Renegotiating Previous Governments\u27 Privatization Deals: The 1997 U.K. Windfall Tax on Utilities and International Law

Investment in privatized utilities leads to a very particular form of political risk--the risk that regulatory conditions change and special taxes are imposed, all measures within the sovereign powers of the state. The normal forms of protection against political risk (investment insurance, stabilization clauses, international investment treaties and international arbitration clauses) have not yet caught up with the emergence of new forms of political risk. The 1997 UK windfall tax announced by the Chancellor of the Exchequer in that year\u27s budget speech is a case in point. This issue is not limited purely to the contemporary UK situation, but illustrates a structural situation which can, and is likely to be repeated wherever utilities are privatized, regulated and exposed to special industry taxes. Such actions are usually undertaken by a new government composed of parties hitherto opposed to privatization, which will be able to combine its previous opposition, and the values therein articulated with the ever present need of governments for new revenue to finance its political popularity objectives. This paper surveys shortly the possible responses by international law, mainly principles and practice of international investment protection, to situations which have recently arisen in the world privatization laboratory (the UK) and situations which are likely to arise in the many countries which currently copy the UK privatization model, once new governments come to power. The UK situation is of particular interest since in the absence of constitutional, federal or judicial constraints the prevailing concept of parliamentary supremacy means that any legal recourse can only be had from external sources of law

Research on armadillos: A review and prospectus

A detailed analysis of 1,039 scientific studies of extant armadillos (Xenarthra: Cingulata, Dasypodidae) published in the last 25 years (1989-2013) revealed substantial biases in coverage, including taxonomically, the locales where field studies were conducted, and in the topics investigated. Examination of the number of other publications that cited each paper revealed that 470 (45%) papers had been cited no more than 10 times, 249 (24%) had never been cited, and 112 (11%) were not even found in the Google Scholar database. The most heavily cited papers were molecular phylogenetic analyses that often used tissues from one or more species of armadillo but were not about the animals per se. Thus, it appears that research on armadillos is plagued by numerous gaps in coverage and is not reaching a wide audience. These data indicate obvious opportunities for future research. In addition, recent findings suggest that even relatively well-studied phenomena may require reexamination. Here, we review recent advances in the study of armadillos and highlight promising areas for future work. One critical need is for a thorough systematic revision of Dasypodidae to be completed. This will make it possible to prioritize those species and populations most in need of study. Additionally, more long-term field studies of populations of marked individuals are required. Although there are many important and interesting questions waiting to be answered, the small number of researchers currently conducting studies of armadillos, particularly in the wild, means that progress will be slow.Facultad de Ciencias Naturales y Muse

The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding

Background: The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells. Methods: Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect of WWOX silencing on TGFβ-signaling. Results: WWOX silencing affected cell proliferation, motility, attachment and deregulated expression of genes involved in cell cycle, motility and DNA damage. Interestingly, we detected an enrichment of targets activated by the SMAD3 transcription factor, including significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts. Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3 via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3 occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches activation of a TGFβ responsive reporter. Additionally, WWOX expression leads to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since the TGFβ target ANGPTL4 plays a key role in lung metastasis development, we performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray datasets from breast carcinomas. We observed a significant inverse correlation between WWOX and ANGPTL4. Furthermore, the WWOXlo/ANGPTL4hi cluster of breast tumors is enriched in triple-negative and basal-like sub-types. Tumors with this gene expression signature could represent candidates for anti-TGFβ targeted therapies. Conclusions: We show for the first time that WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression increases with breast cancer progression and it behaves as an inhibitor of SMAD3 transcriptional activity these observations may help explain, at least in part, the paradoxical pro-tumorigenic effects of TGFβ signaling in advanced breast cancer.Fil: Ferguson, Brent W.. University of Texas; Estados UnidosFil: Gao, Xinsheng. University of Texas; Estados UnidosFil: Zelazowski, Maciej J.. University of Texas; Estados UnidosFil: Lee, Jaeho. University of Texas; Estados UnidosFil: Jeter, Collene R.. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aldaz, Claudio Marcelo. University of Texas; Estados Unido

