Ice volume estimates from ground-penetrating radar surveys, Wedel Jarlsberg Land glaciers, Svalbard

One of the aims of the SvalGlac project is to obtain an improved estimate, with reliable error estimates, of the volume of Svalbard glaciers and their potential contribution to sea level rise. As part of this work, we present volume calculations, with detailed error estimates, for eight glaciers on Wedel Jarlsberg Land, southern Spitsbergen, Svalbard. The volume estimates are based upon a dense net of GPR-retrieved ice thickness data collected over several field campaigns spanning the period 2004-2011. The total area and volume of the ensemble are 502.9±18.6 km2 and 80.72±2.85 km3, respectively. Excluding Ariebreen (a tiny glacier, menor que 0.4 km2 in area), the individual areas, volumes and average ice thickness lie within 4.7-141.0 km2, 0.30-25.85 km3 and 64-183 m, respectively. The maximum recorded ice thickness, ca. 619±13 m, is found in Austre Torellbreen. To estimate the ice volume of small non-echo-sounded tributary glaciers, we used a function providing the best fit to the ice thickness along the centre line of a collection of such tributaries where echo-soundings were available, and assuming parabolic cross-sections. We did some tests on the effect on the measured ice volumes of the distinct radio-wave velocity (RWV) of firn as compared to ice, and cold versus temperate ice, concluding that the changes in volume implied by such corrections were within the error bounds of our volume estimate using a constant RWV for the entire glacier inferred from common mid-point measurements on the upper ablation area.

Ground-penetrating radar surveys and ice volume estimates of Wedel Jarlsberg Land glaciers, Svalbard

We present volume calculations, with detailed error estimates, for eight glaciers on Wedel Jarlsberg Land, southern Spitsbergen, Svalbard, and compare them to those obtained from area-volume scaling relationships. The volume estimates are based upon a dense net of GPR-retrieved ice thickness data collected over several field campaigns spanning the period 2004-2011.

Ice volume estimates from ground-penetrating radar surveys, Wedel Jarlsberg Land glaciers, Svalbard

We present ground-penetrating radar (GPR)—based volume calculations, with associated error estimates, for eight glaciers on Wedel Jarlsberg Land, southwestern Spitsbergen, Svalbard, and compare them with those obtained from volume-area scaling relationships. The volume estimates are based upon GPR ice-thickness data collected during the period 2004–2013. The total area and volume of the ensemble are 502.91 ± 18.60 km2 and 91.91 ± 3.12 km3, respectively. The individual areas, volumes, and average ice thickness lie within 0.37–140.99 km2, 0.01–31.98 km3, and 28–227 m, respectively, with a maximum recorded ice thickness of 619 ± 13 m on Austre Torellbreen. To estimate the ice volume of unsurveyed tributary glaciers, we combine polynomial cross-sections with a function providing the best fit to the measured ice thickness along the center line of a collection of 22 surveyed tributaries. For the time-to-depth conversion of GPR data, we test the use of a glacierwide constant radio-wave velocity chosen on the basis of local or regional common midpoint measurements, versus the use of distinct velocities for the firn, cold ice, and temperate ice layers, concluding that the corresponding volume calculations agree with each other within their error bounds.

N-Methyl-d-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain

Morbidity and mortality from head trauma is highest among children. No animal model mimicking traumatic brain injury in children has yet been established, and the mechanisms of neuronal degeneration after traumatic injury to the developing brain are not understood. In infant rats subjected to percussion head trauma, two types of brain damage could be characterized. The first type or primary damage evolved within 4 hr and occurred by an excitotoxic mechanism. The second type or secondary damage evolved within 6–24 hr and occurred by an apoptotic mechanism. Primary damage remained localized to the parietal cortex at the site of impact. Secondary damage affected distant sites such as the cingulate/retrosplenial cortex, subiculum, frontal cortex, thalamus and striatum. Secondary apoptotic damage was more severe than primary excitotoxic damage. Morphometric analysis demonstrated that the N-methyl-d-aspartate receptor antagonists 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonate and dizocilpine protected against primary excitotoxic damage but increased severity of secondary apoptotic damage. 2-Sulfo-α-phenyl-N-tert-butyl-nitrone, a free radical scavenger, did not affect primary excitotoxic damage but mitigated apoptotic damage. These observations demonstrate that apoptosis and not excitotoxicity determine neuropathologic outcome after traumatic injury to the developing brain. Whereas free radical scavengers may prove useful in therapy of head trauma in children, N-methyl-d-aspartate antagonists should be avoided because of their propensity to increase severity of apoptotic damage.

