Regulation by endogenous dopamine of the expression of the clock protein, PERIOD2, in the forebrain of the male Wistar rat

Daily exposure to light is the most powerful means of entraining circadian rhythms of clock gene expression in the suprachiasmatic nucleus (SCN), the body's master timekeeper, and in other brain regions and peripheral tissues; however, a variety of non-photic stimuli have also been found to entrain rhythmic clock gene expression in the brain, including motivationally significant events such as stressors and rewards. The present experiments investigated the role of the neurotransmitter, dopamine (DA), in entraining the daily rhythm of the clock protein, PERIOD2 (PER2), in the SCN of the male Wistar rat, as well as in several regions of the limbic forebrain that regulate motivational states: namely, the dorsal striatum, the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). In the dorsal striatum, the normal daily peak of PER2 expression was blunted following selective destruction of midbrain DA neurons with 6-hydroxydopamine (6-OHDA) and after blockade of D2 DA receptors with the antagonist, raclopride, whereas daily injections of a D2 agonist but not a D1 agonist restored and entrained the PER2 rhythm in the 6-OHDA-lesioned striatum. Disruption of catecholamine signaling in general using systemic injections of the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (AMPT), or daily morphine injections and withdrawal of morphine also blunted the normal PER2 peak in the dorsal striatum. Together, these results suggest that daily stimulation of D2 receptors is necessary for the striatal PER2 rhythm. In the BNSTov and CEA, daily injections of a D2 agonist or morphine increased PER2 expression near the time of injection, but other manipulations of DA signaling or catecholamines in general had no effect on PER2. In the BLA and DG, disruption of catecholamine signaling using AMPT or morphine injections blunted the normal PER2 peak in these regions but DA-selective manipulations had no effect on PER2. None of these manipulations affected the normal PER2 rhythm in the SCN. Taken together, these findings indicate that daily stimulation of 02 receptors regulates the PER2 rhythm in the dorsal striatum, and that DA does not directly contribute to the normal PER2 rhythm in the SCN or in any other forebrain region examined

A service for children? The development of a new out-of-school centre

Abstract\ud This thesis offers an in-depth analysis of conceptual, methodological, and policy\ud issues in the implementation of children's participation rights. The way in which\ud children's participation is understood and operationalised within and across services\ud affecting children is a related area for study.\ud The thesis explores the varied emphases given to children's participation rights (and\ud multi-agency working) within and across play, educational, health, welfare and out-ofschool\ud services; and it examines and discusses conceptual, policy and practice issues\ud in the implementation of children's participation rights within and across these\ud services.\ud The example of the development of an out-of-school centre known as "A Space" is\ud then used to provide a detailed analysis of the progress and process of participative\ud and multi-agency working. Both the A Space exemplar and the wider public policy\ud context within which it is located are viewed as forms of 'data' -and it is these two\ud forms of data which are considered together.\ud The thesis suggests that whilst it seems possible to make some progress towards\ud implementing some elements of children's participation considerable barriers exist.\ud These barriers include the tensions which exist between the interests of children and\ud of adults; the constraints of public policy agendas, socio-economic considerations,\ud and the kinds of welfarist and developmentalist understandings of children and\ud childhood which underpin the approaches of children's service agencies and the\ud perspectives of the staff therein. It concludes that if the implementation of children's\ud participation is to be anything more than a 'token' exercise then ways will need to be\ud found to overcome these barriers

Studies of the motivational effects of chronic buprenorphine treatment using sucrose pellet reward

Buprenorphine (BUP), a mixed opioid agonist-antagonist, is currently used as a treatment for opioid addiction. Previous research has shown that chronic BUP treatment decreases self-administration of drugs such as heroin and cocaine and drug-seeking behaviour in monkeys, rats, and humans. Furthermore, BUP attenuates the increase in nucleus accumbens (NAc) dopamine (DA) levels in response to an acute injection of heroin in naïve rats, whereas BUP potentiates the DA response to acute cocaine. To establish whether the suppression of drug seeking by BUP stems from an effect on motivated behaviour in general, four experiments were conducted to determine the effect of chronic BUP (3.0mg/kg/day) on responding for sucrose pellet reward. Chronic exposure to BUP was achieved with the use of subcutaneous osmotic minipumps. Results from Experiments 1 and 2 showed that rats exposed to chronic BUP took fewer sucrose pellets and reduced their active lever responding on a fixed ratio (FR) 1 schedule of self-administration; however, no such effect of BUP was observed on FR5 or progressive ratio (PR) schedules. In Experiment 3, chronic BUP slightly reduced sucrose seeking during extinction of self-administration and suppressed reinstatement of responding after sucrose priming. In Experiment 4, it was found using in vivo microdialysis that chronic BUP had no effect on the sucrose- or lab chow-induced rise in NAc DA, but did significantly increase basal DA tone. Overall, these results indicate that chronic BUP decreases motivation induced by sucrose reward and suggest that BUP reduces drug seeking and drug taking by blunting motivation in general

Isolation of Unknown Genes from Human Bone Marrow by Differental Screening and Single-Pass cDNA Sequences Determination

A cDNA sequencing project was initiated to characterize gene expression in human bone marrow and develop strategies to isolate novel genes. Forty-eight random cDNAs from total human bone marrow were subjected to single-pass DNA sequence analysis to determine a limited complexity of mRNAs expressed in the bone marrow. Overall, 8 cDNAs (17%) showed no similarity to known sequences. Information from DNA sequence analysis was used to develop a differential prescreen to subtract unwanted cDNAs and to enrich for unknown cDNAs. Forty-eight cDNAs that were negative with a complex probe were subject to single-pass DNA sequence determination. Of these prescreened cDNAs, the number of unknown sequences increased to 23 (48%). Unknown cDNAs were also characterized by RNA expression analysis using 25 different human leukemic cell lines. Of 13 unknown cDNAs tested, 10 were expressed in all cell types tested and 3 revealed a hematopoietic lineage-restricted expression pattern. Interestingly, while a total of only 96 bone marrow cDNAs were sequenced, 31 of these cDNAs represent sequences from unknown genes and 12 showed significant similarities to sequences in the data bases. One cDNA revealed a significant similarity to a serine/threonine-protein kinase at the amino acid level (56% identity for 123 amino acids) and may represent a previously unknown kinase. Differential screening techniques coupled with single-pass cDNA sequence analysis may prove to be a powerful and simple technique to examine developmental gene expression

Daily morphine injection and withdrawal disrupt 24-h wheel running and PERIOD2 expression patterns in the rat limbic forebrain

Symptoms of opiate withdrawal include disturbances in circadian rhythms. Here, we examined in male Wistar rats the effects of a daily, mid-morning morphine injection (5-40mg/kg, i.p.) and the subsequent withdrawal of morphine on 24-h patterns of wheel running and expression of the clock protein, PERIOD2 (PER2), in the master circadian clock, the suprachiasmatic nucleus (SCN), and regions of the limbic forebrain. Rats were killed either within 24 h of the last morphine injection or 2 days later. Nighttime wheel running was suppressed during daily morphine injections and following the withdrawal of morphine. Daily morphine injections and their subsequent withdrawal did not affect PER2 expression in the SCN, but blunted the normal daily peak of PER2 in the dorsal striatum, oval nucleus of the bed nucleus of the stria terminalis (BNSTov), central nucleus of the amygdala (CEA), basolateral amygdala (BLA), and dentate gyrus of the hippocampus (DG). We then examined the effect of injecting the D2/3 dopamine agonist, quinpirole (1 mg/kg, i.p.), or the alpha 2 adrenergic agonist, clonidine (0.1 mg/kg, i.p.), two drugs that alleviate opiate withdrawal symptoms, following withdrawal of the daily morphine injection. Quinpirole restored the daily PER2 pattern in the BNSTov and CEA, whereas clonidine restored and entrained a new PER2 pattern in the striatum, BLA, and DG. Together, these findings suggest that disruption of daily PER2 patterns in the forebrain might contribute to the circadian symptoms observed in opiate withdrawal. Furthermore, pharmacological treatments for withdrawal can restore PER2 patterns in regions of the limbic forebrain

Disruptive Technologies with Applications in Airline & Marine and Defense Industries

Disruptive Technologies With Applications in Airline, Marine, Defense Industries is our fifth textbook in a series covering the world of Unmanned Vehicle Systems Applications & Operations On Air, Sea, and Land. The authors have expanded their purview beyond UAS / CUAS / UUV systems that we have written extensively about in our previous four textbooks. Our new title shows our concern for the emergence of Disruptive Technologies and how they apply to the Airline, Marine and Defense industries. Emerging technologies are technologies whose development, practical applications, or both are still largely unrealized, such that they are figuratively emerging into prominence from a background of nonexistence or obscurity. A Disruptive technology is one that displaces an established technology and shakes up the industry or a ground-breaking product that creates a completely new industry.That is what our book is about. The authors think we have found technology trends that will replace the status quo or disrupt the conventional technology paradigms.The authors have collaborated to write some explosive chapters in Book 5:Advances in Automation & Human Machine Interface; Social Media as a Battleground in Information Warfare (IW); Robust cyber-security alterative / replacement for the popular Blockchain Algorithm and a clean solution for Ransomware; Advanced sensor technologies that are used by UUVs for munitions characterization, assessment, and classification and counter hostile use of UUVs against U.S. capital assets in the South China Seas. Challenged the status quo and debunked the climate change fraud with verifiable facts; Explodes our minds with nightmare technologies that if they come to fruition may do more harm than good; Propulsion and Fuels: Disruptive Technologies for Submersible Craft Including UUVs; Challenge the ammunition industry by grassroots use of recycled metals; Changing landscape of UAS regulations and drone privacy; and finally, Detailing Bioterrorism Risks, Biodefense, Biological Threat Agents, and the need for advanced sensors to detect these attacks.https://newprairiepress.org/ebooks/1038/thumbnail.jp

DRONE DELIVERY OF CBNRECy – DEW WEAPONS Emerging Threats of Mini-Weapons of Mass Destruction and Disruption (WMDD)

Drone Delivery of CBNRECy – DEW Weapons: Emerging Threats of Mini-Weapons of Mass Destruction and Disruption (WMDD) is our sixth textbook in a series covering the world of UASs and UUVs. Our textbook takes on a whole new purview for UAS / CUAS/ UUV (drones) – how they can be used to deploy Weapons of Mass Destruction and Deception against CBRNE and civilian targets of opportunity. We are concerned with the future use of these inexpensive devices and their availability to maleficent actors. Our work suggests that UASs in air and underwater UUVs will be the future of military and civilian terrorist operations. UAS / UUVs can deliver a huge punch for a low investment and minimize human casualties.https://newprairiepress.org/ebooks/1046/thumbnail.jp

