Development of Mountain Climate Generator and Snowpack model for Erosion Predictions in the Western United States using WEPP, Reserach Completion Report for Phase II

Executive Summary: This report summarizes work conducted during the funding period (July 1 through September 30, 1990) of a Cooperative Agreement between the United States Forest Service (USFS) and the Utah Water Research Laboratory (UWRL), Utah State University. The purpose of the agreement is to develop a Western Mountain Climate Generator (MCLIGEN) similar in function to the existing Climate Generator (CLIGEN), which is part of the Water Erosion Prediction Project (WEPP) procedure. Also, we are developing a Western U.S. snowpack simulation model for inclusion in WEPP. In the Western U.S., few meteorological observations exist in high elecation areas where Forest Service properties are located. Therefore, a procedure for estimating climatological variables in mountainous areas is needed to apply WEPP in these regions. A physically-based approach, using an expanded and improved orographic precipitation model, is being utilized. It will use radiosonde data and also lighning data to simualte convective storms. Climatological sequences thus estimated at ungaged locatiosn will be represented using stochastic models, similar to the approach used in the existing CLIGEN, and their parameters will be available to users through maps. By using these stochastic models, WEPP usters can synthsize climate sequences for input to WEPP. During the reporting period we have implemented the the Rhea orographic precipitation model and begun preliminary model testing in two regions. Also, we have begun formulation of model modifications for handling convective events. Various snowplack and meteorological data sets have been acquired and others have been ordered. Some of these have been applied in ititial applications of several snowpack models which have been recorded in a modeular form. Work has commenced on the statistical analysis of western climate sequences, including the preliminary assessment of the alternative stochastic model structures. Additional review of literature has been commenced for establishing desing storms and design hydrographs for events of various return periods in mountainous regions. Accomplishments are summarized in three parts: 1) climatological process models, 2) snowpack simulation models, and 3) stochastic models of climatological variablse and parameter regionalization. A chapter of the report is devoted to each of these three parts

Iranian Herbalists, But Not Cooks, Are Better at Naming Odors Than Laypeople

Odor naming is enhanced in communities where communication about odors is a central part of daily life (e.g., wine experts, flavorists, and some hunter-gatherer groups). In this study, we investigated how expert knowledge and daily experience affect the ability to name odors in a group of experts that has not previously been investigated in this context—Iranian herbalists; also called attars—as well as cooks and laypeople. We assessed naming accuracy and consistency for 16 herb and spice odors, collected judgments of odor perception, and evaluated participants' odor meta-awareness. Participants' responses were overall more consistent and accurate for more frequent and familiar odors. Moreover, attars were more accurate than both cooks and laypeople at naming odors, although cooks did not perform significantly better than laypeople. Attars' perceptual ratings of odors and their overall odor meta-awareness suggest they are also more attuned to odors than the other two groups. To conclude, Iranian attars—but not cooks—are better odor namers than laypeople. They also have greater meta-awareness and differential perceptual responses to odors. These findings further highlight the critical role that expertise and type of experience have on olfactory functions

Development of Mountain Climate Generator and Snowpack model for Erosion Predictions in the Western United States Using WEPP, Progress Report No. 1

Executive Summary: This report summarizes work conducted during the initial funding period (November 1, 1989 through June 30, 1990) of a Cooperative Agreement between the United States Forest Service (USFS) and the Utah Water Research Laboratory (UWRL), Utah State University. The purpose of the agreement is to develop a procedure for incorporating western mountain climate into the existing Climate Generator (CLIGEN), which is part of the Water Erosion Prediction Project (WEPP) procedure. In the Western U.S., few meteorological observations exist in high elevation areas where Forest Service properties are located. Therefore, a procedure for estimating climatological variables in mountainous areas is needed to apply WEPP in these regions. A physically-based approach, an expanded and improved orographic precipitation model, is proposed in this report. It will use radiosonde data and also lightning data to simulate convective storms. Climatological sequences thus estimated at ungaged locations will be represented using stochastic models, similar to the approach used in the existing CLIGEN, and their parameters will be available to users through maps. By using these stochastic models, WEPP users can synthesize climate sequences for input to WEPP. Several alternative approaches to developing the Mountain Climate Generator (MCLIGEN) have been formulated and evaluated. These options vary in their spatial resolution. Some will provide synthetic climate inputs whereas others will provide synthetic sequences of water delivery to the ground surface or overland flow delivery. The latter will reduce the user\u27s responsibility for judging adequate snowpack or hydrological simulations, but will enormously increase the effort required for parameterization during the developmental phase. Based on our evaluation, we recommend that Option 2 for generating fine scale climate sequences be adopted. This option appears to satisfy the WEPP spatial resolution requirements of the USFS and requires a reasonable level of developmental effort. We also recommend that Option 3 be available to the users. We recomment that under this option snowpack initial conditions at a specified date be available based on a return period or exceedance probability. Under this option discontinuous simulation periods could be considered. The data, models, and parameters needed to implement the recommended approach can be divided into three parts: 1) climatological process models, 2) a snowpack imulation model, and 3) stochastic models of climatological variables and parameter regionalization. A chapter of the report is devoted to each of these three parts. Each chapter includes a literature review and a description of the proposed methodology and work plan for its development. We further recommend that a comprehensive plan for data collection for validation of the entire WEPP methodology applied to the mountainous Western U.S. be developed. Also, we propose that UWRL take the lead in settin gup a user group for orographic precipitation modelers

Calpain-mediated cleavage of Beclin-1 and autophagy deregulation following retinal ischemic injury in vivo

Autophagy is the major intracellular degradation pathway that regulates long-lived proteins and organelles turnover. This process occurs at basal levels in all cells but it is rapidly upregulated in response to starvation and cellular stress. Although being recently implicated in neurodegeneration, it remains still unclear whether autophagy has a detrimental or protective role. In this study, we investigated the dynamics of the autophagic process in retinal tissue that has undergone transient ischemia, an experimental model that recapitulates features of ocular pathologies, including glaucoma, anterior ischemic optic neuropathy and retinal vessels occlusion. Retinal ischemia, induced in adult rats by increasing the intraocular pressure, was characterized by a reduction in the phosphatidylethanolamine-modified form of LC3 (LC3II) and by a significant decrease in Beclin-1. The latter event was associated with a proteolytic cleavage of Beclin-1, leading to the accumulation of a 50-kDa fragment. This event was prevented by intravitreal treatment with the non-competitive N-methyl-D-aspartate antagonist MK801 and calpain inhibitors or by calpain knockdown. Blockade of autophagy by pharmacological inhibition or Beclin-1 silencing in RGC-5 increased cell death, suggesting a pro-survival role of the autophagic process in this neuronal cell type. Altogether, our results provide original evidence for calpain-mediated cleavage of Beclin-1 and deregulation of basal autophagy in the rat retina that has undergone ocular ischemia/reperfusion injury

The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1

Resveratrol is a cancer preventative agent that is found in red wine. Piceatannol is a closely related stilbene that has antileukaemic activity and is also a tyrosine kinase inhibitor. Piceatannol differs from resveratrol by having an additional aromatic hydroxy group. The enzyme CYP1B1 is overexpressed in a wide variety of human tumours and catalyses aromatic hydroxylation reactions. We report here that the cancer preventative agent resveratrol undergoes metabolism by the cytochrome P450 enzyme CYP1B1 to give a metabolite which has been identified as the known antileukaemic agent piceatannol. The metabolite was identified by high performance liquid chromatography analysis using fluorescence detection and the identity of the metabolite was further confirmed by derivatisation followed by gas chromatography–mass spectrometry studies using authentic piceatannol for comparison. This observation provides a novel explanation for the cancer preventative properties of resveratrol. It demonstrates that a natural dietary cancer preventative agent can be converted to a compound with known anticancer activity by an enzyme that is found in human tumours. Importantly this result gives insight into the functional role of CYP1B1 and provides evidence for the concept that CYP1B1 in tumours may be functioning as a growth suppressor enzyme

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey\u27s discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD \u3c 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD

Autophagy–physiology and pathophysiology

“Autophagy” is a highly conserved pathway for degradation, by which wasted intracellular macromolecules are delivered to lysosomes, where they are degraded into biologically active monomers such as amino acids that are subsequently re-used to maintain cellular metabolic turnover and homeostasis. Recent genetic studies have shown that mice lacking an autophagy-related gene (Atg5 or Atg7) cannot survive longer than 12 h after birth because of nutrient shortage. Moreover, tissue-specific impairment of autophagy in central nervous system tissue causes massive loss of neurons, resulting in neurodegeneration, while impaired autophagy in liver tissue causes accumulation of wasted organelles, leading to hepatomegaly. Although autophagy generally prevents cell death, our recent study using conditional Atg7-deficient mice in CNS tissue has demonstrated the presence of autophagic neuron death in the hippocampus after neonatal hypoxic/ischemic brain injury. Thus, recent genetic studies have shown that autophagy is involved in various cellular functions. In this review, we introduce physiological and pathophysiological roles of autophagy

Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci.

Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical impacts upon growth, development and metabolism. Thus, detailed and systematic analysis of IDs can not only identify unifying principles of molecular epigenetics in health and disease, but also support personalisation of diagnosis and management for individual patients and families.All authors are members of the EUCID.net network, funded by COST (BM1208). TE is funded by the German Ministry of research and education (01GM1513B). GPdN is funded by I3SNS Program of the Spanish Ministry of Health (CP03/0064; SIVI 1395/09), Instituto de Salud Carlos III (PI13/00467) and Basque Department of Health (GV2014/111017).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13148-015-0143-

Disinfection of Ocular Cells and Tissues by Atmospheric-Pressure Cold Plasma

Background: Low temperature plasmas have been proposed in medicine as agents for tissue disinfection and have received increasing attention due to the frequency of bacterial resistance to antibiotics. This study explored whether atmospheric-pressure cold plasma (APCP) generated by a new portable device that ionizes a flow of helium gas can inactivate ocular pathogens without causing significant tissue damage. Methodology and Principal Findings: We tested the APCP effects on cultured Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes simplex virus-1, ocular cells (conjunctival fibroblasts and keratocytes) and ex-vivo corneas. Exposure to APCP for 0.5 to 5 minutes significantly reduced microbial viability (colony-forming units) but not human cell viability (MTT assay, FACS and Tunel analysis) or the number of HSV-1 plaque-forming units. Increased levels of intracellular reactive oxygen species (ROS) in exposed microorganisms and cells were found using a FACS-activated 2',7'-dichlorofluorescein diacetate probe. Immunoassays demonstrated no induction of thymine dimers in cell cultures and corneal tissues. A transient increased expression of 8-OHdG, genes and proteins related to oxidative stress (OGG1, GPX, NFE2L2) was determined in ocular cells and corneas by HPLC, qRT-PCR and Western blot analysis. Conclusions: A short application of APCP appears to be an efficient and rapid ocular disinfectant for bacteria and fungi without significant damage on ocular cells and tissues, although the treatment of conjunctival fibroblasts and keratocytes caused a time-restricted generation of intracellular ROS and oxidative stress-related responses