249 research outputs found
Tectonic analysis of Mare Humorum on the lunar surface
Morphology and internal structures of surface features of the Mare Humorum area were interpreted from photographs and topographic maps. The postulated origin of certain features is based on analog comparisons with known terrestrial features. The laws of crate ring and a newly developed computer program were applied to two representative classes of craters to determine the possibility of a meteoritic impact origin. Some of the craters formed by meteoritic impact and others, including those with a radius larger than 10 Km, probably resulted from volcanic activity.
Mare Humorum formed from centripetal subsidence followed by extensive lava eruptions. Spacially related rilles and gravity faults on the east and west of the Mare are tension fractures resulting from directed radial forces produced by the subsidence. Bending and monoclinal centripetal warping on the north and south of the Mare resulted in inward tilted older craters. Wrinkle ridges of sub-parallel marginal pattern are lava filled fissures and surface highs of lava showing a rough anticlinal form. These and similar fractures were the channelways for the extensive lava eruptions which covered the Mare.
An interpretive geologic and tectonic map demonstrated the important structural features of the Mare Humorum area --Abstract, page ii
The Lebanese conflict : a sociological study of its causes and resolution
This thesis argues that the existing conflictual tendencies in the Lebanese
social structure have generated long term and continued cleavages and disharmony
in Lebanese society and polity. Many interpretations have been offered to explain this conflict, but previous research on its genesis and outcome has focused mainly on
variables whose main focus lie outside the social structure. This study deliberately avoids an analysis of external factors. It, rather, concentrates on the role played by domestic factors in the aetiology, dynamism and resolution of the Lebanese conflict. It is assumed that the external factors have
played a contributory rather than a causal role in the conflict. The first premise of the theoretical scheme is that the basic causes of the conflict in Lebanon are inherent in its social structure, which failed to generate a change within itself. The objective is to explore the dynamics, in a historical perspective, of this social structure in order to determine the conflictual tendencies inherent in it.
The second premise is that the persistence of conflictual tendencies in the
social structure tends to keep the socio-political order perpetually unstable.
As a corollary to the first premise it is argued that conflictual tendencies are
inevitable in pluralist societies. Some systems have evolved successful adaptive
mechanisms and strategies to contain destructive responses, but the Lebanese
system did not. It is further argued that the endemic nature of conflictual tendencies,
compounded with the failure or even flaws of the adjustment mechanisms are sufficient to initiate and maintain conflict.
The premises suggested here are analyzed in relation to conflict theory as envisaged by Marx, Dahrendorf, Coser and Ibn Khaldun. Marx's vision of the economic determinacy of the conflict process, and the supremacy of the economic factor in the generation of conflict had been contested by Dahrendorf’s vision of political determinism and the primacy of the authority structure in the genesis of conflict.
The argument developed in this thesis is that Marx's and Dahrendorf's models
need to be revised in order to capture the empirical situation in Lebanon. The validity
of the revised model is assumed in terms of its ability to explain the formation and
behaviour of the conflict groups. For this purpose Ibn Khaldun's concept of asabiya is
offered to supplement Dahrendorf's concept of Authority. On the basis of a causal analysis of the conflict in Lebanon it was concluded that Marx's doctrine of economic determinism must be rejected in favour of
Dahrendorf's concept of 'authority' and by Ibn Khaldun's vision of asabiya and its role
in the aetiology, growth and demise of power groups. In considering the resolution of conflict, this study applies a theoretical strategy developed from conflict management to deeply divided societies such as Lebanon. It explains the manner in which Lebanon managed its communal conflict in three distinct settings: The 1860 civil war, the post independence era (1943-1975), and the 1975 conflict. Each of the three settings investigated exhibited similar conflict management patterns; the first setting established the basis for power sharing, involving authority differentiation and marked communal interdependence.
The second setting witnessed a period of relative and apparent stability due to
the implementation of the power-sharing principle within a consociational context.