Space Systems: Emerging Technologies and Operations

SPACE SYSTEMS: EMERGING TECHNOLOGIES AND OPERATIONS is our seventh textbook in a series covering the world of UASs / CUAS/ UUVs. Other textbooks in our series are Drone Delivery of CBNRECy – DEW Weapons: Emerging Threats of Mini-Weapons of Mass Destruction and Disruption (WMDD); Disruptive Technologies with applications in Airline, Marine, Defense Industries; Unmanned Vehicle Systems & Operations On Air, Sea, Land; Counter Unmanned Aircraft Systems Technologies and Operations; Unmanned Aircraft Systems in the Cyber Domain: Protecting USA’s Advanced Air Assets, 2nd edition; and Unmanned Aircraft Systems (UAS) in the Cyber Domain Protecting USA\u27s Advanced Air Assets, 1st edition. Our previous six titles have received considerable global recognition in the field. (Nichols & Carter, 2022) (Nichols et al., 2021) (Nichols R. K. et al., 2020) (Nichols R. et al., 2020) (Nichols R. et al., 2019) (Nichols R. K., 2018) Our seventh title takes on a new purview of Space. Let\u27s think of Space as divided into four regions. These are Planets, solar systems, the great dark void (which fall into the purview of astronomers and astrophysics), and the Dreamer Region. The earth, from a measurement standpoint, is the baseline of Space. It is the purview of geographers, engineers, scientists, politicians, and romantics. Flying high above the earth are Satellites. Military and commercial organizations govern their purview. The lowest altitude at which air resistance is low enough to permit a single complete, unpowered orbit is approximately 80 miles (125 km) above the earth\u27s surface. Normal Low Earth Orbit (LEO) satellite launches range between 99 miles (160 km) to 155 miles (250 km). Satellites in higher orbits experience less drag and can remain in Space longer in service. Geosynchronous orbit is around 22,000 miles (35,000 km). However, orbits can be even higher. UASs (Drones) have a maximum altitude of about 33,000 ft (10 km) because rotating rotors become physically limiting. (Nichols R. et al., 2019) Recreational drones fly at or below 400 ft in controlled airspace (Class B, C, D, E) and are permitted with prior authorization by using a LAANC or DroneZone. Recreational drones are permitted to fly at or below 400 ft in Class G (uncontrolled) airspace. (FAA, 2022) However, between 400 ft and 33,000 ft is in the purview of DREAMERS. In the DREAMERS region, Space has its most interesting technological emergence. We see emerging technologies and operations that may have profound effects on humanity. This is the mission our book addresses. We look at the Dreamer Region from three perspectives:1) a Military view where intelligence, jamming, spoofing, advanced materials, and hypersonics are in play; 2) the Operational Dreamer Region; whichincludes Space-based platform vulnerabilities, trash, disaster recovery management, A.I., manufacturing, and extended reality; and 3) the Humanitarian Use of Space technologies; which includes precision agriculture wildlife tracking, fire risk zone identification, and improving the global food supply and cattle management. Here’s our book’s breakdown: SECTION 1 C4ISR and Emerging Space Technologies. C4ISR stands for Command, Control, Communications, Computers, Intelligence, Surveillance, and Reconnaissance. Four chapters address the military: Current State of Space Operations; Satellite Killers and Hypersonic Drones; Space Electronic Warfare, Jamming, Spoofing, and ECD; and the challenges of Manufacturing in Space. SECTION 2: Space Challenges and Operations covers in five chapters a wide purview of challenges that result from operations in Space, such as Exploration of Key Infrastructure Vulnerabilities from Space-Based Platforms; Trash Collection and Tracking in Space; Leveraging Space for Disaster Risk Reduction and Management; Bio-threats to Agriculture and Solutions From Space; and rounding out the lineup is a chapter on Modelling, Simulation, and Extended Reality. SECTION 3: Humanitarian Use of Space Technologies is our DREAMERS section. It introduces effective use of Drones and Precision Agriculture; and Civilian Use of Space for Environmental, Wildlife Tracking, and Fire Risk Zone Identification. SECTION 3 is our Hope for Humanity and Positive Global Change. Just think if the technologies we discuss, when put into responsible hands, could increase food production by 1-2%. How many more millions of families could have food on their tables? State-of-the-Art research by a team of fifteen SMEs is incorporated into our book. We trust you will enjoy reading it as much as we have in its writing. There is hope for the future.https://newprairiepress.org/ebooks/1047/thumbnail.jp

The Cancer Research UK Stratified Medicine Programme as a model for delivering personalised cancer care

Genomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies