Colombia’s Progress: Internal Peace and Foreign Trade

The nation of Colombia has made great progress in securing internal peace through an agreement with the Revolutionary Armed Forces of Colombia (FARC) and policing of drug cartels. These important steps have contributed to increased international commerce based on strong trade agreements and a more global outlook than many other Latin American nations have embraced. Colombia stands poised for additional growth; however, the challenges of internal development and wide-spread corruption remain

Laminar flow of two miscible fluids in a simple network

When a fluid comprised of multiple phases or constituents flows through a network, non-linear phenomena such as multiple stable equilibrium states and spontaneous oscillations can occur. Such behavior has been observed or predicted in a number of networks including the flow of blood through the microcirculation, the flow of picoliter droplets through microfluidic devices, the flow of magma through lava tubes, and two-phase flow in refrigeration systems. While the existence of non-linear phenomena in a network with many inter-connections containing fluids with complex rheology may seem unsurprising, this paper demonstrates that even simple networks containing Newtonian fluids in laminar flow can demonstrate multiple equilibria. The paper describes a theoretical and experimental investigation of the laminar flow of two miscible Newtonian fluids of different density and viscosity through a simple network. The fluids stratify due to gravity and remain as nearly distinct phases with some mixing occurring only by diffusion. This fluid system has the advantage that it is easily controlled and modeled, yet contains the key ingredients for network non-linearities. Experiments and 3D simulations are first used to explore how phases distribute at a single T-junction. Once the phase separation at a single junction is known, a network model is developed which predicts multiple equilibria in the simplest of networks. The existence of multiple stable equilibria is confirmed experimentally and a criteria for their existence is developed. The network results are generic and could be applied to or found in different physical systems

Toxicological Characterization of the Inorganic and Organic Arsenic Metabolite Thio-DMAV in Cultured Human Lung Cells

We synthesised and toxicologically characterised the arsenic metabolite thiodimethylarsinic acid (thio-DMAV). Successful synthesis of highly pure thio-DMAV was confirmed by state-of-the-art analytical techniques including 1H-NMR, HPLC-FTMS, and HPLC-ICPMS. Toxicological characterization was carried out in comparison to arsenite and its well-known trivalent and pentavalent methylated metabolites. It comprised cellular bioavailability as well as different cytotoxicity and genotoxicity end points in cultured human A549 lung cells. Of all arsenicals investigated, thio-DMAV exerted the strongest cytotoxicity. Moreover, thio-DMAV did not induce DNA strand breaks and an increased induction of both micronuclei and multinucleated cells occurred only at beginning cytotoxic concentrations, indicating that thio-DMAV does not act via a genotoxic mode of action. Finally, to assess potential implications of thio-DMAV for human health, further mechanistic studies are urgently necessary to identify the toxic mode of action of this highly toxic, unusual pentavalent organic arsenical.

Reduction of microkinetic reaction models for reactor optimization exemplified for hydrogen production from methane

AbstractSustainable and efficient processes require optimal design and operating conditions. The determination of optimal process routes, however, is a challenging task. Either the models and underlying chemical reaction rate equations are not able to describe the process in a wide ranges of reaction conditions and thus limit the optimization space, or the models are too complex and numerically challenging to be used in dynamic optimization. To address this problem, in this contribution, a reduction technique for chemical reaction networks is proposed. It focuses on the sensitivity of the reaction kinetic model with respect to the removal of selected reaction steps and evaluates their significance for the prediction of the overall system behavior. The method is demonstrated for a C1 microkinetic model describing methane conversion to syngas on Rh/Al2O3 as catalyst. The original and the reduced microkinetic model show excellent qualitative and quantitative agreement. Subsequently, the reduced kinetic model is used for the optimization of a methane reformer to produce a hydrogen rich gas mixture as feed for polymer electrolyte membrane (PEM) fuel cell applications

Elemental Bioimaging of Sheep Bone and Articular Cartilage After Single Application of Gadolinium-Based Contrast Agents

BACKGROUND: Gadolinium-based contrast agents (GBCAs) are applied to enhance magnetic resonance imaging. Gadolinium (Gd), a rare earth metal, is used in a chelated form when administered as GBCA to patients. There is an ongoing scientific debate about the clinical significance of Gd retention in tissues after administration of GBCAs. It is known that bone serves as Gd reservoir, but only sparse information on localization of Gd in bone is available. PURPOSE: The aim of this study was to compare Gd tissue concentration and spatial distribution in femoral epiphysis and diaphysis 10 weeks after single-dose injection of linear and macrocyclic GBCAs in a large animal model. MATERIALS AND METHODS: In this prospective animal study, Swiss-Alpine sheep (n = 36; age range, 4-10 years) received a single injection (0.1 mmol/kg) of macrocyclic (gadobutrol, gadoteridol, and gadoterate meglumine), linear (gadodiamide and gadobenate dimeglumine) GBCAs, or saline. Ten weeks after injection, sheep were killed, and femur heads and shafts were harvested. Gadolinium spatial distribution was determined in 1 sample of each treatment group by laser ablation-inductively coupled plasma-mass spectrometry. All bone specimens were analyzed histopathologically. RESULTS: Injection of GBCAs in female Swiss-Alpine sheep (n = 36) resulted in Gd localization at the endosteal and periosteal surface and in a subset of GBCAs additionally at the cement lines and the bone cartilage junction. No histopathological alterations were observed in the investigated tissue specimens. CONCLUSIONS: Ten weeks after single injection of a clinically relevant dose in adult sheep, both linear species of GBCA resulted in considerably higher accumulation than macrocyclic GBCAs. Gadolinium deposits were restricted to distinct bone and cartilage compartments, such as in bone linings, cement lines, and bone cartilage junctions. Tissue histology remained unaffected

