julilili42/papers huggingface dataset:
DeepCEST 3T: Robust MRI parameter determination and uncertainty quantification with neural networks—application to CEST imaging of the human brain at 3T
2019-12-10

Purpose Calculation of sophisticated MR contrasts often requires complex mathematical modeling. Data evaluation is computationally expensive, vulnerable to artifacts, and often sensitive to fit algorithm parameters. In this work, we investigate whether neural networks can provide not only fast model fitting results, but also a quality metric for the predicted values, so called uncertainty quantification, investigated here in the context of multi‐pool Lorentzian fitting of CEST MRI spectra at 3T. Methods A deep feed‐forward neural network including a probabilistic output layer allowing for uncertainty quantification was set up to take uncorrected CEST‐spectra as input and predict 3T Lorentzian parameters of a 4‐pool model (water, semisolid MT, amide CEST, NOE CEST), including the B 0 inhomogeneity. Networks were trained on data from 3 subjects with and without data augmentation, and applied to untrained data from 1 additional subject and 1 brain tumor patient. Comparison to conventional Lorentzian fitting was performed on different perturbations of input data. Results The deepCEST 3T networks provided fast and accurate predictions of all Lorentzian parameters and were robust to input perturbations because of noise or B 0 artifacts. The uncertainty quantification detected fluctuations in input data by increase of the uncertainty intervals. The method generalized to unseen brain tumor patient CEST data. Conclusions The deepCEST 3T neural network provides fast and robust estimation of CEST parameters, enabling online reconstruction of sophisticated CEST contrast images without the typical computational cost. Moreover, the uncertainty quantification indicates if the predictions are trustworthy, enabling confident interpretation of contrast changes.
Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America
2019-12-10

Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV) associated lymphoma, prevalent in Asia and Latin America. Studies in Asian cohorts have identified some recurrent gene mutations in ENKTL; however, the mutational landscape of ENKTL in Latin America is unknown. In this study, we investigated the mutational profile and EBV strains of 71 ENKTL cases from Latin America (42 from Mexico, 17 from Peru, and 12 from Argentina) and compared it with Asian cohorts. The mutational analysis was performed by next generation sequencing (NGS) using an Ion AmpliSeqTM custom panel covering for the most frequently mutated genes identified in ENKTL. STAT3 was the most frequent mutated gene (16 cases: 23%), followed by MSN (10 cases; 14%), BCOR (9 cases; 13%), DDX3X (6 cases; 8%), TP53 (6 cases; 8%), MGA (3 cases; 4%), JAK3 (2 cases; 3%), and STAT5B (1 case; 1%). Mutations in STAT3, BCOR, and DDX3X were nearly mutually exclusive, suggesting different molecular pathways involved in the pathogenesis of ENKTL; whereas mutations in MGA, MSN, and TP53 were concomitant with other mutations. Most cases (75%) carried Type A EBV without the 30-bp LMP1 gene deletion. The overall survival was significantly associated with serum LDH level, Eastern Cooperative Oncology Group (ECOG) performance status, International Prognostic Index (IPI) score, and therapy (p < 0.05), but not associated with any mutation, EBV strain or deletion in EBV LMP1 gene. In conclusion, mutational analysis of ENKTL from Latin America reveals frequent gene mutations leading to activation of the JAK-STAT pathway (25%), mostly STAT3. Compared to Asian cohorts, BCOR, DDX3X and TP53 mutations were also identified but with different frequencies. None of these mutations were associated with prognosis.
Role of the d⁎(2380) dibaryon in NN interaction
2019-12-10

It is demonstrated for the first time that the dibaryon resonance d⁎(2380) discovered reliably in the numerous experiments at the WASA@COSY facility (Jülich FZ) determines almost completely (when supplemented with the peripheral one-pion exchange) NN scattering phase shifts and inelasticities in the coupled partial-wave channels D33–G33 not only near the resonance position, but also in a broad energy range from zero up to about 1 GeV. Keywords: Nucleon-nucleon interaction, Dibaryon resonances
Is the SNR HESS J1731-347 Colliding with Molecular Clouds?
2019-12-10

