The Effect of Movement Rate and Complexity on Functional Magnetic Resonance Signal Change During Pedaling

We used functional magnetic resonance imaging (fMRI) to record human brain activity during slow (30 RPM), fast (60 RPM), passive (30 RPM), and variable rate pedaling. Ten healthy adults participated. After identifying regions of interest, the intensity and volume of brain activation in each region was calculated and compared across conditions (p \u3c .05). Results showed that the primary sensory and motor cortices (S1, M1), supplementary motor area (SMA), and cerebellum (Cb) were active during pedaling. The intensity of activity in these areas increased with increasing pedaling rate and complexity. The Cb was the only brain region that showed significantly lower activity during passive as compared with active pedaling. We conclude that M1, S1, SMA, and Cb have a role in modifying continuous, bilateral, multijoint lower extremity movements. Much of this brain activity may be driven by sensory signals from the moving limbs

The Extremely Luminous Quasar Survey in the Pan-STARRS 1 Footprint (PS-ELQS)

We present the results of the Extremely Luminous Quasar Survey in the $3\pi$ survey of the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS; PS1). This effort applies the successful quasar selection strategy of the Extremely Luminous Survey in the Sloan Digital Sky Survey footprint ($\sim12,000\,\rm{deg}^2$) to a much larger area ($\sim\rm{21486}\,\rm{deg}^2$). This spectroscopic survey targets the most luminous quasars ($M_{1450}\le-26.5$; $m_{i}\le18.5$) at intermediate redshifts ($z\ge2.8$). Candidates are selected based on a near-infrared JKW2 color cut using WISE AllWISE and 2MASS photometry to mainly reject stellar contaminants. Photometric redshifts ($z_{\rm{reg}}$) and star-quasar classifications for each candidate are calculated from near-infrared and optical photometry using the supervised machine learning technique random forests. We select 806 quasar candidates at $z_{\rm{reg}}\ge2.8$ from a parent sample of 74318 sources. After exclusion of known sources and rejection of candidates with unreliable photometry, we have taken optical identification spectra for 290 of our 334 good PS-ELQS candidates. We report the discovery of 190 new $z\ge2.8$ quasars and an additional 28 quasars at lower redshifts. A total of 44 good PS-ELQS candidates remain unobserved. Including all known quasars at $z\ge2.8$, our quasar selection method has a selection efficiency of at least $77\%$. At lower declinations $-30\le\rm{Decl.}\le0$ we approximately triple the known population of extremely luminous quasars. We provide the PS-ELQS quasar catalog with a total of 592 luminous quasars ($m_{i}\le18.5$, $z\ge2.8$). This unique sample will not only be able to provide constraints on the volume density and quasar clustering of extremely luminous quasars, but also offers valuable targets for studies of the intergalactic medium.Comment: 34 pages, 10 figures, accepted to ApJ

Baseline microglial activation correlates with brain amyloidosis and longitudinal cognitive decline in Alzheimer disease

BACKGROUND AND OBJECTIVES: This study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline. METHODS: Twenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation. Baseline CSF concentrations of Aβ42, Aβ42/Aβ40 ratio, tau phosphorylated at position 181 (p-tau181), and total tau (t-tau) were measured. Clinical and cognitive decline were examined with longitudinal CDR and cognitive composite scores (Global and Knight ADRC-Preclinical Alzheimer Cognitive Composite [Knight ADRC-PACC] Score). RESULTS: Participants in the progressor and symptomatic AD groups had significantly elevated [11C]PK11195 standard uptake value ratios (SUVRs) in the hippocampus but not in the precuneus region. In the subcohort with CSF biomarkers (16 of the 24), significant negative correlations between CSF Aβ42 or Aβ42/Aβ40 and [11C]PK11195 SUVR were observed in the hippocampus and precuneus. No correlations were observed between [11C]PK11195 SUVR and CSF p-tau181 or t-tau at baseline in those regions. Higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions predicted longitudinal decline on cognitive tests. DISCUSSION: Microglial activation is increased in individuals with brain amyloidosis and predicts worsening cognition in AD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with AD, higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions was associated with longitudinal decline on cognitive tests

