julilili42/papers huggingface dataset:
A physics-based model explains the prion-like features of neurodegeneration in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis
2018-10-15

Prion disease is characterized by a chain reaction in which infectious misfolded proteins force native proteins into a similar pathogenic structure. Recent studies have reinforced the hypothesis that the prion paradigm–the templated growth and spreading of misfolded proteins–could help explain the progression of a variety of neurodegenerative disorders. However, our current understanding of prion-like growth and spreading is rather empirical. Here we show that a physics-based reaction-diffusion model can explain the growth and spreading of misfolded protein in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. To characterize the progression of misfolded proteins across the brain, we combine the classical Fisher–Kolmogorov equation for population dynamics with an anisotropic diffusion model and simulate misfolding across a sagittal section and across the entire brain. In a systematic sensitivity analysis, we probe the role of the individual model parameters and show that the misfolded protein concentration is sensitive to the coefficients of growth, extracellular diffusion, and axonal transport, to the axonal fiber orientation, and to the initial seeding region. Our model correctly predicts amyloid-β deposits and tau inclusions in Alzheimer’s disease, α-synuclein inclusions in Parkinson’s disease, and TDP-43 inclusions in amyotrophic lateral sclerosis and displays excellent agreement with the histological patterns in diseased human brains. When integrated across the brain, our concentration profiles result in biomarker curves that display a striking similarity with the sigmoid shape and qualitative timeline of clinical biomarker models. Our results suggest that misfolded proteins in various neurodegenerative disorders grow and spread according to a universal law that follows the basic physical principles of nonlinear reaction and anisotropic diffusion. Our findings substantiate the notion of a common underlying principle for the pathogenesis of a wide variety of neurodegenerative disorders, the prion paradigm. A more quantitative understanding of the growth and spreading of misfolded amyloid-β, tau, α-synuclein, and TDP-43 would allow us to establish a prognostic timeframe of disease progression. This could have important clinical implications, ranging from more accurate estimates of the socioeconomic burden of neurodegeneration to a more informed design of clinical trials and pharmacological intervention.
Psychological talent predictors in youth soccer: A systematic review of the prognostic relevance of psychomotor, perceptual-cognitive and personality-related factors
2018-10-15

Within the multidimensional nature of soccer talent, recently there has been an increasing interest in psychological characteristics. The aim of this present research was to systematically review the predictive value of psychological talent predictors and provide better comprehension of the researchers' methodological approaches and the empirical evidence for individual factors (i.e., psychomotor, perceptual-cognitive and personality-related). Results highlighted heterogeneous study designs (e.g., participants, measurement methods, statistical analyses) which may limit the comparability of studies' findings. Analyzing the number of included studies, psychomotor (n = 10) and personality-related factors (n = 8) received more consideration within the literature than perceptual-cognitive factors (n = 4). In regard to empirical evidence, dribbling (0.47 ≤ d ≤ 1.24), ball control (0.57 ≤ d ≤ 1.28) and decision-making (d = 0.81) demonstrated good predictive values as well as the achievement motives hope for success (0.27 ≤ d ≤ 0.74) and fear of failure (0.21 ≤ d ≤ 0.30). In conclusion, there is growing acceptance of the need for more complex statistical analyses to predict future superior performance based on measures of current talent. New research addresses the necessity for large-scale studies that employ multidisciplinary test batteries to assess youth athletes at different age groups prospectively.
Nitrogen chlorosis in unicellular cyanobacteria – a developmental program for surviving nitrogen deprivation
2018-10-15

Summary Cyanobacteria evolved sophisticated mechanisms allowing them to cope with environmental depletion of combined nitrogen. Here, we describe progress in understanding the processes involved in acclimation of nondiazotrophic cyanobacteria to nitrogen shortage, known as nitrogen chlorosis. The process includes immediate metabolic changes and degradation of light harvesting complexes as well as long‐term acclimation responses. Consequently, quiescent cells substantially differing from vegetative cells are obtained. Thus, the process leading to these considerable metabolic and morphological changes is referred to as a developmental program. Current understanding of the relevant regulatory processes depicts an intricate mechanism involving modulation of transcription activators by proteinaceous interacting components, as well as by small metabolites reporting the energy status and carbon–nitrogen balance of the cell. In addition, we describe in detail the quiescent state characterizing cells under prolonged starvation and the process of recovery from this dormant chlorotic state. Accumulated data provide an in depth understanding of the mechanisms accompanying the cycling of cyanobacterial cells between vegetative growth, the quiescent‐state and the recovery program, allowing them to regain proliferative growth upon nutrient replenishment.
Assessment of cognitive‐driven activity of daily living impairment in non‐demented Parkinson's patients
2018-10-15

The core criterion for Parkinson's disease dementia ( PDD ) is the impairment in activities of daily living ( ADL ) function primarily caused by cognitive, not motor symptoms. There is evidence to assume that mild ADL impairments in mild cognitive impairment ( PD ‐ MCI ) characterize those patients at high risk for dementia. Data of 216 Parkinson's disease ( PD ) patients assessed with comprehensive motor and neuropsychological assessments were analysed. Based on linear regression models, subscores of the Functional Activities Questionnaire ( FAQ ) primarily reflecting patients’ global cognitive status ( FAQ C ) or PD ‐related motor severity ( FAQ M ) were developed. A quotient ( FAQ Q ) of both scores was calculated, with values &gt;1 indicating more cognitive‐ compared to motor‐driven ADL impairment. Both FAQ C and FAQ M scores were higher in PD ‐ MCI than cognitively normal ( PD ‐ CN ) patients, indicating more severe cognitive‐ and motor‐driven ADL impairments in this group. One third (31.6%) of the PD ‐ MCI group had a FAQ Q score &gt;1, which was significantly different from patients with PD ‐ CN ( p = .02). PD ‐ MCI patients with an FAQ Q score &gt;1 were more impaired on tests assessing attention ( p = .019) and language ( p = .033) compared to PD ‐ MCI patients with lower FAQ Q values. The differentiation between cognitive‐ and motor‐driven ADL is important, as the loss of functional capacity is the defining factor for a diagnosis of PDD . We were able to differentiate the cognitive‐driven from the motor‐driven ADL impairments for the FAQ . PD ‐ MCI patients with more cognitive‐ compared to motor‐driven ADL impairments may pose a risk group for conversion to PDD and can be targeted for early treatments.
Assessment of uveal melanomas using advanced diffusion-weighted imaging techniques: value of reduced field of view DWI (“zoomed DWI”) and readout-segmented DWI (RESOLVE)
2018-10-15

Background Diffusion-weighted imaging (DWI) has become an important tool for lesion characterization. Advanced techniques of DWI may be used to improve image quality. Purpose To evaluate multi-shot segmented DWI (rs-EPI, RESOLVE) and reduced field-of view DWI (rFOV-EPI, “zoomed” EPI) in patients with ocular melanoma and to compare image quality and diagnostic performance in differentiation of melanoma from retinal detachment. Material and Methods In this prospective and IRB-approved trial, we examined 26 patients using methods including conventional single-shot echo-planar DWI (ss-EPI), rs-EPI, and rFOV-EPI. Subjective image quality was compared using a four-point score and the maximum tumor length was measured in all sequences. Apparent diffusion coefficient (ADC) measurements were performed using a region-of interest analysis. Tumor delineation and differences in ADC values between melanomas and retinal detachments were compared. Results Diffusion restriction was markedly reduced in melanomas in all applied image techniques. Subjective image quality was significantly higher for rFOV-EPI (score = 3.5 ± 0.5) compared with rs-EPI (score = 3.3 ± 0.6) and ss-EPI (score = 2.5 ± 0.9). Regarding tumor diameter measurements, rFOV-EPI showed the best agreement compared with high-resolution conventional sequences. ADC measurements of the tumor and retinal detachment differed significantly ( P &lt; 0.001) with the rFOV-EPI performing best (sensitivities and specificities compared with T1-weighted ss-EPI 61%/82%; rFOV-EPI 86%/92%; rs-EPI 79%/92%, respectively). Conclusion rFOV-EPI showed improved image quality compared with ss-EPI and rs-EPI, the most accurate tumor delineation and the best differentiation from retinal detachments in our patients.
The Roman circus and southwestern city quarter of Carthage: first results of a new international research project
2018-10-15

Abstract The paper presents first results of a joint German–Tunisian research project in Carthage, Tunisia. Archaeological fieldwork has been undertaken (preceded by a geophysical survey) in the southwestern quarter of the ancient city to study the architecture, chronology and urban context of the circus. The area has, unlike the rest of Carthage, not been targeted by excavations of the late nineteenth/early twentieth centuries and, also unlike the rest of Carthage, is mostly not overbuilt, although under pressure from neighbouring communities. The area is the last one allowing a large-scale diachronic urban study in which the circus and its impact on the quarter is in the centre. From our first results, we can date the beginning of the construction of the circus to the late first century AD, with interventions in the early third century and usage continuing into the sixth. We were able to define the extension of the northern cavea and to study the western part of the spina and identify the meta at this point. Information has been obtained on early Roman, pre-circus use of the area as well as data on the Punic phases. Sixth- and seventh-century levels are also well preserved.
Moral Enhancement – And the Opposite: Making People More or Less Moral
2018-10-15