Abstract The supernova remnant HESS J1731-347 is a young supernova remnant (SNR) that displays a nonthermal X-ray and TeV shell structure. A molecular cloud at a distance of ∼3.2 kpc is spatially coincident with the western part of the SNR, and it was likely hit by the SNR. The X-ray emission from this part of the shell is much lower than from the rest of the SNR. Moreover, a compact GeV emission region coincident with the cloud has been detected with a soft spectrum. These observations seem to imply a shock-cloud collision scenario at this area, where the stalled shock can no longer accelerate super-TeV electrons or maintain strong magnetic turbulence downstream, while the GeV cosmic rays (CRs) are released through this stalled shock. To test this hypothesis, we have performed a detailed Fermi -LAT reanalysis of the HESS J1731-347 region with over nine years of data. Two distinct GeV components are found, one displaying a soft spectrum is from the compact GeV emission region, the other one displaying a hard spectrum is from the rest of the SNR (excluding the cloud region). A hadronic model involving a shock-cloud collision scenario is built to explain the γ -ray emission from this area. It consists of three CR sources: run-away super-TeV CRs that have escaped from the fast shock, leaked GeV CRs from the stalled shock, and the local CR sea. The X-ray and γ -ray emission of the SNR excluding the shock-cloud interaction region is explained in a one-zone leptonic model. Our shock-cloud collision model explains the GeV–TeV observations from the clouds around HESS J1731-347, i.e., a cloud in contact with the SNR and a distant cloud in spatial coincidence to the TeV source HESS J1729-345. We find however that the leaked GeV CRs from the shock-cloud collision do not necessarily dominate the GeV emission from the clouds, due to a comparable contribution from the local CR sea.
Innovative efficiency as a lever to overcome financial constraints in R&D contests
2019-12-10

Often the winner of an R&amp;D contest seems unexpected or surprising, e.g. small firms win a disproportionate number of R&amp;D contests despite having limited funds and on average lower market power. Here, different contest situations are modeled by considering variations in the innovative efficiency, patent valuation and financial resources of firms. It is found that small firms can be the Nash winner through highly efficient innovation despite financial constraints and low patent valuation. The results are helpful in understanding and predicting the probability of a firm's successful innovation.
Access to d- and l-Psicose Derivatives via Hydroxy Methylation of Ribono Lactone
2019-12-10

2,3,5-Tri-O-benzyl- and 2,3,5-tri-O-methyl-d-ribono-γ-lactone were converted with (methoxyethoxymethoxy)methyl and benzyloxy tributylstannane into the corresponding protected d-psicoses as mixtures of anomers in 31%–72% yield. Treatment of 2,3,5-tri-O-methyl-l-ribono-γ-lactone with benzyloxy tributylstannane afforded the corresponding l-psicose derivative as an anomeric mixture in 72% yield. Both methylated psicoses were further converted into 1,2-O-isopropylidene-3,4,6-tri-O-methyl-d- and l-psicofuranosides, the respective α- and β-anomers of which could be separated and characterized.
Multi-level Steiner Trees
2019-12-10

In the classical Steiner tree problem, given an undirected, connected graph G =( V , E ) with non-negative edge costs and a set of terminals T ⊆ V , the objective is to find a minimum-cost tree E &amp;prime ⊆ E that spans the terminals. The problem is APX-hard; the best-known approximation algorithm has a ratio of ρ = ln (4)+ε &lt; 1.39. In this article, we study a natural generalization, the multi-level Steiner tree (MLST) problem: Given a nested sequence of terminals T l ⊂ ... ⊂ T 1 ⊆ V , compute nested trees E l ⊆ ... ⊆ E 1 ⊆ E that span the corresponding terminal sets with minimum total cost. The MLST problem and variants thereof have been studied under various names, including Multi-level Network Design, Quality-of-Service Multicast tree, Grade-of-Service Steiner tree, and Multi-tier tree. Several approximation results are known. We first present two simple O (l)-approximation heuristics. Based on these, we introduce a rudimentary composite algorithm that generalizes the above heuristics, and determine its approximation ratio by solving a linear program. We then present a method that guarantees the same approximation ratio using at most 2l Steiner tree computations. We compare these heuristics experimentally on various instances of up to 500 vertices using three different network generation models. We also present several integer linear programming formulations for the MLST problem and compare their running times on these instances. To our knowledge, the composite algorithm achieves the best approximation ratio for up to l = 100 levels, which is sufficient for most applications, such as network visualization or designing multi-level infrastructure.
Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ1-42 decrease with age, whereas NT1 tau and NfL increase
2019-12-10