The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding

Background: The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells. Methods: Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect of WWOX silencing on TGFβ-signaling. Results: WWOX silencing affected cell proliferation, motility, attachment and deregulated expression of genes involved in cell cycle, motility and DNA damage. Interestingly, we detected an enrichment of targets activated by the SMAD3 transcription factor, including significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts. Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3 via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3 occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches activation of a TGFβ responsive reporter. Additionally, WWOX expression leads to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since the TGFβ target ANGPTL4 plays a key role in lung metastasis development, we performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray datasets from breast carcinomas. We observed a significant inverse correlation between WWOX and ANGPTL4. Furthermore, the WWOX lo/ANGPTL4hi cluster of breast tumors is enriched in triple-negative and basal-like sub-types. Tumors with this gene expression signature could represent candidates for anti-TGFβ targeted therapies. Conclusions: We show for the first time that WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression increases with breast cancer progression and it behaves as an inhibitor of SMAD3 transcriptional activity these observations may help explain, at least in part, the paradoxical pro-tumorigenic effects of TGFβ signaling in advanced breast cancer.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Research on armadillos: A review and prospectus

A detailed analysis of 1,039 scientific studies of extant armadillos (Xenarthra: Cingulata, Dasypodidae) published in the last 25 years (1989-2013) revealed substantial biases in coverage, including taxonomically, the locales where field studies were conducted, and in the topics investigated. Examination of the number of other publications that cited each paper revealed that 470 (45%) papers had been cited no more than 10 times, 249 (24%) had never been cited, and 112 (11%) were not even found in the Google Scholar database. The most heavily cited papers were molecular phylogenetic analyses that often used tissues from one or more species of armadillo but were not about the animals per se. Thus, it appears that research on armadillos is plagued by numerous gaps in coverage and is not reaching a wide audience. These data indicate obvious opportunities for future research. In addition, recent findings suggest that even relatively well-studied phenomena may require reexamination. Here, we review recent advances in the study of armadillos and highlight promising areas for future work. One critical need is for a thorough systematic revision of Dasypodidae to be completed. This will make it possible to prioritize those species and populations most in need of study. Additionally, more long-term field studies of populations of marked individuals are required. Although there are many important and interesting questions waiting to be answered, the small number of researchers currently conducting studies of armadillos, particularly in the wild, means that progress will be slow.Facultad de Ciencias Naturales y Muse

Ethno-religious voting in Nigeria: interrogating voting patterns in the 2019 presidential election

This article analyses voting patterns in Nigeria’s 2019 presidential election. Its main objective is to gauge continuity or change in ethnic, regional and religious voting in Nigeria’s elections. The paper takes a historical approach in examining voting patterns in the past elections as a background to the examination of the 2019 presidential election. It was discovered that ethnic, regional and religious sentiments were still major factors that shaped voting choice in the election

Thermo-mechanical properties prediction of Ni-reinforced Al2_2O3_3 composites using micro-mechanics based representative volume elements

For effective cutting tool inserts that absorb thermal shock at varying temperature gradients, improved thermal conductivity and toughness are required. In addition, parameters such as the coefficient of thermal expansion must be kept within a reasonable range. This work presents a novel material design framework based on a multi-scale modeling approach that proposes nickel (Ni)-reinforced alumina (Al$_2$O$_3$) composites to tailor the mechanical and thermal properties required for ceramic cutting tools by considering numerous composite parameters. The representative volume elements (RVEs) are generated using the DREAM.3D software program and the output is imported into a commercial finite element software ABAQUS. The RVEs which contain multiple Ni particles with varying porosity and volume fractions are used to predict the effective thermal and mechanical properties using the computational homogenization methods under appropriate boundary conditions (BCs). The RVE framework is validated by the sintering of Al$_2$O$_3$-Ni composites in various compositions. The predicted numerical results agree well with the measured thermal and structural properties. The properties predicted by the numerical model are comparable with those obtained using the rules of mixtures and SwiftComp, as well as the Fast Fourier Transform (FFT) based computational homogenization method. The results show that the ABAQUS, SwiftComp and FFT results are fairly close to each other. The effects of porosity and Ni volume fraction on the mechanical and thermal properties are also investigated. It is observed that the mechanical properties and thermal conductivities decrease with the porosity, while the thermal expansion remains unaffected. The proposed integrated modeling and empirical approach could facilitate the development of unique Al$_2$O$_3$-metal composites with the desired thermal and mechanical properties for ceramic cutting inserts

The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding

Background: The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells. Methods: Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect of WWOX silencing on TGFβ-signaling. Results: WWOX silencing affected cell proliferation, motility, attachment and deregulated expression of genes involved in cell cycle, motility and DNA damage. Interestingly, we detected an enrichment of targets activated by the SMAD3 transcription factor, including significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts. Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3 via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3 occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches activation of a TGFβ responsive reporter. Additionally, WWOX expression leads to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since the TGFβ target ANGPTL4 plays a key role in lung metastasis development, we performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray datasets from breast carcinomas. We observed a significant inverse correlation between WWOX and ANGPTL4. Furthermore, the WWOX lo/ANGPTL4hi cluster of breast tumors is enriched in triple-negative and basal-like sub-types. Tumors with this gene expression signature could represent candidates for anti-TGFβ targeted therapies. Conclusions: We show for the first time that WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression increases with breast cancer progression and it behaves as an inhibitor of SMAD3 transcriptional activity these observations may help explain, at least in part, the paradoxical pro-tumorigenic effects of TGFβ signaling in advanced breast cancer.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability

Aim: Symptoms of autonomic failure are frequently the presentation of advanced age and neurodegenerative diseases that impair adaptation to common physiologic stressors. The aim of this work was to examine the interaction between the sympathetic and motor nervous system, the involvement of the sympathetic nervous system (SNS) in neuromuscular junction (NMJ) presynaptic motor function, the stability of postsynaptic molecular organization, and the skeletal muscle composition and function. Methods: Since muscle weakness is a symptom of diseases characterized by autonomic dysfunction, we studied the impact of regional sympathetic ablation on muscle motor innervation by using transcriptome analysis, retrograde tracing of the sympathetic outflow to the skeletal muscle, confocal and electron microscopy, NMJ transmission by electrophysiological methods, protein analysis, and state of the art microsurgical techniques, in C57BL6, MuRF1KO and Thy-1 mice. Results: We found that the SNS regulates motor nerve synaptic vesicle release, skeletal muscle transcriptome, muscle force generated by motor nerve activity, axonal neurofilament phosphorylation, myelin thickness, and myofibre subtype composition and CSA. The SNS also modulates the levels of postsynaptic membrane acetylcholine receptor by regulating the Gα i2 -Hdac4-Myogenin-MuRF1pathway, which is prevented by the overexpression of the guanine nucleotide-binding protein Gα i2 (Q205L), a constitutively active mutant G protein subunit. Conclusion: The SNS regulates NMJ transmission, maintains optimal Gα i2 expression, and prevents any increase in Hdac4, myogenin, MuRF1, and miR-206. SNS ablation leads to upregulation of MuRF1, muscle atrophy, and downregulation of postsynaptic AChR. Our findings are relevant to clinical conditions characterized by progressive decline of sympathetic innervation, such as neurodegenerative diseases and aging.Fil: Rodrigues, Anna C. Zaia. Wake Forest School of Medicine; Estados UnidosFil: Messi, Maria Laura. Wake Forest School of Medicine; Estados UnidosFil: Wang, Zhong Min. Wake Forest School of Medicine; Estados UnidosFil: Abba, Martín Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Pereyra, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Wake Forest School of Medicine; Estados UnidosFil: Birbrair, Alexander. Wake Forest School of Medicine; Estados UnidosFil: Zhang, Tan. Wake Forest School of Medicine; Estados UnidosFil: O´Meara, Meaghan. Wake Forest School of Medicine; Estados UnidosFil: Kwan, Ping. Wake Forest School of Medicine; Estados UnidosFil: Lopez, Elsa I. S.. Wake Forest School of Medicine; Estados UnidosFil: Willis, Monte S.. University of North Carolina; Estados UnidosFil: Mintz, Akiva. Wake Forest School of Medicine; Estados UnidosFil: Files, D. Clark. University of North Carolina; Estados UnidosFil: Furdui, Cristina. Wake Forest School of Medicine; Estados UnidosFil: Oppenheim, Ronald W.. Wake Forest School of Medicine; Estados UnidosFil: Delbono, Osvaldo. Wake Forest School of Medicine; Estados Unido