The Paleoecological Record of 6 ka BP Climate in the Canadian Prairie Provinces

Synthesis of available paleoecological studies in the Prairie provinces of Canada indicates that although the peak in postglacial aridity that characterized early Holocene climate of the western foothills and plains had passed, conditions remained warmer and drier than present throughout the region ca. 6000 yr BP Compared to today, treeline elevations were higher and alpine glaciers were reduced in size in the Rocky Mountains, lake levels were lower over much of the Interior Plains, and the grassland and boreal forest ecozones extended north of their present positions. Forest fires were more prevalent ca. 6000 yr BP than they are today, aiding westward migration of jack pine (Pinus banksiana) through the boreal forest and increasing the area occupied by grassland in boreal and montane forest regions. Attempts to quantify the magnitude of 6 ka temperature and precipitation differences have produced variable results, but suggest that mean annual temperature was 0.50°C to 1.50°C higher than today (summer temperature may have been up to 3°C higher) and mean annual precipitation was reduced by 65 mm (or summer precipitation was reduced by 50 mm), compared to present. The nature and scale of these changes suggests that a vigorous zonal atmospheric circulation pattern, similar to that of the 1930s but shifted northward, prevailed at 6 ka.La synthèse des études paléoécologiques montrent qu'à 6 ka le maximum d'aridité, qui caractérisait l'Holocène inférieur, avait été atteint, mais le climat demeurait plus chaud et plus sec que maintenant dans toute la région. Les différentes limites des arbres étaient plus élevées qu'aujourd'hui et la superficie des glaciers alpins étaient plus petite, les niveaux lacustres étaient moins élevés dans la plus grande partie des plaines intérieures et les écozones des Prairies et de la forêt boréale s'étendaient plus au nord qu'aujourd'hui. Les feux de forêt étaient plus fréquents à 6 ka qu'actuellement, ce qui a favorisé la migration du pin gris (Pinus banksiana) vers l'ouest à travers la forêt boréale et accru la superficie de la prairie dans les zones de forêts boréale et alpine. Les essais faits dans le but de mesurer l'ampleur des différences de températures et de précipitations à 6 ka ont donné des résultats variables, mais montrent que la température était de 0,5 à 1,5°C plus élevé que maintenant (avec une température estivale jusqu'à 3°C plus élevée) et les précipitations annuelles moyennes étaient de 65 mm inférieures (avec des précipitations estivales de 50 mm inférieures) à maintenant. La nature et le degré des changements laissent croire qu'une forte circulation atmosphérique zonale, semblable à celle des années 1930, mais plus nordique, existait à 6 ka.Die Synthèse der verfùgbaren palâoôkologischen Studien in den Prârie-Provinzen Kanadas zeigt, daf3 das Klima in der ganzen Region um etwa 6000 Jahre v.u.Z. warmer und trockener als gegenwârtig blieb, wenn auch das Maximum an postglazialer Trockenheit, welches im frùhen Holozàn das Klima der westlichen Gebirgsauslâufer und Ebenen charakterisierte, vorùber war. Verglichen mit heute waren die Baumgrenzen hôher und die alpinen Gletscher in den Rocky Mountains kleiner, die Seehôhen waren niedriger im grôBten Teil der inneren Ebenen, und die Ôkozonen von Grasland und nôrdlichem WaId erstreckten sich weiter nôrdlich als heute. Waldbrânde traten um etwa 6000 v.u.Z. hâufiger als gegenwârtig auf und haben so die Westwàrtswanderung von Graukiefer (Pinus banksiana) durch den nôrdlichen WaId begùnstigt und die Graslandflàchen in den Gebieten des nôrdlichen und alpinen Waldes vergrôBert. Versuche, den Umfang der Unterschiede in Temperatur und Niederschlàgen um 6 ka zu bestimmen, ergaben wechselnde Ergebnissse, doch zeigen sie, daB die durchschnittliche jâhrliche Temperatur 0.5° C bis 1.50C hôher als gegenwârtig war (die Sommertemperatur dûrfte bis zu 3°C hôher gewesen sein) und die durchschnittlichen jâhrlichen Niederschlâge waren um 65 mm geringer (oder die Sommer-Niederschlàge waren um 50 mm geringer) verglichen mit heute. Die Natur und der Grad dieser Wechsel lassen vermuten, daB eine krâftige zonale atmosphàrische Strômung, àhnlich der von den 1930 iger Jahren aber nôrdlicher gelagert, um 6 ka vorherrschte

1.3 mm Wavelength VLBI of Sagittarius A*: Detection of Time-Variable Emission on Event Horizon Scales

Sagittarius A*, the ~4 x 10^6 solar mass black hole candidate at the Galactic Center, can be studied on Schwarzschild radius scales with (sub)millimeter wavelength Very Long Baseline Interferometry (VLBI). We report on 1.3 mm wavelength observations of Sgr A* using a VLBI array consisting of the JCMT on Mauna Kea, the ARO/SMT on Mt. Graham in Arizona, and two telescopes of the CARMA array at Cedar Flat in California. Both Sgr A* and the quasar calibrator 1924-292 were observed over three consecutive nights, and both sources were clearly detected on all baselines. For the first time, we are able to extract 1.3 mm VLBI interferometer phase information on Sgr A* through measurement of closure phase on the triangle of baselines. On the third night of observing, the correlated flux density of Sgr A* on all VLBI baselines increased relative to the first two nights, providing strong evidence for time-variable change on scales of a few Schwarzschild radii. These results suggest that future VLBI observations with greater sensitivity and additional baselines will play a valuable role in determining the structure of emission near the event horizon of Sgr A*.Comment: 8 pages, submitted to ApJ

Detection of intrinsic source structure at ~3 Schwarzschild radii with Millimeter-VLBI observations of SAGITTARIUS A*

We report results from very long baseline interferometric (VLBI) observations of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230 GHz). The observations were performed in 2013 March using six VLBI stations in Hawaii, California, Arizona, and Chile. Compared to earlier observations, the addition of the APEX telescope in Chile almost doubles the longest baseline length in the array, provides additional {\it uv} coverage in the N-S direction, and leads to a spatial resolution of $\sim$30 $\mu$as ($\sim$3 Schwarzschild radii) for Sgr A*. The source is detected even at the longest baselines with visibility amplitudes of $\sim$4-13% of the total flux density. We argue that such flux densities cannot result from interstellar refractive scattering alone, but indicate the presence of compact intrinsic source structure on scales of $\sim$3 Schwarzschild radii. The measured nonzero closure phases rule out point-symmetric emission. We discuss our results in the context of simple geometric models that capture the basic characteristics and brightness distributions of disk- and jet-dominated models and show that both can reproduce the observed data. Common to these models are the brightness asymmetry, the orientation, and characteristic sizes, which are comparable to the expected size of the black hole shadow. Future 1.3 mm VLBI observations with an expanded array and better sensitivity will allow a more detailed imaging of the horizon-scale structure and bear the potential for a deep insight into the physical processes at the black hole boundary.Comment: 11 pages, 5 figures, accepted to Ap

Diversity-Oriented Synthesis Yields a Novel Lead for the Treatment of Malaria

Here, we describe the discovery of a novel antimalarial agent using phenotypic screening of Plasmodium falciparum asexual blood-stage parasites. Screening a novel compound collection created using diversity-oriented synthesis (DOS) led to the initial hit. Structure–activity relationships guided the synthesis of compounds having improved potency and water solubility, yielding a subnanomolar inhibitor of parasite asexual blood-stage growth. Optimized compound 27 has an excellent off-target activity profile in erythrocyte lysis and HepG2 assays and is stable in human plasma. This compound is available via the molecular libraries probe production centers network (MLPCN) and is designated ML238.Chemistry and Chemical Biolog

Structural covariance of the ventral visual stream predicts posttraumatic intrusion and nightmare symptoms: a multivariate data fusion analysis

Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant\u27s loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms

Prior Sexual Trauma Exposure Impacts Posttraumatic Dysfunction and Neural Circuitry Following a Recent Traumatic Event in the AURORA Study

Background: Prior sexual trauma (ST) is associated with greater risk for posttraumatic stress disorder after a subsequent traumatic event; however, the underlying neurobiological mechanisms remain opaque. We investigated longitudinal posttraumatic dysfunction and amygdala functional dynamics following admission to an emergency department for new primarily nonsexual trauma in participants with and without previous ST. Methods: Participants (N = 2178) were recruited following acute trauma exposure (primarily motor vehicle collision). A subset (n = 242) completed magnetic resonance imaging that included a fearful faces task and a resting-state scan 2 weeks after the trauma. We investigated associations between prior ST and several dimensions of posttraumatic symptoms over 6 months. We further assessed amygdala activation and connectivity differences between groups with or without prior ST. Results: Prior ST was associated with greater posttraumatic depression (F1,1120 = 28.35, p = 1.22 × 10−7, ηp2 = 0.06), anxiety (F1,1113 = 17.43, p = 3.21 × 10−5, ηp2 = 0.05), and posttraumatic stress disorder (F1,1027 = 11.34, p = 7.85 × 10−4, ηp2 = 0.04) severity and more maladaptive beliefs about pain (F1,1113 = 8.51, p = .004, ηp2 = 0.02) but was not related to amygdala reactivity to fearful versus neutral faces (all ps \u3e .05). A secondary analysis revealed an interaction between ST and lifetime trauma load on the left amygdala to visual cortex connectivity (peak Z value: −4.41, corrected p \u3c .02). Conclusions: Findings suggest that prior ST is associated with heightened posttraumatic dysfunction following a new trauma exposure but not increased amygdala activity. In addition, ST may interact with lifetime trauma load to alter neural circuitry in visual processing regions following acute trauma exposure. Further research should probe the relationship between trauma type and visual circuitry in the acute aftermath of trauma

The AURORA Study: A Longitudinal, Multimodal Library of Brain Biology and Function after Traumatic Stress Exposure

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions