Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.

Chromosome segregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the metaphase-to-anaphase transition. Separase is inhibited prior to metaphase by the tightly bound securin protein, which contains a pseudosubstrate motif that blocks the separase active site. To investigate separase substrate specificity and regulation, here we develop a system for producing recombinant, securin-free human separase. Using this enzyme, we identify an LPE motif on the Scc1 substrate that is distinct from the cleavage site and is required for rapid and specific substrate cleavage. Securin also contains a conserved LPE motif, and we provide evidence that this sequence blocks separase engagement of the Scc1 LPE motif. Our results suggest that rapid cohesin cleavage by separase requires a substrate docking interaction outside the active site. This interaction is blocked by securin, providing a second mechanism by which securin inhibits cohesin cleavage

Use of neuroimaging to inform optimal neurocognitive criteria for detecting HIV-associated brain abnormalities

OBJECTIVE: Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV. METHOD: Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria. RESULTS: When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure. CONCLUSIONS: The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction

The neural correlates of ideation in product design engineering practitioners

In product design engineering (PDE), ideation involves the generation of technical behaviours and physical structures to address specific functional requirements. This differs from generic creative ideation tasks, which emphasise functional and technical considerations less. To advance knowledge about the neural basis of PDE ideation, we present the first fMRI study on professional product design engineers practising in industry. We aimed to explore brain activation during ideation, and compare activation in open-ended and constrained tasks. Imagery manipulation tasks were contrasted with ideation tasks in a sample of 29 PDE professionals. The key findings were: (1) PDE ideation is associated with greater activity in left cingulate gyrus; (2) there were no significant differences between open-ended and constrained tasks; and (3) a preliminary association with activity in the right superior temporal gyrus was also observed. The results are consistent with existing fMRI work on generic creative ideation, suggesting that PDE ideation may share a number of similarities at the neural level. Future work includes: functional connectivity analysis of open-ended and constrained ideation to further investigate potential differences; investigating the effects of aspects of design expertise/training on processing; and the use of novelty measures directly linked to the designer’s internal processing in fMRI analysis

Further properties on the core partial order and other matrix partial orders

This paper carries further the study of core partial order initiated by Baksalary and Trenkler [Core inverse of matrices, Linear Multilinear Algebra. 2010;58:681-697]. We have extensively studied the core partial order, and some new characterizations are obtained in this paper. In addition, simple expressions for the already known characterizations of the minus, the star (and one-sided star), the sharp (and one-sided sharp) and the diamond partial orders are also obtained by using a Hartwig-Spindelbck decomposition.This author was partially supported by Ministry of Education of Spain [grant number DGI MTM2010-18228] and by Universidad Nacional de La Pampa, Argentina, Facultad de Ingenieria [grant number Resol. No 049/11].Malik, SB.; Rueda, LC.; Thome, N. (2014). Further properties on the core partial order and other matrix partial orders. Linear and Multilinear Algebra. 62(12):1629-1648. https://doi.org/10.1080/03081087.2013.839676S162916486212Mitra, S. K., & Bhimasankaram, P. (2010). MATRIX PARTIAL ORDERS, SHORTED OPERATORS AND APPLICATIONS. SERIES IN ALGEBRA. doi:10.1142/9789812838452Baksalary, J. K., & Hauke, J. (1990). A further algebraic version of Cochran’s theorem and matrix partial orderings. Linear Algebra and its Applications, 127, 157-169. doi:10.1016/0024-3795(90)90341-9Baksalary, O. M., & Trenkler, G. (2010). Core inverse of matrices. Linear and Multilinear Algebra, 58(6), 681-697. doi:10.1080/03081080902778222Baksalary, J. K., Baksalary, O. M., & Liu, X. (2003). Further properties of the star, left-star, right-star, and minus partial orderings. Linear Algebra and its Applications, 375, 83-94. doi:10.1016/s0024-3795(03)00609-8Groβ, J., Hauke, J., & Markiewicz, A. (1999). Partial orderings, preorderings, and the polar decomposition of matrices. Linear Algebra and its Applications, 289(1-3), 161-168. doi:10.1016/s0024-3795(98)10108-8Mosić, D., & Djordjević, D. S. (2012). Reverse order law for the group inverse in rings. Applied Mathematics and Computation, 219(5), 2526-2534. doi:10.1016/j.amc.2012.08.088Patrício, P., & Costa, A. (2009). On the Drazin index of regular elements. Open Mathematics, 7(2). doi:10.2478/s11533-009-0015-6Rakić, D. S., & Djordjević, D. S. (2012). Space pre-order and minus partial order for operators on Banach spaces. Aequationes mathematicae, 85(3), 429-448. doi:10.1007/s00010-012-0133-2Tošić, M., & Cvetković-Ilić, D. S. (2012). Invertibility of a linear combination of two matrices and partial orderings. Applied Mathematics and Computation, 218(9), 4651-4657. doi:10.1016/j.amc.2011.10.052Hartwig, R. E., & Spindelböck, K. (1983). Matrices for whichA∗andA†commute. Linear and Multilinear Algebra, 14(3), 241-256. doi:10.1080/03081088308817561Baksalary, O. M., Styan, G. P. H., & Trenkler, G. (2009). On a matrix decomposition of Hartwig and Spindelböck. Linear Algebra and its Applications, 430(10), 2798-2812. doi:10.1016/j.laa.2009.01.015Mielniczuk, J. (2011). Note on the core matrix partial ordering. Discussiones Mathematicae Probability and Statistics, 31(1-2), 71. doi:10.7151/dmps.1134Meyer, C. (2000). Matrix Analysis and Applied Linear Algebra. doi:10.1137/1.978089871951

Application of an Equilibrium Vaporization Model to the Ablation of Chondritic and Achondritic Meteoroids

We modeled equilibrium vaporization of chondritic and achondritic materials using the MAGMA code. We calculated both instantaneous and integrated element abundances of Na, Mg, Ca, Al, Fe, Si, Ti, and K in chondritic and achondritic meteors. Our results are qualitatively consistent with observations of meteor spectra.Comment: 8 pages, 4 figures; in press, Earth, Moon, and Planets, Meteoroids 2004 conference proceeding

Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in U.S. Army Soldiers

Crossâ sectional associations between attention deficit hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) have been observed, but longitudinal studies assessing this association are lacking. This prospective study evaluated the association between predeployment ADHD and postdeployment PTSD among U.S. Army soldiers. Soldiers who deployed to Afghanistan were surveyed before deployment (T0) and approximately 1 month (T1), 3 months (T2), and 9 months (T3) after their return. Logistic regression was performed to estimate the association between predeployment ADHD and postdeployment (T2 or T3) PTSD among 4,612 soldiers with data at all waves and no record of stimulant medication treatment during the study. To evaluate specificity of the ADHDâ PTSD association, we examined associations among predeployment ADHD, postdeployment major depressive episode (MDE), generalized anxiety disorder (GAD), and suicidal ideation. Weighted prevalence of ADHD predeployment was 6.1% (SE = 0.4%). Adjusting for other risk factors, predeployment ADHD was associated with risk of postdeployment PTSD, adjusted odds ratio (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001, including incidence among soldiers with no predeployment history of PTSD, AOR = 2.50, 95% CI [1.69, 3.69], p < .001. ADHD was associated with postdeployment MDE, AOR = 2.80, 95% CI [2.01, 3.91], p < .001, and GAD, AOR = 3.04, 95% CI [2.10, 4.42], p < .001, but not suicidal ideation. Recognition of associations between predeployment ADHD and postdeployment PTSD, MDE, and GAD may inform targeted prevention efforts. Future research should examine whether treatment of ADHD is protective against PTSD and related disorders in traumaâ exposed individuals.ResumenSpanish Abstracts by Asociación Chilena de Estrés Traumático (ACET)El trastorno de déficit atencional con hiperactividad y el riesgo del trastorno de estrés postraumático y trastornos relacionados: Una evaluación longitudinal prospectiva en soldados del ejército estadounidenseTDAH Y RIESGO DE TEPT EN SOLDADOS DEL EJà RCITO DE EE.UU.Se han observado asociaciones transversales entre el trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno por estrés postraumático (TEPT), pero faltan estudios longitudinales que evalúen esta asociación. Este estudio prospectivo evaluó la asociación entre el TDAH previo al despliegue y el TEPT posterior al despliegue entre los soldados del Ejército de Estados Unidos. Los soldados desplegados en Afganistán fueron encuestados antes del despliegue (T0) y aproximadamente 1 mes (T1), 3 meses (T2), y 9 meses (T3) después de su regreso del despliegue. Se realizó una regresión logística para estimar la asociación entre el TDAH previo al despliegue y el TEPT posterior al despliegue (T2 o T3) en 4.612 soldados con datos en todas las etapas y sin registro de tratamiento con medicamentos estimulantes durante el estudio. Para evaluar la especificidad de la asociación TDAHâ TEPT, examinamos las asociaciones entre el TDAH previo al despliegue, el episodio depresivo mayor posterior al despliegue (EDM), el trastorno de ansiedad generalizada (TAG), y la ideación suicida. La prevalencia ponderada del TDAH previo al despliegue fue de 6.1% (SE = 0.4%). Al controlar los otros factores de riesgo, el TDAH previo al despliegue se asoció con el riesgo de TEPT posterior al despliegue, odds ratio ajustado (AOR en su sigla en inglés) = 2.13, IC del 95% [1.51, 3.00], p <.001, incluida la incidencia entre soldados sin historial previo al despliegue de TEPT, AOR = 2.50, IC del 95% [1.69, 3.69], p <.001. El TDAH se asoció con el EDM posterior al despliegue, AOR = 2.80, IC del 95% [2.01, 3.91], p <.001, y TAG, AOR = 3.04, IC del 95% [2.10, 4.42], p <.001, pero no con ideación suicida. El reconocimiento de las asociaciones entre el TDAH previo al despliegue y el TEPT, el EDM, y el TAG posterior al despliegue puede informar los esfuerzos de prevención específicos. Las investigaciones futuras deberían examinar si el tratamiento del TDAH protege contra el TEPT y los trastornos relacionados en personas expuestas a trauma.æ ½è±¡Traditional and Simplified Chinese Abstracts by the Asian Society for Traumatic Stress Studies (AsianSTSS)ç°¡é« å ç¹ é« ä¸­æ æ ®è¦ ç ±äº æ´²å µå ·å¿ ç ç  ç©¶å­¸æ 翻譯Attention Deficit Hyperactivity Disorder and Risk of Posttraumatic Stress and Related Disorders: A Prospective Longitudinal Evaluation in US Army SoldiersTraditional Chineseæ¨ é¡ : å° æ³¨å ä¸ è¶³æ é åº¦æ´»èº ç è æ £å µå ·å¾ å£ å ç å ç ¸é ç ¾ç ç é¢¨é ª:å° ç¾ å è» äººé ²è¡ ç å ç »ç¸±è²«ç  ç©¶æ ®è¦ : é å¾ ä¸ ç ´æ ç  ç©¶æª¢è¦ å° æ³¨å ä¸ è¶³æ é åº¦æ´»èº ç (ADHD)è å µå ·å¾ å£ å ç (PTSD)ä¹ é ç æ©«æ ·æ §é é £, å ¯æ ¯, æ å ä» æ¬ ç¼ºæª¢è¦ å ©è é é £ç ç¸±è²«ç  ç©¶ã æ ¬å ç »ç  ç©¶æ ¨å ¨é é ç¾ è» æ¨£æ ¬, è© ä¼°æ å½¹å ADHDè· æ å½¹å¾ PTSDç é é £ã æ¨£æ ¬ç ºå å¾ é ¿å¯ æ± æ å½¹ç è» äºº, å ¨æ å½¹å (T0)å å® æ æ å½¹å¾ ç´ 1å æ (T1)ã 3å æ (T2)å 9å æ (T3)æ ¥å èª¿æ ¥ã æ å 以é 輯迴歸å æ å æ æ 波段ç æ ¸æ , ä¼°è¨ 4,612å è» äººæ å½¹å ADHDè· æ å½¹å¾ (T2 æ T3)PTSDç é é £ã ç  ç©¶ä¸­, æ¨£æ ¬ä¸¦ç ¡æ ç ¨è å¥®è ¥ç ©ã ç ºäº è§£ADHDâ PTSDç ç ¹æ® é é £, æ å æª¢è¦ ä»¥ä¸ é  ç ®ä¹ é ç é é £:æ å½¹å ADHDã å® æ æ å½¹å¾ ç å ´é æ é¬±ç¯ æ®µ(MDE)ã å»£æ³ æ §ç ¦æ ®ç (GAD)ã è ªæ®ºæ 念ã æ å½¹å ADHDæ ®é åº¦ç º6.1% (SE = 0.4%)ã å° å ¶ä» é¢¨é ªå  ç´ ä½ èª¿ç¯ å¾ , æ å½¹å ADHDè· æ å½¹å¾ æ £PTSDç é¢¨é ªæ æ é é £(å·²èª¿ç¯ å ç® æ¯ (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001), ç ¶ä¸­å æ ¬æ å½¹å ä¸¦ç ¡PTSDç è» äºº(AOR = 2.50, 95% CI [1.69, 3.69], p < .001)ã ADHDè· å® æ æ å½¹å¾ æ £MDEç (AOR = 2.80, 95% CI [2.01, 3.91], p < .001)å GAD(AOR = 3.04, 95% CI [2.10, 4.42] p < .001)é ½æ é , ä½ è· è ªæ®ºæ å¿µç ¡é ã äº è§£æ å½¹å ADHDè· æ å½¹å¾ PTSDã MDEå GADç é é £, å ¯è ½æ å ©ç ¼å± é å° æ §ç é  é ²å·¥ä½ ã æ ªä¾ ç  ç©¶æ æª¢è¦ å° å å µäººå£«æ ä¾ ADHDæ²»ç , æ ¯å ¦å° å ¶PTSDå ç ¸é ç ¾ç æ ä¿ è­·æ æ ã Simplified Chineseæ  é¢ : ä¸ æ³¨å ä¸ è¶³æ è¿ åº¦æ´»è· ç ä¸ æ £å 伤å å å ç å ç ¸å ³ç ¾ç ç é£ é ©:å¯¹ç¾ å ½å äººè¿ è¡ ç å ç »çºµè´¯ç  ç©¶æ ®è¦ : è¿ å¾ ä¸ ç ´æ ç  ç©¶æ£ è§ ä¸ æ³¨å ä¸ è¶³æ è¿ åº¦æ´»è· ç (ADHD)ä¸ å 伤å å å ç (PTSD)ä¹ é ´ç æ¨ªæ ­æ §å ³è¿ , å ¯æ ¯, æ ä»¬ä» æ¬ ç¼ºæ£ è§ ä¸¤è å ³è¿ ç çºµè´¯ç  ç©¶ã æ ¬å ç »ç  ç©¶æ ¨å ¨é è¿ ç¾ å æ ·æ ¬, è¯ ä¼°æ å½¹å ADHDè· æ å½¹å PTSDç å ³è¿ ã æ ·æ ¬ä¸ºå å¾ é ¿å¯ æ± æ å½¹ç å 人, å ¨æ å½¹å (T0)å å® æ æ å½¹å 约1个æ (T1)ã 3个æ (T2)å 9个æ (T3)æ ¥å è° æ ¥ã æ ä»¬ä»¥é »è¾ å å½ å æ å æ æ 波段ç æ °æ ®, 估计4,612å å 人æ å½¹å ADHDè· æ å½¹å (T2 æ T3)PTSDç å ³è¿ ã ç  ç©¶ä¸­, æ ·æ ¬å¹¶æ  æ ç ¨å ´å¥ è ¯ç ©ã ä¸ºäº è§£ADHDâ PTSDç ç ¹æ® å ³è¿ , æ ä»¬æ£ è§ ä»¥ä¸ é¡¹ç ®ä¹ é ´ç å ³è¿ :æ å½¹å ADHDã å® æ æ å½¹å ç 严é æ é è 段(MDE)ã å¹¿æ³ æ §ç ¦è ç (GAD)ã è ªæ æ 念ã æ å½¹å ADHDæ ®é 度为6.1% (SE = 0.4%)ã å¯¹å ¶ä» é£ é ©å  ç´ ä½ è° è å , æ å½¹å ADHDè· æ å½¹å æ £PTSDç é£ é ©æ æ å ³è¿ (å·²è° è è ç® æ¯ (AOR) = 2.13, 95% CI [1.51, 3.00], p < .001), å½ ä¸­å æ ¬æ å½¹å å¹¶æ  PTSDç å 人(AOR = 2.50, 95% CI [1.69, 3.69], p < .001)ã ADHDè· å® æ æ å½¹å æ £MDEç (AOR = 2.80, 95% CI [2.01, 3.91], p < .001)å GAD(AOR = 3.04, 95% CI [2.10, 4.42] p < .001)é ½æ å ³, ä½ è· è ªæ æ å¿µæ  å ³ã äº è§£æ å½¹å ADHDè· æ å½¹å PTSDã MDEå GADç å ³è¿ , å ¯è ½æ å ©å å± é å¯¹æ §ç é¢ é ²å·¥ä½ ã æ ªæ ¥ç  ç©¶åº æ£ è§ å¯¹å å 人士æ ä¾ ADHDæ²»ç , æ ¯å ¦å¯¹å ¶PTSDå ç ¸å ³ç ¾ç æ ä¿ æ ¤æ åº ãPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146971/1/jts22347_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146971/2/jts22347.pd

Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

SummaryBackgroundHematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease.MethodsThis study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition.ResultsThe frequencies of neutropenia (absolute neutrophil count ≤1.3×109/l), anemia (hemoglobin ≤10g/dl), and thrombocytopenia (platelets ≤125×109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p<0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection.ConclusionsDifferences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings

Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder

A pathfinder version of CHIME (the Canadian Hydrogen Intensity Mapping Experiment) is currently being commissioned at the Dominion Radio Astrophysical Observatory (DRAO) in Penticton, BC. The instrument is a hybrid cylindrical interferometer designed to measure the large scale neutral hydrogen power spectrum across the redshift range 0.8 to 2.5. The power spectrum will be used to measure the baryon acoustic oscillation (BAO) scale across this poorly probed redshift range where dark energy becomes a significant contributor to the evolution of the Universe. The instrument revives the cylinder design in radio astronomy with a wide field survey as a primary goal. Modern low-noise amplifiers and digital processing remove the necessity for the analog beamforming that characterized previous designs. The Pathfinder consists of two cylinders 37\,m long by 20\,m wide oriented north-south for a total collecting area of 1,500 square meters. The cylinders are stationary with no moving parts, and form a transit instrument with an instantaneous field of view of $\sim$100\,degrees by 1-2\,degrees. Each CHIME Pathfinder cylinder has a feedline with 64 dual polarization feeds placed every $\sim$30\,cm which Nyquist sample the north-south sky over much of the frequency band. The signals from each dual-polarization feed are independently amplified, filtered to 400-800\,MHz, and directly sampled at 800\,MSps using 8 bits. The correlator is an FX design, where the Fourier transform channelization is performed in FPGAs, which are interfaced to a set of GPUs that compute the correlation matrix. The CHIME Pathfinder is a 1/10th scale prototype version of CHIME and is designed to detect the BAO feature and constrain the distance-redshift relation.Comment: 20 pages, 12 figures. submitted to Proc. SPIE, Astronomical Telescopes + Instrumentation (2014