Bulletin No. 364 - The Halogeton Problem in Utah

Halogeton (Halogeton glomeratus) although introduced into Utah only 20 years ago, has spread widely on the west desert and into extensive areas on the east desert. This plant has become the most feared poisonous plant in the state because people have been lead to believe that it would limit livestock production to areas kept free of the weed

Bulletin No. 372 - The Nutritive Value of Winter Range Plants in the Great Basin as Determined with Digestion Trials with Sheep

During the winter grazing seasons from 1946 to 1953, studies were carried on throughout the desert ranges of western Utah to determine nutritive content and digestibility of range forage plants. These desert areas receive about 7 inches of precipitation annually and the vegetation consists, chiefly, of saltbush and sagebrush types. The average floral composition of the desert areas studied was about 74 percent browse, 25 percent grass, and 1 percent forbs. However, on some areas there was more grass than browse and, on still others, large quantities of forbs were present, primarily Russian-thistle. Digestion trials were carried out under normal range conditions by the use of the lignin-ratio method. Desert ranges in winter were found to be from borderline to decidedly deficient in digestible protein, phosphorus, and metabolizable energy. Diets containing appreciable quantity of browse furnished more than 10 times the minimum requirement of carotene, whereas, grass ranges were decidedly deficient in this respect

Bulletin No. 385 - Comparitive Nutritive Value and Palatability of Some Introduced and Native Forage Plants for Spring and Summer Grazing

From 1952 to 1954 studies were conducted on foothill ranges of central Utah to determine the forage production, palatability, and nutritive value of some of the more important native and introduced species used for spring and summer grazing. Plants studied were four introduced wheatgrasses (crested, tall, pubescent, and intermediate) , four native grasses (western wheatgrass, beardless wheatgrass, squirreltail grass, and Indian ricegrass), and two introduced annual forbs (Russian-thistle, and smother weed). Field digestibility trials were conducted to determine the nutrient content by the lignin-ratio technique. In addition, both sheep and cattle preferences were studied on areas where both introduced and native species were planted

A Push-Button Molecular Switch

The preparation, characterization, and switching mechanism of a unique single-station mechanically switchable hetero[2]catenane are reported. The facile synthesis utilizing a “threading-followed-by-clipping” protocol features Cu^(2+)-catalyzed Eglinton coupling as a mild and efficient route to the tetrathiafulvalene-based catenane in high yield. The resulting mechanically interlocked molecule operates as a perfect molecular switch, most readily described as a “push-button” switch, whereby two discrete and fully occupied translational states are toggled electrochemically at incredibly high rates. This mechanical switching was probed using a wide variety of experimental techniques as well as quantum-mechanical investigations. The fundamental distinctions between this single-station [2]catenane and other more traditional bi- and multistation molecular switches are significant

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Analysis of periosteal lesions from commingled human remains at the Xagħra Circle hypogeum reveals the first case of probable scurvy from Neolithic Malta

Abstract Objectives Palaeopathological analysis is key for characterising population health at the individual level and across large assemblages but is rarely exploited to unite the remains of disarticulated individuals. This study explores the potential for individual identification through differential diagnosis of periosteal lesions in a commingled deposit, both to ascertain the number of individuals represented and provide a differential diagnosis. Materials and Methods The late Neolithic Xag?ra Circle hypogeum on Gozo contains the remains of more than 800 individuals, most of which were transformed to a collective disarticulated assemblage. Across the excavated population, pathological observations are strikingly low. In one specific 1???1-m area in a single stratigraphic context, fragmented and disarticulated cranial and post-cranial non-adult bones were identified that displayed periosteal new bone formation. To aid differential diagnosis, macroscopic analysis, taphonomic analysis and micro-computed tomography (?CT) imaging were integrated. Results This approach, when combined with osteobiographical analyses, reveals that the elements most likely derive from one individual, a young child, who presents a probable case of scurvy. The potential for micronutrient co-morbidities are explored, but without further microscopic study it cannot be determined if this individual also experienced iron-deficiency anaemia and/or rickets. Discussion In the context of the Mediterranean and Europe in later prehistory, reported cases of scurvy are currently low and often reveal periods of environmental instability and resource insufficiency. Our finding of non-adult scurvy in late 3rd millennium BC Malta contributes to a developing picture of an increasingly unstable palaeoenvironment and declining population health at this time, although it may also indicate an individual case of poor childhood health within this broader context.1 Introduction 1.1 Archaeological context of the Xagħra Circle hypogeum 2 Materials and methods 2.1 Remains presenting periosteal lesions 2.2 Macroscopic and micro-CT analysis 3 Macroscopic and radiological observations of pathology 3.1 Frontal bone (FB0039, FB0040) and zygoma (FB0041) 3.2 Mandible (FB0042) 3.3 Left rib (FB0043) and right rib (FB0044) 3.4 Ulna (FB0045) 4 Differential diagnosis 4.1 Frontal bone (FB0039, FB0040) and zygoma (FB0041) 4.2 Mandible (FB0042) 4.3 Left rib (FB0043) and right rib (FB0044) 4.4 Ulna (FB0045) 5 Discussion 5.1 Scurvy: Causes, consequences and comorbidities 5.2 Scurvy in prehistory 5.3 The Maltese context 6 Conclusio

