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Subsurface monitoring of permafrost conditions at depths up to 20-30 m is crucial to assess the safety and reliability of mountain infrastructure, because permafrost degradation critically affects rock slope stability in high mountains. Electrical resistivity tomography (ERT) provides a straightforward tool for monitoring near-surface bedrock permafrost at monthly or longer intervals. But as rockfalls are often prepared over periods of hours or days, ERT for early warning purposes should also detect short-term triggering events such as pressurised water flow. Here, we present the first approach to monitor steep permafrost rock walls quasi-continuously with ERT. We measured ERT every 4 h at the up to 67° steep rock wall below the Kitzsteinhorn cable car, Austria. Wenner datasets (n = 996) were analysed from February 2013 to February 2014 in terms of data stability, raw data characteristics and measurement errors coinciding with potential disturbing factors. Strong resistivity changes coincided with rapid freezing or water inundating rock fractures. Automatically detected periods with large resistivity changes produce ERT time series with low resistivities extending from the bottom upwards during times of snowmelt. We infer that flow of pressurised water in fractures warms the surrounding rock in an upward direction, based on fracture inventories, visual observations of cleftwater and near-surface temperature measurements. We develop a strategy for ERT monitoring suitable for potential early warning systems, where high apparent resistivity changes in 4 h intervals may precede critical hydrostatic events confined by permafrost rocks. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) animal models have revealed neuroprotective actions of Bryostatin-1 mediated by activation of novel PKC isoforms, suppression of beta-amyloid and downregulation of inflammatory and angiogenic events, making Bryostatin-1 an attractive candidate for attenuating AD-associated neural, vascular, and cognitive disturbances., Objective: To further enhance Bryostatin-1 efficacy, nanoparticle-encapsulated Bryostatin-1 formulations were prepared., Methods: We compared nano-encapsulated and unmodified Bryostatin-1 in in vitro models of neuronal PKC-d, PKC-e isoforms, α-secretase and studied nano-encapsulated Bryostatin-1 in an AD mouse model of spatial memory (BC3-Tg (APPswe, PSEN1 dE9) 85Dbo/J mice)., Results: We found that nanoencapsulated Bryostatin-1 formulations displayed activity greater or equal to that of unmodified Bryostatin-1 in PKC-δ and -ε and α-secretase activation assays. We next evaluated how treatment with a nanoencapsulated Bryostatin-1 formulation facilitated spatial learning in the Morris water maze. AD transgenic mice (6.5 to 8 months of age) were treated with nanoparticle encapsulated Bryostatin-1 formulation (1, 2.5, or 5 μg/mouse) three times the week before testing and then daily for each of the 5 days of testing. Across the acquisition phase, mice treated with nanoencapsulated Bryostatin-1 had shorter latencies, increased % time in the target zone and decreased % time in the opposite quadrant. The mice were given retention testing after a 2-week period without drug treatment. Mice treated with nanoencapsulated Bryostatin-1 had shorter latencies to find the escape platform, indicating retention of spatial memory., Conclusion: These data suggest that cognitive deficits associated with AD could be treated using highly potent nanoparticle-encapsulated formulations of Bryostatin-1., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Permafrost in northern Canada is susceptible to degradation due to rapid climate change, with hazard mapping promoted as an important activity to guide sustainable community adaptation and planning. This paper presents a framework for evaluating permafrost mapping exercises designed to inform climate change adaptation actions. We apply the framework using a case study of the Incorporating Climate Change into Land Development-Terrain Analysis project (ICCiLD). ICCiLD is a hazard mapping project utilizing interferometric synthetic aperture radar to monitor ground disturbance and categorize land development suitability in seven communities in the territory of Nunavut, Canada. We looked at one of the communities, Arviat, as our case study. We examined technical data and drew upon semi-structured interviews ( n  = 19) with map creators and users. We found ICCiLD added new and relevant information for community planning, increased awareness of the risks posed by permafrost thaw and built stakeholder relations. Strong coordination and high public consciousness of local climate impacts emerged as key factors underpinning project success. Nevertheless, in the case of Arviat, the effectiveness of the hazard maps in influencing land-use planning was constrained by communication challenges between project creators and end-users. These challenges included limited community access to the data and uncertainty surrounding how to operationalize the map suitability classifications. Broader climate change adaptation challenges included the presence of other more immediate community planning priorities and a limited ability to incorporate Indigenous ways of knowing into a technical mapping project. The lessons from this evaluation provide insight for the development of mapping-based adaptations across Arctic regions.

Background: Proteomic analysis of cerebrospinal fluid (CSF) has shown great promise in identifying potential markers of injury in neurodegenerative diseases [1-13]. Here we compared CSF proteomes in healthy individuals, with patients diagnosed with traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) in order to characterize molecular biomarkers which might identify these different clinical states and describe different molecular mechanisms active in each disease state., Methods: Patients presenting to the Neurosurgery service at the Louisiana State University Hospital-Shreveport with an admitting diagnosis of TBI or SAH were prospectively enrolled. Patients undergoing CSF sampling for diagnostic procedures were also enrolled as controls. CSF aliquots were subjected to 2-dimensional gel electrophoresis (2D GE) and spot percentage densities analyzed. Increased or decreased spot expression (compared to controls) was defined in terms of in spot percentages, with spots showing consistent expression change across TBI or SAH specimens being followed up by Matrix-Assisted Laser Desorption/Ionization mass spectrometry (MALDI-MS). Polypeptide masses generated were matched to known standards using a search of the NCBI and/or GenPept databases for protein matches. Eight hundred fifteen separately identifiable polypeptide migration spots were identified on 2D GE gels. MALDI-MS successfully identified 13 of 22 selected 2D GE spots as recognizable polypeptides., Results: Statistically significant changes were noted in the expression of fibrinogen, carbonic anhydrase-I (CA-I), peroxiredoxin-2 (Prx-2), both α and β chains of hemoglobin, serotransferrin (Tf) and N-terminal haptoglobin (Hp) in TBI and SAH specimens, as compared to controls. The greatest mean fold change among all specimens was seen in CA-I and Hp at 30.7 and -25.7, respectively. TBI specimens trended toward greater mean increases in CA-I and Prx-2 and greater mean decreases in Hp and Tf., Conclusions: Consistent CSF elevation of CA-I and Prx-2 with concurrent depletion of Hp and Tf may represent a useful combination of biomarkers for the prediction of severity and prognosis following brain injury., (Copyright © 2017. Published by Elsevier B.V.)

In recent years, remote sensing, morphometric analysis, and other computational concepts and tools have invigorated the field of geomorphological mapping. Automated interpretation of digital terrain data based on impartial rules holds substantial promise for large dataset processing and objective landscape classification. However, the geomorphological realm presents tremendous complexity and challenges in the translation of qualitative descriptions into geomorphometric semantics. Here, the simple, conventional distinction of V-shaped fluvial and U-shaped glacial valleys was analyzed quantitatively using multi-scale curvature and a novel morphometric variable termed Difference of Minimum Curvature (DMC). We used this automated terrain analysis approach to produce a raster map at a scale of 1:6,000,000 showing the distribution of glaciated valleys across Europe and western Asia. The data set has a cell size of 3 arc seconds and consists of more than 40 billion grid cells. Glaciated U-shaped valleys commonly associated with erosion by warm-based glaciers are abundant in the alpine regions of mid Europe and western Asia but also occur at the margins of mountain ice sheets in Scandinavia. The high-level correspondence with field mapping and the fully transferable semantics validate this approach for automated analysis of yet unexplored terrain around the globe and qualify for potential applications on other planetary bodies like Mars.

Background: Previous studies showed that Bryostatin-1, a potent PKC modulator and alphasecretase activator, can improve cognition in models of Alzheimer's disease (AD) with chronic (>10 weeks), intraperitoneal (i.p.) administration of the drug. We compared learning and spatial memory in the APPswe, PSEN1dE985Dbo (APP/PS1) mouse model of AD and studied the ability of acute intraperitoneal and oral Bryostatin-1 to reverse cognitive deficits in this model. Compared to wild-type (WT) mice, APP/PS1 mice showed significant delays in learning the location of a submerged platform in the Morris water maze. Bryostatin-1 was administered over a 2-week course prior to and during water maze testing., Results: Acute i.p. Bryostatin-1 administration did not improve latency to escape but oral Bryostatin-1 significantly improved memory (measured by a reduction in latency to escape). This benefit of oral Bryostatin-1 administration was most apparent during the first 3 days of testing. These findings show that: 1) Bryostatin-1 is orally active in models of learning and memory, 2) this effect can be produced in less than 2 weeks and 3) this effect is not seen with i.p. administration. We conclude that oral Bryostatin-1 represents a novel, potent and long-acting memory enhancer with future clinical applications in the treatment of human AD.

Erosion by glacial and fluvial processes shapes mountain landscapes in a long-recognized and characteristic way. Upland valleys incised by fluvial processes typically have a V-shaped cross-section with uniform and moderately steep slopes, whereas glacial valleys tend to have a U-shaped profile with a changing slope gradient. We present a novel regional approach to automatically differentiate between fluvial and glacial mountain landscapes based on the relation of multi-scale curvature and drainage area. Sample catchments are delineated and multiple moving window sizes are used to calculate per-cell curvature over a variety of scales ranging from the vicinity of the flow path at the valley bottom to catchment sections fully including valley sides. Single-scale curvature can take similar values for glaciated and non-glaciated catchments but a comparison of multi-scale curvature leads to different results according to the typical cross-sectional shapes. To adapt these differences for automated classification of mountain landscapes into areas with V- and U-shaped valleys, curvature values are correlated with drainage area and a new and simple morphometric parameter, the Difference of Minimum Curvature ( DMC ), is developed. At three study sites in the western United States the DMC thresholds determined from catchment analysis are used to automatically identify 5 × 5 km quadrats of glaciated and non-glaciated landscapes and the distinctions are validated by field-based geological and geomorphological maps. Our results demonstrate that DMC is a good predictor of glacial imprint, allowing automated delineation of glacially and fluvially incised mountain landscapes.

Purpose: Patients treated with radiotherapy for head-and-neck cancer invariably suffer its deleterious side effect, xerostomia. Salivary hypofunction ensuing from the irreversible destruction of glands is the most common and debilitating oral complication affecting patients undergoing regional radiotherapy. Given that the current management of xerostomia is palliative and ineffective, efforts are now directed toward preventive measures to preserve gland function. The human homolog of Tousled protein, TLK1B, facilitates chromatin remodeling at DNA repair sites and improves cell survival against ionizing radiation (IR). Therefore, we wanted to determine whether a direct transfer of TLK1B protein to rat salivary glands could protect against IR-induced salivary hypofunction., Methods: The cell-permeable TAT-TLK1B fusion protein was generated. Rat acinar cell line and rat salivary glands were pretreated with TAT peptide or TAT-TLK1B before IR. The acinar cell survival in vitro and salivary function in vivo were assessed after radiation., Results: We demonstrated that rat acinar cells transduced with TAT-TLK1B were more resistant to radiation (D₀ = 4.13 ± 1.0 Gy; α/β = 0 Gy) compared with cells transduced with the TAT peptide (D₀ = 4.91 ± 1.0 Gy; α/β = 20.2 Gy). Correspondingly, retroductal instillation of TAT-TLK1B in rat submandibular glands better preserved salivary flow after IR (89%) compared with animals pretreated with Opti-MEM or TAT peptide (31% and 39%, respectively; p < 0.01)., Conclusions: The results demonstrate that a direct transfer of TLK1B protein to the salivary glands effectively attenuates radiation-mediated gland dysfunction. Prophylactic TLK1B-protein therapy could benefit patients undergoing radiotherapy for head-and-neck cancer., (Published by Elsevier Inc.)

