Differential Tissue Response to Growth Hormone in Mice

Growth hormone (GH) has been shown to act directly on multiple tissues throughout the body. Historically, it was believed that GH acted directly in the liver and only indirectly in other tissues via insulin‐like growth hormone 1 (IGF‐1). Despite extensive work to describe GH action in individual tissues, a comparative analysis of acute GH signaling in key metabolic tissues has not been performed. Herein, we address this knowledge gap. Acute tissue response to human recombinant GH was assessed in mice by measuring signaling via phospho‐STAT5 immunoblotting. STAT5 activation is an easily and reliably detected early marker of GH receptor engagement. We found differential tissue sensitivities; liver and kidney were equally GH‐sensitive and more sensitive than white adipose tissue, heart, and muscle (gastrocnemius). Gastrocnemius had the greatest maximal response compared to heart, liver, white adipose tissue, and whole kidney. Differences in maximum responsiveness were positively correlated with tissue STAT5 abundance, while differences in sensitivity were not explained by differences in GH receptor levels. Thus, GH sensitivity and responsiveness of distinct metabolic tissues differ and may impact physiology and disease

Space shuttle: High angle of attack transition and low angle of attack launch phase aerodynamic stability and control of GD/C B-18E-2, B-18E-3 delta wing booster, and launch configuration of MSC-040A orbiter and twin pressure fed boosters

The test was a conventional stability and control test except for two aspects. One was the very high angles of attack at which the delta wing configurations were tested (up to 60 degrees) at Mach numbers of 3 and 4.96. The other was the installation of the orbiter and twin boosters in a manner that caused the support system to induce normal forces and side forces on the aft portion of the boosters at all Mach numbers; i.e., the support and the booster bodies were close together, side by side

Space shuttle: Longitudinal and lateral aerodynamic characteristics of the 0.0035-scale GD/C aerospace booster (B-15B-1)

Force tests on a 0.0035-scale model of the General Dynamics/Convair space shuttle B-15B-1 booster were conducted in the MSFC trisonic wind tunnel during February and March 1971. Longitudinal and lateral characteristics were obtained at Mach numbers from 0.6 to 4.96. The configuration tested had a low delta wing, all-movable canard controls of delta planform, and a single vertical tail. Most of the test was devoted to obtaining data relevant to the transition from atmospheric reentry to subsonic cruise. In that portion of the test the angles of attack ranged from 6 degrees to 60 degrees, and yaw runs were made at angles of attack of 15 and 35 degrees. The rest of the test was devoted to obtaining booster-alone buildup data relevant to the launch phase. For the launch phase, the Mach number range was from 0.6 to 2.0, the angles of attack were from -10 to +10 degrees, and yaw runs were made at zero angle of attack

Pressure ulcer related pain in community populations: a prevalence survey.

BACKGROUND: Pressure ulcers are costly to the healthcare provider and can have a major impact on patient's quality of life. One of the most distressing symptoms reported is pain. There is very little published data on the prevalence and details of pain experienced by patients with pressure ulcers, particularly in community populations. The study was conducted in two community NHS sites in the North of England. METHODS: The aim was to estimate the prevalence of pressure area related pain within a community population. We also explored the type and severity of the pain and its association with pressure ulcer classification. A cross-sectional survey was performed of community nurses caseloads to identify adult patients with pressure ulcers and associated pain. Consenting patients then had a full pain assessment and verification of pressure ulcer grade. RESULTS: A total of 287 patients were identified with pressure ulcers (0.51 per 1000 adult population). Of the 176 patients who were asked, 133 (75.6%) reported pain. 37 patients consented to a detailed pain assessment. Painful pressure ulcers of all grades and on nearly all body sites were identified. Pain intensity was not related to number or severity of pressure ulcer. Both inflammatory and neuropathic pain were reported at all body sites however the proportion of neuropathic pain was greater in pressure ulcers on lower limbs. CONCLUSIONS: This study has identified the extent and type of pain suffered by community patients with pressure ulcers and indicates the need for systematic and regular pain assessment and treatment

Microwave Schottky diagnostic systems for the Fermilab Tevatron, Recycler, and CERN LHC

A means for non-invasive measurement of transverse and longitudinal characteristics of bunched beams in synchrotrons has been developed based on high sensitivity slotted waveguide pickups. The pickups allow for bandwidths exceeding hundreds of MHz while maintaining good beam sensitivity characteristics. Wide bandwidth is essential to allow bunch-by-bunch measurements by means of a fast gate. The Schottky detector system is installed and successfully commissioned in the Fermilab Tevatron, Recycler and CERN LHC synchrotrons. Measurement capabilities include tune, chromaticity, and momentum spread of single or multiple beam bunches in any combination. With appropriate calibrations, emittance can also be measured by integrating the area under the incoherent tune sidebands

The Great Disruption: How Machine Intelligence Will Transform the Role of Lawyers in the Delivery of Legal Services

