A Combinatorial Approach to the Variable Selection in Multiple Linear Regression: Analysis of Selwood et al Data set -A Case Study.

A combinatorial protocol (CP) is introduced here to interface it with the multiple linear regression (MLR) for variable selection. The efficiency of CP-MLR is primarily based on the restriction of entry of correlated variables to the model development stage. It has been used for the analysis of Selwood et al data set [16], and the obtained models are compared with those reported from GFA [8] and MUSEUM [9] approaches. For this data set CP-MLR could identify three highly independent models (27, 28 and 31) with Q2 value in the range of 0.632-0.518. Also, these models are divergent and unique. Even though, the present study does not share any models with GFA [8], and MUSEUM [9] results, there are several descriptors common to all these studies, including the present one. Also a simulation is carried out on the same data set to explain the model formation in CP-MLR. The results demonstrate that the proposed method should be able to offer solutions to data sets with 50 to 60 descriptors in reasonable time frame. By carefully selecting the inter-parameter correlation cutoff values in CP-MLR one can identify divergent models and handle data sets larger than the present one without involving excessive computer time.

A Cooperative and Adaptive Variable Neighborhood Search for the Multi Depot Vehicle Routing Problem with Time Windows

In this paper we propose two cooperation schemes to compose new parallel variants of the Variable Neighborhood Search (VNS). On the one hand, a coarse-grained cooperation scheme is introduced which is well suited for being enhanced with a solution warehouse to store and manage the so far best found solutions and a self-adapting mechanism for the most important search parameters. This makes an a priori parameter tuning obsolete. On the other hand, a fine-grained scheme was designed to reproduce the successful properties of the sequential VNS. In combination with the use of parallel exploration threads all of the best solutions and 11 out of 20 new best solutions for the Multi Depot Vehicle Routing Problem with Time Windows were found.

Expression Analysis of the Theileria parva Subtelomere-Encoded Variable Secreted Protein Gene Family

Background The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs) form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm. Methodology/Principal Findings We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals. Conclusions Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic proteins.

Splitting of a prevalent Mycobacterium bovis spoligotype by variable-number tandem-repeat typing reveals high heterogeneity in an evolving clonal group

Mycobacterium bovis populations in countries with persistent bovine tuberculosis usually show a prevalent spoligotype with a wide geographical distribution. This study applied mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing to a random panel of 115 M. bovis isolates that are representative of the most frequent spoligotype in the Iberian Peninsula, SB0121. VNTR typing targeted nine loci: ETR-A (alias VNTR2165), ETR-B (VNTR2461), ETR-D (MIRU4, VNTR580), ETR-E (MIRU31, VNTR3192), MIRU26 (VNTR2996), QUB11a (VNTR2163a), QUB11b (VNTR2163b), QUB26 (VNTR4052), and QUB3232 (VNTR3232). We found a high degree of diversity among the studied isolates (discriminatory index [D] = 0.9856), which were split into 65 different MIRU-VNTR types. An alternative short-format MIRU-VNTR typing targeting only the four loci with the highest variability values was found to offer an equivalent discriminatory index. Minimum spanning trees using the MIRU-VNTR data showed the hypothetical evolution of an apparent clonal group. MIRU-VNTR analysis was also applied to the isolates of 176 animals from 15 farms infected by M. bovis SB0121; in 10 farms, the analysis revealed the coexistence of two to five different MIRU types differing in one to six loci, which highlights the frequency of undetected heterogeneity.