The third setting manifested analogous conflict patterns and corresponding
conflict resolution strategies in spite of the time lapse involved. Power-sharing and
communal interdependence remain a viable option for the resolution of the existing
conflict. The three settings provide the study with an empirical base to suggest that
pluralist societies are not condemned to continuing conflict as long as they apply
conflict resolution strategies based on flexible, but solid, consociational principles. On the other hand such societies cannot free themselves totally from conflict, basically because conflict is a natural phenomenon in human society
Surviving your genes-the role of PNPLA3 variation in end-stage liver disease
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin
Conflict and HIV: A framework for risk assessment to prevent HIV in conflict-affected settings in Africa
In sub-Saharan Africa, HIV/AIDS and violent conflict interact to shape population health and development in dramatic ways. HIV/AIDS can create conditions conducive to conflict. Conflict can affect the epidemiology of HIV/AIDS. Conflict is generally understood to accelerate HIV transmission, but this view is simplistic and disregards complex interrelationships between factors that can inhibit and accelerate the spread of HIV in conflict and post conflict settings, respectively. This paper provides a framework for understanding these factors and discusses their implications for policy formulation and program planning in conflict-affected settings
Chronic Morphine Alters the Presynaptic Protein Profile: Identification of Novel Molecular Targets Using Proteomics and Network Analysis
Opiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes in the presynaptic protein profile following a paradigm of chronic morphine administration that leads to the development of dependence. For this, we isolated presynaptic fractions from the striata of rats treated with saline or escalating doses of morphine, and analyzed the proteins in these fractions using differential isotopic labeling. We identified 30 proteins that were significantly altered by morphine and integrated them into a protein-protein interaction (PPI) network representing potential morphine-regulated protein complexes. Graph theory-based analysis of this network revealed clusters of densely connected and functionally related morphine-regulated clusters of proteins. One of the clusters contained molecular chaperones thought to be involved in regulation of neurotransmission. Within this cluster, cysteine-string protein (CSP) and the heat shock protein Hsc70 were downregulated by morphine. Interestingly, Hsp90, a heat shock protein that normally interacts with CSP and Hsc70, was upregulated by morphine. Moreover, treatment with the selective Hsp90 inhibitor, geldanamycin, decreased the somatic signs of naloxone-precipitated morphine withdrawal, suggesting that Hsp90 upregulation at the presynapse plays a role in the expression of morphine dependence. Thus, integration of proteomics, network analysis, and behavioral studies has provided a greater understanding of morphine-induced alterations in synaptic composition, and identified a potential novel therapeutic target for opiate dependence
SNAVI: Desktop application for analysis and visualization of large-scale signaling networks
<p>Abstract</p> <p>Background</p> <p>Studies of cellular signaling indicate that signal transduction pathways combine to form large networks of interactions. Viewing protein-protein and ligand-protein interactions as graphs (networks), where biomolecules are represented as nodes and their interactions are represented as links, is a promising approach for integrating experimental results from different sources to achieve a systematic understanding of the molecular mechanisms driving cell phenotype. The emergence of large-scale signaling networks provides an opportunity for topological statistical analysis while visualization of such networks represents a challenge.</p> <p>Results</p> <p>SNAVI is Windows-based desktop application that implements standard network analysis methods to compute the clustering, connectivity distribution, and detection of network motifs, as well as provides means to visualize networks and network motifs. SNAVI is capable of generating linked web pages from network datasets loaded in text format. SNAVI can also create networks from lists of gene or protein names.</p> <p>Conclusion</p> <p>SNAVI is a useful tool for analyzing, visualizing and sharing cell signaling data. SNAVI is open source free software. The installation may be downloaded from: <url>http://snavi.googlecode.com</url>. The source code can be accessed from: <url>http://snavi.googlecode.com/svn/trunk</url></p
Accurate non-invasive diagnosis and staging of non-alcoholic fatty liver disease using the urinary steroid metabolome
Background: The development of accurate, non-invasive markers to diagnose and stage non-alcoholic fatty liver disease (NAFLD) is critical to reduce the need for an invasive liver biopsy and to identify patients who are at the highest risk of hepatic and cardio-metabolic complications.Aim(s): As the liver represents the main site of steroid hormone metabolism, and disruption of specific pathways has been described in patients with NAFLD, we hypothesised that assessment of the urinary steroid metabolome may provide a novel, non-invasive biomarker strategy to stage NAFLD.Methods: We analysed the urinary steroid metabolome in 275 subjects (121 with biopsy-proven NAFLD, 48 with alcohol-related cirrhosis, 106 controls), using gas chromatography-mass spectrometry (GC-MS) coupled with machine learning-based generalised matrix learning vector quantisation (GMLVQ) analysis.Results: GMLVQ analysis achieved excellent separation of early (F0-F2) from advanced (F3-F4) fibrosis (AUC ROC: 0.92 [0.91-0.94]). Furthermore, there was near perfect separation of controls from patients with advanced fibrotic NAFLD (AUC ROC=0.99 [0.98-0.99]) and from those with NAFLD cirrhosis (AUC ROC=1.0 [1.0-1.0]). This approach was also able to distinguish patients with NAFLD cirrhosis from those with alcohol-related cirrhosis (AUC ROC=0.83 [0.81-0.85]).Conclusions: Unbiased GMLVQ analysis of the urinary steroid metabolome offers excellent potential as a non-invasive biomarker approach to stage NAFLD fibrosis as well as to screen for NAFLD. A highly sensitive and specific urinary biomarker is likely to have clinical utility both in secondary care and in the broader general population within primary care and could significantly decrease the need for liver biopsy
Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder
Pharmacological treatment of several diseases, such as attention-deficit hyperactivity disorder (ADHD), presents marked variability in efficiency and its adverse effects. The genotyping of specific single nucleotide polymorphisms (SNPs) can support the prediction of responses to drugs and the genetic risk of presenting comorbidities associated with ADHD. This study presents two rapid and affordable microarray-based strategies to discriminate three clinically important SNPs in genes ADRA2A, SL6CA2, and OPRM1 (rs1800544, rs5569, and rs1799971, respectively). These approaches are allele-specific oligonucleotide hybridization (ASO) and a combination of allele-specific amplification (ASA) and solid-phase hybridization. Buccal swab and blood samples taken from ADHD patients and controls were analyzed by ASO, ASA, and a gold-reference method. The results indicated that ASA is superior in genotyping capability and analytical performance.This research has been funded through projects FEDER MINECO INNPACTO IPT-2011-1132-010000, CTQ/2013/45875R, and PrometeoII/2014/040 (GVA).Tortajada-Genaro, LA.; Mena-Mollá, S.; Niñoles Rodenes, R.; Puigmule, M.; Viladevall, L.; Maquieira Catala, Á. (2016). Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder. Analytical and Bioanalytical Chemistry. 408(9):2339-2345. https://doi.org/10.1007/s00216-016-9332-3S233923454089Cortese S. The neurobiology and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD): what every clinician should know. Eur J Paediatr Neurol. 2012;16:422–33.Contini V, Rovaris DL, Victor MM, Grevet EH, Rohde LA, Bau CH. Pharmacogenetics of response to methylphenidate in adult patients with attention-deficit/hyperactivity disorder (ADHD): a systematic review. Eur Neuropsychopharmacol. 2013;23:555–60.Gardiner SJ, Begg EJ. 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Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35
Peripheral artery disease (PAD) is a form of atherosclerotic cardiovascular disease, affecting ∼8 million Americans, and is known to have racial and ethnic disparities. PAD has been reported to have a significantly higher prevalence in African Americans (AAs) compared to non-Hispanic European Americans (EAs). Hispanic/Latinos (HLs) have been reported to have lower or similar rates of PAD compared to EAs, despite having a paradoxically high burden of PAD risk factors; however, recent work suggests prevalence may differ between sub-groups. Here, we examined a large cohort of diverse adults in the BioMe biobank in New York City. We observed the prevalence of PAD at 1.7% in EAs vs. 8.5% and 9.4% in AAs and HLs, respectively, and among HL sub-groups, the prevalence was found at 11.4% and 11.5% in Puerto Rican and Dominican populations, respectively. Follow-up analysis that adjusted for common risk factors demonstrated that Dominicans had the highest increased risk for PAD relative to EAs [OR = 3.15 (95% CI 2.33–4.25), p < 6.44 × 10−14]. To investigate whether genetic factors may explain this increased risk, we performed admixture mapping by testing the association between local ancestry and PAD in Dominican BioMe participants (N = 1,813) separately from European, African, and Native American (NAT) continental ancestry tracts. The top association with PAD was an NAT ancestry tract at chromosome 2q35 [OR = 1.96 (SE = 0.16), p < 2.75 × 10−05) with 22.6% vs. 12.9% PAD prevalence in heterozygous NAT tract carriers versus non-carriers, respectively. Fine-mapping at this locus implicated tag SNP rs78529201 located within a long intergenic non-coding RNA (lincRNA) LINC00607, a gene expression regulator of key genes related to thrombosis and extracellular remodeling of endothelial cells, suggesting a putative link of the 2q35 locus to PAD etiology. Efforts to reproduce the signal in other Hispanic cohorts were unsuccessful. In summary, we showed how leveraging health system data helped understand nuances of PAD risk across HL sub-groups and admixture mapping approaches elucidated a putative risk locus in a Dominican population
Interaction proteomics of synapse protein complexes
The brain integrates complex types of information, and executes a wide range of physiological and behavioral processes. Trillions of tiny organelles, the synapses, are central to neuronal communication and information processing in the brain. Synaptic transmission involves an intricate network of synaptic proteins that forms the molecular machinery underlying transmitter release, activation, and modulation of transmitter receptors and signal transduction cascades. These processes are dynamically regulated and underlie neuroplasticity, crucial to learning and memory formation. In recent years, interaction proteomics has increasingly been used to elucidate the constituents of synaptic protein complexes. Unlike classic hypothesis-based assays, interaction proteomics detects both known and novel interactors without bias. In this trend article, we focus on the technical aspects of recent proteomics to identify synapse protein complexes, and the complementary methods used to verify the protein–protein interaction. Moreover, we discuss the experimental feasibility of performing global analysis of the synapse protein interactome
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