Abstract Background: Down syndrome (DS) is the most common genetic cause of Alzheimer’s Disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS – Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years.Methods: Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. The analytes were: Aβ1-42, NfL, and tau. The latter was measured by an assay (NT1) which detects forms of tau containing at least residues 6-198.Results: High Aβ1-42 and NT1 tau, and low NfL, were observed in infants. Across all ages, Aβ1-42 levels were higher in DS than controls. Levels of Aβ1-42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents and young adults, but thereafter increased in DS compared to controls. Conclusions: High levels of Aβ1-42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas, the changes seen in later life are consistent with emergence of pathological alterations. Our plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e. 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age, should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with emerging AD therapies.
The ornithological remains from Marathousa 1 (Middle Pleistocene; Megalopolis Basin, Greece)
2019-12-10

In the Middle Pleistocene open-air locality Marathousa 1 (Megalopolis Basin, Peloponnese, Greece), lithic artefacts are spatially and stratigraphically associated with faunal remains. Among the latter, birds are known by over 120 skeletal elements and represent an important part of the vertebrate fauna. The majority of them are identified as anseriform birds of various sizes, from swan size (Cygnus olor) to teal size (Anas crecca). The next largest group is gruiform birds, while, at least one small-sized passerine is also present (cf. Cinclus cinclus). A number of taxa are recorded for the first time in the Pleistocene of Greece. The taphonomic analysis of the deposit points to a minimal transfer of the avian skeletal elements, accumulated possibly through the combined action of some raptors and natural transfer of unconsumed avian remains. The palaeoecological analysis reveals a rich lakeshore environment, under temperate climatic conditions, that would support large numbers of aquatic and terrestrial invertebrates and small vertebrates. The avifaunal composition and its richness demonstrate the importance of the palaeolake system, which would have contributed to the development of habitats capable of supporting a variety of species including hominins.
Revisiting Ursus etruscus (Carnivora, Mammalia) from the Early Pleistocene of Greece with description of new material
2019-12-10

The Villafranchian ursids of Greece are scanty, represented by a few isolated teeth and bones. During our last field campaigns in the Mygdonia Basin (Macedonia, Greece) we discovered an almost complete cranium, as well as some cranial, dental and postcranial remains, which are presented in this article. The new material originates from the locality Tsiotra Vryssi (TSR), dated to the late Villafranchian (1.8–1.2 Ma). The specimens are described and compared with ursids from various European localities; their morphological characters and dimensions place it with Ursus etruscus Cuvier, 1823, while the dental features are most similar to the specimens from Pietrafitta (Italy). The TSR cranium was CT-scanned in order to create a 3D virtual model and study its internal anatomy. Its observed endocranial traits exhibit primitive conditions, confirming the basal position of U. etruscus among the Pleistocene European ursids. Most of these features are shared with U. arctos and clearly differ from U. deningeri and U. spelaeus. Finally, we provide a revision of the known Greek material of U. etruscus and the biostratigraphic distribution of the Miocene–Pleistocene ursids of Greece. The earliest secure appearance of Ursus etruscus in Greece is found in the locality Dafnero (Western Macedonia), dated to the end of the middle Villafranchian at ~2.0 Ma, whereas its probable last occurrence is known from the locality Apollonia 1 of the Mygdonia Basin, dated to the latest Villafranchian at ~1.2 Ma.
The Lower Palaeolithic site of Marathousa 1, Megalopolis, Greece: overview of the evidence
2019-12-10

Marathousa 1 is a Lower Palaeolithic open-air site located in the Megalopolis basin, an area<br> in Southern Greece known for its fossiliferous sediments. Mining activities in the basin<br> uncovered a thick sequence of Middle Pleistocene lacustrine deposits representing the<br> environment of a palaeolake. Marathousa 1 was discovered in 2013 during a targeted<br> palaeoanthropological survey and excavated subsequently by an interdisciplinary team from<br> the Ephoreia of Palaeoanthropology–Speleology of Greece and the University of Tübingen,<br> Germany. This article presents results from the ongoing investigation and reviews the state<br> of knowledge about the site.<br> Systematic excavations during five field seasons have exposed a total of 72 m2 and revealed<br> a partial skeleton of the elephant Palaeoloxodon antiquus and remains of other large<br> mammals in spatial and stratigraphic association with a “small tool” lithic assemblage.<br> Faunal and taphonomic studies indicate the presence of cut-marks and percussion damage<br> on elephant and other large mammal bones. The study of site formation processes, together<br> with taphonomic and geostatistic spatial analyses confirm the association of fossil and<br> hominin activity remains and the stratigraphic integrity of the site. Radiometric dating,<br> geological and biostratigraphical evidence suggest that hominin activity at the site occurred<br> between 0.5–0.4 Ma.<br> Marathousa 1 is the oldest currently known archaeological site in Greece and the only Lower<br> Palaeolithic butchering site in the Southern Balkans. It is also a key site for documenting high<br> resolution palaeoclimatic, palaeoenvironmental and cultural records of a wider geographical<br> area that potentially acted as a refugium during the successive waves of hominin<br> colonization of Europe.
Muscle-Liver Substrate Fluxes in Exercising Humans and Potential Effects on Hepatic Metabolism
2019-12-11

Abstract Context The liver is crucial to maintain energy homeostasis during exercise. Skeletal muscle-derived metabolites can contribute to the regulation of hepatic metabolism. Objective We aim to elucidate which metabolites are released from the working muscles and taken up by the liver in exercising humans and their potential influence on hepatic function. Methods In two separate studies, young healthy men fasted overnight and then performed an acute bout of exercise. Arterial-to-venous differences of metabolites over the hepato-splanchnic bed and over the exercising and resting leg were investigated by capillary electrophoresis- and liquid chromatography-mass spectrometry metabolomics platforms. Liver transcriptome data of exercising mice were analyzed by pathway analysis to find a potential overlap between exercise-regulated metabolites and activators of hepatic transcription. Results During exercise, hepatic O2 uptake and CO2 delivery were increased two-fold. In contrast to all other free fatty acids (FFA), those FFA with 18 or more carbon atoms and a high degree of saturation showed a constant release in the liver vein and only minor changes by exercise. FFA 6:0 and 8:0 were released from the working leg and taken up by the hepato-splanchnic bed. Succinate and malate showed a pronounced hepatic uptake during exercise and were also released from the exercising leg. The transcriptional response in the liver of exercising mice indicates the activation of HIF-, NRF2-, and cAMP-dependent gene transcription. These pathways can also be activated by succinate. Conclusion Metabolites circulate between working muscles and the liver and may support the metabolic adaption to exercise by acting both as substrates and as signaling molecules.
Association of Longitudinal Changes in Cerebrospinal Fluid Total Tau and Phosphorylated Tau 181 and Brain Atrophy With Disease Progression in Patients With Alzheimer Disease
2019-12-11

These findings suggest that CSF tTau and pTau181 may have different associations with brain atrophy across the disease time course. These results have implications for understanding the dynamics of disease pathobiology and interpreting neuronal injury biomarker concentrations in response to Alzheimer disease progression and disease-modifying therapies.
New Insights into Multistep-Phosphorelay (MSP)/Two-Component System (TCS) Regulation: Are Plants and Bacteria That Different?
2019-12-11

The Arabidopsis multistep-phosphorelay (MSP) is a signaling mechanism based on a phosphorelay that involves three different types of proteins: Histidine kinases, phosphotransfer proteins, and response regulators. Its bacterial equivalent, the two-component system (TCS), is the most predominant device for signal transduction in prokaryotes. The TCS has been extensively studied and is thus generally well-understood. In contrast, the MSP in plants was first described in 1993. Although great advances have been made, MSP is far from being completely comprehended. Focusing on the model organism Arabidopsis thaliana, this review summarized recent studies that have revealed many similarities with bacterial TCSs regarding how TCS/MSP signaling is regulated by protein phosphorylation and dephosphorylation, protein degradation, and dimerization. Thus, comparison with better-understood bacterial systems might be relevant for an improved study of the Arabidopsis MSP.
Measuring individual differences in cognitive abilities in the lab and on the web
2019-12-11

The present study compared lab-based and web-based versions of cognitive individual difference measures widely used in second language research (working memory and declarative memory). Our objective was to validate web-based versions of these tests for future research and to make these measures available for the wider second language research community, thus contributing to the study of individual differences in language learning. The establishment of measurement equivalence of the two administration modes is important because web-based testing allows researchers to address methodological challenges such as restricted population sampling, low statistical power, and small sample sizes. Our results indicate that the lab-based and web-based versions of the tests were equivalent, i.e., scores of the two test modes correlated. The strength of the relationships, however, varied as a function of the kind of measure, with equivalence appearing to be stronger in both the working memory and the verbal declarative memory tests, and less so in the nonverbal declarative memory test. Overall, the study provides evidence that web-based testing of cognitive abilities can produce similar performance scores as in the lab.
Syntrophy via interspecies H2transfer betweenChristensenellaandMethanobrevibacterunderlies their global co-occurrence in the human gut
2019-12-11

Abstract Across human populations, 16S rRNA gene-based surveys of gut microbiomes have revealed that the bacterial family Christensenellacea e and the archaeal family Methanobacteriaceae co-occur and are enriched in individuals with a lean, compared to an obese, BMI. Whether these association patterns reflect interactions between metabolic partners remains to be ascertained, as well as whether these associations play a role in the lean host phenotype with which they associate. Here, we validated previously reported co-occurrence patterns of the two families, and their association with a lean BMI, with a meta-analysis of 1,821 metagenomes derived from 10 independent studies. Furthermore, we report positive associations at the genus and species level between Christensenella spp. and Methanobrevibacter smithii, the most abundant methanogen of the human gut. By co-culturing three Christensenella spp. With M. smithii, we show that Christensenella spp. efficiently support the of M. smithii via H 2 production, far better than Bacteroides thetaiotaomicron . C. minuta forms flocs colonized by M. smithii even when H 2 is in excess. In culture with C. minuta , H 2 consumption by M. smithii shifts the metabolic output of C. minuta ’s fermentation towards acetate rather than butyrate. Together, these results indicate that the widespread co-occurrence of these microbiota is underpinned by both physical and metabolic interactions. Their combined metabolic activity may provide insights into their association with a lean host BMI. Importance The human gut microbiome is made of trillions of microbial cells, most of which are Bacteria , with a subset of Archaea . The bacterial family Christensenellaceae and the archaeal family Methanobacteriaceae are widespread in human guts. They correlate with each other and with a lean body type. Whether species of these two families interact, and how they affect the body type, are unanswered questions. Here, we showed that species within these families correlate with each other across people. We also demonstrated that particular species of these two families grow together in dense flocs, wherein the bacteria provide hydrogen gas to the archaea, which then make methane. When the archaea are present, the ratio of bacterial products (which are nutrients for humans) is changed. These observations indicate when these species grow together, their products have the potential to affect the physiology of their human host.