Rockville, Maryland : National Institute on Drug Abuse, 1991.

Jared W. Young
Mar 4, 2009; 29:2663-2665
Journal Club

PR Montague
Mar 1, 1996; 16:1936-1947
Articles

More than any other factor, it is our asset that determines our adversary. For most of us, our asset is the corpus of sensitive personal details used for online transactions. This all comes down to how much data an adversary can glean from you, and how thoroughly it can analyze it. If your data passes through some software or hardware, its developer or maintainer enjoys some measure of control.

Giving birth triggers a wide repertoire of physiological and behavioral changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the CNS, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca²⁺ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro to examine whether they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stable. An increase in the hyperpolarization-activated mixed cation current, I_h, possibly through unmasking as dopamine release drops during nursing, may partially explain the reconfiguration of TIDA rhythms. These findings identify a reversible plasticity in hypothalamic network activity that can serve to adapt the dam for motherhood.

SIGNIFICANCE STATEMENT Motherhood requires profound behavioral and physiological adaptations to enable caring for offspring, but the underlying CNS changes are poorly understood. Here, we show that, during lactation, neuroendocrine dopamine neurons, the "TIDA" cells that control prolactin secretion, reorganize their trademark oscillations to discharge in faster frequencies. Unlike previous studies, which typically have focused on structural and transcriptional changes during pregnancy and lactation, we demonstrate a functional switch in activity and one that, distinct from previously described puerperal modifications, reverses fully on weaning. We further provide evidence that a specific conductance (I_h) contributes to the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity.

Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated. In Drosophila melanogaster brain explant preparations, DA is released specifically onto α3/α'3 compartments of mushroom body (MB) neurons that have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO), which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in postsynaptic MB neurons, and CO-evoked DA release requires Ca²⁺ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons use two distinct modes of transmission to produce global and local DA signaling.

SIGNIFICANCE STATEMENT Dopamine (DA) is needed for various higher brain functions, including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation.

A rare bloom of microscopic organisms capable of making their own blue light has transformed several of the state’s beaches

In a written decision released Thursday, a panel of three appeal court judges said the judge who granted the award to McCaw North Drilling and Blasting Ltd. misinterpreted a clause in the contract for the cleanup.

A new study facilitated by the Workplace Safety and Insurance Board of Ontario states miners who were forced to inhale an aluminum powder were found to have a higher risk of Parkinson’s disease.

The World Curling Federation announced Thursday it is proposing to the International Olympic Committee that the 2021 world curling championships will determine which countries will book their tickets to Beijing 2022.

Colleen Jones, Sidney Crosby among many preeminent local sports figures reacting in the aftermath of Sunday's killing rampage.

CNA Staff, May 5, 2020 / 03:01 pm (CNA).- At least 51 workers have been infected with the novel coronavirus at the Grasberg mine in Indonesia, the world’s largest gold mine.

Nine employees of Freeport McMoRan, the organization who operates the mine, have been hospitalized due to COVID-19 and another 42 have been forced into quarantine, UCA News reported May 5.

The mine is located in Papua and is known for its production of gold and copper. The operation includes around 20,000 employees.

Riza Pratama, vice president of Freeport, said the company will fully cooperate with the government's coronavirus task force but will continue mining operations to support the national economy. He said the company will prioritize the health and safety of workers and will conduct regular health screenings, implement social distancing, provide a quarantine area for employees, according to UCA News.

Father Ansel Amo, who heads the Justice, Peace, and Integrity of Creation Commission for the Archdiocese of Merauke, said these measures are not enough to protect workers.

“Freeport management should limit workers’ activities so that they don’t transmit the disease to other people, including local people. They should stop its operations temporarily,” he told UCA News.

Indonesia has seen more than 12,000 cases from the coronavirus, leading to 872 reported deaths as of May 5. Globally, more than 3.7 million cases of the virus have been reported, and a quarter of a million deaths.

SCOTTISH energy storage start-up Gravitricity has received £300,000 from government agency Innovate UK to explore the potential to use gold mine shafts in South Africa as energy stores.

Prenatal methamphetamine exposure has been related to deficits in fetal growth, changes in infant neurobehavior, and fine motor deficits, but little is known about its developmental effects on behavior problems in early childhood.

This is the first prospective study to identify behavior problems associated with prenatal methamphetamine exposure. Mood difficulties and acting-out behavior are increased in exposed children by age 3 years. Early identification and intervention may prevent escalation into delinquency and psychopathology. (Read the full article)

Forearm fractures are unique injuries which are associated with lower bone mineral density in adults and white children. The relationships among bone mineral density, 25-hydroxyvitamin D status, and risk for forearm fracture have not been investigated in African American children.

Our data support an association between both lower bone mineral density and vitamin D deficiency and increased odds of forearm fracture in African American children. Promotion of bone health is indicated in this population. (Read the full article)

Brain maturation processes of very premature children are adversely affected by serious neonatal infections. Differences in brain development persist into childhood and adolescence, and underpin widespread neurocognitive and behavioral deficits in very preterm children.

We present evidence for long-term beneficial effects of early nutritional intervention with glutamine in very preterm infants on brain development at 8 years of age, mediated by a decrease in the number of serious neonatal infections. (Read the full article)

First drink before age 15 greatly increases the likelihood for later alcohol abuse or dependence. Separate investigations have linked many variables to alcohol initiation, but few have attempted to identify the optimal combination of predictors for age of alcohol initiation.

This article supports the screening questions selected in the joint National Institute on Alcohol Abuse and Alcoholism and the American Academy of Pediatrics initiative to identify and initiate intervention in youth at risk for early use of alcohol. (Read the full article)

A la veille de l’entrée en vigueur le 15 avril de l’obligation de rendre publique l’origine des minerais pour les grandes compagnies basées aux Etats-Unis, ICG a effectué une mission au Nord Kivu afin d’évaluer les différentes stratégies de lutte contre les minerais des conflits et leur impact sur le terrain.

As legislation requiring large U.S. companies to disclose the origins of the minerals they use is meant to come into force this year, Crisis Group sent a mission to North Kivu to assess the different strategies used to fight conflict minerals and their impact in the field.

Treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP+Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) at 4-day intervals, plus allopurinol at 30 mg/kg/12 h p.o. during 130 days; LC+Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose), plus allopurinol during 130 days; Allop, treated with allopurinol only; non-treated control. Parasite loads were evaluated by quantitative PCR in liver, spleen and bone marrow and by immunohistochemistry in the ear skin, before, just after treatment and 4 months later. LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen and bone marrow 4 months after treatment, compared to the pre-treatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin, in comparison to the control group. On the basis of clinical staging and parasitological evaluations, LCP formulation exhibited a more favorable therapeutic profile, when compared to LC one, being therefore promising for treatment of canine visceral leishmaniasis.

Background: MRSA pose significant therapeutic challenges, related to their: frequency in clinical infections; innate virulence properties; and propensity for multi-antibiotic resistance. MRSA are among the most common causes of endovascular infections, including infective endocarditis (IE).

Objective: To employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE.

Study Design: TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (vs daptomycin alone). Primary intravegetation outcomes were: maximum size; weights at sacrifice; and MRSA counts at infection baseline vs after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment Day 1).

Results: A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase + daptomycin vs the daptomycin-alone therapy groups (p = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower vs daptomycin-alone (p < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (p = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower vs untreated controls (p<0.0001) and the daptomycin-alone group (p<0.0001).

Conclusion: This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size and weight. Moreover, TTE appears to be an efficient non-invasive tool to assess therapeutic efficacies in experimental MRSA IE.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

The Coronavirus and International Affairs Roundtable, taking place 9:30 a.m. Friday, April 17, via Zoom, will bring together experts in law and international affairs from Asia, Europe, the Middle East, North America, and the Caribbean to discuss the broader impact of COVID-19.

UEFA Best Women’s Player in Europe 2012/13 – Shortlist of top three announced

The impact the Coronavirus outbreak has had on children and young people is to be explored by Holyrood’s Education and Skills Committee as it announces its work in response to the current public health crisis.

The Scottish Government’s testing strategy during the coronavirus pandemic is to be investigated by the Health and Sport Committee.

California's budget reductions will result in some state curricular materials not reaching the state's schools until 2017 or later, Jack O'Connell says.

The employee had travelled from Polokwane with four other colleagues who are currently in isolation at the mine's health facility.

The Riverboat community sailed from port-to-port to mobilise believers into missions and share the Hope of God together. How is life after the Riverboat?

Saeed Abbas A. Aloqili has been selected as the College of Earth and Mineral Sciences’ student marshal for Penn State's spring 2020 Commencement ceremony, which will be held virtually at 2 p.m. on May 9.

Karl P. Schneider, a Schreyer Scholar, has been selected as the College of Earth and Mineral Sciences’ science honor marshal for Penn State's spring 2020 Commencement ceremony, which will be held virtually at 2 p.m. on May 9.

The Weather Risk Management Club has continued meeting via Zoom during the remote learning period, carrying on their work examining the impacts of severe weather events on the economy.

After considering the evidences and conclusions in previous trials, the Court could not establish that the Trial Courts or the High Court were wrong in holding the case against the appellant. Implied consent for the trainer to fly an aircraft do not apply here, as there were telephonic signals sent to the aircraft, to bring it back. Wrongful gain can be mere unlawful acquisition of a property, creating ‘temporary’ loss to the Government. The circumstances conclude both the essential ingredients of theft – absence of consent and unlawfulness of means. From the factual analysis, the Court concludes that the wrongful gain and loss were intentional. However, considering that the appellant has already undergone imprisonment, his sentence was modified to the period already undergone. The appeal was dismissed while maintaining the conviction.

There is an issue in the world for stopping uncontrolled immigration of nonwhite, as it adversely affects the world.Boris Johnson the UK Prime Minister has made a campaign promise to make an onslaught on migration to control and check it. There is a…

The push for a comprehensive inquiry into the origin of the novel coronavirus is being hampered by the US narrative that Covid-19 may have stemmed from a lab in China, Australian diplomatic and intelligence sources told Reuters.
Read Full Article at RT.com

A study within the National Estuarine Research Reserve System to determine the destructiveness of crabs to salt marshes found that, while crabs can be a problem in some areas, a far greater threat facing marshes is sea level rise. Crabs play an important role in maintaining a balanced ecosystem in salt marshes, but too many […]

The post Study Examines Crab Impact on Salt Marsh Health appeared first on DNERR Blog - State of Delaware.

However, the Bench refused to interfere in the matter after the petitioners informed the judges that they were not personally affected and had filed the PILs in public interest.

Differentiating good IP from mediocre or bad IP is getting more difficult, in part because it depends upon how and where it is used and in part, because even the best IP may work better in one system than another—even in chips developed by the same vendor.  

So, how do you measure IP quality and why it is so complicated?

The answer depends on who is asking. Most of the time, the definition of IP quality depends on your vantage point.  If you are an R&D manager, IP quality means something. If you are a global supply manager, IP quality means something else. If you are an SoC start-up, your measure of quality is quite different from that of an established fabless company. If you are designing IP in-house, then your considerations are very different than being a commercial IP vendor. If you are designing an automotive SoC, then we are in a totally different category. How about as an IP vendor? How do you articulate IP quality metrics to your customers?

This varies greatly by the type of IP, as well. When it comes to interface (hard) IP and controllers, if you are an R&D manager, your goal is to design IP that meets the IP specifications and PPA (power, performance, and area) targets. You need to validate your design via silicon test chips. This applies to all hard PHYs, which must be mapped to a particular foundry process. For controllers that are in RTL form—we called these soft IP—you have to synthesize them into a particular target library in a particular foundry process in order to realize them in a physical form suitable for SoC integration. Of course, your design will need to go through a series of design validation steps via simulation, design verification and passing the necessary DRC checks, etc. In addition, you want to see the test silicon in various process corners to ensure the IP is robust and will perform well under normal process variations in the production wafers.

For someone in IP procurement, the measure of quality will be based on the maturity of the IP. This involves the number of designs that have been taped out using this IP and the history of bug reports and subsequent fixes. You will be looking for quality of the documentation and the technical deliverables. You will also benchmark the supplier’s standard operating procedures for bug reporting and technical support, as well as meeting delivery performance in prior programs. This is in addition to the technical teams doing their technical diligence.

An in-house team that is likely to design IP for a particular SoC project will be using an established design flow and will have legacy knowledge of last generation’s IP. They may be required to design the IP with some reusability in mind for future programs. However, such reusability requirements will not need to be as stringent and as broad as those of commercial IP vendors because there are likely to be established metrics and procedures in place to follow as part of the design team’s standard operating procedures. Many times, new development based on a prior design that has been proven in use will be started, given this stable starting point. All of these criteria help the team achieve a quality outcome more easily.

Then, if designing for an automotive SoC, additional heavy lifting is required.  Aside from ensuring that the IP meets the specifications of the protocol standards and passes the compliance testing, you also must pay attention to meeting functional safety requirements. This means adherence to ISO 26262 requirements and subsequently achieving ASIL certification. Oftentimes, even for IP, you must perform some AEC-Q100-related tests that are relevant to IP, such as ESD, LU, and HTOL.

To read more, please visit: https://semiengineering.com/why-ip-quality-is-so-difficult-to-determine/

Hi Folks, A question that I've often received from designers, "Is there a method to determine the amount of memory required before I submit a job? I use distributed processing and need to provide an estimate before submitting jobs." The answer...(read more)

•Annual event in Shanghai gathers global decision-makers to discuss digital trends, insights and best practices for sustainable manufacturing in the Industry Renaissance •Speakers include thought leaders from ABB, Accenture, China Center for Information Industry Development, FAW Group Corporation, Huawei, IDC, SATS •Interactive workshops featuring the 3DEXPERIENCE platform highlight the transformative role of virtual worlds on the creation of new customer experiences

Tanzania's economy is booming and its tourism sector is thriving. However, concerns about the president's strong-arm tactics and delays in the completion of key infrastructure projects are threatening this growth.

London has retained its position as fDi’s European City of the Future, while Paris has climbed to second place, knocking Dublin into the third spot. 

Toronto-based Hydrostor Inc., a leader in advanced compressed-air energy storage (A-CAES), has announced a A$30 million technology demonstration project at the former Angas Zinc mine in Strathalbyn, Adelaide.