Representation of transport: A Rural Destination Analysis

Moscovici’s social representations perspective is applied to a study of transport in a rural destination. The principles are demonstrated using empirical data from a questionnaire survey, developed following in-depth qualitative research. The data analysis strategy was founded on inductive reasoning, by employing cluster analysis and correspondence analysis. A social representations analysis demonstrates how individuals draw on socially accepted explanations of transport where they have little or no direct knowledge or experience of the actual transport modes (notably the alternatives to the car). By so doing, ideas are further perpetuated. Importantly there is ambiguity surrounding responsibility to take positive action yet a key to addressing transport issues is acknowledgement of responsibility. Keywords: social representations, transport, rural destinations

Translation inhibition by rocaglates activates a species-specific cell death program in the emerging fungal pathogen Candida auris

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen Candida auris has caused considerable concern because most C. auris isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against C. auris, we screened 2,454 compounds from a diversity-oriented synthesis collection. Of the five hits identified, most shared a common rocaglate core structure and displayed fungicidal activity against C. auris These rocaglate hits inhibited translation in C. auris but not in its pathogenic relative Candida albicans Species specificity was contingent on variation at a single amino acid residue in Tif1, a fungal member of the eukaryotic initiation factor 4A (eIF4A) family of translation initiation factors known to be targeted by rocaglates. Rocaglate-mediated inhibition of translation in C. auris activated a cell death program characterized by loss of mitochondrial membrane potential, increased caspase-like activity, and disrupted vacuolar homeostasis. In a rocaglate-sensitized C. albicans mutant engineered to express translation initiation factor 1 (Tif1) with the variant amino acid that we had identified in C. auris, translation was inhibited but no programmed cell death phenotypes were observed. This surprising finding suggests divergence between these related fungal pathogens in their pathways of cellular responses to translation inhibition. From a therapeutic perspective, the chemical biology that we have uncovered reveals species-specific vulnerability in C. auris and identifies a promising target for development of new, mechanistically distinct antifungals in the battle against this emerging pathogen. IMPORTANCE Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that C. auris is surprisingly sensitive to translation inhibition by a class of compounds known as rocaglates (also known as flavaglines). Despite the high level of conservation across fungi in their protein synthesis machinery, these compounds inhibited translation initiation and activated a cell death program in C. auris but not in its relative Candida albicans Our findings highlight a surprising divergence across the cell death programs operating in Candida species and underscore the need to understand the specific biology of a pathogen in attempting to develop more-effective treatments against it.Published versio

Giardia Cyst Wall Protein 1 Is a Lectin That Binds to Curled Fibrils of the GalNAc Homopolymer

The infectious and diagnostic stage of Giardia lamblia (also known as G. intestinalis or G. duodenalis) is the cyst. The Giardia cyst wall contains fibrils of a unique β-1,3-linked N-acetylgalactosamine (GalNAc) homopolymer and at least three cyst wall proteins (CWPs) composed of Leu-rich repeats (CWPLRR) and a C-terminal conserved Cys-rich region (CWPCRR). Our goals were to dissect the structure of the cyst wall and determine how it is disrupted during excystation. The intact Giardia cyst wall is thin (~400 nm), easily fractured by sonication, and impermeable to small molecules. Curled fibrils of the GalNAc homopolymer are restricted to a narrow plane and are coated with linear arrays of oval-shaped protein complex. In contrast, cyst walls of Giardia treated with hot alkali to deproteinate fibrils of the GalNAc homopolymer are thick (~1.2 µm), resistant to sonication, and permeable. The deproteinated GalNAc homopolymer, which forms a loose lattice of curled fibrils, is bound by native CWP1 and CWP2, as well as by maltose-binding protein (MBP)-fusions containing the full-length CWP1 or CWP1LRR. In contrast, neither MBP alone nor MBP fused to CWP1CRR bind to the GalNAc homopolymer. Recombinant CWP1 binds to the GalNAc homopolymer within secretory vesicles of Giardia encysting in vitro. Fibrils of the GalNAc homopolymer are exposed during excystation or by treatment of heat-killed cysts with chymotrypsin, while deproteinated fibrils of the GalNAc homopolymer are degraded by extracts of Giardia cysts but not trophozoites. These results show the Leu-rich repeat domain of CWP1 is a lectin that binds to curled fibrils of the GalNAc homopolymer. During excystation, host and Giardia proteases appear to degrade bound CWPs, exposing fibrils of the GalNAc homopolymer that are digested by a stage-specific glycohydrolase. Author SummaryWhile the walls of plants and fungi contain numerous sugar homopolymers (cellulose, chitin, and β-1,3-glucans) and dozens of proteins, the cyst wall of Giardia is relatively simple. The Giardia wall contains a unique homopolymer of β-1,3-linked N-acetylgalactosamine (GalNAc) and at least three cyst wall proteins (CWPs), each of which is composed of Leu-rich repeats and a C-terminal Cys-rich region. The three major discoveries here are: 1) Fibrils of the GalNAc homopolymer are curled and form a lattice that is compressed into a narrow plane by bound protein in intact cyst walls. 2) Leu-rich repeats of CWP1 form a novel lectin domain that is specific for fibrils of the GalNAc homopolymer, which can be isolated by methods used to deproteinate fungal walls. 3) A cyst-specific glycohydrolase is able to degrade deproteinated fibrils of the GalNAc homopolymer. We incorporate these findings into a new curled fiber and lectin model of the intact Giardia cyst wall and a protease and glycohydrolase model of excystation.National Institutes of Health (AI048082, AI44070, GM31318, RR1088

Acceleration and Substructure Constraints in a Quasar Outflow

We present observations of probable line-of-sight acceleration of a broad absorption trough of C IV in the quasar SDSS J024221.87+004912.6. We also discuss how the velocity overlap of two other outflowing systems in the same object constrains the properties of the outflows. The Si IV doublet in each system has one unblended transition and one transition which overlaps with absorption from the other system. The residual flux in the overlapping trough is well fit by the product of the residual fluxes in the unblended troughs. For these optically thick systems to yield such a result, at least one of them must consist of individual subunits rather than being a single structure with velocity-dependent coverage of the source. If these subunits are identical, opaque, spherical clouds, we estimate the cloud radius to be r = 3.9 10^15 cm. If they are identical, opaque, linear filaments, we estimate their width to be w = 6.5 10^14 cm. These subunits are observed to cover the Mg II broad emission line region of the quasar, at which distance from the black hole the above filament width is equal to the predicted scale height of the outer atmosphere of a thin accretion disk. Insofar as that scale height is a natural size scale for structures originating in an accretion disk, these observations are evidence that the accretion disk can be a source of quasar absorption systems. Based on data from ESO program 075.B-0190(A).Comment: 14 emulateapj pages, 7 figures, ApJ in pres

The Ursinus Weekly, March 23, 1964

Campus Chest activities will begin April 6th • Craig Hill named Weekly editor-in-chief; Bell, Bradley and Davis will head staffs • Nelson Bortz April 8 Forum guest speaker: Labor - management relations topic • Peek to study in Munich • Miller featured in Cuban program: TV appearance set on Great Decisions, 1964 • Students and faculty enter benefit show: Talent and auction for Campus Chest • Spring Festival chairmen reveal plans for musical • Informal rush planned in April: Sorority parties • APO seeks funds for amplification system in gym • Students organize to fight against discrimination • Class of \u2767 sponsors coffee house dance • Editorial: Whatever we\u27ve done • Letters to the editor • Should students 21 be restricted from legal privileges: Student drinking • Forum: Dr. John Noss; Inter-religious communication subject of talk • New dining hall • Is sex education a moral issue? • IRC participates in thirty-seventh National Model General Assembly • Greek gleanings • Dr. J.E. Wagner guest preacher for Holy Week • Kitty Award • Dean\u27s list • Women cagers fall in overtime to West Chester • Mermaids sweep Swarthmore, 48-21 • Shreiner unbeaten: Playoff Tuesday • Intramural champ, Bock, challenges all star teamhttps://digitalcommons.ursinus.edu/weekly/1269/thumbnail.jp

Forage crops for swine

The imperative need of green pastures in pork production is emphasized in the results of 3 years’ investigations at the Iowa Agricultural Experiment Station. They show that the profits on forage fed spring pigs can be increased more than five fold over those fed in dry lot. Alfalfa grazed pigs in 1911 returned a profit of more than $3.00 each as compared to 61 cents in dry lot. Profits of from$30.00 to $80.00 an acre, counting corn at 50 cents and hogs at$5.00, have been easily secured with our good forages. An acre of alfalfa in 1911 netted on this basis $65.99; red clover in 1909,$32.34, in 1910, $34.62; rape in 1909,$27.50 and $27.72; in 1910,$37.51, and in 1911, $80.37; sweet clover in 1910,$42.07, 1911, $23.46; a mixture of oats, clover and rape in 1909,$32.30; a mixture of oats, Canadian field peas and rape in 1909, $22.83; in 1911,$39.52, $53.45 and$64.63; and blue grass and timothy in 1909, $15.23

Forage crops for hogs

When it is understood that the profits on forage fed spring pigs can be increased more than five fold over those fed in dry lot, the great value of green pastures in pork production becomes clear. In 1911, pigs grazed upon alfalfa at the Iowa Agricultural Experiment station returned a profit of more than $3.00 each, as compared to 61 cents in dry lot. The yearly net profits with spring pigs on an acre of forage at Ames, counting corn at 50 cents a bushel and hogs at$5.00, has ranged with the best forages from $30.00 to$80.00. In 1909, an acre of red clover netted on this basis, $32.34; oats, red clover and rape,$32.30; in 1910, sweet clover, $42.07; rape,$37.57; and red clover, $34.62; in 1911, rape,$80.37; alfalfa, $65.99; and oats, field peas and rape,$64.63. Such profits encourage the growing of hog forages. The average daily profit on young pigs grazing in forage is invariably higher than on those confined to pens

Vitamin D with Calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials

Introduction: Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium. Subjects and Methods: Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies. Results: The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62–77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88–0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84–0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88–0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91–1.06). Conclusion: Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone

Comparing attentional bias to smoking cues in current smokers, former smokers, and non-smokers using a dot-probe task

Much evidence documents that individuals with emotional and drug-use disorders demonstrate biased attention toward stimuli associated with their disorder. This bias appears to diminish following successful treatment. Two studies examined whether current cigarette smokers show biased attention toward smoking-related images compared with non-smokers (Studies 1 and 2) and whether this bias is less pronounced in former smokers (Study 2). Attentional bias toward cigarette-related photographs was examined using the dot-probe task. Pairs of images (one smoking-related) appeared side by side for 500 ms on a computer screen prior to the presentation of a probe (an asterisk) replacing one of the photographs. Subjects struck a key as quickly as possible to indicate the probe location. Attentional bias was defined as faster reaction times when the probe replaced the smoking-related image. In both studies, current smokers displayed significantly greater attentional bias toward cigarette stimuli than did non-smokers. Former smokers in Study 2 displayed an intermediate level of bias, but did not differ significantly in bias score from either of the other groups. These results support further use of the dot-probe task as a measure of attentional bias in non-abstinent smokers and in individuals undergoing smoking cessation treatment

The Ursinus Weekly, October 28, 1963

69 women pledge sororities at bid signing Saturday • Class of 1966 to sell slaves at Bazaar • Annual Founders Day November 3; Five honorary degrees to be awarded • Navy debate team bows UC 31-29 • Young Democrats begin activities • Halloween reading night October 30 • Indians warpath at Jr. turnabout • Pre-med society hears Dr. French • Biggest bargain of the year: 1964 Ruby sales begin • $8500 scholarships available for Univ. of Hawaii • Editorial: Which way out?; Action, please • Letters to the editor • Conservatism reconsidered: Spencer\u27s article decried • Human understanding theme of presentation • Fundamental need unfilled • Penna. seeks librarians • Groups schedule career conf. • Federal service exam November 23 • Greek gleanings • Kaffee klatsch: Foreign students reception • Bears topple Swarthmore on fine team effort, 14-6 • Player of the week • Soccer team bows twice • Hockey team still undefeatedhttps://digitalcommons.ursinus.edu/weekly/1255/thumbnail.jp