Structure–activity analysis of buforin II, a histone H2A-derived antimicrobial peptide: The proline hinge is responsible for the cell-penetrating ability of buforin II

Buforin II is a 21-aa potent antimicrobial peptide that forms, in a hydrophobic medium, an amphipathic structure consisting of an N-terminal random coil region (residues 1–4), an extended helical region (residues 5–10), a hinge (residue 11), and a C-terminal regular α-helical region (residues 12–21). To elucidate the structural features of buforin II that are required for its potent antimicrobial activity, we synthesized a series of N- and C-terminally truncated or amino acid-substituted synthetic buforin II analogs and examined their antimicrobial activity and mechanism of action. Deletion of the N-terminal random coil region increased the antibacterial activity ≈2-fold, but further N-terminal truncation yielded peptide analogs with progressively decreasing activity. Removal of four amino acids from the C-terminal end of buforin II resulted in a complete loss of antimicrobial activity. The substitution of leucine for the proline hinge decreased significantly the antimicrobial activity. Confocal fluorescence microscopic studies showed that buforin II analogs with a proline hinge penetrated the cell membrane without permeabilization and accumulated in the cytoplasm. However, removal of the proline hinge abrogated the ability of the peptide to enter cells, and buforin II analogs without a proline hinge localized on the cell surface, permeabilizing the cell membrane. In addition, the cell-penetrating efficiency of buforin II and its truncated analogs, which depended on the α-helical content of the peptides, correlated linearly with their antimicrobial potency. Our results demonstrate clearly that the proline hinge is responsible for the cell-penetrating ability of buforin II, and the cell-penetrating efficiency determines the antimicrobial potency of the peptide.

ZK200775: A phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma

Stroke and head trauma are worldwide public health problems and leading causes of death and disability in humans, yet, no adequate neuroprotective treatment is available for therapy. Glutamate antagonists are considered major drug candidates for neuroprotection in stroke and trauma. However, N-methyl-d-aspartate antagonists failed clinical trials because of unacceptable side effects and short therapeutic time window. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists derived from the quinoxalinedione scaffold cannot be used in humans because of their insolubility and resulting renal toxicity. Therefore, achieving water solubility of quinoxalinediones without loss of selectivity and potency profiles becomes a major challenge for medicinal chemistry. One of the major tenets in the chemistry of glutamate antagonists is that the incorporation of phosphonate into the glutamate framework results in preferential N-methyl-d-aspartate antagonism. Therefore, synthesis of phosphonate derivatives of quinoxalinediones was not pursued because of a predicted loss of their selectivity toward AMPA. Here, we report that introduction of a methylphosphonate group into the quinoxalinedione skeleton leaves potency as AMPA antagonists and selectivity for the AMPA receptor unchanged and dramatically improves solubility. One such novel phosphonate quinoxalinedione derivative and competitive AMPA antagonist ZK200775 exhibited a surprisingly long therapeutic time window of >4 h after permanent occlusion of the middle cerebral artery in rats and was devoid of renal toxicity. Furthermore, delayed treatment with ZK200775 commencing 2 h after onset of reperfusion in transient middle cerebral artery occlusion resulted in a dramatic reduction of the infarct size. ZK200775 alleviated also both cortical and hippocampal damage induced by head trauma in the rat. These observations suggest that phosphonate quinoxalinedione-based AMPA antagonists may offer new prospects for treatment of stroke and trauma in humans.