As part of our characterization of the developmental consequences of prenatal cocaine exposure, cocaine was injected into eggs containing viable chicken embryos on embryonic day (E) 18 and the fever response to the endotoxin lipopolysaccharide (LPS) and a delayed-type hypersensitivity response to phytohemagglutinin (PHA) were assessed postnatally. E18 cocaine exposure did not affect basal body temperature. LPS induced a fever in the chicks at 4 h post-injection on post-hatch day (D) 4 and 2 h post-injection on D24. E18 cocaine exposure suppressed the peak LPS-induced fever by 50% at both ages. E18 cocaine exposure also suppressed the hypersensitivity reaction to an intradermal injection of PHA on D17, while having no effect on the response to a saline injection. To determine the importance of serotonin(2) (5-HT(2)) receptors in the developmental toxicity of cocaine, varying doses of the 5-HT(2) antagonist ritanserin were injected on E17 followed by cocaine on E18. Ritanserin, like cocaine, did not alter basal temperature, but it dose-relatedly attenuated or blocked cocaine's effect on LPS-induced fever on both D4 and D24. Ritanserin pretreatment was also able to block the blunted isolation stress response seen in D16 chicks following E18 cocaine exposure. Thus, late prenatal cocaine exposure significantly alters adaptive fever and hypersensitivity responses, and embryonic 5-HT(2) receptors played a mediating role in the fever effect.

Over the last 10 years there has been an increasing awareness of the limitation of resources even in the Health Care System and that rationing can, therefore, not be avoided. However, it is possible to reduce "hard" rationing by introducing rationalizing techniques. To achieve this goal it will be necessary to assess the values of medical interventions. In the present paper, we describe a method for rationalization of health care services which has been applied in a health centre. This includes the explanation of the concept of Evidence-based Medicine, the six steps in which this concept is realized and the criteria which have to be met to gain support from physicians for this project. The results which have been made so far are discussed.

Prior studies in our laboratory have demonstrated that prenatal treatment with the serotonin2 (5-HT2) antagonist ritanserin is effective in blocking some of the lethal, dysmorphic, cardiovascular, and behavioral consequences of excessive direct or indirect stimulation of 5-HT2 receptors in the developing chicken. The efficacious dose range for ritanserin in these studies had very little or no effect on the above measures of toxicity when administered alone. In the present study, we extend our characterization of ritanserin's potential toxicity, or lack thereof, to include the normal behavioral and endocrine responses to immune system stimulation by the endotoxin lipopolysaccharide (LPS). LPS administration induces a syndrome collectively known as sickness behavior, manifest as altered thermoregulatory processes leading to fever, and increased serum concentrations of neuroendocrine hormones, including corticosterone. These survival-promoting responses to LPS were assessed in young chickens that had been treated with doses of ritanserin ranging from 0 to 2.7 mg/kg on embryonic day 17 (E17). When sickness behavior was assessed in 5-7-day-old chicks 1 h post-LPS injection, E17 ritanserin-treated subjects did not differ from controls. At 4-6 h post-LPS, 4-day-old chicks displayed a robust fever, and E17 ritanserin did not affect the magnitude of this response. Similarly, E17 ritanserin treatment failed to affect corticosterone concentrations 2 h post-LPS in 14-day-old chicks. Thus, ritanserin treatment during late embryogenesis, a time when it is effective against direct and indirect acting 5-HT2 agonists, failed to modify the survival promoting and beneficial interactions between the nervous, endocrine, and immune systems that are elicited following immunostimulation.

NZB x NZW F1 hybrid (B/W) mice develop altered behavior in the elevated plus maze and novel object tasks between 6 and 12 weeks of age in parallel with lupus-like autoimmune disease. To confirm the relationship between disease progression and development of behavioral abnormalities, B/W and nonautoimmune NZW mice received chronic treatment with a soluble IFN gamma receptor (sIFN gamma R), a treatment known to retard autoimmune disease progression, or vehicle, beginning at 6 weeks of age. After 6 weeks of treatment, elevated plus maze and novel object testing revealed that although sIFN gamma R treated B/W mice still differed from NZW mice, chronic sIFN gamma R treatment significantly retarded the development of behavioral abnormalities in the B/W mice, while the NZW mice were not affected by this treatment. sIFN gamma R treated B/W mice were more active in both the plus maze and novel object tasks, and displayed less plus maze anxiety behavior and more exploratory activity in the novel object task compared to vehicle treated B/W mice. To clarify the role of acute action of the sIFN gamma R on the elevated IFN gamma levels of B/W mice, a second experiment examined the effects of a single injection of sIFN gamma R on B/W and NZW mice. Unlike chronic treatment, acute treatment with the same dose of sIFN gamma R did not affect plus maze or novel object behavior in 12-week-old mice. These results add to the growing evidence that lupus-associated behavioral abnormalities are a direct effect of the autoimmune disease.

