Edith Silverglied Lisansky Gomberg, PhD 1920–2005

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65886/1/j.1530-0277.2006.00043.x.pd

A Comprehensive Workflow for General-Purpose Neural Modeling with Highly Configurable Neuromorphic Hardware Systems

In this paper we present a methodological framework that meets novel requirements emerging from upcoming types of accelerated and highly configurable neuromorphic hardware systems. We describe in detail a device with 45 million programmable and dynamic synapses that is currently under development, and we sketch the conceptual challenges that arise from taking this platform into operation. More specifically, we aim at the establishment of this neuromorphic system as a flexible and neuroscientifically valuable modeling tool that can be used by non-hardware-experts. We consider various functional aspects to be crucial for this purpose, and we introduce a consistent workflow with detailed descriptions of all involved modules that implement the suggested steps: The integration of the hardware interface into the simulator-independent model description language PyNN; a fully automated translation between the PyNN domain and appropriate hardware configurations; an executable specification of the future neuromorphic system that can be seamlessly integrated into this biology-to-hardware mapping process as a test bench for all software layers and possible hardware design modifications; an evaluation scheme that deploys models from a dedicated benchmark library, compares the results generated by virtual or prototype hardware devices with reference software simulations and analyzes the differences. The integration of these components into one hardware-software workflow provides an ecosystem for ongoing preparative studies that support the hardware design process and represents the basis for the maturity of the model-to-hardware mapping software. The functionality and flexibility of the latter is proven with a variety of experimental results

Quantal Glutamate Release Is Essential for Reliable Neuronal Encodings in Cerebral Networks

Background: The neurons and synapses work coordinately to program the brain codes of controlling cognition and behaviors. Spike patterns at the presynaptic neurons regulate synaptic transmission. The quantitative regulations of synapse dynamics in spike encoding at the postsynaptic neurons remain unclear. Methodology/Principal Findings: With dual whole-cell recordings at synapse-paired cells in mouse cortical slices, we have investigated the regulation of synapse dynamics to neuronal spike encoding at cerebral circuits assembled by pyramidal neurons and GABAergic ones. Our studies at unitary synapses show that postsynaptic responses are constant over time, such as glutamate receptor-channel currents at GABAergic neurons and glutamate transport currents at astrocytes, indicating quantal glutamate release. In terms of its physiological impact, our results demonstrate that the signals integrated from quantal glutamatergic synapses drive spike encoding at GABAergic neurons reliably, which in turn precisely set spike encoding at pyramidal neurons through feedback inhibition. Conclusion/Significance: Our studies provide the evidences for the quantal glutamate release to drive the spike encodings precisely in cortical circuits, which may be essential for programming the reliable codes in the brain to manage wellorganize

Human Umbilical Cord Blood Cells Restore Brain Damage Induced Changes in Rat Somatosensory Cortex

Intraperitoneal transplantation of human umbilical cord blood (hUCB) cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury

Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport

Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T804M mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis

Impact of national malaria control scale-up programmes in Africa: magnitude and attribution of effects

<p>Abstract</p> <p>Background</p> <p>Since 2005, malaria control scale-up has progressed in many African countries. Controlled studies of insecticide-treated mosquito nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment during pregnancy (IPTp) and malaria case management suggested that when incorporated into national programmes a dramatic health impact, likely more than a 20% decrease in all-cause childhood mortality, was possible. To assess the extent to which national malaria programmes are achieving impact the authors reviewed African country programme data available through 2009.</p> <p>Methods</p> <p>National survey data, published literature, and organization or country reports produced during 2000-2009 were reviewed to assess available malaria financing, intervention delivery, household or target population coverage, and reported health benefits including infection, illness, severe anaemia, and death.</p> <p>Results</p> <p>By the end of 2009, reports were available for ITN household ownership (n = 34) and IPTp use (n = 27) in malaria-endemic countries in Africa, with at least two estimates (pre-2005 and post-2005 intervals). Information linking IRS and case management coverage to impact were more limited. There was generally at least a three-fold increase in household ITN ownership across these countries between pre-2005 (median of 2.4% of households with at least one ITN) and post-2005 (median of 32.5% of households with at least one ITN). Ten countries had temporal data to assess programme impact, and all reported progress on at least one impact indicator (typically on mortality); in under-five year mortality rates most observed a decline of more than 20%. The causal relationship between malaria programme scale-up and reduced child illness and mortality rates is supported by biologic plausibility including mortality declines consistent with experience from intervention efficacy trials, consistency of findings across multiple countries and different epidemiologic settings, and temporal congruity where morbidity and mortality declines have been documented in the 18 to 36 months following intervention scale-up.</p> <p>Conclusions</p> <p>Several factors potentially have contributed to recent health improvement in African countries, but there is substantial evidence that achieving high malaria control intervention coverage, especially with ITNs and targeted IRS, has been the leading contributor to reduced child mortality. The documented impact provides the evidence required to support a global commitment to the expansion and long-term investment in malaria control to sustain and increase the health impact that malaria control is producing in Africa.</p

A Research Strategy Case Study of Alcohol and Drug Prevention by Non-Governmental Organizations in Sweden 2003-2009

<p>Abstract</p> <p>Background</p> <p>Alcohol and drug prevention is high on the public health agenda in many countries. An increasing trend is the call for evidence-based practice. In Sweden in 2002 an innovative project portfolio including an integrated research and competence-building strategy for non-governmental organisations (NGOs) was designed by the National Board of Health and Welfare (NBHW). This research strategy case study is based on this initiative.</p> <p>Methods</p> <p>The embedded case study includes 135 projects in 69 organisations and 14 in-depth process or effect studies. The data in the case study has been compiled using multiple methods - administrative data; interviews and questionnaires to project leaders; focus group discussions and seminars; direct and participatory observations, interviews, and documentation of implementation; consultations with the NBHW and the NGOs; and a literature review. Annual reports have been submitted each year and three bi-national conferences Reflections on preventions have been held.</p> <p>Results</p> <p>A broad range of organisations have been included in the NBHW project portfolio. A minority of the project were run by Alcohol or drug organisations, while a majority has children or adolescents as target groups. In order to develop a trustful partnership between practitioners, national agencies and researchers a series of measures were developed and implemented: meeting with project leaders, project dialogues and consultations, competence strengthening, support to documentation, in-depth studies and national conferences. A common element was that the projects were program-driven and not research-driven interventions. The role of researchers-as-technical advisors was suitable for the fostering of a trustful partnership for research and development. The independence of the NGOs was regarded as important for the momentum in the project implementation. The research strategy also includes elements of participatory research.</p> <p>Conclusions</p> <p>This research strategy case study shows that it is possible to integrate research into alcohol and drug prevention programs run by NGOs, and thereby contribute to a more evidence-based practice. A core element is developing a trustful partnership between the researchers and the organisations. Moreover, the funding agency must acknowledge the importance of knowledge development and allocating resources to research groups that is capable of cooperating with practitioners and NGOs.</p

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January–August 2020

Background Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). Methods Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. Results As of August 2020, 442,677 (range: 18–185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112–1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. Conclusions Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta