Functional preservation of vascular smooth muscle tissue

The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included

Gesture analysis for physics education researchers

Systematic observations of student gestures can not only fill in gaps in students' verbal expressions, but can also offer valuable information about student ideas, including their source, their novelty to the speaker, and their construction in real time. This paper provides a review of the research in gesture analysis that is most relevant to physics education researchers and illustrates gesture analysis for the purpose of better understanding student thinking about physics.Comment: 14 page

Note and Comment

American Bar Association Meeting; Disbarment or Suspension of Attorney; Is the Property Owner Negligent if He Fails to Exercise Reasonable Care to Prevent an Injury to An Infant Trespasser?; Liability of Water companies for Losses by Fire; Evidence in Deportation Proceedings Under the Act of congress of May 5th, 1892; Duty of a Bank to a Surety to Apply Funds of a Principal Debtor to Satisfy a Debt Due the Bank

Global alterations to the choroid plexus blood-CSF barrier in amyotrophic lateral sclerosis

© 2020 The Author(s). The choroid plexus (CP) is a highly vascularized structure located in the ventricles that forms the blood-CSF barrier (BCSFB) and separates the blood from the cerebrospinal fluid (CSF). In addition to its role as a physical barrier, the CP functions in CSF secretion, transport of nutrients into the central nervous system (CNS) and a gated point of entry of circulating immune cells into the CNS. Aging and neurodegeneration have been reported to affect CP morphology and function and increase protein leakage from blood to the CSF. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both upper and lower motor neuron loss, as well as altered proteomic and metabolomic signatures in the CSF. The role of the BCSFB and the CP in ALS is unknown. Here we describe a transcriptomic and ultrastructural analysis of BCSFB and CP alterations in human postmortem tissues from ALS and non-neurologic disease controls. ALS-CP exhibited widespread disruptions in tight junctional components of the CP epithelial layer and vascular integrity. In addition, we detected loss of pericytes around ALS blood vessels, accompanied by activation of platelet aggregation markers vWF and Fibrinogen, reminiscent of vascular injury. To investigate the immune component of ALS-CP, we conducted a comprehensive analysis of cytokines and chemokine panels in CP lysates and found a significant down-regulation of M-CSF and V-CAM1 in ALS, as well as up-regulation of VEGF-A protein. This phenotype was accompanied by an infiltration of MERTK positive macrophages into the parenchyma of the ALS-CP when compared to controls. Taken together, we demonstrate widespread structural and functional disruptions of the BCSFB in human ALS increasing our understanding of the disease pathology and identifying potential new targets for ALS therapeutic development

Physicality and Cooperative Design

CSCW researchers have increasingly come to realize that material work setting and its population of artefacts play a crucial part in coordination of distributed or co-located work. This paper uses the notion of physicality as a basis to understand cooperative work. Using examples from an ongoing fieldwork on cooperative design practices, it provides a conceptual understanding of physicality and shows that material settings and co-worker’s working practices play an important role in understanding physicality of cooperative design

Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells

Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic homeostasis. How this negative regulator of T cell activation executes its functions has remained controversial. We now provide evidence that CTLA-4 mediates a cell-intrinsic counterbalance to restrict the clonal expansion of proliferating CD4+ T cells. The regulation of CTLA-4 expression and function ensures that, after ∼3 cell divisions of expansion, most progeny will succumb to either proliferative arrest or death over the ensuing three cell divisions. The quantitative precision of the counterbalance hinges on the graded, time-independent induction of CTLA-4 expression during the first three cell divisions. In contrast to the limits imposed on unpolarized cells, T helper type 1 (Th1) and Th2 effector progeny may be rescued from proliferative arrest by interleukin (IL)-12 and IL-4 signaling, respectively, allowing appropriately stimulated progeny to proceed to the stage of tissue homing. These results suggest that the cell-autonomous regulation of CTLA-4 induction may be a central checkpoint of clonal expansion of CD4+ T cells, allowing temporally and spatially restricted growth of progeny to be dictated by the nature of the threat posed to the host

Tracking Changes in Bioavailable Fe Within High-Nitrate Low-Chlorophyll Oceanic Waters: A First Estimate Using a Heterotrophic Bacterial Bioreporter

It is conventional knowledge that heterotrophic bacteria play a key role in the biogeochemical cycling of oceanic carbon. However, only recently has their role in marine iron ( Fe) biogeochemical cycles been examined. Research during this past decade has demonstrated an inextricable link between Fe chemistry and the biota, as \u3e99% of Fe in marine systems is complexed to organic chelates of unknown but obviously biotic origin. Here we present a novel approach to assess and compare Fe bioavailability in low Fe HNLC waters using a bioluminescent bacterial reporter that quantitatively responds to the concentration of bioavailable Fe by producing light. Originally tested in freshwater environments, this study presents the first characterization of this halotolerant reporter organism in a defined seawater medium and then subsequently in marine surface waters. Laboratory characterizations demonstrate that this reporter displays a dose-dependent response to Fe availability in our defined marine medium. Field tests were performed during the 10-day mesoscale FeCycle experiment ( February 2003) in the Pacific sub-Antarctic high-nitrate low-chlorophyll region. Data from both biogeochemical measures and bioreporter assays are provided which describe how the bioreporter detected changes in Fe bioavailability that occurred during a natural shift in ambient dissolved Fe concentrations (similar to 40 pM). Our data explore the use of heterotrophic bioluminescent reporters as a comparable tool for marine ecosystems and demonstrate the potential utility of this tool in elucidating the relationship between Fe bioavailability and Fe chemistry in complex marine systems

