques E. 
Published: September 2006

Abstract
Bcl-2 is an antiapoptotic protein that is up-regulated in several tumor types, and its expression levels have strong correlation to development of resistance to therapy and poor prognosis. We have shown recently that Bcl-2 also functions as a proangiogenic signaling molecule that activates a nuclear factor-κB–mediated pathway resulting in up-regulation of the angiogenic chemokines CXCL1 and CXCL8 by neovascular endothelial cells. Here, we evaluate the antiangiogenic effect of the novel small-molecule inhibitor of Bcl-2 (TW37) developed using a structure-based design strategy. We observed that TW37 has an IC50 of 1.8 μmol/L for endothelial cells but showed no cytotoxic effects for fibroblasts at concentrations up to 50 μmol/L. The mechanism of TW37-induced endothelial cell death was apoptosis, in a process mediated by mitochondrial depolarization and activation of caspase-9 and caspase-3. The effect of TW37 on endothelial cell apoptosis was not prevented by coexposure to the growth factor milieu secreted by tumor cells. Inhibition of the angiogenic potential of endothelial cells (i.e., migration and capillary sprouting assays) and expression of the angiogenic chemokines CXCL1 and CXCL8 were accomplished at subapoptotic TW37 concentrations (0.005-0.05 μmol/L). Notably, administration of TW37 i.v. resulted in a decrease in the density of functional human microvessels in the severe combined immunodeficient mouse model of human angiogenesis. In conclusion, we describe functionally separate proapoptotic and antiangiogenic mechanisms for a small-molecule inhibitor of Bcl-2 and show the potential for Bcl-2 inhibition as a target for antiangiogenic therapy. (Cancer Res 2006; 66(17): 8698-706)