Alkaloids of Alstonia Muelleriana

Four indole alkaloids have been isolated and characterized from the tree bark of Alstonia muelleriana Domin. One of these is the previously known dimeric indole alkaloid, villalstonine (I). A second probably dimeric indole alkaloid, alstonisidine (II), and two monomeric indole alkaloids, alstonisine (III) and alstonerine (IV) are also described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34203/1/0000492.pd

Topological organization of whole-brain white matter in HIV infection

Infection with human immunodeficiency virus (HIV) is associated with neuroimaging alterations. However, little is known about the topological organization of whole-brain networks and the corresponding association with cognition. As such, we examined structural whole-brain white matter connectivity patterns and cognitive performance in 29 HIV+ young adults (mean age = 25.9) with limited or no HIV treatment history. HIV+ participants and demographically similar HIV− controls (n = 16) residing in South Africa underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural network models were constructed using diffusion MRI-based multifiber tractography and T(1)-weighted MRI-based regional gray matter segmentation. Global network measures included whole-brain structural integration, connection strength, and structural segregation. Cognition was measured using a neuropsychological global deficit score (GDS) as well as individual cognitive domains. Results revealed that HIV+ participants exhibited significant disruptions to whole-brain networks, characterized by weaker structural integration (characteristic path length and efficiency), connection strength, and structural segregation (clustering coefficient) than HIV− controls (p < 0.05). GDSs and performance on learning/recall tasks were negatively correlated with the clustering coefficient (p < 0.05) in HIV+ participants. Results from this study indicate disruption to brain network integrity in treatment-limited HIV+ young adults with corresponding abnormalities in cognitive performance

Fast Fourier Optimization: Sparsity Matters

Many interesting and fundamentally practical optimization problems, ranging from optics, to signal processing, to radar and acoustics, involve constraints on the Fourier transform of a function. It is well-known that the {\em fast Fourier transform} (fft) is a recursive algorithm that can dramatically improve the efficiency for computing the discrete Fourier transform. However, because it is recursive, it is difficult to embed into a linear optimization problem. In this paper, we explain the main idea behind the fast Fourier transform and show how to adapt it in such a manner as to make it encodable as constraints in an optimization problem. We demonstrate a real-world problem from the field of high-contrast imaging. On this problem, dramatic improvements are translated to an ability to solve problems with a much finer grid of discretized points. As we shall show, in general, the "fast Fourier" version of the optimization constraints produces a larger but sparser constraint matrix and therefore one can think of the fast Fourier transform as a method of sparsifying the constraints in an optimization problem, which is usually a good thing.Comment: 16 pages, 8 figure

Mice Expressing Low Levels of CalDAG-GEFI Exhibit Markedly Impaired Platelet Activation With Minor Impact on HemostasisHighlights

OBJECTIVE: The tight regulation of platelet adhesiveness, mediated by the αIIbβ3 integrin, is critical for hemostasis and prevention of thrombosis. We recently demonstrated that integrin affinity in platelets is controlled by the guanine nucleotide exchange factor, CalDAG-GEFI (CD-GEFI), and its target, RAP1. In this study, we investigated whether low-level expression of CD-GEFI leads to protection from thrombosis without pathological bleeding in mice. APPROACH AND RESULTS: Cdg1(low) mice were generated by knockin of human CD-GEFI cDNA into the mouse Cdg1 locus. CD-GEFI expression in platelets from Cdg1(low) mice was reduced by ≈90% when compared with controls. Activation of RAP1 and αIIbβ3 was abolished at low agonist concentrations and partially inhibited at high agonist concentrations in Cdg1(low) platelets. Consistently, the aggregation response of Cdg1(low) platelets was weaker than that of wild-type platelets, but more efficient than that observed in Cdg1(-/-) platelets. Importantly, Cdg1(low) mice were strongly protected from arterial and immune complex-mediated thrombosis, with only minimal impact on primary hemostasis. CONCLUSIONS: Together, our studies suggest the partial inhibition of CD-GEFI function as a powerful new approach to safely prevent thrombotic complications

Exercise training to improve brain health in older people living with HIV: Study protocol for a randomized controlled trial

BACKGROUND: With the advent of antiretrovirals, people living with HIV are living near-normal lifespans. However, people living with HIV are at greater risk of experiencing cognitive impairment and reduced brain integrity despite well-controlled viremia. A robust literature supports exercise interventions as a method of improving cognition and structural brain integrity in older individuals without HIV. The effects of exercise on cardiometabolic, neurocognitive, and neural structures in middle-aged to older people living with HIV are less well known, with few prospective studies examining these measures. OBJECTIVE: This prospective randomized clinical trial will examine the effects of a 6-month exercise training intervention compared to a 6-month stretching intervention (control) on cardiorespiratory fitness, physical function and strength, cognition, and neuroimaging measures of brain volumes and cerebral blood flow in people living with HIV. METHODS: Sedentary middle-aged to older people living with HIV (ages≥40; n=150) with undetectable HIV viral load (\u3c20 copies/mL) will be enrolled in the study. At the baseline and final visit, fasting plasma lipid, insulin, glucose, and brain neurotrophic factor concentrations; cardiorespiratory fitness; cognitive performance; brain volumes; and cerebral blood flow via a magnetic resonance imaging scan will be measured. Participants will be randomized in a 2:1 ratio to either the exercise or control stretching intervention. All participants will complete their assigned programs at a community fitness center 3 times a week for 6 months. A professional fitness trainer will provide personal training guidance at all sessions for individuals enrolled in both arms. Individuals randomized to the exercise intervention will perform endurance and strength training exercises, while those randomized to the control intervention will perform stretches to increase flexibility. A midpoint visit (at 3 months) will assess cognitive performance, and at the end point visit, subjects will undergo cardiorespiratory fitness and cognition testing, and a magnetic resonance imaging scan. Physical activity throughout the duration of the trial will be recorded using an actigraph. RESULTS: Recruitment and data collection are complete as of December 2020. Data processing, cleaning, and organization are complete as of December 2021. Data analysis began in January 2022, with the publication of study results for primary aims 1 and 2 expected by early 2023. CONCLUSIONS: This study will investigate the effects of a 6-month aerobic and resistance exercise training intervention to improve cardiometabolic risk factors, cognitive performance, cerebral structure, and blood flow in sedentary people living with HIV. Results will inform clinicians and patients of the potential benefits of a structured aerobic exercise training program on the cognitive, functional, and cardiometabolic health status of older people living with HIV. Assessment of compliance will inform the development and implementation of future exercise programs for people living with HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT02663934; https://clinicaltrials.gov/ct2/show/NCT02663934. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41421

Identification of atypical flight patterns

Method and system for analyzing aircraft data, including multiple selected flight parameters for a selected phase of a selected flight, and for determining when the selected phase of the selected flight is atypical, when compared with corresponding data for the same phase for other similar flights. A flight signature is computed using continuous-valued and discrete-valued flight parameters for the selected flight parameters and is optionally compared with a statistical distribution of other observed flight signatures, yielding atypicality scores for the same phase for other similar flights. A cluster analysis is optionally applied to the flight signatures to define an optimal collection of clusters. A level of atypicality for a selected flight is estimated, based upon an index associated with the cluster analysis

A thin layer angiogenesis assay: a modified basement matrix assay for assessment of endothelial cell differentiation

BACKGROUND: Basement matrices such as Matrigel™ and Geltrex™ are used in a variety of cell culture assays of anchorage-dependent differentiation including endothelial cell tube formation assays. The volumes of matrix recommended for these assays (approximately 150 μl/cm(2)) are costly, limit working distances for microscopy, and require cell detachment for subsequent molecular analysis. Here we describe the development and validation of a thin-layer angiogenesis (TLA) assay for assessing the angiogenic potential of endothelial cells that overcomes these limitations. RESULTS: Geltrex™ basement matrix at 5 μl/cm(2) in 24-well (10 μl) or 96-well (2 μl) plates supports endothelial cell differentiation into tube-like structures in a comparable manner to the standard larger volumes of matrix. Since working distances are reduced, high-resolution single cell microscopy, including DIC and confocal imaging, can be used readily. Using MitoTracker dye we now demonstrate, for the first time, live mitochondrial dynamics and visualise the 3-dimensional network of mitochondria present in differentiated endothelial cells. Using a standard commercial total RNA extraction kit (Qiagen) we also show direct RNA extraction and RT-qPCR from differentiated endothelial cells without the need to initially detach cells from their supporting matrix. CONCLUSIONS: We present here a new thin-layer assay (TLA) for measuring the anchorage-dependent differentiation of endothelial cells into tube-like structures which retains all the characteristics of the traditional approach but with the added benefit of a greatly lowered cost and better compatibility with other techniques, including RT-qPCR and high-resolution microscopy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-014-0041-5) contains supplementary material, which is available to authorized users

Foot Injuries in Michigan, USA, Gray Wolves (\u3ci\u3eCanis lupus\u3c/i\u3e), 1992–2014

The range of gray wolves (Canis lupus) in the contiguous US is expanding. Research and monitoring to support population recovery and management often involves capture via foothold traps. A population-level epidemiologic assessment of the effect of trap injuries on wolf survival remains needed to inform management. We describe the baseline rate, type, and severity of foot injuries of wolves born 1992–2013 in Michigan’s Upper Peninsula, evaluate the reliability of field-scoring trap-related injuries, and the effect of injuries on wolf survival. We assessed foot injuries by physical and radiographic exam at postmortem and/or time of capture for 351 wolves using the International Organization for Standardization 10990-5 standard and the effects of injuries, sex, age, previous capture and body condition on survival using proportional hazards regression. We used ordinal regression to evaluate epidemiologic associations between sex, age, previous capture, body condition, cause of death and injury severity. Most wolves (53%) experienced no physically or radiographically discernable foot injuries over their lifetimes. Among those wolves that did experience injuries, 33% scored as mild. Foot injuries had little epidemiologically discernable effect on survival rates. Wolves with higher foot trauma scores did experience an increased risk of dying, but the magnitude of the increase was modest. Most limb injuries occurred below the carpus or tarsus, and scoring upper-limb injuries added little predictive information to population-level epidemiologic measures of survival and injury severity. There was little association between injury severity and cause of death. Based on necropsy exams, previous trap injuries likely contributed to death in only four wolves (1.1%). Our results suggest that injuries resulting from foothold traps are unlikely to be a limiting factor in recovery and ongoing survival of the Michigan gray wolf population

Quaternary geology of the Northern Great Plains

The Great Plains physiographic province lies east of the Rocky Mountains and extends from southern Alberta and Saskatchewan nearly to the United States-Mexico border. This chapter covers only the northern part of the unglaciated portion of this huge region, from Oklahoma almost to the United StatesCanada border, a portion that herein will be referred to simply as the Northern Great Plains (Fig. 1). This region is in the rain shadow of the Rocky Mountains. Isoheyets are roughly longitudinal, and mean annual precipitation decreases from about 750 mm at the southeastern margin to less than 380 mm in the western and northern parts (Fig. 2). Winters typically are cold with relatively little precipitation, mostly as snow; summers are hot with increased precipitation, chiefly associated with movement of Pacific and Arctic air masses into warm, humid air masses from the Gulf of Mexico. Vegetation is almost wholly prairie grassland, due to the semiarid, markedly seasonal climate. The Northern Great Plains is a large region of generally low relief sloping eastward from the Rocky Mountains toward the Missouri and Mississippi Rivers. Its basic bedrock structure is a broad syncline, punctuated by the Black Hills and a few smaller uplifts, and by structural basins such as the Williston, Powder River, and Denver-Julesburg Basins (Fig. 3). Its surface bedrock is chiefly Cretaceous and Tertiary sediments, with small areas of older rocks in the Black Hills, central Montana, and eastern parts of Wyoming, Kansas, and Oklahoma. During the Laramide orogeny (latest Cretaceous through Eocene), while the Rocky Mountains and Black Hills were rising, synorogenic sediments (frequently with large amounts of volcanic ash from volcanic centers in the Rocky Mountains) were deposited in the subsiding Denver-Julesburg, Powder River, and other basins. From Oligocene to Miocene time, sedimentation generally slowed with declining tectonism and volcanism in the Rocky Mountains. However, since the later Miocene, epeirogenic uplift, probably associated with the East Pacific Rise, affected the Great Plains and particularly the Rocky Mountains. During the last 10 m.y. the Rocky Mountain front has risen 1.5 to 2 km, and the eastern margin of the Great Plains 100 to 500 m (Gable and Hatton, 1983), with half to one-quarter of these amounts during the last 5 m.y. Thus, during the later Miocene the Great Plains became a huge aggrading piedmont sloping gently eastward from the Rocky Mountains and Black Hills, with generally eastward drainage, on which the Ogallala Formation and equivalents was deposited. The Ogallala underlies the High Plains Surface, the highest and oldest geomorphic surface preserved in this region. It has been completely eroded along some parts of the western margin of the region (e.g., the Colorado Piedmont), but eastward, it (and its equivalents, such as the Flaxville gravels in Montana) locally is preserved as caprock or buried by Quaternary sediments (Alden, 1924, 1932; Howard, 1960; Stanley, 1971, 1976; Pearl, 1971; Scott, 1982; Corner and Diffendal, 1983; Diffendal and Corner, 1984; Swinehart and others, 1985; Aber, 1985). During the Pliocene, regional aggradation slowly changed to dissection by the principal rivers. In the western part of the region the rivers flowed eastward, but the continental drainage divide Figure 3. Major bedrock structures of the Northern Great Plains. extended northeast from the Black Hills through central South Dakota, far south of its present position. The ancestral upper Missouri, Little Missouri, Yellowstone, and Cheyenne Rivers drained northeast to Hudson Bay, whereas the ancestral White, Platte, and Arkansas Rivers went to the Gulf of Mexico (Fig 4A). Their courses are marked by scattered surface and subsurface gravel remnants; in Montana and North Dakota, deposits of the preglacial Missouri River and its tributaries are buried deeply beneath glacial and other sediments (Howard, 1960; Bluemle, 1972)