Imaging of Glioma Tumor with Endogenous Fluorescence Tomography

Tomographic imaging of a glioma tumor with endogenous fluorescence is demonstrated using a noncontact single-photon counting fan-beam acquisition system interfaced with microCT imaging. The fluorescence from protoporphyrin IX (PpIX) was found to be detectable, and allowed imaging of the tumor from within the cranium, even though the tumor presence was not visible in the microCT image. The combination of single-photon counting detection and normalized fluorescence to transmission detection at each channel allowed robust imaging of the signal. This demonstrated use of endogenous fluorescence stimulation from aminolevulinic acid (ALA) and provides the first in vivo demonstration of deep tissue tomographic imaging with protoporphyrin IX. Fluorescence tomography provides a tool for preclinical molecular contrast agent assessment in oncology.1, 2, 3, 4 Systems have advanced in complexity to where noncontact imaging,5 automated boundary recovery,6 and sophisticated internal tissue shapes can be included in the recovered images. The translation of this work to humans will require molecular contrast agents that are amenable to regulatory approval and maintain tumor specificity in humans, where often nonspecific uptake of molecular imaging agents can decrease their utility. In this study, a new fluorescence tomography system coupled to microCT7 was used to illustrate diagnostic detection of orthotopic glioma tumors that were not apparent in the microCT images, using endogenous fluorescent contrast from protoporphyrin IX (PpIX). Glioma tumors provide significant endogenous fluorescence from PpIX,8, 9, 10, 11 and this is enhanced when the subject imaged has been administered aminolevulinic acid (ALA). The endogenous production process of PpIX is known to stem from the administered, ALA bypassing the regulatory inhibition of ALA synthase, allowing the heme synthesis pathway to proceed uninhibited. Since there is a limited supply of iron in the body, this process produces overabundance of PpIX rather than heme, and many tumors have been shown to have high yields of PpIX. Clinical trials with PpIX fluorescence guided resection of tumors have shown significant promise,12 and yet deep tissue imaging with PpIX fluorescence has not been exploited in clinical use. Early studies have shown that detection of these tumors with PpIX is feasible,13, 14 but no tomographic imaging has been used. This limitation in development has largely been caused by problems in wavelength filtering and low signal intensity, as well as background fluorescence from the skin limiting sensitivity to deeper structures. In the system developed and used here, this feasibility is demonstrated by imaging a human xenograft glioma model. To solve the sensitivity problem and study the ability to diagnostically image PpIX in vivo, time-correlated single-photon counting was used in the fluorescence tomography system, which provides maximum sensitivity. Figure 1a shows the system designed to match up with a microCT, allowing both x-ray structural and optical functional imaging sequentially. Lens-coupled detection of signals is acquired from the mouse using five time-resolved photomultiplier tubes (H7422P-50, Hamamatsu, Japan) with single-photon counting electronics (SPC-134 modules, Becker and Hickl GmbH, Germany). The system has fan-beam transmission geometry similar to a standard CT scanner, with single source delivery of a1-mW role= presentation \u3e1-mW pulsed diode laser light at 635nm role= presentation \u3e635nm , collimated to a 1-mm role= presentation \u3e1-mm effective area on the animal. The five detection lenses were arranged in an arc, each with 22.5-deg role= presentation \u3e22.5-deg angular separation, centered directly on the opposite side of the animal with long working distance pickup,7 allowing noncontact measurement of the diffuse light through the animal. The diffuse intensity signals collected at each of the five channels were then translated via 400-μm role= presentation \u3e400-μm fibers and split using beamsplitters to be directed toward the fluorescence (95%) and transmission (5%) channel detectors. A 650-nm role= presentation \u3e650-nm long-pass filter was used in the fluorescence channels to isolate the signal, and in the transmitted intensity signals, a neutral density filter (2 OD) was used to attenuate the signals. This latter filtering was necessary to ensure that the fluorescence and transmission. Intensity signals fell within the same dynamic range, allowing a single 1s role= presentation \u3e1s acquisition for each detector. Scans were then performed by rotating the fan-beam around the specimen to 32 locations. A GE eXplore Locus SP scanner (GE Healthcare, London, Ontario, Canada) that incorporated a detector with 94-micronpixel role= presentation \u3e94-micronpixel resolution, a 80-kV role= presentation \u3e80-kV peak voltage, and a tube current of 450μAs role= presentation \u3e450μAs , was used in acquiring the microCT data, as displayed in Fig. 2 . In this example, since soft tissue was being imaged, the CT data was largely used to image the exterior of the animal, although in future studies, it could be used to isolate the cranium region as well

Change management: The case of the elite sport performance team

The effective and efficient implementation of change is often required for both successful performance and management survival across a host of contemporary domains. However, although of major theoretical and practical significance, research to date has overlooked the application of change management (hereafter CM) knowledge to the elite sport performance team environment. Considering that the success of ‘off-field’ sports businesses are largely dependent on the performances of their ‘on-field’ team, this article explores the application of current CM theorizing to this specific setting and the challenges facing its utility. Accordingly, we identify the need and importance of developing theory specific to this area, with practical application in both sport and business, through examination of current knowledge and identification of the domain's unique, dynamic and contested properties. Markers of successful change are then suggested to guide initial enquiry before the article concludes with proposed lines of research which may act to provide a valid and comprehensive theoretical account of CM to optimize the research and practice of those working in the field