Showing papers by "University of Coimbra published in 2015"
TL;DR: A new kernelized correlation filter is derived, that unlike other kernel algorithms has the exact same complexity as its linear counterpart, which is called dual correlation filter (DCF), which outperform top-ranking trackers such as Struck or TLD on a 50 videos benchmark, despite being implemented in a few lines of code.
Abstract: The core component of most modern trackers is a discriminative classifier, tasked with distinguishing between the target and the surrounding environment. To cope with natural image changes, this classifier is typically trained with translated and scaled sample patches. Such sets of samples are riddled with redundancies—any overlapping pixels are constrained to be the same. Based on this simple observation, we propose an analytic model for datasets of thousands of translated patches. By showing that the resulting data matrix is circulant, we can diagonalize it with the discrete Fourier transform, reducing both storage and computation by several orders of magnitude. Interestingly, for linear regression our formulation is equivalent to a correlation filter, used by some of the fastest competitive trackers. For kernel regression, however, we derive a new kernelized correlation filter (KCF), that unlike other kernel algorithms has the exact same complexity as its linear counterpart. Building on it, we also propose a fast multi-channel extension of linear correlation filters, via a linear kernel, which we call dual correlation filter (DCF). Both KCF and DCF outperform top-ranking trackers such as Struck or TLD on a 50 videos benchmark, despite running at hundreds of frames-per-second, and being implemented in a few lines of code (Algorithm 1). To encourage further developments, our tracking framework was made open-source.
4,994 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
TL;DR: This survey analyzes existing protocols and mechanisms to secure communications in the IoT, as well as open research issues and analyzes the open challenges and strategies for future research work in the area.
Abstract: The Internet of Things (IoT) introduces a vision of a future Internet where users, computing systems, and everyday objects possessing sensing and actuating capabilities cooperate with unprecedented convenience and economical benefits. As with the current Internet architecture, IP-based communication protocols will play a key role in enabling the ubiquitous connectivity of devices in the context of IoT applications. Such communication technologies are being developed in line with the constraints of the sensing platforms likely to be employed by IoT applications, forming a communications stack able to provide the required power—efficiency, reliability, and Internet connectivity. As security will be a fundamental enabling factor of most IoT applications, mechanisms must also be designed to protect communications enabled by such technologies. This survey analyzes existing protocols and mechanisms to secure communications in the IoT, as well as open research issues. We analyze how existing approaches ensure fundamental security requirements and protect communications on the IoT, together with the open challenges and strategies for future research work in the area. This is, as far as our knowledge goes, the first survey with such goals.
968 citations
University of Copenhagen1, Finnish Institute of Occupational Health2, University of Southern Denmark3, University of Basel4, Lund University5, Autonomous University of Barcelona6, University of Coimbra7, Katholieke Universiteit Leuven8, University of Osnabrück9, Karolinska Institutet10, VU University Amsterdam11, Jagiellonian University Medical College12, St Thomas' Hospital13, University of Erlangen-Nuremberg14
TL;DR: The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed‐type hypersensitivity skin and mucosal conditions.
Abstract: The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
930 citations
University of Konstanz1, University of Vienna2, Academy of Sciences of the Czech Republic3, University of Potsdam4, University of Göttingen5, Russian Academy of Sciences6, University of Canterbury7, Spanish National Research Council8, Monash University9, Alexander von Humboldt Biological Resources Research Institute10, University of Costa Rica11, Tomsk State University12, Nelson Mandela Metropolitan University13, University of Coimbra14, University of Concepción15, Botanic Garden Meise16, University of Delhi17, University of the Republic18, Southern Illinois University Carbondale19, Department of National Parks, Wildlife and Plant Conservation20, Martin Luther University of Halle-Wittenberg21, University of Oldenburg22, Sun Yat-sen University23, King Saud University24, Naturalis25, Wageningen University and Research Centre26, Stellenbosch University27, Charles University in Prague28
TL;DR: The results quantify for the first time the extent of plant naturalizations worldwide, and illustrate the urgent need for globally integrated efforts to control, manage and understand the spread of alien species.
Abstract: All around the globe, humans have greatly altered the abiotic and biotic environment with ever-increasing speed. One defining feature of the Anthropocene epoch is the erosion of biogeographical barriers by human-mediated dispersal of species into new regions, where they can naturalize and cause ecological, economic and social damage. So far, no comprehensive analysis of the global accumulation and exchange of alien plant species between continents has been performed, primarily because of a lack of data. Here we bridge this knowledge gap by using a unique global database on the occurrences of naturalized alien plant species in 481 mainland and 362 island regions. In total, 13,168 plant species, corresponding to 3.9% of the extant global vascular flora, or approximately the size of the native European flora, have become naturalized somewhere on the globe as a result of human activity. North America has accumulated the largest number of naturalized species, whereas the Pacific Islands show the fastest increase in species numbers with respect to their land area. Continents in the Northern Hemisphere have been the major donors of naturalized alien species to all other continents. Our results quantify for the first time the extent of plant naturalizations worldwide, and illustrate the urgent need for globally integrated efforts to control, manage and understand the spread of alien species.
704 citations
TL;DR: It is indicated that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders.
Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
630 citations
World Health Organization1, University College London2, Public Health Agency of Canada3, Centers for Disease Control and Prevention4, The Catholic University of America5, European Centre for Disease Prevention and Control6, University of Milan7, Karolinska University Hospital8, University of Brescia9, Israel Ministry of Health10, Norwegian Institute of Public Health11, Médecins Sans Frontières12, Istituto Superiore di Sanità13, International Federation of Red Cross and Red Crescent Societies14, Robert Koch Institute15, Helsinki University Central Hospital16, International Organization for Migration17, University of California, San Francisco18, Carlos III Health Institute19, Ministero della Salute20, University of Coimbra21, Statens Serum Institut22, Institut Jules Bordet23, Health Protection Scotland24, University of Sassari25, Japanese Ministry of Health, Labour and Welfare26
TL;DR: An action framework for countries with low tuberculosis (TB) incidence sets out priority interventions required for these countries to progress first towards “pre-elimination” and eventually the elimination of TB as a public health problem.
Abstract: This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.
627 citations
TL;DR: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy and addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH).
Abstract: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations
MR1. ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 – 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence). MR4. ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence). MR5. ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 – 120 minutes prior to upper gastrointestinal [GI] endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence). MR7. Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early ( MR8. ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence). MR10. In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence). MR11. ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence). MR14. In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of Helicobacter pylori in the acute setting with initiation of appropriate antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be performed in those patients with a negative test in the acute setting. Documentation of successful H. pylori eradication is recommended (strong recommendation, high quality evidence). MR15. In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).
611 citations
TL;DR: The structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), is described, uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases, which has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors.
Abstract: A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 A structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds.
603 citations
University of British Columbia1, Institute of Molecular Pathology and Immunology of the University of Porto2, BC Cancer Agency3, McGill University Health Centre4, University of Coimbra5, Instituto Português de Oncologia Francisco Gentil6, St. John's University7, Mayo Clinic8, Technische Universität München9, University of Otago10, Mount Sinai Hospital, Toronto11, European Institute of Oncology12, University of Siena13, University of Cambridge14
TL;DR: HGC syndrome may be best defined by mutations in CDH1 and closely related genes, rather than through clinical criteria that capture families with heterogeneous susceptibility profiles, providing more precise estimates of age-associated risks of gastric and breast cancer that will improve counseling of unaffected carriers.
Abstract: Importance E-cadherin ( CDH1 ) is a cancer predisposition gene mutated in families meeting clinically defined hereditary diffuse gastric cancer (HDGC). Reliable estimates of cancer risk and spectrum in germline mutation carriers are essential for management. For families without CDH1 mutations, genetic-based risk stratification has not been possible, resulting in limited clinical options. Objectives To derive accurate estimates of gastric and breast cancer risks in CDH1 mutation carriers and determine if germline mutations in other genes are associated with HDGC. Design, Setting, and Participants Testing for CDH1 germline mutations was performed on 183 index cases meeting clinical criteria for HDGC. Penetrance was derived from 75 mutation-positive families from within this and other cohorts, comprising 3858 probands (353 with gastric cancer and 89 with breast cancer). Germline DNA from 144 HDGC probands lacking CDH1 mutations was screened using multiplexed targeted sequencing for 55 cancer-associated genes. Main Outcomes and Measures Accurate estimates of gastric and breast cancer risks in CDH1 mutation carriers and the relative contribution of other cancer predisposition genes in familial gastric cancers. Results Thirty-one distinct pathogenic CDH1 mutations (14 novel) were identified in 34 of 183 index cases (19%). By the age of 80 years, the cumulative incidence of gastric cancer was 70% (95% CI, 59%-80%) for males and 56% (95% CI, 44%-69%) for females, and the risk of breast cancer for females was 42% (95% CI, 23%-68%). In CDH1 mutation–negative index cases, candidate mutations were identified in 16 of 144 probands (11%), including mutations within genes of high and moderate penetrance: CTNNA1 , BRCA2 , STK11 , SDHB , PRSS1 , ATM , MSR1 , and PALB2 . Conclusions and Relevance This is the largest reported series of CDH1 mutation carriers, providing more precise estimates of age-associated risks of gastric and breast cancer that will improve counseling of unaffected carriers. In HDGC families lacking CDH1 mutations, testing of CTNNA1 and other tumor suppressor genes should be considered. Clinically defined HDGC families can harbor mutations in genes (ie, BRCA2) with different clinical ramifications from CDH1 . Therefore, we propose that HDGC syndrome may be best defined by mutations in CDH1 and closely related genes, rather than through clinical criteria that capture families with heterogeneous susceptibility profiles.
516 citations
TL;DR: In this article, a review of the literature on 2,5-furandicarboxylic acid derived polymers is presented, covering recent aspects related with challenges in developing polyesters, polyamides and their precursors.
TL;DR: In this paper, the authors study the shadows of Kerr black holes with scalar hair and show that for non-Kerr-like horizons and ultracompact BS-like hair, novel shapes arise, sizes are considerably smaller, and multiple shadows of a single BH become possible.
Abstract: Using backwards ray tracing, we study the shadows of Kerr black holes with scalar hair (KBHSH). KBHSH interpolate continuously between Kerr BHs and boson stars (BSs), so we start by investigating the lensing of light due to BSs. Moving from the weak to the strong gravity region, BSs-which by themselves have no shadows-are classified, according to the lensing produced, as (i) noncompact, which yield not multiple images, (ii) compact, which produce an increasing number of Einstein rings and multiple images of the whole celestial sphere, and (iii) ultracompact, which possess light rings, yielding an infinite number of images with (we conjecture) a self-similar structure. The shadows of KBHSH, for Kerr-like horizons and noncompact BS-like hair, are analogous to, but distinguishable from, those of comparable Kerr BHs. But for non-Kerr-like horizons and ultracompact BS-like hair, the shadows of KBHSH are drastically different: novel shapes arise, sizes are considerably smaller, and multiple shadows of a single BH become possible. Thus, KBHSH provide quantitatively and qualitatively new templates for ongoing (and future) very large baseline interferometry observations of BH shadows, such as those of the Event Horizon Telescope.
Harvard University1, Lawrence Livermore National Laboratory2, Massachusetts Institute of Technology3, University of the Basque Country4, University of Liège5, Forschungszentrum Jülich6, Queen's University Belfast7, University of Coimbra8, University of Zaragoza9, Martin Luther University of Halle-Wittenberg10, Max Planck Society11
TL;DR: This article discusses how the real-space approach has allowed for the recent development of new ideas for the simulation of electronic systems, and the exact solution of the Schrödinger equation for low-dimensionality systems.
Abstract: Real-space grids are a powerful alternative for the simulation of electronic systems. One of the main advantages of the approach is the flexibility and simplicity of working directly in real space where the different fields are discretized on a grid, combined with competitive numerical performance and great potential for parallelization. These properties constitute a great advantage at the time of implementing and testing new physical models. Based on our experience with the Octopus code, in this article we discuss how the real-space approach has allowed for the recent development of new ideas for the simulation of electronic systems. Among these applications are approaches to calculate response properties, modeling of photoemission, optimal control of quantum systems, simulation of plasmonic systems, and the exact solution of the Schrodinger equation for low-dimensionality systems.
Charité1, Medical University of Graz2, University of Southern Denmark3, University of Silesia in Katowice4, University of Genoa5, Federal University of São Paulo6, Autonomous University of Barcelona7, University of Coimbra8, St. John's University9, Hiroshima University10, Medical University of South Carolina11, Hannover Medical School12, Hospital Kuala Lumpur13, University of Zurich14, University of Manitoba15, University of Mainz16, University of Toronto17, University of Bari18, Peking University19
TL;DR: This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomecha.
Abstract: This guideline is the result of a systematic literature review using the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA 2 LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomecha
TL;DR: Commonly used methods for assessing status and estimating timing and two relatively recent anthropometric (non-invasive) methods (status—percentage of predicted near adult height attained at observation, timing—predicted maturity offset/age at PHV) are described and evaluated.
Abstract: The search for talent is pervasive in youth sports. Selection/exclusion in many sports follows a maturity-related gradient largely during the interval of puberty and growth spurt. As such, there is emphasis on methods for assessing maturation. Commonly used methods for assessing status (skeletal age, secondary sex characteristics) and estimating timing (ages at peak height velocity (PHV) and menarche) in youth athletes and two relatively recent anthropometric (non-invasive) methods (status—percentage of predicted near adult height attained at observation, timing—predicted maturity offset/age at PHV) are described and evaluated. The latter methods need further validation with athletes. Currently available data on the maturity status and timing of youth athletes are subsequently summarised. Selection for sport and potential maturity-related correlates are then discussed in the context of talent development and associated models. Talent development from novice to elite is superimposed on a constantly changing base—the processes of physical growth, biological maturation and behavioural development, which occur simultaneously and interact with each other. The processes which are highly individualised also interact with the demands of a sport per se and with involved adults (coaches, trainers, administrators, parents/guardians).
TL;DR: In this overview only phenolic antioxidant compounds that display significant anticancer activity have been described and the principal mechanisms for their anti-proliferative effects were also described.
TL;DR: A multidisciplinary view of the issues raised by the development of PDT is presented, showing how spectroscopy, photophysics, photochemistry and pharmacokinetics of photosensitizers determine the mechanism of cell death and clinical protocols.
Abstract: Photodynamic therapy (PDT) requires a medical device, a photosensitizing drug and adequate use of both to trigger biological mechanisms that can rapidly destroy the primary tumour and provide long-lasting protection against metastasis. We present a multidisciplinary view of the issues raised by the development of PDT. We show how spectroscopy, photophysics, photochemistry and pharmacokinetics of photosensitizers determine the mechanism of cell death and clinical protocols. Various examples of combinations with chemotherapies and immunotherapies illustrate the opportunities to potentiate the outcome of PDT. Particular emphasis is given to the mechanisms that can be exploited to establish PDT as a systemic treatment of solid tumours and metastatic disease.
TL;DR: This review summarizes the evidence pointing to a role for BDNF in generating functional and structural changes at synapses required for both early- and late phases of LTP in the hippocampus and discusses the effects of BDNF on the synaptic proteome.
Wellcome Trust Centre for Human Genetics1, National Institute for Health Research2, University of Oxford3, Illumina4, University of Coimbra5, Laboratory of Molecular Biology6, University of Ulm7, Cliniques Universitaires Saint-Luc8, University of Zurich9, University Hospital Southampton NHS Foundation Trust10, Northwestern University11, Queen's University Belfast12, Imperial College London13, Copenhagen University Hospital14, Belfast City Hospital15, King's College London16, Shriners Hospitals for Children17
TL;DR: It is found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy.
Abstract: To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.
TL;DR: This work discusses current combinatorial approaches to convert otherwise non-immunogenic instances of RCD into bona fide ICD, and suggests that novel therapeutic regimens that trigger ICD are urgently awaited.
Abstract: The term “immunogenic cell death” (ICD) is commonly employed to indicate a peculiar instance of regulated cell death (RCD) that engages the adaptive arm of the immune system. The inoculation of cancer cells undergoing ICD into immunocompetent animals elicits a specific immune response associated with the establishment of immunological memory. Only a few agents are intrinsically endowed with the ability to trigger ICD. These include a few chemotherapeutics that are routinely employed in the clinic, like doxorubicin, mitoxantrone, oxaliplatin, and cyclophosphamide, as well as some agents that have not yet been approved for use in humans. Accumulating clinical data indicate that the activation of adaptive immune responses against dying cancer cells is associated with improved disease outcome in patients affected by various neoplasms. Thus, novel therapeutic regimens that trigger ICD are urgently awaited. Here, we discuss current combinatorial approaches to convert otherwise non-immunogenic instances of RCD into bona fide ICD.
TL;DR: It is described here that the specific combination of phenazine/triphenylmethane polymers with CNT leads to an improved performance of the resulting sensing devices, because of their complementary electrical, electrochemical and mechanical properties, and also due to synergistic effects.
Agro ParisTech1, Institut national de la recherche agronomique2, Oeschger Centre for Climate Change Research3, Chinese Academy of Sciences4, Université du Québec à Chicoutimi5, University of Zaragoza6, University of Coimbra7, Mendel University8, Spanish National Research Council9, Sukachev Institute of Forest10, Siberian Federal University11, University of Ljubljana12, University of Innsbruck13, Charles University in Prague14, Queen's University15
TL;DR: High-resolution cellular based measurements of wood formation dynamics in three coniferous forest sites in northeastern France are presented and it is suggested that forecasted changes in the annual cycle of climatic factors may shift the phase timing of stem size increase and woody biomass production in the future.
Abstract: Wood is the main terrestrial biotic reservoir for long-term carbon sequestration(1), and its formation in trees consumes around 15% of anthropogenic carbon dioxide emissions each year(2). However, the seasonal dynamics of woody biomass production cannot be quantified from eddy covariance or satellite observations. As such, our understanding of this key carbon cycle component, and its sensitivity to climate, remains limited. Here, we present high-resolution cellular based measurements of wood formation dynamics in three coniferous forest sites in northeastern France, performed over a period of 3 years. We show that stem woody biomass production lags behind stem-girth increase by over 1 month. We also analyse more general phenological observations of xylem tissue formation in Northern Hemisphere forests and find similar time lags in boreal, temperate, subalpine and Mediterranean forests. These time lags question the extension of the equivalence between stem size increase and woody biomass production to intra-annual time scales(3, 4, 5, 6). They also suggest that these two growth processes exhibit differential sensitivities to local environmental conditions. Indeed, in the well-watered French sites the seasonal dynamics of stem-girth increase matched the photoperiod cycle, whereas those of woody biomass production closely followed the seasonal course of temperature. We suggest that forecasted changes in the annual cycle of climatic factors(7) may shift the phase timing of stem size increase and woody biomass production in the future.
Maastricht University1, Heidelberg University2, University of Erlangen-Nuremberg3, University of Göttingen4, University of Bonn5, Charité6, University of Genoa7, University of Geneva8, University of Cologne9, Aix-Marseille University10, VU University Amsterdam11, King's College London12, University of Eastern Finland13, Medical University of Łódź14, University of Perugia15, Aristotle University of Thessaloniki16, French Institute of Health and Medical Research17, University of Oxford18, University of Brescia19, University of Liège20, University of Gothenburg21, University of Lisbon22, University of Coimbra23, University of Antwerp24, Karolinska University Hospital25, Lund University26, Pierre-and-Marie-Curie University27, VU University Medical Center28
TL;DR: The use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage and the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis are supported.
Abstract: Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
TL;DR: The Standard Model (SM) Higgs boson hypothesis is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons, and the observed distributions of variables sensitive to the non- SM tensor couplings are compatible with the SM predictions.
Abstract: Studies of the spin, parity and tensor couplings of the Higgs boson in the [Formula: see text], [Formula: see text] and [Formula: see text] decay processes at the LHC are presented. The investigations are based on [Formula: see text] of pp collision data collected by the ATLAS experiment at [Formula: see text] TeV and [Formula: see text] TeV. The Standard Model (SM) Higgs boson hypothesis, corresponding to the quantum numbers [Formula: see text], is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons. All tested alternative models are excluded in favour of the SM Higgs boson hypothesis at more than 99.9 % confidence level. Using the [Formula: see text] and [Formula: see text] decays, the tensor structure of the interaction between the spin-0 boson and the SM vector bosons is also investigated. The observed distributions of variables sensitive to the non-SM tensor couplings are compatible with the SM predictions and constraints on the non-SM couplings are derived.
TL;DR: In this review, aspects and problems on the role of intracellular ROS formation and nutrition with the link to diseases and their problematic therapeutical issues are discussed.
Abstract: Within the last twenty years the view on reactive oxygen species (ROS) has changed; they are no longer only considered to be harmful but also necessary for cellular communication and homeostasis in different organisms ranging from bacteria to mammals In the latter, ROS were shown to modulate diverse physiological processes including the regulation of growth factor signaling, the hypoxic response, inflammation and the immune response During the last 60–100 years the life style, at least in the Western world, has changed enormously This became obvious with an increase in caloric intake, decreased energy expenditure as well as the appearance of alcoholism and smoking; These changes were shown to contribute to generation of ROS which are, at least in part, associated with the occurrence of several chronic diseases like adiposity, atherosclerosis, type II diabetes, and cancer In this review we discuss aspects and problems on the role of intracellular ROS formation and nutrition with the link to diseases and their problematic therapeutical issues
TL;DR: The potential to improve phytoextraction of soils contaminated with multiple heavy metals by inoculating metal hyperaccumulating plants with their own selected functional endophytic bacterial strains is demonstrated.
TL;DR: This is the first paper that highlights the novel and future therapeutic perspectives for the treatment of skin malignancies, new therapeutic agents and promising technological approaches, from nanotechnology to immunotherapy.
TL;DR: It is shown that caffeine prevents the maladaptive changes caused by CUS in a manner mimicked by the selective blockade of adenosine A2A receptors (A2AR), suggesting A2AR as candidate targets to alleviate the consequences of chronic stress on brain function.
Abstract: The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine A2A receptor (A2AR) antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection Therefore we tested the ability of A2AR to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of A2AR in glutamatergic terminals in the hippocampus Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective A2AR antagonist KW6002 (3 mg/kg, po); (iii) global A2AR deletion; and (iv) selective A2AR deletion in forebrain neurons Notably, A2AR blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the A2AR antagonist SCH58261 (01 mg/kg, ip) reversed the mood and synaptic dysfunction caused by CUS These results herald a key role for synaptic A2AR in the control of chronic stress-induced modifications and suggest A2AR as candidate targets to alleviate the consequences of chronic stress on brain function
TL;DR: Analysis of some of the most prominent open government portals suggests that this type of open data portal does not possess important structural and organizational elements needed to fully support ordinary citizens engaged in public accountability efforts.
Aix-Marseille University1, University of Grenoble2, University of Savoy3, Joint Institute for Nuclear Research4, National University of La Plata5, University of Science and Technology of China6, University of Coimbra7, University of Milan8, University of Paris-Sud9, Dresden University of Technology10, Columbia University11, University of Iowa12, Shandong University13
TL;DR: In this article, the authors reported the observation of Higgs boson decays to $WW^{\ast}$ based on an excess over background of 6.1 standard deviations, where the Standard Model expectation is 5.8 standard deviations.
Abstract: We report the observation of Higgs boson decays to $WW^{\ast}$ based on an excess over background of 6.1 standard deviations in the dilepton final state, where the Standard Model expectation is 5.8 standard deviations. Evidence for the vector-boson fusion (VBF) production process is obtained with a significance of 3.2 standard deviations. The results are obtained from a data sample corresponding to an integrated luminosity of $25 \textrm{pb}^{-1}$ from $\sqrt{s}=7$ and 8 TeV $pp$ collisions recorded by the ATLAS detector at the LHC. For a Higgs boson mass of 125.36 GeV, the ratio of the measured value to the expected value of the total production cross section times branching fraction is $1.09^{+0.16}_{-0.15} \textrm{(stat.)}^{+0.17}_{-0.14} \textrm{(syst.)}$. The corresponding ratios for the gluon fusion and vector-boson fusion production mechanisms are $1.02\pm 0.19 \textrm{(stat.)}^{+0.22}_{-0.18} \textrm{(syst.)}$ and $1.27^{+0.44}_{-0.40} \textrm{(stat.)}^{+0.30}_{-0.21} \textrm{(syst.)}$, respectively. At $\sqrt{s}=8$ TeV, the total production cross sections are measured to be $\sigma(gg\to H\rightarrow WW^\ast) = 4.6\pm0.9\,\textrm{(stat.)}\,^{+0.8}_{-0.7}\,\textrm{(syst.)}\textrm{pb}$ and $\sigma(\textrm{VBF} H\rightarrow WW^\ast) = 0.51\,^{+0.17}_{-0.15}\,\textrm{(stat.)}\,^{+0.13}_{-0.08}\,\textrm{(syst.)}\textrm{pb}$. The fiducial cross section is determined for the gluon-fusion process in exclusive final states with zero or one associated jet.