Proceedings of the MECA Workshop on The Evoluation of the Martian Atmosphere

Topics addressed include: Mars' volatile budget; climatic implications of martian channels; bulk composition of Mars; accreted water inventory; evolution of CO2; dust storms; nonlinear frost albedo feedback on Mars; martian atmospheric evolution; effects of asteroidal and cometary impacts; and water exchange between the regolith and the atmosphere/cap system over obliquity timescales

Is reduction in the risk of vision loss the only benefit of photodynamic therapy in predominantly classic subfoveal choroidal neovascularization?

Nicola G Ghazi, rian P Conway, James S Tiedeman, Steven J YoonUniversity of Virginia Health System, Department of Ophthalmology, Charlottesville, VA, USAPurpose: To emphasize the effect of photodynamic therapy (PDT) on the size and progression of the neovascular lesion (NL) and evolution of the disciform scar (DS) in predominantly classic subfoveal choroidal neovascularization (SFCNV).Methods: A retrospective study of 62 eyes treated with PDT for SFCNV was performed. The greatest linear dimension (GLD) before and at last follow-up after treatment and the size of the DS post-PDT were analyzed. A subgroup of patients with DS in their fellow eye at presentation without prior PDT was also studied. The size of the scar in these eyes was compared to that following PDT.Results: After an average follow-up at 9 months, the size of the NL was stabilized or reduced in 64% of the study eyes with absence of fluorescein leakage in 45%. Only 3 eyes (5%) developed DS. At presentation, 14 patients already had DS in their fellow eye, the size of which was significantly larger than that post-PDT (p = 0.044). It was also significantly larger than that of the potential scar in the study eyes of the same subgroup of patients (p = 0.002) and of the rest of the patients (p = 0.0001).Conclusion: This study demonstrates a beneficial effect for PDT on the size of the NL and DS in SFCNV, which might be of great significance, particularly when PDT fails to prevent severe vision loss.Keywords: age-related macular degeneration, choroidal neovascularization, classic choroidal neovascularization, disciform scarring, fluorescein angiography, photodynamic therap

Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine

Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly solid tumours. This is due to a generally late-stage diagnosis of a primarily treatment-refractory disease. Several large-scale sequencing and mass spectrometry approaches have identified key drivers of this disease and in doing so highlighted the vast heterogeneity of lower frequency mutations that make clinical trials of targeted agents in unselected patients increasingly futile. There is a clear need for improved biomarkers to guide effective targeted therapies, with biomarker-driven clinical trials for personalised medicine becoming increasingly common in several cancers. Interestingly, many of the aberrant signalling pathways in PDAC rely on downstream signal transduction through the mitogen-activated protein kinase and phosphoinositide 3-kinase (PI3K) pathways, which has led to the development of several approaches to target these key regulators, primarily as combination therapies. The following review discusses the trend of PDAC therapy towards molecular subtyping for biomarker-driven personalised therapies, highlighting the key pathways under investigation and their relationship to the PI3K pathway

Code wars: steganography, signals intelligence, and terrorism

This paper describes and discusses the process of secret communication known as steganography. The argument advanced here is that terrorists are unlikely to be employing digital steganography to facilitate secret intra-group communication as has been claimed. This is because terrorist use of digital steganography is both technically and operationally implausible. The position adopted in this paper is that terrorists are likely to employ low-tech steganography such as semagrams and null ciphers instead

Role of Gluconeogenesis and the Tricarboxylic Acid Cycle in the Virulence of \u3cem\u3eSalmonella enterica\u3c/em\u3e Serovar Typhimurium in BALB/c Mice

In Salmonella enterica serovar Typhimurium, the Cra protein (catabolite repressor/activator) regulates utilization of gluconeogenic carbon sources by activating transcription of genes in the gluconeogenic pathway, the glyoxylate bypass, the tricarboxylic acid (TCA) cycle, and electron transport and repressing genes encoding glycolytic enzymes. A serovar Typhimurium SR-11 Δcra mutant was recently reported to be avirulent in BALB/c mice via the peroral route, suggesting that gluconeogenesis may be required for virulence. In the present study, specific SR-11 genes in the gluconeogenic pathway were deleted (fbp, glpX, ppsA, and pckA), and the mutants were tested for virulence in BALB/c mice. The data show that SR-11 does not require gluconeogenesis to retain full virulence and suggest that as yet unidentified sugars are utilized by SR-11 for growth during infection of BALB/c mice. The data also suggest that the TCA cycle operates as a full cycle, i.e., a sucCD mutant, which prevents the conversion of succinyl coenzyme A to succinate, and an ΔsdhCDA mutant, which blocks the conversion of succinate to fumarate, were both attenuated, whereas both an SR-11 ΔaspA mutant and an SR-11 ΔfrdABC mutant, deficient in the ability to run the reductive branch of the TCA cycle, were fully virulent. Moreover, although it appears that SR-11 replenishes TCA cycle intermediates from substrates present in mouse tissues, fatty acid degradation and the glyoxylate bypass are not required, since an SR-11 ΔfadD mutant and an SR-11 ΔaceA mutant were both fully virulent