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"Howells, William"
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Negative Theology and Desire in Spiritual Transformation According to John of the Cross
Desire is central to John of the Cross’ treatment of the mystical ascent to God. He holds that God is desire and that there is a meeting between human and divine desire in the state of union with God, which is the goal. But it is less clear how this desire is to be understood against John’s programmatic negation of desire on the spiritual journey in both its sensory and spiritual forms, according to his negative theology. He regards the lack of satisfaction of desire, which he expresses in terms of darkness and emptiness, as the main manifestation of desire in the process of spiritual transformation. The question arises as to where he locates the meeting between human desire and divine desire, when they seem to be only opposed to one another. The answer lies in the gradual uncovering, through this process, of what is happening beneath the presenting experience of desire, in the human soul’s constitution as the subject. Desire is transformed, but in a way that can be affirmed only at the level of this transformation of the subject. This article examines how John of the Cross understands the relationship between desire and negative theology.
Journal Article
مسافر من الجزيرة : رواية خيالية
تمزج هذه الرواية بين الواقع والخيال. تدور أحداث الرواية في أواخر القرن التاسع عشر، حيث يصل السيد هوموس، وهو زائر من جزيرة ألتروريا الطوباوية، إلى الولايات المتحدة لاستكشاف المجتمع الأمريكي، تبدأ الرواية بوصول السيد هوموس إلى أمريكا، حيث يلتقي بمجموعة من الشخصيات التي تمثل مختلف الطبقات الاجتماعية، من خلال تفاعلاته مع هذه الشخصيات، يكشف السيد هوموس عن الفروقات الكبيرة بين المجتمع الطوباوي في ألتروريا والمجتمع الرأسمالي في أمريكا. يتناول الحوار بين الشخصيات قضايا مثل العدالة الاجتماعية، والمساواة، والاقتصاد، تنتهي الرواية بتقديم نقد لاذع للرأسمالية الأمريكية، مسلطة الضوء على التفاوتات الاجتماعية والاقتصادية، ومقارنة ذلك بالمجتمع المثالي في ألتروريا حيث تسود المساواة والعدالة، الرواية تعتبر نقدا اجتماعيا وسياسيا للمجتمع الأمريكي في ذلك الوقت، وتندرج تحت أدب المدن الفاسدة (ديستوبيا) حيث تهدف إلى كشف عيوب المجتمعات الاستبدادية والرأسمالية.
Book
genome-wide association study of alcohol dependence
Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10⁻⁵, but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor α2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.
Journal Article
London Films
A rambling and sometimes scathing look at the City of London, presented as if in a series of mental 'films' by the American realist author William Dean Howells.
eBook
Hyperacute changes in blood mRNA expression profiles of rats after middle cerebral artery occlusion: Towards a stroke time signature
Stroke evolution is a highly dynamic but variable disease which makes clinical decision making difficult. Biomarker discovery programs intended to aid clinical decision making have however largely ignored the rapidity of stroke evolution. We have used gene array technology to determine blood mRNA expression changes over the first day after stroke in rats. Blood samples were collected from 8 male spontaneously hypertensive rats at 0, 1, 2, 3, 6 and 24h post stroke induction by middle cerebral artery occlusion. RNA was extracted from whole blood stabilized in PAXgene tubes and mRNA expression was detected by oligonucleotide Affymetrix microarray. Using a pairwise comparison model, 1932 genes were identified to vary significantly over time (p≤0.5x10(-7)) within 24h after stroke. Some of the top20 most changed genes are already known to be relevant to the ischemic stroke physiopathology (e.g. Il-1R, Nos2, Prok2). Cluster analysis showed multiple stereotyped and time dependent profiles of gene expression. Direction and rate of change of expression for some profiles varied dramatically during these 24h. Profiles with potential clinical utility including hyper acute or acute transient upregulation (with expression peaking from 2 to 6h after stroke and normalisation by 24h) were identified. We found that blood gene expression varies rapidly and stereotypically after stroke in rats. Previous researchers have often missed the optimum time for biomarker measurement. Temporally overlapping profiles have the potential to provide a biological \"stroke clock\" able to tell the clinician how far an individual stroke has evolved.
Journal Article
Dosage Transmission Disequilibrium Test (dTDT) for Linkage and Association Detection
Both linkage and association studies have been successfully applied to identify disease susceptibility genes with genetic markers such as microsatellites and Single Nucleotide Polymorphisms (SNPs). As one of the traditional family-based studies, the Transmission/Disequilibrium Test (TDT) measures the over-transmission of an allele in a trio from its heterozygous parents to the affected offspring and can be potentially useful to identify genetic determinants for complex disorders. However, there is reduced information when complete trio information is unavailable. In this study, we developed a novel approach to \"infer\" the transmission of SNPs by combining both the linkage and association data, which uses microsatellite markers from families informative for linkage together with SNP markers from the offspring who are genotyped for both linkage and a Genome-Wide Association Study (GWAS). We generalized the traditional TDT to process these inferred dosage probabilities, which we name as the dosage-TDT (dTDT). For evaluation purpose, we developed a simulation procedure to assess its operating characteristics. We applied the dTDT to the simulated data and documented the power of the dTDT under a number of different realistic scenarios. Finally, we applied our methods to a family study of alcohol dependence (COGA) and performed individual genotyping on complete families for the top signals. One SNP (rs4903712 on chromosome 14) remained significant after correcting for multiple testing Methods developed in this study can be adapted to other platforms and will have widespread applicability in genomic research when case-control GWAS data are collected in families with existing linkage data.
Journal Article
Discovery and Longitudinal Evaluation of Candidate Biomarkers for Ischaemic Stroke by Mass Spectrometry-Based Proteomics
Application of acute therapies such as thrombolysis for ischaemic stroke (IS) is constrained because of diagnostic uncertainty and the dynamic nature of stroke biology. To investigate changes in blood proteins after stroke and as a result of thrombolysis treatment we performed label-free quantitative proteomics on serum samples using high-resolution mass spectrometry and long high-performance liquid chromatography gradient (5 hours) combined with a 50-cm column to optimise the peptide separation. We identified (false discovery rate [FDR]: 1%) and quantified a total of 574 protein groups from a total of 92 samples from 30 patients. Ten patients were treated by thrombolysis as part of a randomised placebo-controlled trial and up to 5 samples were collected from each individual at different time points after stroke. We identified 26 proteins differently expressed by treatment group (FDR: 5%) and significant changes of expression over time for 23 proteins (FDR: 10%). Molecules such as fibrinogen and C-reactive protein showed expression profiles with a high-potential clinical utility in the acute stroke setting. Protein expression profiles vary acutely in the blood after stroke and have the potential to allow the construction of a stroke clock and to have an impact on IS treatment decision making.
Journal Article