Asteroid Lightcurve Inversion

The application of convex profile inversion (CPI) to the interpretation of asteroid lightcurves is discussed. This technique investigates the problem of extracting information about an asteroid's shape from its lightcurve. Whenever four ideal conditions are met, P is an estimator for the asteroids mean cross section C, a convex set defined as the average of all cross sections C(Z) cut by planes a distance z above the asteroids equatorial plane. C is therefore a 2-D average of the asteroids 3-D shape. The method is tested by inverting lightcurves generated analytically for geometrically scattered ellipsoids (GSE's) with semiaxes a or = B or = C. Using a defined 'distance measure' to quantify the difference between any two profiles, the deviation of P from C for GSE's as a function of lightcurve noise level, rotation phase sampling interval delta theta, and departure from ideal conditions is calibrated. The distance between P and a circle provides a gauge of the asteroid's nonsphericity and incorporates all the information contained in the lightcurve

Fkh1 and Fkh2 bind multiple chromosomal elements in the S. cerevisiae genome with distinct specificities and cell cycle dynamics

Forkhead box (FOX) transcription factors regulate a wide variety of cellular functions in higher eukaryotes, including cell cycle control and developmental regulation. In Saccharomyces cerevisiae, Forkhead proteins Fkh1 and Fkh2 perform analogous functions, regulating genes involved in cell cycle control, while also regulating mating-type silencing and switching involved in gamete development. Recently, we revealed a novel role for Fkh1 and Fkh2 in the regulation of replication origin initiation timing, which, like donor preference in mating-type switching, appears to involve long-range chromosomal interactions, suggesting roles for Fkh1 and Fkh2 in chromatin architecture and organization. To elucidate how Fkh1 and Fkh2 regulate their target DNA elements and potentially regulate the spatial organization of the genome, we undertook a genome-wide analysis of Fkh1 and Fkh2 chromatin binding by ChIP-chip using tiling DNA microarrays. Our results confirm and extend previous findings showing that Fkh1 and Fkh2 control the expression of cell cycle-regulated genes. In addition, the data reveal hundreds of novel loci that bind Fkh1 only and exhibit a distinct chromatin structure from loci that bind both Fkh1 and Fkh2. The findings also show that Fkh1 plays the predominant role in the regulation of a subset of replication origins that initiate replication early, and that Fkh1/2 binding to these loci is cell cycle-regulated. Finally, we demonstrate that Fkh1 and Fkh2 bind proximally to a variety of genetic elements, including centromeres and Pol III-transcribed snoRNAs and tRNAs, greatly expanding their potential repertoire of functional targets, consistent with their recently suggested role in mediating the spatial organization of the genome

Sexual behavior research on a Cohort of gay men, 1984–1990: Can we predict how men will respond to interventions?

In 1984, over 1000 gay and bisexual men volunteered to participate in both the Chicago Multicenter AIDS Cohort Study (MACS) and a companion psychosocial study, the Coping and Change Study (CCS). Participants in the semiannual Chicago MACS/CCS evaluations comprise the largest cohort of high-risk men under continuous medical, behavioral, and psychosocial observation. Chicago MACS/CCS researchers prospectively chart the sexual behavior change patterns of the cohort and relate those behavioral changes to psychosocial correlates and actual HIV infection risk. This report summarizes the behavioral natural history of the Chicago MACS/CCS cohort from 1984 to 1990, focusing on receptive anal sex practices and use patterns for alcohol and the most frequently used recreational drugs. As these are prospective observational and not controlled intervention studies, psychosocial correlates of sexual behavior change by members of the cohort are suggestive of factors influencing behavior change rather than indicative of causal relationships. However, the voluntary availability to participants in the Chicago MACS/CCS of HIV-1 antibody test results beginning in late 1985 provided the opportunity to examine whether demographic, psychosocial, or behavioral factors were indicators of sexual behavior change following disclosure and counseling about HIV-1 serostatus. Recommendations for promotion and maintenance of safer sexual behavior for the long run, and limitations in the generalizability of these findings to the much more diverse populations of men who have sex with other men conclude this article.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44099/1/10508_2005_Article_BF01541496.pd

The growth and strategic functioning of One Health networks: a systematic analysis.

BACKGROUND: The recent increase in attention to linkages between human health, animal health, and the state of the environment has resulted in the rapid growth of networks that facilitate collaboration between these sectors. This study ascertained whether duplication of efforts is occurring across networks, which stakeholders are being engaged, and how frequently monitoring and evaluation of investments is being reported. METHODS: This study is a systematic analysis of One Health networks (OHNs) in Africa, Asia, and Europe. We defined an OHN as an engagement between two or more discrete organisations with at least two of the following sectors represented: animal health, human health, and the environment or ecosystem. Between June 5 and Sept 29, 2017, we systematically searched for OHNs in PubMed, Google, Google Scholar, and relevant conference websites. No language restrictions were applied, but we were only able to translate from English and French. Data about OHNs, including their year of initiation, sectors of engagement, regions of operation, activities conducted, and stakeholders involved, were extracted with a standardised template and analysed descriptively. FINDINGS: After screening 2430 search results, we identified and analysed 100 unique OHNs, of which 86 were formed after 2005. 32 OHNs covered only human and animal health, without engaging with the role of the environment on health. 78 OHNs involved academic bodies and 78 involved government bodies, with for-profit organisations involved in only 23 and community groups involved in only ten. There were few collaborations exclusively between networks in the developing world (four OHNs) and only 15 OHNs reported monitoring and evaluation information. The majority of OHNs worked on supporting communication, collaboration, information sharing, and capacity building. INTERPRETATION: Amid concerns about there being insufficient strategic direction and coordination in the growth of OHNs, our study provides empirical evidence about limitations in stakeholder representation, apparently absent or ambiguous monitoring and evaluation structures, and potential areas of duplication. The collective strategic functioning of OHNs might be improved by more transparent reporting of goals and outcomes of OHN activities, as well as more collaborations led by networks within the developing world and increased attention to environmental health. FUNDING: None

Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by Bilirubin at the Blood-CSF and Blood-Brain Barriers in the Gunn Rat

Accumulation of unconjugated bilirubin (UCB) in the brain causes bilirubin encephalopathy. Pgp (ABCb1) and Mrp1 (ABCc1), highly expressed in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj) Gunn rats compared to heterozygous, not jaundiced (Jj) littermates at different developmental stages (2, 9, 17 and 60 days after birth). BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16–27% of adult values), despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17–P60, respectively); Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60–70% of the adult values) in both jj and Jj at P2, but was markedly (50%) down-regulated in jj pups starting at P9, particularly in the 4th ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity

Computational chemical analysis of unconjugated bilirubin anions and insights into pKa values clarification

The pKa, the negative logarithm of the acid dissociation equilibrium constant, of the carboxylic acid groups of unconjugated bilirubin in water is a discussed issue because there are quite different experimental values reported. Using quantum mechanical calculations we have studied the conformational behavior of unconjugated bilirubin species (in gas phase and in solution modeled implicitly and explicitly) to provide evidence that may clarify pKa values because of its pathophysiological relevance. Our results show that rotation of carboxylate group, which is not restricted, settles it in a suitable place to establish stronger interactions that stabilizes the monoanion and the dianion to be properly solvated, demonstrating that the rationalization used to justify the high pKa values of unconjugated bilirubin is inappropriate. Furthermore, low unconjugated bilirubin (UCB) pKa values were estimated from a linear regression analysis.Fil: Vega Hissi, Esteban Gabriel. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Estrada, Mario Rinaldo. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica; ArgentinaFil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Química Inorgánica; ArgentinaFil: Pis Diez, Reinaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Química Inorgánica; Argentin

Long-Term Effectiveness and Safety of Childhood Growth Hormone Treatment in Noonan Syndrome

Introduction: Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS). Objective: To evaluate the effectiveness and safety of GH treatment in NS in clinical practice. Methods: Height gain, near-adult height (NAH), and safety were assessed in 2 complementary non-interventional studies: NordiNet® IOS and ANSWER. The safety analysis included 412 patients, and the effectiveness analysis included 84 GH-treated patients (male, n = 67) with ≥4 years’ height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data. Results: The mean (SD) baseline age was 8.38 (3.57) years; HSDS, −2.76 (1.03); GH dose, 41.6 (11.1) µg/kg/day. The mean (SD) HSDS increase from baseline (ΔHSDS) was 0.49 (0.37) (first year), 0.79 (0.58) (second year), and 1.01 (0.60) (third year) (NR). The mean (SD) HSDS at year 3 was −1.66 (1.00) (NR; 1.06 [1.12] [NSS]). Twenty-four patients achieved NAH. The mean (SD) NAH SDS (NR) was −1.51 (0.60) (154.90 [3.21] cm) in females and −1.79 (1.09) (165.61 [7.19] cm) in males; 70.8% (17/24) had NAH SDS ≥ −2. Adverse drug reactions and GH-unrelated serious adverse events (n = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred. Conclusions: GH-treated children with NS achieved substantial height gain during the first 3 years of follow-up. Overall, 24 patients achieved NAH, with 70.8% having NAH SDS ≥ –2. There was no evidence to support a higher prevalence of neoplasm, or cardiac or other comorbidities.publishedVersio

Recreational drugs and sexual behavior in the Chicago MACS/CCS cohort of homosexually active men

Since initial reports emerged of an association between recreational drug use and high-risk sexual behaviors in gay men, there has been interest in studying this relationship for its relevance to behavioral interventions. Reported here are the longitudinal patterns of alcohol and recreational drug use in the Chicago Multicenter AIDS Cohort Study (MACS)/Coping and Change Study (CCS) of gay men. A pattern of decreasing drug use over 6 years was observed that paralleled a decline in high-risk sexual behavior (i.e., unprotected anal intercourse). In contrast, alcohol consumption tended to be more stable over time, and to show no relationship to sexual behavior change. Men who combined volatile nitrite (popper) use with other recreational drugs were at highest risk both behaviorally and in terms of human immunodeficiency virus-1 (HIV) seroconversion throughout the study. Popper use also was associated independently with lapse from safer sexual behaviors (failure to use a condom during receptive anal sex). Use of other recreational substances showed no relationship to sexual behavior change patterns, and stopping popper use was unrelated to improvement in safer sexual behavior. When popper use and lapse from safer sex were reanalyzed, controlling for primary relationship status, popper use was associated with failure to use condoms during receptive anal sex among nonmonogamous men only. These findings suggest an association between popper use and high-risk sexual behavior among members of the Chicago MACS/CCS cohort that has relevance to HIV prevention intervention efforts.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31072/1/0000749.pd