A general guide to applying machine learning to computer architecture

The resurgence of machine learning since the late 1990s has been enabled by significant advances in computing performance and the growth of big data. The ability of these algorithms to detect complex patterns in data which are extremely difficult to achieve manually, helps to produce effective predictive models. Whilst computer architects have been accelerating the performance of machine learning algorithms with GPUs and custom hardware, there have been few implementations leveraging these algorithms to improve the computer system performance. The work that has been conducted, however, has produced considerably promising results. The purpose of this paper is to serve as a foundational base and guide to future computer architecture research seeking to make use of machine learning models for improving system efficiency. We describe a method that highlights when, why, and how to utilize machine learning models for improving system performance and provide a relevant example showcasing the effectiveness of applying machine learning in computer architecture. We describe a process of data generation every execution quantum and parameter engineering. This is followed by a survey of a set of popular machine learning models. We discuss their strengths and weaknesses and provide an evaluation of implementations for the purpose of creating a workload performance predictor for different core types in an x86 processor. The predictions can then be exploited by a scheduler for heterogeneous processors to improve the system throughput. The algorithms of focus are stochastic gradient descent based linear regression, decision trees, random forests, artificial neural networks, and k-nearest neighbors.This work has been supported by the European Research Council (ERC) Advanced Grant RoMoL (Grant Agreemnt 321253) and by the Spanish Ministry of Science and Innovation (contract TIN 2015-65316P).Peer ReviewedPostprint (published version

Laser-based 3D printing of hydrogel barrier models for microfludic applications

The placenta secures the survival and development of the fetus. As placental tissue connects the fetus with the mother and is responsible for endogenous and exogenous material transfer. The maternal and fetal blood are thereby separated, by the so-called placental barrier, which is made up by the trophoblastic syncytium and the fetal capillary wall. Research in the field of placenta biology represents a challenging topic, as current approaches are difficult to perform, time consuming and often carry the risk of harming the fetus. The establishment of a reproducible in-vitro model, simulating the placental transport is necessary to study fetal development and for identification of underlying causes of maldevelopment. In this study, a photosensitive hydrogel material, in combination with two-photon polymerisation, was used to produce high resolution structures with nanometre precision geometries. Gelatine modified with methacrylamide and amino-ethyl-methacrylate (GelMOD AEMA) was thereby crosslinked within a customised microfluidic-device under the addition of photoinitiator, separating the chip in two different compartments (Figure 1). The fetal compartment contains HUVEC cells which are cultivated in EGM2, while BeWo B30 cells are supplied with DMEM Ham-F12 to mimic the maternal compartment. This microfluidic approach in combination with native flow profiles can be used to precisely remodel the microenvironment of placental tissue. The establishment of a functional placenta-on-a-chip-model allows the modulation of different clinical and biological scenarios in the future. A potential application can be found in the simulation of altered sugar transport across the placental membrane and evaluation of the effects of altered nutrient balance in-utero Please click Additional Files below to see the full abstract

Patrón de abundancia espacio-temporal de la gamba de altura, Parapenaeus longirostris, y de la cigala, Nephrops norvegicus, en las aguas mediterráneas europeas

The main characteristics concerning the distribution of two of the most important decapod crustaceans of commercial interest in the Mediterranean Sea, the deep-water rose shrimp, Parapenaeus longirostris, and the Norway lobster, Nephrops norvegicus, are studied in the European Mediterranean waters. The study is based on data collected under the MEDITS trawl surveys from 1994 to 2015 from the Gibraltar Straits to the northeastern Levantine Basin (Cyprus waters). The observed differences can be interpreted as different responses to environmental drivers related to the differing life history traits of the two species. In fact, N. norvegicus is a long-living, benthic burrowing species with low growth and mortality rates, while P. longirostris is an epibenthic, short-living species characterized by higher rates of growth and mortality.Se investigaron las características de la distribución de dos de los crustáceos decápodos más importantes a nivel comercial del mar Mediterráneo, la gamba de altura, Parapenaeus longirostris y la cigala, Nephrops norvegicus, en aguas mediterráneas europeas. El presente estudio se basa en datos recopilados en las campañas de pesca experimental de arrastre MEDITS, relizadas de 1994 a 2015 desde el estrecho de Gibraltar hasta la cuenca levantina nororiental (aguas de Chipre). Las diferencias observadas en el patrón de distribución se pueden interpretar como distintas respuestas a factores ambientales relacionados con los diferentes rasgos del ciclo vital de las dos especies. De hecho, N. norvegicus es una especie bentónica de vida larga, con bajas tasas de crecimiento y mortalidad, mientras que P. longirostris es una especie epibentónica de vida corta, caracterizada por tasas más altas de crecimiento y de mortalidad

Fabrication of biomimetic placental barrier structures within a microfluidic device utilizing two-photon polymerization

The placenta is a transient organ, essential for development and survival of the unborn fetus. It interfaces the body of the pregnant woman with the unborn child and secures transport of endogenous and exogenous substances. Maternal and fetal blood are thereby separated at any time, by the so-called placental barrier. Current in vitro approaches fail to model this multifaceted structure, therefore research in the field of placental biology is particularly challenging. The present study aimed at establishing a novel model, simulating placental transport and its implications on development, in a versatile but reproducible way. The basal membrane was replicated using a gelatin-based material, closely mimicking the composition and properties of the natural extracellular matrix. The microstructure was produced by using a high-resolution 3D printing method - the two-photon polymerization (2PP). In order to structure gelatin by 2PP, its primary amines and carboxylic acids are modified with methacrylamides and methacrylates (GelMOD-AEMA), respectively. High-resolution structures in the range of a few micrometers were produced within the intersection of a customized microfluidic device, separating the x-shaped chamber into two isolated cell culture compartments. Human umbilical-vein endothelial cells (HUVEC) seeded on one side of this membrane simulate the fetal compartment while human choriocarcinoma cells, isolated from placental tissue (BeWo B30) mimic the maternal syncytium. This barrier model in combination with native flow profiles can be used to mimic the microenvironment of the placenta, investigating different pharmaceutical, clinical and biological scenarios. As proof-of-principle, this bioengineered placental barrier was used for the investigation of transcellular transport processes. While high molecular weight substances did not permeate, smaller molecules in the size of glucose were able to diffuse through the barrier in a time-depended manner. We envision to apply this bioengineered placental barrier for pathophysiological research, where altered nutrient transport is associated with health risks for the fetus

On the origin of European sheep as revealed by the diversity of the Balkan breeds and by optimizing population-genetic analysis tools

Background: In the Neolithic, domestic sheep migrated into Europe and subsequently spread in westerly and northwesterly directions. Reconstruction of these migrations and subsequent genetic events requires a more detailed characterization of the current phylogeographic differentiation. Results: We collected 50 K single nucleotide polymorphism (SNP) profiles of Balkan sheep that are currently found near the major Neolithic point of entry into Europe, and combined these data with published genotypes from southwest-Asian, Mediterranean, central-European and north-European sheep and from Asian and European mouflons. We detected clines, ancestral components and admixture by using variants of common analysis tools: geography-informative supervised principal component analysis (PCA), breed-specific admixture analysis, across-breed f 4 profiles and phylogenetic analysis of regional pools of breeds. The regional Balkan sheep populations exhibit considerable genetic overlap, but are clearly distinct from the breeds in surrounding regions. The Asian mouflon did not influence the differentiation of the European domestic sheep and is only distantly related to present-day sheep, including those from Iran where the mouflons were sampled. We demonstrate the occurrence, from southeast to northwest Europe, of a continuously increasing ancestral component of up to 20% contributed by the European mouflon, which is assumed to descend from the original Neolithic domesticates. The overall patterns indicate that the Balkan region and Italy served as post-domestication migration hubs, from which wool sheep reached Spain and north Italy with subsequent migrations northwards. The documented dispersal of Tarentine wool sheep during the Roman period may have been part of this process. Our results also reproduce the documented 18th century admixture of Spanish Merino sheep into several central-European breeds. Conclusions: Our results contribute to a better understanding of the events that have created the present diversity pattern, which is relevant for the management of the genetic resources represented by the European sheep population

Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial

<p>Abstract</p> <p>Background</p> <p>COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-κB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors.</p> <p>Methods</p> <p>Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days) or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days), in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily.</p> <p>Results</p> <p>No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease.</p> <p>Conclusion</p> <p>The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated.</p> <p>Trial registration number</p> <p>NCT00290680.</p

Workshop to scope and preselect indicators for criterion D3C3 under MSFD decision (EU) 2017/848 (WKD3C3SCOPE)

The workshop to scope and preselect indicators for Descriptor 3 criterion 3 under MSFD Commission Decision (EU) 2017/848 (WKD3C3SCOPE) provided a platform for experts from the EU member states and relevant regional bodies to meet and support development and progress the assessment methodology, based on a request by the EC (DGENV). WKD3C3SCOPE is the first of a series of three workshops (WKD3C3THRESHOLDS and WKSIMULD3) to provide guidance in relation to operational indicators for MSFD D3C3. The workshop was organized as a series of presentations with intermittent group discussions. On the first day of the workshop the participants discussed what defines a ‘healthy population structure’ for species with different life history traits (ToR a). During the following days, the group discussed and identified relevant D3C3 indicators (ToR b) and developed criteria to select among the identified D3C3 indicators to allow further testing and setting of thresholds at WKD3C3THRESHOLDS (ToR c). The participants found that overall, healthy fish stocks are characterized by high productivity, wide age and size structuring in the population, and the ability to quickly recover from disturbances. The groups noted that environmental factors, along with stock biomass and fishing pressure, influence the productivity and health of a stock, with environment playing a particularly large role in the recruitment of short-lived stocks. It was suggested that the age structure of a stock might be more relevant for evaluating the health of long-lived stocks. However, it was acknowledged that not all stocks have sufficient data to evaluate all proposed indicators, and a single indicator is unlikely to suffice for all stocks. Data availability, species- specific factors and regional or sub-regional variation are thus also important considerations. In relation to ToR b, the participants presented their work on potential indicators including: recruitment time-series, proportion of fish larger than the mean size of first sexual maturation, F rec/Fbar, length distribution L 90, relative proportion of old fish above A 90, indicators of spawner quality, and SSB/R. A discussion on pros/cons, benefits to the population of high or low indicator values, benefits supported by empirical evidence, applicability to data-poor stocks and benefits supported by simulation/theoretical considerations followed the presentations. Finally, in relation to ToR c, the difficulty emerged in ranking the indicators alone without considering the data used to estimate them and a new set of evaluation criteria for use in WKD3C3THRESHOLDS were defined. Based on the outputs of the meeting a list of indicators to be further evaluated has been drafted, which also emphasizes the stocks for which studies have empirically demonstrated effects on productivity. In addition to the listed indicators, indicators of genetic diversity and proportion of fish with parasite infestation were mentioned but to the knowledge of the participants, widespread data for these are currently not publicly available.info:eu-repo/semantics/publishedVersio

COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals:EAACI recommendations

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals

Establishing an online resource to facilitate global collaboration and inclusion of underrepresented populations:Experience from the MJFF Global Genetic Parkinson's Disease Project

Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder, currently affecting ~7 million people worldwide. PD is clinically and genetically heterogeneous, with at least 10% of all cases explained by a monogenic cause or strong genetic risk factor. However, the vast majority of our present data on monogenic PD is based on the investigation of patients of European White ancestry, leaving a large knowledge gap on monogenic PD in underrepresented populations. Gene-targeted therapies are being developed at a fast pace and have started entering clinical trials. In light of these developments, building a global network of centers working on monogenic PD, fostering collaborative research, and establishing a clinical trial-ready cohort is imperative. Based on a systematic review of the English literature on monogenic PD and a successful team science approach, we have built up a network of 59 sites worldwide and have collected information on the availability of data, biomaterials, and facilities. To enable access to this resource and to foster collaboration across centers, as well as between academia and industry, we have developed an interactive map and online tool allowing for a quick overview of available resources, along with an option to filter for specific items of interest. This initiative is currently being merged with the Global Parkinson's Genetics Program (GP2), which will attract additional centers with a focus on underrepresented sites. This growing resource and tool will facilitate collaborative research and impact the development and testing of new therapies for monogenic and potentially for idiopathic PD patients.</p

Management of anaphylaxis due to COVID-19 vaccines in the elderly

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.Peer reviewe