The importance of glucocorticoids and their perturbation during development is an active research area. Developmental insults, including direct and indirect consequences of exposure to drugs of abuse or withdrawal from them, may act upon or via the neuroendocrine axis of the pregnant experimental subject (e.g. rat) and/or directly upon the neuroendocrine axis of the embryo or fetus. The use of the domestic chicken embryo may constitute a good experimental subject for studying these effects in the absence of maternal influences. Thus, the pattern of brain glucocorticoid cytosolic receptors were characterized in an early developing brain region, the optic tectum (OT) and a later developing region with a different function, the hyperstriatum-hippocampus-parahippocampal (HHP) area, on embryonic days (E) 11, 15, 18 and on the day of hatching (HD). The influence of the glucocorticoid synthesis inhibitor metyrapone, injected into eggs on E14 and on E17, upon glucocorticoid receptors (on E15 and E18) was also studied to determine effects of a 'chemical adrenalectomy'. Receptors for this steroid are high on E11 and E15, decreasing as they approach the time of hatching, with the HHP generally showing greater numbers of specific binding sites for [3H]-corticosterone (CORT). Although metyrapone treatment did not alter the apparent number of receptors on E15, on E18 it unmasked receptors otherwise occupied by endogenous ligand(s) and/or induced their synthesis, resulting in significantly more receptors identified with [3H]-CORT. Nevertheless, the HHP continued to display more of these receptors than the OT on E15 and E18 after injection of metyrapone. These observations are consistent with the hypotheses that the HHP of embryos of this species contains a higher density of glucocorticoid receptors than does the OT; that glucocorticoid receptor quantification is related to steroid synthesis inhibition in late embryonic development; and that neuroendocrine feedback control of serum glucocorticoids may become functional between E15 and E18. The results also suggest the use of this experimental approach for assessing the effects of developmental insults with drugs, other than metyrapone, as a marker for altered neuroendocrine development and/or function.

Using defined rearing or training paradigms, environmental stimulation has been found to increase brain weight (especially forebrain), cortical thickness, the number of glial cells, the glia to neuron ratio, neuronal cell body and nucleus size, and to alter synaptic profiles by increasing dendritic branching, dendritic spine density and the number of discontinuous synapses. Examples will be given from both animal and human studies that document these profound changes. Controversy exists as to whether enriched environments and/or training can compensate for neural deficits produced earlier in life. Examples will be given from animal studies with induced cortical lesions and prenatal genetic neural anomalies that support a role for environmental manipulations ameliorating earlier central nervous system damage.

Behavioral changes often accompany the autoimmune disease systemic lupus erythematosus (SLE) in humans and animals. In a mouse model of SLE, the NZB x NZW F1 (B/W) hybrid, 12-week-old mice display more anxiety behavior, less activity, and less exploratory behavior than non-autoimmune female NZW mice. To determine whether these behaviors result from the autoimmune disease or genetic differences between B/W and NZW mice, they were assessed prior to and during disease emergence (6 and 12 weeks of age, respectively). B/W mice were less active at both ages, suggesting a genetic component to this behavioral difference. Anxiety behavior and exploratory behavior did not differ between B/W and NZW mice at 6 weeks; however, at 12 weeks B/W mice displayed more anxiety behavior and less exploratory behavior, indicating that these behaviors were related with the development of autoimmune disease. Prior experience with these tasks increased anxiety behavior in B/W but not NZW mice, suggesting that B/W mice may be more sensitive to anxiogenic experiences.