Precursor ion scanning for detection and structural characterization of heterogeneous glycopeptide mixtures

AbstractThe structure of N-linked glycans is determined by a complex, anabolic, intracellular pathway but the exact role of individual glycans is not always clear. Characterization of carbohydrates attached to glycoproteins is essential to aid understanding of this complex area of biology. Specific mass spectral detection of glycopeptides from protein digests may be achieved by on-line HPLC-MS, with selected ion monitoring (SIM) for diagnostic product ions generated by cone voltage fragmentation, or by precursor ion scanning for terminal saccharide product ions, which can yield the same information more rapidly. When glycosylation is heterogeneous, however, these approaches can result in spectra that are complex and poorly resolved. We have developed methodology, based around precursor ion scanning for ions of high m/z, that allows site specific detection and structural characterization of glycans at high sensitivity and resolution. These methods have been developed using the standard glycoprotein, fetuin, and subsequently applied to the analysis of the N-linked glycans attached to the scrapie-associated prion protein, PrPSc. These glycans are highly heterogeneous and over 30 structures have been identified and characterized site specifically. Product ion spectra have been obtained on many glycopeptides confirming structure assignments. The glycans are highly fucosylated and carry Lewis X or sialyl Lewis X epitopes and the structures are in-line with previous results. [Abbreviations: Hex–Hexose, C6H12O6 carbohydrates, including mannnose and galactose; HexNAc—N-acetylhexosamine, C8H15NO6 carbohydrates, including N-acetylglucosamine and N-acetylgalactosamine; GlcNAc—N-acetylglucosamine; GalNAc—N-acetylgalactosamine; Fuc–Fucose; NeuAC—N-acetylneuraminic acid or sialic acid; TSE—Transmissible Spongiform Encephalopathy.

Estimation in a growth study with irregular measurement times

Between 1982 and 1988 a growth study was carried out at the Division of Pediatric Oncology of the University Hospital of Groningen. A special feature of the project was that sample sizes are small and that ages at entry may be very different. In addition the intended design was not fully complied with. This paper highlights some aspects of the statistical analysis which is based on (1) reference scores, (2) statistical procedures allowing for an irregular pattern of measurement times caused by missing data and shifted measurement times

Suicide and self-harm in Britain: researching risk and resilience using UK surveys

Aim The main aim of this study was to raise awareness of surveys that could be used to inform self-harm and suicide prevention work. We asked: What UK survey datasets are available for research? What aspects of people’s lives are associated with self-harm and attempted suicide? How do statistical findings resonate with people’s lived experience? What implications do they see? Findings Survey analyses revealed that risk factors for self-harm are wide ranging and include: Mental health Physical health and health behaviours Social relationships Stressful events Employment and financial circumstances Identity and demographics Many different factors are independently associated with self-harm. There is a dose relationship, with more exposure to a factor linked with increased risk. Risks are cumulative that is, exposure to multiple factors is associated with greater risk. Through facilitated consultation, men with lived experience, bereaved family members, and practitioners identified recommendations for responding to suicidal distress in men. These related to the following three main areas: 1. Recognising need: who is ‘ill enough’? Permission - men said that they often did not know they were entitled to help Ask - people who outwardly appear to be functioning may not be Persistence - ask and offer help more than once. 2. Facilitating access: right words, time and place What is available - support is needed with ongoing stress as well as for crises Find the words - men wanted examples of how to ask for help Allow time - employers expect recovery to be swift, some men felt rushed to come off medications or were discharged from services they still needed. 3. Adjusting delivery: equal engagement Power - some were uncomfortable with service dynamics, preferring peer support Every service contact counts - negative contacts had particular impact Safe spaces - may be different for men and women. Methods There were three strands of work: Secondary analysis of nine survey series, spanning more than twenty years Linkage of 144,000 survey participants to information on whether they were alive in 2013 and whether they had taken their own life Facilitated consultation, through depth interviews with people with lived experience

Statistical analysis of heaped duration data

This paper shows how heaping of duration data eg caused by rounding due to memory eects can be analyzed If the data are heaped Coxs partial likelihood approach which is often used in survival analysis is no longer appropriate We show how this problem can be overcome by considering the problem as a missing data problem A variant of Coxs Proportional Hazard Model is constructed that takes heaping into account and is estimated by maximum likelihood using the EM algorithm with many nuisance parameters simultaneously for all parameters Ingredients of our method are application of the EM algorithm Cox regression and nonparametric maximumlikelihood calculation with predicted data in each M step An example from practice where jackknife is used to estimate the variances illustrates the power of the new methodolog

Effect of integrated nitrogen management on NPK uptake in basmati rice (Oryza sativa L.)