Development of Values after Compulsory School: Work comes first, then family

During school-to-work transition, adolescents develop values and prioritize what is im-portant in their life. Values are concepts or beliefs about desirable states or behaviors that guide the selection or evaluation of behavior and events, and are ordered by their relative importance (Schwartz & Bilsky, 1987). Stressing the important role of values, career re-search has intensively studied the effect of values on educational decisions and early career development (e.g. Eccles, 2005; Hirschi, 2010; Rimann, Udris, & Weiss, 2000). Few re-searchers, however, have investigated so far how values develop in the early career phase and how value trajectories are influenced by individual characteristics. Values can be oriented towards specific life domains, such as work or family. Work values include intrinsic and extrinsic aspects of work (e.g., self-development, cooperation with others, income) (George & Jones, 1997). Family values include the importance of partner-ship, the creation of an own family and having children (Mayer, Kuramschew, & Trommsdroff, 2009). Research indicates that work values change considerably during early career development (Johnson, 2001; Lindsay & Knox, 1984). Individual differences in work values and value trajectories are found e.g., in relation to gender (Duffy & Sedlacek, 2007), parental background (Loughlin & Barling, 2001), personality (Lowry et al., 2012), educa-tion (Battle, 2003), and the anticipated timing of school-to-work transition (Porfeli, 2007). In contrast to work values, research on family value trajectories is rare and knowledge about the development during the school-to-work transition and early career development is lack-ing. This paper aims at filling this research gap. Focusing on family values and intrinsic work values and we expect a) family and work val-ues to change between ages 16 and 25, and b) that initial levels of family and work values as well as value change to be predicted by gender, reading literacy, ambition, and expected du-ration of education. Method. Using data from 2620 young adults (59.5% females), who participated in the Swiss longitudinal study TREE, latent growth modeling was employed to estimate the initial level and growth rate per year for work and family values. Analyses are based on TREE-waves 1 (year 2001, first year after compulsory school) to 8 (year 2010). Variables in the models included family values and intrinsic work values, gender, reading literacy, ambition and ex-pected duration of education. Language region was included as control variable. Results. Family values did not change significantly over the first four years after leaving compulsory school (mean slope = -.03, p =.36). They increased, however, significantly five years after compulsory school (mean slope = .13, p >.001). Intercept (.23, p < .001), first slope (.02, p < .001), and second slope (.01, p < .001) showed significant variance. Initial levels were higher for men and those with higher ambitions. Increases were found to be steeper for males as well as for participants with lower educational duration expectations and reading skills. Intrinsic work values increased over the first four years (mean slope =.03, p <.05) and showed a tendency to decrease in the years five to ten (mean slope = -.01, p < .10). Intercept (.21, p < .001), first slope (.01, p < .001), and second slope (.01, p < .001) showed signifi-cant variance, meaning that there are individual differences in initial levels and growth rates. Initial levels were higher for females, and those with higher ambitions, expecting longer educational pathways, and having lower reading skills. Growth rates were lower for the first phase and steeper for the second phase for males compared to females. Discussion. In general, results showed different patterns of work and family value trajecto-ries, and different individual factors related to initial levels and development after compul-sory school. Developments seem to fit to major life and career roles: in the first years after compulsory school young adults may be engaged to become established in one's job; later on, raising a family becomes more important. That we found significant gender differences in work and family trajectories may reflect attempts to overcome traditional roles, as over-all, women increase in work values and men increase in family values, resulting in an over-all trend to converge.

Crystal chemistry and hydrogen bonding of rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2 with variable OH, Cl, F

Three samples of the skarn mineral rustumite Ca10(Si2O7)2(SiO4)(OH)2Cl2, space group C2/c, a ≈7.6, b ≈ 18.5, c ≈ 15.5 Å, β ≈ 104°, with variable OH, Cl, F content were investigated by electron microprobe, single-crystal X-ray structure refinements, and Raman spectroscopy. “Rust1LCl” is a low chlorine rustumite Ca10(Si2O7)2(SiO4)(OH1.88F0.12)(Cl1.28,OH0.72) from skarns associated with the Rize batholith near Ikizedere, Turkey. “Rust2F” is a F-bearing rustumite Ca10(Si2O7)2(SiO4)(OH1.13F0.87) (Cl1 96OH0.04) from xenoliths in ignimbrites of the Upper Chegem Caldera, Northern Caucasus, Russia. “Rust3LClF” represents a low-Cl, F-bearing rustumite Ca10(Si2O7)2(SiO4)0.87(H4O4)0.13(OH1.01F0.99) (Cl1.00 OH1.00) from altered merwinite skarns of the Birkhin massif, Baikal Lake area, Eastern Siberia, Russia. Rustumite from Birkhin massif is characterized by a significant hydrogarnet-like or fluorine substitution at the apices of the orthosilicate group, leading to specific atomic displacements. The crystal structures including hydrogen positions have been refined from single-crystal X-ray data to R1 = 0.0205 (Rust1_LCl), R1 = 0.0295 (Rust2_F), and R1 = 0.0243 (Rust3_LCl_F), respectively. Depletion in Cl and replacement by OH is associated with smaller unit-cell dimensions. The substitution of OH by F leads to shorter hydrogen bonds O-H⋯F instead of O-H⋯OH. Raman spectra for all samples have been measured and confirm slight strengthening of the hydrogen bonds with uptake of F.This study discusses the complex crystal chemistry of the skarn mineral rustumite and may provide a wider understanding of the chemical reactions related to contact metamorphism of limestones.

Time-variable gravity signal in Greenland revealed by high-low satellite-to-satellite tracking

[1] In the event of a termination of the Gravity Recovery and Climate Experiment (GRACE) mission before the launch of GRACE Follow-On (due for launch in 2017), high-low satellite-to-satellite tracking (hl-SST) will be the only dedicated observing system with global coverage available to measure the time-variable gravity field (TVG) on a monthly or even shorter time scale. Until recently, hl-SST TVG observations were of poor quality and hardly improved the performance of Satellite Laser Ranging observations. To date, they have been of only very limited usefulness to geophysical or environmental investigations. In this paper, we apply a thorough reprocessing strategy and a dedicated Kalman filter to Challenging Minisatellite Payload (CHAMP) data to demonstrate that it is possible to derive the very long-wavelength TVG features down to spatial scales of approximately 2000 km at the annual frequency and for multi-year trends. The results are validated against GRACE data and surface height changes from long-term GPS ground stations in Greenland. We find that the quality of the CHAMP solutions is sufficient to derive long-term trends and annual amplitudes of mass change over Greenland. We conclude that hl-SST is a viable source of information for TVG and can serve to some extent to bridge a possible gap between the end-of-life of GRACE and the availability of GRACE Follow-On.

Identifying Distinct Quitting Trajectories after an Unassisted Smoking Cessation Attempt: An Ecological Momentary Assessment Study

Objectives: This study aimed at identifying distinct quitting trajectories over 29 days after an unassisted smoking ces- sation attempt by ecological momentary assessment (EMA). In order to validate these trajectories we tested if they predict smoking frequency up to six months later. Methods: EMA via mobile phones was used to collect real time data on smoking (yes/no) after an unassisted quit attempt over 29 days. Smoking frequency one, three and six months after the quit attempt was assessed with online questionnaires. Latent class growth modeling was used to analyze the data of 230 self-quitters. Results: Four different quitting trajectories emerged: quitter (43.9%), late quitter (11.3%), returner (17%) and persistent smoker (27.8%). The quitting trajectories predicted smoking frequency one, three and six months after the quit attempt (all p < 0.001). Conclusions: Outcome after a smoking cessation attempt is better described by four distinct trajectories instead of a binary variable for abstinence or relapse. In line with the relapse model by Marlatt and Gordon, late quitter may have learned how to cope with lapses during one month after the quitting attempt. This group would have been allocated to the relapse group in traditional outcome studies.

Transcriptional regulation of the Borrelia burgdorferi antigenically variable VlsE surface protein.

The Lyme disease agent Borrelia burgdorferi can persistently infect humans and other animals despite host active immune responses. This is facilitated, in part, by the vls locus, a complex system consisting of the vlsE expression site and an adjacent set of 11 to 15 silent vls cassettes. Segments of nonexpressed cassettes recombine with the vlsE region during infection of mammalian hosts, resulting in combinatorial antigenic variation of the VlsE outer surface protein. We now demonstrate that synthesis of VlsE is regulated during the natural mammal-tick infectious cycle, being activated in mammals but repressed during tick colonization. Examination of cultured B. burgdorferi cells indicated that the spirochete controls vlsE transcription levels in response to environmental cues. Analysis of PvlsE::gfp fusions in B. burgdorferi indicated that VlsE production is controlled at the level of transcriptional initiation, and regions of 5' DNA involved in the regulation were identified. Electrophoretic mobility shift assays detected qualitative and quantitative changes in patterns of protein-DNA complexes formed between the vlsE promoter and cytoplasmic proteins, suggesting the involvement of DNA-binding proteins in the regulation of vlsE, with at least one protein acting as a transcriptional activator.

Effects of variable Gs expression on $\beta\sb2$-adrenergic receptor stimulated adenylyl cyclase response

An exact knowledge of the kinetic nature of the interaction between the stimulatory G protein (G$\sb{\rm s}$) and the adenylyl cyclase catalytic unit (C) is essential for interpreting the effects of Gs mutations and expression levels on cellular response to a wide variety of hormones, drugs, and neurotransmitters. In particular, insight as to the association of these proteins could lead to progress in tumor biology where single spontaneous mutations in G proteins have been associated with the formation of tumors (118). The question this work attempts to answer is whether the adenylyl cyclase activation by epinephrine stimulated $\beta\sb2$-adrenergic receptors occurs via G$\sb{\rm s}$ proteins by a G$\sb{\rm s}$ to C shuttle or G$\sb{\rm s}$-C precoupled mechanism. The two forms of activation are distinguishable by the effect of G$\sb{\rm s}$ levels on epinephrine stimulated EC50 values for cyclase activation.^ We have made stable transfectants of S49 cyc$\sp-$ cells with the gene for the $\alpha$ protein of G$\sb{\rm s}$ $(\alpha\sb{\rm s})$ which is under the control of the mouse mammary tumor virus LTR promoter (110). Expression of G$\sb{\rm s}\alpha$ was then controlled by incubation of the cells for various times with 5 $\mu$M dexamethasone. Expression of G$\sb{\rm s}\alpha$ led to the appearance of GTP shifts in the competitive binding of epinephrine with $\sp{125}$ICYP to the $\beta$-adrenergic receptors and to agonist dependent adenylyl cyclase activity. High expression of G$\sb{\rm s}\alpha$ resulted in lower EC50's for the adenylyl cyclase activity in response to epinephrine than did low expression. By kinetic modelling, this result is consistent with the existence of a shuttle mechanism for adenylyl cyclase activation by hormones.^ One item of concern that remains to be addressed is the extent to which activation of adenylyl cyclase occurs by a "pure" shuttle mechanism. Kinetic and biochemical experiments by other investigators have revealed that adenylyl cyclase activation, by hormones, may occur via a Gs-C precoupled mechanism (80, 94, 97). Activation of adenylyl cyclase, therefore, probably does not occur by either a pure "'Shuttle" or "Gs-C Precoupled" mechanism, but rather by a "Hybrid" mechanism. The extent to which either the shuttle or precoupled mechanism contributes to hormone stimulated adenylyl cyclase activity is the subject of on-going research. ^