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

In this study, an integrated approach is developed for the formation, identification and biological characterization of electrochemical conversion products of p38α mitogen-activated protein kinase inhibitors. This work demonstrates the hyphenation of an electrochemical reaction cell with a continuous-flow bioaffinity assay and parallel LC-HR-MS. Competition of the formed products with a tracer (SKF-86002) that shows fluorescence enhancement in the orthosteric binding site of the p38α kinase is the readout for bioaffinity. Parallel HR-MSn experiments provided information on the identity of binders and non-binders. Finally, the data produced with this on-line system were compared to electrochemical conversion products generated off-line. The electrochemical conversion of 1-{6-chloro-5-[(2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazine-1-carbonyl]-3aH-indol-3-yl}-2-morpholinoethane-1,2-dione resulted in eight products, three of which showed bioaffinity in the continuous-flow p38α bioaffinity assay used. Electrochemical conversion of BIRB796 resulted, amongst others, in the formation of the reactive quinoneimine structure and its corresponding hydroquinone. Both products were detected in the p38α bioaffinity assay, which indicates binding to the p38α kinase

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Development of an online p38α mitogen-activated protein kinase binding assay and integration of LC–HR-MS

A high-resolution screening method was developed for the p38α mitogen-activated protein kinase to detect and identify small-molecule binders. Its central role in inflammatory diseases makes this enzyme a very important drug target. The setup integrates separation by high-performance liquid chromatography with two parallel detection techniques. High-resolution mass spectrometry gives structural information to identify small molecules while an online enzyme binding detection method provides data on p38α binding. The separation step allows the individual assessment of compounds in a mixture and links affinity and structure information via the retention time. Enzyme binding detection was achieved with a competitive binding assay based on fluorescence enhancement which has a simple principle, is inexpensive, and is easy to interpret. The concentrations of p38α and the fluorescence tracer SK&F86002 were optimized as well as incubation temperature, formic acid content of the LC eluents, and the material of the incubation tubing. The latter notably improved the screening of highly lipophilic compounds. For optimization and validation purposes, the known kinase inhibitors BIRB796, TAK715, and MAPKI1 were used among others. The result is a high-quality assay with Z′ factors around 0.8, which is suitable for semi-quantitative affinity measurements and applicable to various binding modes. Furthermore, the integrated approach gives affinity data on individual compounds instead of averaged ones for mixtures

ImageCLEF 2022: Multimedia Retrieval in Medical, Nature, Fusion, and Internet Applications

ImageCLEF is part of the Conference and Labs of the Evaluation Forum (CLEF) since 2003. CLEF 2022 will take place in Bologna, Italy. ImageCLEF is an ongoing evaluation initiative which promotes the evaluation of technologies for annotation, indexing, and retrieval of visual data with the aim of providing information access to large collections of images in various usage scenarios and domains. In its 20th edition, ImageCLEF will have four main tasks: (i) a Medical task addressing concept annotation, caption prediction, and tuberculosis detection; (ii) a Coral task addressing the annotation and localisation of substrates in coral reef images; (iii) an Aware task addressing the prediction of real-life consequences of online photo sharing; and (iv) a new Fusion task addressing late fusion techniques based on the expertise of the pool of classifiers. In 2021, over 100 research groups registered at ImageCLEF with 42 groups submitting more than 250 runs. These numbers show that, despite the COVID-19 pandemic, there is strong interest in the evaluation campaign

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Pedaling alters the excitability and modulation of vastus medialis H-reflexes after stroke

Objective Individuals post-stroke display abnormal Group Ia reflex excitability. Pedaling has been shown to reduce Group Ia reflexes and to normalize the relationship between EMG and reflex amplitude in the paretic soleus (SO). The purpose of this study was to determine whether these changes extend to the paretic quadriceps. Methods H-reflexes were used to examine Group Ia reflex excitability of the vastus medialis (VM). H-reflexes were elicited in paretic (n = 13) and neurologically intact (n = 13) individuals at 11 positions in the pedaling cycle and during static knee extension at comparable limb positions and levels of VM EMG. Results VM H-reflexes were abnormally elevated in the paretic limb of stroke survivors. During static muscle activation, H-reflex amplitude did not change with the level of background VM activity. Pedaling reduced the amplitude of paretic VM H-reflexes and restored the normal relationship between VM EMG and H-reflex amplitude. Conclusions Pedaling-induced changes in Group Ia reflex excitability that have been reported for the paretic SO are evident in the paretic VM. Pedaling may have a generalized effect on lower extremity Group Ia reflexes post-stroke. Significance Pedaling may be therapeutic for reducing Group Ia reflexes after stroke