bluuebunny/crossref_metadata_2025_split huggingface dataset:
MK-2206, a Novel Allosteric Inhibitor of Akt, Synergizes with Gefitinib against Malignant Glioma via Modulating Both Autophagy and Apoptosis
Authors: Cheng Yan , Zhang Yi , Zhang Li , Ren Xingcong , Huber-Keener Kathryn J. , Liu Xiaoyuan , Zhou Lei , Liao Jason , Keihack Heike , Yan Li , Rubin Eric , Yang Jin-Ming 
Published: November 2011

AbstractGefitinib, a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase, has been shown to induce autophagy as well as apoptosis in tumor cells. Yet, how to use autophagy and apoptosis to improve therapeutic efficacy of this drug against cancer remains to be explored. We reported here that MK-2206, a potent allosteric Akt inhibitor currently in phase I trials in patients with solid tumors, could reinforce the cytocidal effect of gefitinib against glioma. We found that cotreatment with gefitinib and MK-2206 increased the cytotoxicity of this growth factor receptor inhibitor in the glioma cells, and the CompuSyn synergism/antagonism analysis showed that MK-2206 acted synergistically with gefitinib. The benefit of the combinatorial treatment was also shown in an intracranial glioma mouse model. In the presence of MK-2206, there was a significant increase in apoptosis in glioma cells treated with gefitinib. MK-2206 also augmented the autophagy-inducing effect of gefitinib, as evidenced by increased levels of the autophagy marker, LC3-II. Inhibition of autophagy by silencing of the key autophagy gene, beclin 1 or 3-MA, further increased the cytotoxicity of this combinatorial treatment, suggesting that autophagy induced by these agents plays a cytoprotective role. Notably, at 48 hours following the combinatorial treatment, the level of LC3-II began to decrease but Bim was significantly elevated, suggesting a switch from autophagy to apoptosis. On the basis of the synergistic effect of MK-2206 on gefitinib observed in this study, the combination of these two drugs may be utilized as a new therapeutic regimen for malignant glioma. Mol Cancer Ther; 11(1); 154–64. ©2011 AACR.
Risk Modification of Colorectal Adenoma byCYP7A1Polymorphisms and the Role of Bile Acid Metabolism in Carcinogenesis
Authors: Wertheim Betsy C. , Smith Jeffrey W. , Fang Changming , Alberts David S. , Lance Peter , Thompson Patricia A. 
Published: November 2011

AbstractCholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, is a postulated gene modifier of colorectal cancer risk and target for the therapeutic bile acid, ursodeoxycholic acid (UDCA). We investigated associations between CYP7A1 polymorphisms and fecal bile acids, colorectal adenoma (CRA), and UDCA efficacy for CRA prevention. Seven tagging, single-nucleotide polymorphisms (SNP) in CYP7A1 were measured in 703 (355 UDCA, 348 placebo) participants of a phase III chemoprevention trial, of which 495 had known baseline fecal bile acid concentrations. In the placebo arm, participants with two minor Grs8192871 alleles (tag for a low activity promoter polymorphism at −204) had lower odds of high secondary bile acids (OR = 0.26, 95% CI: 0.10–0.69), and CRA at 3 years' follow-up (OR = 0.41, 95% CI: 0.19–0.89), than AA carriers. Haplotype construction from the six polymorphic SNPs showed participants with the third most common haplotype (Crs10957057Crs8192879Grs8192877Trs11786580Ars8192871Grs13251096) had higher odds of high primary bile acids (OR = 2.34, 95% CI: 1.12–4.89) and CRA (OR = 1.89, 95% CI: 1.00–3.57) than those with the most common CTACAG haplotype. Furthermore, three SNPs (rs8192877, rs8192871, and rs13251096) each modified UDCA efficacy for CRA prevention, and CCGTAG-haplotype carriers experienced 71% lower odds of CRA recurrence with UDCA treatment, an effect not present for other haplotypes (test for UDCA–haplotype interaction, P = 0.020). Our findings support CYP7A1 polymorphisms as determinants of fecal bile acids and risk factors for CRA. Furthermore, UDCA efficacy for CRA prevention may be modified by genetic variation in CYP7A1, limiting treatment benefit to a subgroup of the population. Cancer Prev Res; 5(2); 197–204. ©2011 AACR.
Inhaled NO and Sildenafil Combination in Cardiac Surgery Patients With Out-of-Proportion Pulmonary Hypertension
Authors: Matamis Dimitrios , Pampori Smaro , Papathanasiou Athanasios , Papakonstantinou Panagiota , Tsagourias Mathew , Galiatsou Eftichia , Koulouras Vasilios , Nakos George 
Published: November 2011

Background—
The goal of this study was to examine the effects of coadministration of sildenafil and inhaled nitric oxide (iNO) in patients with out-of-proportion pulmonary hypertension who underwent cardiac valve replacement surgery.

Methods and Results—

Twenty consecutive cardiac surgery patients with out-of-proportion pulmonary hypertension were randomly assigned postoperatively into 2 groups: group A received 10 ppm of iNO followed by sildenafil (100 mg) orally 30 minutes later, and group B initially received sildenafil (100 mg) orally followed by 10 ppm of iNO 60 minutes later. Hemodynamic and gas exchange data were obtained at baseline, after administration of either iNO or sildenafil alone, and at 90 minutes from baseline. In group A, iNO resulted in a significant reduction in mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance index (PVRI) (by 9.6% and 20.8%, respectively). In group B, sildenafil administration also resulted in a significant decrease in mean arterial pressure, MPAP, pulmonary artery occlusive pressure, PVRI, and systemic vascular resistance index but also in the PaO
2
/inspired fraction of oxygen ratio (by 18.7%, 22.0%, 15.7%, 31.6%, 21.3%, and 14%, respectively). In both groups, the coadministration of the 2 drugs resulted in a significant further reduction of mean arterial pressure, MPAP, pulmonary artery occlusive pressure, systemic vascular resistance index, and PVRI, whereas cardiac index and mixed venous oxygen saturation remained unchanged. The hypoxemia after sildenafil administration in group B improved after the coadministration of iNO, and thus PaO
2
/inspired fraction of oxygen returned to values near baseline.

Conclusion—
In this study, the postoperative coadministration of iNO and oral sildenafil in patients with out-of-proportion pulmonary hypertension undergoing cardiac surgery is safe and results in an additive favorable effect on pulmonary arterial pressure and pulmonary vascular resistance, without systemic hypotension and ventilation/perfusion mismatch.
Notes on the Implementation by Latin American Courts of the ILO Convention 169 on Indigenous Peoples
Authors: Courtis Christian 
Published: November 2011

AbstractThis article presents some emblematic cases of the application of the International Labour Organization (ILO) Convention 169 Concerning Indigenous and Tribal Peoples in Independent Nations by Latin American courts. I chose a small number of cases that cover diverse topics and represent different countries in the region, as well as the regional court of human rights – the Inter-American Court of Human Rights. It is clear that there has been considerable experience in the application of Convention 169 in Latin America, with some countries having developed important jurisprudence through a significant number of judgments in the field. Therefore, this work makes no pretence of being an exhaustive review of the material: the perspective adopted is simply to select a handful of cases, based on the novelty of interpretation offered or on the relevance of its consequences. Before outlining the cases, I make some preliminary clarifications that may be useful in explaining the material presented here, and the context in which they should be understood.
A Constitutional Moment?: United Nations Peacekeeping in the Democratic Republic of Congo
Authors: Sheeran Scott P. 
Published: November 2011

AbstractThe United Nations (UN) is the world's most prominent international organization, and a key issue is its responsibility under international law. The contemporary growth in UN powers and activities has not been matched by parallel developments in accountability and checks and balances within the UN legal order. This was recently brought to the fore in the instance of UN peacekeepers providing support to Congolese army forces responsible for serious violations of international humanitarian and human rights law. It became a significant public issue and the Secretary-General eventually withdrew UN support from a unit of the Congolese army. This article demonstrates that this withdrawal of support by the Secretary-General represents a constitutional moment for the United Nations. It confirmed a key premise that the Secretary-General is normatively constrained under the Charter, including by the Organization's obligations, when implementing the decisions of the Security Council. This is a legal development which engages a number of emerging and uncertain areas of international law relating to the United Nations, including the UN's constitutional law, the responsibility of international organizations, the substantive obligations of the Organization, and the role of international law in peace and security. Recognizing this important development not only confirms the Secretary-General's legal responsibility under the Charter, it reinforces the view of the Charter as a living instrument and provides an effective and important means for incorporating the law of responsibility into the UN constitutional order and a check upon the expansive application of the Security Council's implied powers doctrine.
The security Council's Responsibility to Protect
Authors: Peters Anne 
Published: November 2011

AbstractThe objective of this paper is to spell out the legal consequences of the concept "responsibility to protect" (R2P), postulated as a binding legal principle of international law, for the Security Council and its members. The paper is a thought experiment, because the binding legal force of R2P is not settled. My argument is that, once R2P is accepted as a full-fledged legal principle, the Security Council (and its members) would be under a legal obligation to authorize or to take sufficiently robust action in R2P situations. The paper then discusses the problems engendered by the acceptance of such a material obligation and suggests a procedural obligation to justify inaction instead.
The Holy Spirit of Life, Work, and Inspired Speech: Responding to John (Jack) R. Levison, Filled with the Spirit
Authors: Waddell Robby 
Published: November 2011

AbstractThis brief review and response commends Levison's Filled with the Spirit for its fresh articulation of biblical pneumatologies and seeks to examine and explore possible effects of Levison's methodology and conclusions for future Pentecostal scholarship on pneumatology.
Prosperity and Prophecy in African Pentecostalism
Authors: Quayesi-Amakye Joseph 
Published: November 2011

AbstractThis essay discusses how prosperity is understood and articulated in Ghanaian Pentecostal prophetic circles. It seeks to show that in the peripheral prophetism of Pentecostalism, prosperity is perceived as the good life Christ offers those who believe in him. The good life is a religious and social quest of Ghanaians. The bad life is a privation of goodness in this life. Coping with the bad life has necessitated the patronage of Ghanaian prophetic services where rituals of transformation are employed to negotiate evil and suffering in the life of the faithful. Critical in the discussion is the role of the 'Other' who creates conditions of impoverishment for people and who justifies the necessity of prophetic negotiation. The paper also analyses the content of the bad life and finally attempts to show that Christ's parables in Luke 16 propose a guiding paradigm for conceiving prosperity as a tool for harmonious interhuman relations.
A Distinctive Leadership for a Distinctive Network of Churches? Psychological Type Theory and the Apostolic Networks
Authors: Francis Leslie J. , Kay William K. , Robbins Mandy 
Published: November 2011

AbstractThis study compares the personality profile of male leaders connected with twelve apostolic networks of churches in the UK with the profile of Church of England clergymen. It makes a further comparison with the UK population norms. Data provided by 164 male apostolic network leaders demonstrated that, compared with the Church of England clergymen, they were more likely to prefer extraversion and less likely to prefer intuition. Compared with the UK male population norms, these leaders were more likely to prefer extraversion, intuition, feeling and judging. The implications of these findings are discussed for ministry and mission.
Lighting in Sick Building Syndrome: Urban and rural environments
Authors: Tonello Graciela , Kirschbaum Carlos 
Published: November 2011

Sick Building Syndrome (SBS) is characterized by a significant proportion of people experiencing allergy-like symptoms that disappear or diminish when they leave the building. The exact causes remain unknown and the inclusion of lighting into SBS models deserves further research Within this context, the field study described here measured different environmental variables and their perception, especially lighting, in 97 urban and rural users. This research provides data and results in order to contribute to a more holistic model of SBS, which could be useful to architects and designers interested in meeting the needs of users
Adjustment to Radiative Forcing in a Simple Coupled Ocean–Atmosphere Model
Authors: Miller R. L. 
Published: November 2011

Abstract
This study calculates the adjustment to radiative forcing in a simple model of a mixed layer ocean coupled to the overlying atmosphere. One application of the model is to calculate how dust aerosols perturb the temperature of the atmosphere and ocean, which in turn influence tropical cyclone development. Forcing at the top of the atmosphere (TOA) is the primary control upon both the atmospheric and ocean temperature anomalies, both at equilibrium and during most of the adjustment to the forcing. Ocean temperature is directly influenced by forcing only at the surface, but is indirectly related to forcing at TOA due to heat exchange with the atmosphere. Within a few days of the forcing onset, the atmospheric temperature adjusts to heating within the aerosol layer, reducing the net transfer of heat from the ocean to the atmosphere. For realistic levels of aerosol radiative forcing, the perturbed net surface heating strongly opposes forcing at the surface. This means that surface forcing dominates the ocean response only within the first few days following a dust outbreak, before the atmosphere has responded. This suggests that, to calculate the effect of dust upon the ocean temperature, the atmospheric adjustment must be taken into account explicitly and forcing at TOA must be considered in addition to the surface forcing. The importance of TOA forcing should be investigated in a model where vertical and lateral mixing of heat are calculated with fewer assumptions than in the simple model presented here. Nonetheless, the fundamental influence of TOA forcing appears to be only weakly sensitive to the model assumptions.
Eddy-Driven Recirculations from a Localized Transient Forcing
Authors: Waterman Stephanie , Jayne Steven R. 
Published: November 2011

Abstract
The generation of time-mean recirculation gyres from the nonlinear rectification of an oscillatory, spatially localized vorticity forcing is examined analytically and numerically. Insights into the rectification mechanism are presented and the influence of the variations of forcing parameters, stratification, and mean background flow are explored. This exploration shows that the efficiency of the rectification depends on the properties of the energy radiation from the forcing, which in turn depends on the waves that participate in the rectification process. The particular waves are selected by the relation of the forcing parameters to the available free Rossby wave spectrum. An enhanced response is achieved if the parameters are such to select meridionally propagating waves, and a resonant response results if the forcing selects the Rossby wave with zero zonal group velocity and maximum meridional group velocity, which is optimal for producing rectified flows. Although formulated in a weakly nonlinear wave limit, simulations in a more realistic turbulent system suggest that this understanding of the mechanism remains useful in a strongly nonlinear regime with consideration of mean flow effects and wave–mean flow interaction now needing to be taken into account. The problem presented here is idealized but has general application in the understanding of eddy–eddy and eddy–mean flow interactions as the contrasting limit to that of spatially broad (basinwide) forcing and is relevant given that many sources of oceanic eddies are localized in space.
Symptom Prevalence in the Last days of Life in Germany
Authors: Pinzón Luis Carlos Escobar , Claus Matthias , Zepf Kirsten Isabel , Fischbeck Sabine , Weber Martin 
Published: November 2011

Investigations have shown that symptom prevalence varies according to the place of death. We sought to assess the symptom prevalence of chronically ill people in Germany and how this prevalence differs depending on the place of death. We sent questionnaires to 5000 bereaved people in Rhineland-Palatinate (Germany), whose relatives died between May 25 and August 24, 2008. In all, 3832 questionnaires were delivered and 1378 completed (response 36.0%). Most decedents had moderate-to-severe weakness (94.5%), fatigue (93.5%), need for help in daily activities (87.9%), and appetite loss (87.4%). Pain and dyspnea were most severe in hospitals; fatigue, confusion/disorientation, and problems with wound care in nursing homes; and need for help in daily activities and overburden of family at home. Associations persisted after adjusting for potential confounders.
The Minimal Access Deep Plane Extended Vertical Facelift
Authors: Jacono Andrew A. , Parikh Sachin S. 
Published: November 2011

Abstract
Background: Modern facelift techniques have benefited from a “repopularization” of shorter incisions, limited skin elevation, and more limited dissection of the superficial musculoaponeurotic system (SMAS) and platysma in order to shorten postoperative recovery times and reduce surgical risks for patients.
Objectives: The authors describe their minimal access deep plane extended (MADE) vertical vector facelift, which is a hybrid technique combining the optimal features of the deep plane facelift and the short scar, minimal access cranial suspension (MACS) lift.
Methods: The authors retrospectively reviewed the case records of 181 patients who underwent facelift procedures performed by the senior author (AAJ) during a two year period between March 2008 and March 2010. Of those patients, 153 underwent facelifting with the MADE vertical technique. With this technique, deep plane dissection releases the zygomatico-cutaneous ligaments, allowing for more significant vertical motion of the midface and jawline during suspension. Extended platysmal dissection was utilized with a lateral platysmal myotomy, which is not traditionally included in a deep plane facelift. The lateral platysmal myotomy allowed for separation of the vertical vector of suspension in the midface and jawline from the superolateral vector of suspension that is required for neck rejuvenation, obviating the need for additional anterior platysmal surgery.
Results: The average age of the patients was 57.8 years. The average length of follow-up was 12.7 months. In 69 consecutive patients from this series, average vertical skin excision measured 3.02 cm on each side of the face at the junction of the pre auricular and temporal hair tuft incision (resulting in a total excision of 6.04 cm of skin). Data from the entire series revealed a revision rate of 3.9%, a hematoma rate of 1.9%, and a temporary facial nerve injury rate of 1.3%.
Conclusions: The common goal of all facelifting procedures is to provide a long-lasting, natural, balanced, rejuvenated aesthetic result with few complications and minimal downtime. The MADE vertical facelift fulfills these criteria and often yields superior results in the midface and neck areas, where many short scar techniques fail. Furthermore, this procedure can be performed under local anesthesia, which is a benefit to both patients and surgeons.
Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts
Authors: Horos Rastislav , IJspeert Hanna , Pospisilova Dagmar , Sendtner Regine , Andrieu-Soler Charlotte , Taskesen Erdogan , Nieradka Andrzej , Cmejla Radek , Sendtner Michael , Touw Ivo P. , von Lindern Marieke 
Published: November 2011

Abstract
Diamond-Blackfan anemia (DBA) is associated with developmental defects and profound anemia. Mutations in genes encoding a ribosomal protein of the small (eg, RPS19) or large (eg, RPL11) ribosomal subunit are found in more than half of these patients. The mutations cause ribosomal haploinsufficiency, which reduces overall translation efficiency of cellular mRNAs. We reduced the expression of Rps19 or Rpl11 in mouse erythroblasts and investigated mRNA polyribosome association, which revealed deregulated translation initiation of specific transcripts. Among these were Bag1, encoding a Hsp70 cochaperone, and Csde1, encoding an RNA-binding protein, and both were expressed at increased levels in erythroblasts. Their translation initiation is cap independent and starts from an internal ribosomal entry site, which appeared sensitive to knockdown of Rps19 or Rpl11. Mouse embryos lacking Bag1 die at embryonic day 13.5, with reduced erythroid colony forming cells in the fetal liver, and low Bag1 expression impairs erythroid differentiation in vitro. Reduced expression of Csde1 impairs the proliferation and differentiation of erythroid blasts. Protein but not mRNA expression of BAG1 and CSDE1 was reduced in erythroblasts cultured from DBA patients. Our data suggest that impaired internal ribosomal entry site–mediated translation of mRNAs expressed at increased levels in erythroblasts contributes to the erythroid phenotype of DBA.