Solution-Phase Combinatorial Chemistry in Lead Discovery

Solution-phase approaches in combinatorial chemistry complement solid-phase approaches and each can be used to advantage in particular circumstances. Solution-phase synthesis of pools of compounds, whilst allowing successful identification of a selection of good lead structures for medicinal chemistry programmes, also reinforced a number of the disadvantages of such an approach. Solution-phase parallel synthesis of discrete compounds has, however, proved to be a very useful and popular approach both for lead generation and in lead optimisation work. The range of chemistry suitable for use in such approaches is expanding rapidly and some of these chemistries are discussed. The current focus is on enhancing the quality of compounds prepared in array formats, and we describe a number of useful approaches which are being developed to that end

Prevalence and risk factors of major depressive disorder in HIV/AIDS as seen in semi-urban Entebbe district, Uganda

BACKGROUND: Not much is known about the risk factors of major depressive disorder (MDD) in HIV/AIDS in the African socio-cultural context. Therefore a study was undertaken to examine the prevalence and risk factors of MDD in HIV/AIDS in semi-urban Uganda. METHODS: A cross-sectional study was undertaken among 618 respondents attending two HIV clinics in Uganda. RESULTS: Prevalence of MDD was 8.1%. Factors associated with MDD at univariate analysis only were female gender, family history of mental illness, negative coping style, alcohol dependency disorder, food insecurity and stress; not associated with MDD were social support, neurocognitive impairment, CD4 counts and BMI. Factors independently associated with MDD were psychosocial impairment, adverse life events, post traumatic stress disorder, generalised anxiety disorder and life-time attempted suicide. CONCLUSION: Psychological and social factors were the main risk factors of MDD among ambulatory HIV positive persons with no evidence for the role of the neurotoxic effects of HIV. Treatment approaches for MDD in this patient group should be modeled on those used among non-HIV groups

Applying a gender lens to understand pathways through care for acutely ill young children in Kenyan urban informal settlements

Background: In many African settings, gender strongly influences household treatment-seeking and decision-making for childhood illnesses. While mothers are often the primary engagers with health facilities, their independence in illness-related decisions is shaped by various factors. Drawing on a gender lens, we explored treatment-seeking pathways pre- and post-hospital admission for acutely ill young children living in low income settlements in Nairobi, Kenya; and the gendered impact of child illness both at the household and health system level. Methods: Household members of 22 children admitted to a public hospital were interviewed in their homes several times post hospital discharge. In-depth interviews covered the child's household situation, health and illness; and the family's treatment-seeking choices and experiences. Children were selected from an observational cohort established by the Childhood Acute Illness and Nutrition (CHAIN) Network. Results: Treatment-seeking pathways were often long and complex, with mothers playing the key role in caring for their children and in treatment decision-making. Facing many anxieties and dilemmas, mothers often consulted with significant influencers - primarily women - particularly where illnesses were prolonged or complex. In contrast to observations in rural African contexts, fathers were less prominent as influencers than (often female) neighbours, grandparents and other relatives. Mothers were sometimes blamed for their child's condition at home and at health facilities. Children's illness episode and associated treatment-seeking had significant gendered socio-economic consequences for households, including through mothers having to take substantial time off work, reduce their working hours and income, or even losing their jobs. Conclusion: Women in urban low-income settings are disproportionately impacted by acute child illness and the related treatment-seeking and recovery process. The range of interventions needed to support mothers as they navigate their way through children's illnesses and recovery include: deliberate engagement of men in child health to counteract the dominant perception of child health and care as a 'female-domain'; targeted economic strategies such as cash transfers to safeguard the most vulnerable women and households, combined with more robust labour policies to protect affected women; as well as implementing strategies at the health system level to improve interactions between health workers and community members.The primary author (KM) was funded through the DELTAS Africa Initiative [DEL-15-003]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. This work was supported by the Bill and Melinda Gates Foundation awarded to the CHAIN Network (grant: OPP1131320)

Azimuthal anisotropy and correlations in the hard scattering regime at RHIC

Azimuthal anisotropy ($v_2$) and two-particle angular correlations of high $p_T$ charged hadrons have been measured in Au+Au collisions at $\sqrt{s_{NN}}$=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high $p_T$ partons. The monotonic rise of $v_2(p_T)$ for $p_T<2$ GeV/c is consistent with collective hydrodynamical flow calculations. At \pT>3 GeV/c a saturation of $v_2$ is observed which persists up to $p_T=6$ GeV/c.Comment: As publishe

Azimuthal anisotropy of K0S and Lambda + Lambda -bar production at midrapidity from Au+Au collisions at sqrt[sNN]=130 GeV

We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, Lambda , and Lambda -bar at midrapidity in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider. The value of v2 as a function of transverse momentum, pt, of the produced particle and collision centrality is presented for both particles up to pt~3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.Alle Autoren: C. Adler, Z. Ahammed, C. Allgower, J. Amonett, B. D. Anderson, M. Anderson, G. S. Averichev, J. Balewski, O. Barannikova, L. S. Barnby, J. Baudot, S. Bekele, V. V. Belaga, R. Bellwied, J. Berger, H. Bichsel, A. Billmeier, L. C. Bland, C. O. Blyth, B. E. Bonner, A. Boucham, A. Brandin, A. Bravar, R. V. Cadman, H. Caines, M. Calderón de la Barca Sánchez, A. Cardenas, J. Carroll, J. Castillo, M. Castro, D. Cebra, P. Chaloupka, S. Chattopadhyay, Y. Chen, S. P. Chernenko, M. Cherney, A. Chikanian, B. Choi, W. Christie, J. P. Coffin, T. M. Cormier, J. G. Cramer, H. J. Crawford, W. S. Deng, A. A. Derevschikov, L. Didenko, T. Dietel, J. E. Draper, V. B. Dunin, J. C. Dunlop, V. Eckardt, L. G. Efimov, V. Emelianov, J. Engelage, G. Eppley, B. Erazmus, P. Fachini, V. Faine, K. Filimonov, E. Finch, Y. Fisyak, D. Flierl, K. J. Foley, J. Fu, C. A. Gagliardi, N. Gagunashvili, J. Gans, L. Gaudichet, M. Germain, F. Geurts, V. Ghazikhanian, O. Grachov, V. Grigoriev, M. Guedon, E. Gushin, T. J. Hallman, D. Hardtke, J. W. Harris, T. W. Henry, S. Heppelmann, T. Herston, B. Hippolyte, A. Hirsch, E. Hjort, G. W. Hoffmann, M. Horsley, H. Z. Huang, T. J. Humanic, G. Igo, A. Ishihara, Yu. I. Ivanshin, P. Jacobs, W. W. Jacobs, M. Janik, I. Johnson, P. G. Jones, E. G. Judd, M. Kaneta, M. Kaplan, D. Keane, J. Kiryluk, A. Kisiel, J. Klay, S. R. Klein, A. Klyachko, A. S. Konstantinov, M. Kopytine, L. Kotchenda, A. D. Kovalenko, M. Kramer, P. Kravtsov, K. Krueger, C. Kuhn, A. I. Kulikov, G. J. Kunde, C. L. Kunz, R. Kh. Kutuev, A. A. Kuznetsov, L. Lakehal-Ayat, M. A. C. Lamont, J. M. Landgraf, S. Lange, C. P. Lansdell, B. Lasiuk, F. Laue, A. Lebedev, R. Lednický, V. M. Leontiev, M. J. LeVine, Q. Li, S. J. Lindenbaum, M. A. Lisa, F. Liu, L. Liu, Z. Liu, Q. J. Liu, T. Ljubicic, W. J. Llope, G. LoCurto, H. Long, R. S. Longacre, M. Lopez-Noriega, W. A. Love, T. Ludlam, D. Lynn, J. Ma, R. Majka, S. Margetis, C. Markert, L. Martin, J. Marx, H. S. Matis, Yu. A. Matulenko, T. S. McShane, F. Meissner, Yu. Melnick, A. Meschanin, M. Messer, M. L. Miller, Z. Milosevich, N. G. Minaev, J. Mitchell, V. A. Moiseenko, C. F. Moore, V. Morozov, M. M. de Moura, M. G. Munhoz, J. M. Nelson, P. Nevski, V. A. Nikitin, L. V. Nogach, B. Norman, S. B. Nurushev, G. Odyniec, A. Ogawa, V. Okorokov, M. Oldenburg, D. Olson, G. Paic, S. U. Pandey, Y. Panebratsev, S. Y. Panitkin, A. I. Pavlinov, T. Pawlak, V. Perevoztchikov, W. Peryt, V. A Petrov, M. Planinic, J. Pluta, N. Porile, J. Porter, A. M. Poskanzer, E. Potrebenikova, D. Prindle, C. Pruneau, J. Putschke, G. Rai, G. Rakness, O. Ravel, R. L. Ray, S. V. Razin, D. Reichhold, J. G. Reid, F. Retiere, A. Ridiger, H. G. Ritter, J. B. Roberts, O. V. Rogachevski, J. L. Romero, A. Rose, C. Roy, V. Rykov, I. Sakrejda, S. Salur, J. Sandweiss, A. C. Saulys, I. Savin, J. Schambach, R. P. Scharenberg, N. Schmitz, L. S. Schroeder, A. Schüttauf, K. Schweda, J. Seger, D. Seliverstov, P. Seyboth, E. Shahaliev, K. E. Shestermanov, S. S. Shimanskii, V. S. Shvetcov, G. Skoro, N. Smirnov, R. Snellings, P. Sorensen, J. Sowinski, H. M. Spinka, B. Srivastava, E. J. Stephenson, R. Stock, A. Stolpovsky, M. Strikhanov, B. Stringfellow, C. Struck, A. A. P. Suaide, E. Sugarbaker, C. Suire, M. Šumbera, B. Surrow, T. J. M. Symons, A. Szanto de Toledo, P. Szarwas, A. Tai, J. Takahashi, A. H. Tang, J. H. Thomas, M. Thompson, V. Tikhomirov, M. Tokarev, M. B. Tonjes, T. A. Trainor, S. Trentalange, R. E. Tribble, V. Trofimov, O. Tsai, T. Ullrich, D. G. Underwood, G. Van Buren, A. M. VanderMolen, I. M. Vasilevski, A. N. Vasiliev, S. E. Vigdor, S. A. Voloshin, F. Wang, H. Ward, J. W. Watson, R. Wells, G. D. Westfall, C. Whitten, Jr., H. Wieman, R. Willson, S. W. Wissink, R. Witt, J. Wood, N. Xu, Z. Xu, A. E. Yakutin, E. Yamamoto, J. Yang, P. Yepes, V. I. Yurevich, Y. V. Zanevski, I. Zborovský, H. Zhang, W. M. Zhang, R. Zoulkarneev, and A. N. Zubarev (STAR Collaboration

Disappearance of back-to-back high pTp_T hadron correlations in central Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

Azimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudo-rapidity range and full azimuth in Au+Au and p+p collisions at $\sqrt{s_{NN}}$ = 200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes already observed in elementary collisions. A strong back-to-back correlation exists for p+p and peripheral Au + Au. In contrast, the back-to-back correlations are reduced considerably in the most central Au+Au collisions, indicating substantial interaction as the hard-scattered partons or their fragmentation products traverse the medium.Comment: submitted to Phys. Rev. Let

Identified baryon and meson distributions at large transverse momenta from Au+Au collisions at sNN=200\sqrt{s_{_{NN}}} = 200 GeV

Transverse momentum spectra of $\pi^{\pm}$, $p$ and $\bar{p}$ up to 12 GeV/c at mid-rapidity in centrality selected Au+Au collisions at $\sqrt{s_{_{NN}}} = 200$ GeV are presented. In central Au+Au collisions, both $\pi^{\pm}$ and $p(\bar{p})$ show significant suppression with respect to binary scaling at $p_T >$ 4 GeV/c. Protons and anti-protons are less suppressed than $\pi^{\pm}$, in the range 1.5 $< p_{T} <$6 GeV/c. The $\pi^-/\pi^+$ and $\bar{p}/p$ ratios show at most a weak $p_T$ dependence and no significant centrality dependence. The $p/\pi$ ratios in central Au+Au collisions approach the values in p+p and d+Au collisions at $p_T >$ 5 GeV/c. The results at high $p_T$ indicate that the partonic sources of $\pi^{\pm}$, $p$ and $\bar{p}$ have similar energy loss when traversing the nuclear medium.Comment: 6 pages, 4 figure

Transverse-momentum dependent modification of dynamic texture in central Au+Au collisions at sqrt(S_NN)=200 GeV

Correlations in the hadron distributions produced in relativistic Au+Au collisions are studied in the discrete wavelet expansion method. The analysis is performed in the space of pseudorapidity (|eta| < 1) and azimuth (full 2 pi) in bins of transverse momentum (p_t) from 0.14 < p_t < 2.1 GeV/c. In peripheral Au+Au collisions a correlation structure ascribed to mini-jet fragmentation is observed. It evolves with collision centrality and p_t in a way not seen before which suggests strong dissipation of minijet fragmentation in the longitudinally-expanding medium.Comment: 6 pages, 3 figure, accepted as Phys.Rev.C Rapid Communication. This version fixes journal style issue

Production of e+e−e^+e^- Pairs Accompanied by Nuclear Dissociation in Ultra-Peripheral Heavy Ion Collision

We present the first data on $e^+e^-$ pair production accompanied by nuclear breakup in ultra-peripheral gold-gold collisions at a center of mass energy of 200 GeV per nucleon pair. The nuclear breakup requirement selects events at small impact parameters, where higher-order corrections to the pair production cross section should be enhanced. We compare the pair kinematic distributions with two calculations: one based on the equivalent photon approximation, and the other using lowest-order quantum electrodynamics (QED); the latter includes the photon virtuality. The cross section, pair mass, rapidity and angular distributions are in good agreement with both calculations. The pair transverse momentum, $p_T$, spectrum agrees with the QED calculation, but not with the equivalent photon approach. We set limits on higher-order contributions to the cross section. The $e^+$ and $e^-$ $p_T$ spectra are similar, with no evidence for interference effects due to higher-order diagrams.Comment: 6 pages with 3 figures Slightly modified version that will appear in Phys. Rev.

Rapidity and centrality dependence of proton and antiproton production from 197Au + 197Au collisions at √SNN = 130 GeV

We report on the rapidity and centrality dependence of proton and antiproton transverse mass distributions from 197Au + 197Au collisions at sqrt[sNN ]=130 GeV as measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). Our results are from the rapidity and transverse momentum range of |y| <0.5 and 0.35< pt <1.00 GeV/c . For both protons and antiprotons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y| <0.5 . Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton (antiproton) yields and transverse mass distributions the possibility of prehadronic collective expansion may have to be taken into account