Retrospective observational study to assess the clinical management and outcomes of hospitalised patients with complicated urinary tract infection in countries with high prevalence of multidrug resistant Gram-negative bacteria (RESCUING)

INTRODUCTION: The emergence of multidrug resistant (MDR) Gram-negative bacteria (GNB), including carbapenemase-producing strains, has become a major therapeutic challenge. These MDR isolates are often involved in complicated urinary tract infection (cUTI), and are associated with poor clinical outcomes. The study has been designed to gain insight into the epidemiology, clinical management, outcome and healthcare cost of patients with cUTI, especially in countries with high prevalence of MDR GNB. METHODS AND ANALYSIS: This multinational and multicentre observational, retrospective study will identify cases from 1 January 2013 to 31 December 2014 in order to collect data on patients with cUTI as a cause of hospital admission, and patients who develop cUTI during their hospital stay. The primary end point will be treatment failure defined as the presence of any of the following criteria: (1) signs or symptoms of cUTI present at diagnosis that have not improved by days 5–7 with appropriate antibiotic therapy, (2) new cUTI-related symptoms that have developed within 30 days of diagnosis, (3) urine culture taken within 30 days of diagnosis, either during or after completion of therapy, that grows ≥104 colony-forming unit/mL of the original pathogen and (4) death irrespective of cause within 30 days of the cUTI diagnosis. SAMPLE SIZE: 1000 patients afford a power of 0.83 (α=0.05) to detect an absolute difference of 10% in the treatment failure rate between MDR bacteria and other pathogens. This should allow for the introduction of about 20 independent risk factors (or their interaction) in a logistic regression model looking at risk factors for failure. ETHICS AND DISSEMINATION: Approval will be sought from all relevant Research Ethics Committees. Publication of this study will be considered as a joint publication by the participating investigator leads, and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE)

Potent Activity of the HIV-1 Maturation Inhibitor Bevirimat in SCID-hu Thy/Liv Mice

The HIV-1 maturation inhibitor, 3-O-(3',3'-dimethylsuccinyl) betulinic acid (bevirimat, PA-457) is a promising drug candidate with 10 nM in vitro antiviral activity against multiple wild-type (WT) and drug-resistant HIV-1 isolates. Bevirimat has a novel mechanism of action, specifically inhibiting cleavage of spacer peptide 1 (SP1) from the C-terminus of capsid which results in defective core condensation.Oral administration of bevirimat to HIV-1-infected SCID-hu Thy/Liv mice reduced viral RNA by >2 log(10) and protected immature and mature T cells from virus-mediated depletion. This activity was observed at plasma concentrations that are achievable in humans after oral dosing, and bevirimat was active up to 3 days after inoculation with both WT HIV-1 and an AZT-resistant HIV-1 clinical isolate. Consistent with its mechanism of action, bevirimat caused a dose-dependent inhibition of capsid-SP1 cleavage in HIV-1-infected human thymocytes obtained from these mice. HIV-1 NL4-3 with an alanine-to-valine substitution at the N-terminus of SP1 (SP1/A1V), which is resistant to bevirimat in vitro, was also resistant to bevirimat treatment in the mice, and SP1/AIV had replication and thymocyte kinetics similar to that of WT NL4-3 with no evidence of fitness impairment in in vivo competition assays. Interestingly, protease inhibitor-resistant HIV-1 with impaired capsid-SP1 cleavage was hypersensitive to bevirimat in vitro with a 50% inhibitory concentration 140 times lower than for WT HIV-1.These results support further clinical development of this first-in-class maturation inhibitor and confirm the usefulness of the SCID-hu Thy/Liv model for evaluation of in vivo antiretroviral efficacy, drug resistance, and viral fitness

Mesoscopic Superconducting Disc with Short-Range Columnar Defects

Short-range columnar defects essentially influence the magnetic properties of a mesoscopic superconducting disc.They help the penetration of vortices into the sample, thereby decrease the sample magnetization and reduce the upper critical field. Even the presence of weak defects split a giant vortex state (usually appearing in a clean disc in the vicinity of the transition to a normal state) into a number of vortices with smaller topological charges. In a disc with a sufficient number of strong enough defects vortices are always placed onto defects. The presence of defects lead to the appearance of additional magnetization jumps related to the redistribution of vortices which are already present on the defects and not to the penetration of new vortices.Comment: 14 pgs. RevTex, typos and figures corrected. Submitted to Phys. Rev.