Elemental bioimaging and transcriptomics reveal unchanged gene expression in mouse cerebellum following a single injection of Gadolinium-based contrast agents

Gadolinium (Gd) deposition in the brain, first and foremost in the dentate nucleus in the cerebellum, following contrast enhanced MRI, rose awareness of potential adverse effects of gadolinium-based contrast agent (GBCA) administration. According to previous in vitro experiments, a conceivable side-effect of Gd deposition could be an alteration of gene expression. In the current study, we aimed to investigate the influence of GBCA administration on gene expression in the cerebellum of mice using a combination of elemental bioimaging and transcriptomics. In this prospective animal study, three groups of eight mice each were intravenously injected with either linear GBCA gadodiamide, macrocyclic GBCA gadoterate (1 mmol GBCA/kg body weight) or saline (NaCl 0.9%). Animals were euthanized four weeks after injection. Subsequently, Gd quantification via laser ablation-ICP-MS and whole genome gene expression analysis of the cerebellum were performed. Four weeks after single application of GBCAs to 24-31 days old female mice, traces of Gd were detectable in the cerebellum for both, the linear and macrocyclic group. Subsequent transcriptome analysis by RNA sequencing using principal component analysis did not reveal treatment-related clustering. Also differential expression analysis did not reveal any significantly differentially expressed genes between treatments

Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone

The adrenal hormone corticosterone transcriptionally regulates responsive genes in the rodent hippocampus through nuclear mineralocorticoid and glucocorticoid receptors. Via this genomic pathway the hormone alters properties of hippocampal cells slowly and for a prolonged period. Here we report that corticosterone also rapidly and reversibly changes hippocampal signaling. Stress levels of the hormone enhance the frequency of miniature excitatory postsynaptic potentials in CA1 pyramidal neurons and reduce paired-pulse facilitation, pointing to a hormone-dependent enhancement of glutamate-release probability. The rapid effect by corticosterone is accomplished through a nongenomic pathway involving membrane-located receptors. Unexpectedly, the rapid effect critically depends on the classical mineralocorticoid receptor, as evidenced by the effectiveness of agonists, antagonists, and brain-specific inactivation of the mineralocorticoid but not the glucocorticoid receptor gene. Rapid actions by corticosterone would allow the brain to change its function within minutes after stress-induced elevations of corticosteroid levels, in addition to responding later through gene-mediated signaling pathways

Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial.

BACKGROUND: The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS: Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel. RESULTS: Norovirus infection was self-limited and resolved within 24 hours, with the subsequent development of anti-norovirus antibodies. Serum pro- and anti-inflammatory cytokine levels, including IL-10, peaked during the symptomatic period of infection, coincident with increased frequencies of monocytes and neutrophils. At the same time, the frequency of regulatory CD4 + T cell (Treg), effector T cell (Teff) CD4 + and CD8 + subsets were dynamically reduced, rebounding to baseline levels or above at the next sampling point 24 hours later.  NK cells and NKT cells transiently increased CD69 expression and classical monocytes expressed increased levels of CD40, HLA-DR and SIGLEC-1, biomarkers of an interferon response. We also observed activation and mobilisation of Teffs, where increased frequencies of CD69 + and Ki-67 + effector memory Teffs were followed by the emergence of memory CD8 + Teff expressing the mucosal tissue homing markers CD103 and β7 integrin. Treg responses were coincident with the innate cell, Teff and cytokine response. Key Treg molecules FOXP3, CTLA-4, and CD25 were upregulated following infection, alongside an increase in frequency of Tregs with the capacity to home to tissues. CONCLUSIONS: The results illustrate the innate, adaptive and counter-regulatory immune responses to norovirus infection. Low-dose IL-2 administration induces many of the Treg responses observed during infection

A comparative study on approximate entropy measure and poincaré plot indexes of minimum foot clearance variability in the elderly during walking

Background: Trip-related falls which is a major problem in the elderly population, might be linked to declines in the balance control function due to ageing. Minimum foot clearance (MFC) which provides a more sensitive measure of the motor function of the locomotor system, has been identified as a potential gait parameter associated with trip-related falls in older population. This paper proposes nonlinear indexes (approximate entropy (ApEn) and Poincaré plot indexes) of MFC variability and investigates the relationship of MFC with derived indexes of elderly gait patterns. The main aim is to find MFC variability indexes that well correlate with balance impairments. Methods: MFC data during treadmill walking for 14 healthy elderly and 10 elderly participants with balance problems and a history of falls (falls risk) were analysed using a PEAK-2D motion analysis system. ApEn and Poincaré plot indexes of all MFC data sets were calculated and compared. Results: Significant relationships of mean MFC with Poincaré plot indexes (SD1, SD2) and ApEn (r = 0.70, p < 0.05; r = 0.86, p < 0.01; r = 0.74, p < 0.05) were found in the falls-risk elderly group. On the other hand, such relationships were absent in the healthy elderly group. In contrast, the ApEn values of MFC data series were significantly (p < 0.05) correlated with Poincaré plot indexes of MFC in the healthy elderly group, whereas correlations were absent in the falls-risk group. The ApEn values in the falls-risk group (mean ApEn = 0.18 ± 0.03) was significantly (p < 0.05) higher than that in the healthy group (mean ApEn = 0.13 ± 0.13). The higher ApEn values in the falls-risk group might indicate increased irregularities and randomness in their gait patterns and an indication of loss of gait control mechanism. ApEn values of randomly shuffled MFC data of falls risk subjects did not show any significant relationship with mean MFC. Conclusion: Results have implication for quantifying gait dynamics in normal and pathological conditions, thus could be useful for the early diagnosis of at-risk gait. Further research should provide important information on whether falls prevention intervention can improve the gait performance of falls risk elderly by monitoring the change in MFC variability indexes