A field experiment entitled NPK uptake influenced by integrated nitrogen management in basmati rice (Oryza sativa L.) was conducted at Punjab Agricultural University, Ludhiana during kharif 2010. The experiment was conducted in randomized block design with 13 treatment combinations of chemical fertilizer, green manuring (GM) with Crotalaria juncea, farmyard manure (FYM) and organic preparations [OP (Jeevamrit and Panchagavya)] in four replications. The highest grain yield (34.9±0.54 q ha-1 ) was obtained with combined application of FYM and 50 per cent of recommended nitrogen (RN) followed by GM+FYM+OP (33.7 q ha-1 ) and GM+FYM (33.4±0.99 q ha-1 ). Straw yield (63.1 q ha-1 ) increased significantly (P<0.01) in treatment where FYM combined with 50 per cent of RN was applied. Among different nitrogen management treatments, the maximum N, P and K uptake in grain and straw were observed under treatment T8 (FYM +50 per cent of RN) viz. integrated nitrogen treatment followed by T11 (GM+FYM+OP) and T9 (GM+FYM). Thus, combined application of FYM @ 19.76 t ha-1- with reduced fertilizer dose (50 % of RN) increased the yield and NPK uptake in basmati rice

Acute Liver Failure Secondary to Hemophagocytic Lymphohistiocytosis during Pregnancy.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune activation that mimics and occurs with other systemic diseases. A 35-year-old female presented with signs of viral illness at 13 weeks of pregnancy and progressed to acute liver failure (ALF). We discuss the diagnosis of HLH and Kikuchi-Fujimoto (KF) lymphadenitis in the context of pregnancy and ALF. HLH may respond to comorbid disease-specific therapy, and more toxic treatment can be avoided

Efficacy of anthranilic insecticide E2Y45 20 SC (Chlorantraniliprole) against Plutella xylostella L. in cabbage, Brassica oleracea var. capitata

Experiments were conducted at farmer’s cabbage fields to evaluate the bioefficacy of anthranilic insecticide i.e. E2Y45 20 SC (Chlorantraniliprole) having novel mode of action against the diamondback moth Plutella xylostella L. E2Y45 20 SC was applied @ 25.0, 37.5 and 50.0 ml/ha and was compared with Padan 50 SP (cartap hydrochloride) @ 500 g/ha and the untreated control. Lowest mean larval population after two sprays was recorded in higher dose of E2Y 45 20 SC i.e. @ 50.0 ml/ha (0.08 larvae/plant) at 7 days after treatment followed by medium and lower dose of E2Y 45 20 SC i.e. @ 37.5ml/ha (0.10 larvae/plant) and 25.0 ml/ha (0.33 larvae/plant). The larval population in these treatments was significantly lower than standard check, Padan 50 SP (2.56 larvae/plant), and untreated control (9.73 larvae/plant). The highest marketable yield (262.89 q/ha) was recorded in E2Y 45 20 SC @ 50.0 ml/ha which was significantly higher than Padan 50 SP (239.65 q/ha). Lowest yields were recorded in untreated control (106.00 q/ha). Conclusively, medium (37.5 ml/ha) and higher (50.0 ml/ha) dose of E2Y 45 20 SC (chlorantraniliprole) significantly reduced the larval population of P. xylostella and increased the cabbage yield

Unique Mass Texture for Quarks and Leptons

Texture specific quark mass matrices which are hermitian and hierarchical are examined in detail . In the case of texture 6 zeros matrices, out of sixteen possibilities examined by us, none is able to fit the low energy data (LED), for example, $V_{us} = 0.2196 \pm 0.0023$, $V_{cb} = 0.0395 \pm 0.0017$, $\frac{V_{ub}}{V_{cb}} = 0.08 \pm 0.02$, $V_{td}$ lies in the range $0.004 - 0.013$ (PDG). Similarly none of the 32 texture 5 zeros mass matrices considered is able to reproduce LED. In particular, the latest data from LEP regarding $|V_{ub}|/|V_{cb}|(=0.093\pm0.016)$ rules out all of them. In the texture 4 zeros case, we find that there is a unique texture structure for $U$ and $D$ mass matrices which is able to fit the data.Comment: 12 pages, LaTeX,some changes in the references,minor changes in the text,to appear in Phys Rev D(Rapid communications

Seismic Deformation of Dams by Correlative Methods

Analyses are presented of the anticipated earthquake performance of three generally similar earth dams, situated in a seismically active area of northern California. The series of analyses illustrates a cost-effective approach which involved full-scale finite element analyses of one dam, and the use of limited dynamic analysis techniques and correlations to evaluate the other two. The simplified techniques were applied only after testing them against the finite element analyses, information is also presented on how the results of simplified and full-scale dynamic analysis procedures correlate