Objective: to analyze the influence of machine intelligence on legal practice and services.Methods: dialectical approach to cognition of social phenomena, allowing to analyze them in the historical development and functioning in the context of a set of objective and subjective factors, which determined the choice of the following research methods: formal-logical, comparative-legal, state and legal modeling.Results: The market for electronic legal services is at a relatively early, yet significant, stage in terms of the disruptive effect of machine intelligence in undermining lawyers' monopoly. As machine intelligence in lawyering develops exponentially, it will take an increasingly larger role in legal practice. Eventually, machine intelligence will prove faster and more efficient than many lawyers in providing those services. Lawyers will continue to provide services that cannot be commoditized if they are superstars, practice in highly specialized areas of law subject to rapid change, appear in court, or provide services where human relationships are central to their quality. Otherwise, no effective barriers to the advance of machine lawyering in legal practices exist - not even in the law and ethics of lawyering. Lawyers will continue to embrace machine intelligence as an input and fail to prevent non-lawyers from using it to deliver legal services. Ultimately, therefore, the disruptive effect of machine intelligence will trigger the end of lawyers' monopoly and provide a benefit to society and clients as legal services become more transparent and affordable to consumers, and access to justice thereby becomes more widely available. Scientific novelty: for the first time, the authors formulate the five areas of legal practice which will significantly change in the nearest future under the influence of machine intelligence: (1) discovery, (2) legal search, (3) generation of documents, (4) creation of briefs and memoranda, and (5) predictive analytics. Machine intelligence has already begun to significantly compete with lawyers and undermine their monopoly. Today, sizeable financial industries use machine intelligence to deliver legal services, even though the most economically significant developments have occurred in only three of the five areas identified above. The three areas that have proven most profitable are legal research, discovery, and document generation. Practical significance: the key results and conclusions of the research can be used in scientific, educational and law-enforcing activities when considering the issues related to the influence of machine intelligence on legal practice and services

Nondestructive Evaluation of Standing Trees With a Stress Wave Method

The primary objective of this study was to investigate the usefulness of a stress wave technique for evaluating wood strength and stiffness of young-growth western hemlock and Sitka spruce in standing trees. A secondary objective was to determine if the effects of silvicultural practices on wood quality can be identified using this technique. Stress wave measurements were conducted on 168 young-growth western hemlock and Sitka spruce trees. After in situ measurements, a 0.61-m-long bole section in the test span was taken from 56 felled trees to obtain small, clear wood specimens. Stress wave and static bending tests were then performed on these specimens to determine strength and stiffness. Results of this study indicate that in situ stress wave measurements could provide relatively accurate and reliable information that would enable nondestructive evaluation of wood properties in standing trees. The mean values of stress wave speed and dynamic modulus of elasticity for trees agreed with those determined from small, clear wood specimens. Statistical regression analyses revealed good correlations between stress wave properties of trees and static bending properties of small, clear wood specimens obtained from the trees. Regression models showed statistical significance at the 0.01 confidence level. Results of this study also demonstrate that the effect of silvicultural practices on wood properties can be identified with the stress wave properties of trees. This indicates that this nondestructive stress wave technique can be used to track property changes in trees and help determine how forests could be managed to meet desired wood and fiber qualities

Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model.

BACKGROUND: Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments. Currently, gaps exist as to whether these treatments impact the brain in individuals with or without tumors and with regard to the underlying mechanisms. RESULTS: Combined treatment with precision RT and checkpoint inhibitor IT achieved control of tumor growth. However, BALB/c mice receiving combined treatment demonstrated changes in measures of anxiety levels, regardless of tumor status. C57BL/6J mice with tumors demonstrated increased anxiety, except following combined treatment. Object recognition memory was impaired in C57BL/6J mice without tumors following combined treatment. All mice with tumors showed impaired object recognition, except those treated with RT alone. Mice with tumors demonstrated impaired amygdala-dependent cued fear memory, while maintaining hippocampus-dependent context fear memory. These behavioral alterations and cognitive impairments were accompanied by increased microglial activation in mice receiving immunotherapy alone or combined with RT. Finally, based on tumor status, there were significant changes in proinflammatory cytokines (IFN-γ, IL-6, IL-5, IL-2, IL-10) and a growth factor (FGF-basic). MATERIALS AND METHODS: Here we test the hypothesis that IT combined with peripheral RT have detrimental behavioral and cognitive effects as a result of an enhanced proinflammatory environment in the brain. BALB/c mice with or without injected hind flank CT26 colorectal carcinoma or C57BL/6J mice with or without Lewis Lung carcinoma were used for all experiments. Checkpoint inhibitor IT, using an anti-CTLA-4 antibody, and precision CT-guided peripheral RT alone and combined were used to closely model clinical treatment. We assessed behavioral and cognitive performance and investigated the immune environment using immunohistochemistry and multiplex assays to analyze proinflammatory mediators. CONCLUSIONS: Although combined treatment achieved tumor growth control, it affected the brain and induced changes in measures of anxiety, cognitive impairments, and neuroinflammation

Mechanisms Underlying Age- and Performance-related Differences in Working Memory

This study took advantage of the subsecond temporal resolution of ERPs to investigate mechanisms underlying age- and performance-related differences in working memory. Young and old subjects participated in a verbal n-back task with three levels of difficulty. Each group was divided into high and low performers based on accuracy under the 2-back condition. Both old subjects and low-performing young subjects exhibited impairments in preliminary mismatch/match detection operations (indexed by the anterior N2 component). This may have undermined the quality of information available for the subsequent decision-making process (indexed by the P3 component), necessitating the appropriation of more resources. Additional anterior and right hemisphere activity was recruited by old subjects. Neural efficiency and the capacity to allocate more resources to decision-making differed between high and low performers in both age groups. Under low demand conditions, high performers executed the task utilizing fewer resources than low performers (indexed by the P3 amplitude). As task requirements increased, high-performing young and old subjects were able to appropriate additional resources to decision-making, whereas their low-performing counterparts allocated fewer resources. Higher task demands increased utilization of processing capacity for operations other than decision-making (e.g., sustained attention) that depend upon a shared pool of limited resources. As demands increased, all groups allocated additional resources to the process of sustaining attention (indexed by the posterior slow wave). Demands appeared to have exceeded capacity in low performers, leading to a reduction of resources available to the decision-making process, which likely contributed to a decline in performance