Abstract ‘Moral enhancement’ refers to the possibility of using biomedical means for making individuals morally better in practice. It has generated a heated debate, especially in terms of the strategies for enhancement, the means that provide the desired enhancement effects and the populations that are supposed to be enhanced. It is important to note the history of moral enhancement, reasons that have been given in the recent discussions for engaging in moral enhancement and possible targets of intervention (cognition, volition or effect). There is some evidence that suggests that psychopharmacological (Oxytocin and stimulant drugs), electromagnetic (noninvasive brain stimulation) and genetic means (selective reproduction and direct genome editing) could be used for such a purpose. However, no safe and effective means of moral enhancement are available at this time. Key Concepts Moral enhancement refers to the (speculative) possibility of using biomedical means for making individuals morally better. Bioliberals typically emphasise the importance of morphological and reproductive freedom in a liberal state. Transhumanists do not merely want to enhance humanity but overcome the limits of humankind and guide evolution towards a ‘posthuman’ age. Moral malleability refers to the idea that moral cognition is amenable to pharmacological, electromagnetic and possibly even genetic interventions. Psychopathic individuals have impaired capacity for empathy, guilt and remorse, and consequently commit a disproportionate amount of immoral acts, thus they are considered the key population in need of moral enhancement.
Impact of Organic Matter on Iron(II)-Catalyzed Mineral Transformations in Ferrihydrite–Organic Matter Coprecipitates
2018-10-16

Poorly crystalline Fe(III) (oxyhydr)oxides like ferrihydrite are abundant in soils and sediments and are often associated with organic matter (OM) in the form of mineral-organic aggregates. Under anoxic conditions, interactions between aqueous Fe(II) and ferrihydrite lead to the formation of crystalline secondary minerals, like lepidocrocite, goethite, or magnetite. However, the extent to which Fe(II)-catalyzed mineral transformations are influenced by ferrihydrite-associated OM is not well understood. We therefore reacted ferrihydrite-PGA coprecipitates (PGA = polygalacturonic acid, C:Fe molar ratios = 0-2.5) and natural Fe-rich organic flocs (C:Fe molar ratio = 2.2) with 0.5-5.0 mM isotopically labeled <sup>57</sup>Fe(II) at pH 7 for 5 weeks. Relying on the combination of stable Fe isotope tracers, a novel application of the PONKCS method to Rietveld fitting of X-ray diffraction (XRD) patterns, and <sup>57</sup>Fe Mössbauer spectroscopy, we sought to follow the temporal evolution in Fe mineralogy and elucidate the fate of adsorbed <sup>57</sup>Fe(II). At low C:Fe molar ratios (0-0.05), rapid oxidation of surface-adsorbed <sup>57</sup>Fe(II) resulted in <sup>57</sup>Fe-enriched crystalline minerals and nearly complete mineral transformation within days. With increasing OM content, the atom exchange between the added aqueous <sup>57</sup>Fe(II) and Fe in the organic-rich solids still occurred; however, XRD analysis showed that crystalline mineral precipitation was strongly inhibited. For high OM-content materials (C:Fe ≥ 1.2), Mössbauer spectroscopy revealed up to 39% lepidocrocite in the final Fe(II)-reacted samples. Because lepidocrocite was not detectable by XRD, we suggest that the Mössbauer-detected lepidocrocite consisted of nanosized clusters with lepidocrocite-like local structure, similar to the lepidocrocite found in natural flocs. Collectively, our results demonstrate that the C content of ferrihydrite-OM coprecipitates strongly impacts the degree and pathways of Fe mineral transformations and iron atom exchange during reactions with aqueous Fe(II).
Motion Segmentation & Multiple Object Tracking by Correlation Co-Clustering
2018-10-16

Models for computer vision are commonly defined either w.r.t. low-level concepts such as pixels that are to be grouped, or w.r.t. high-level concepts such as semantic objects that are to be detected and tracked. Combining bottom-up grouping with top-down detection and tracking, although highly desirable, is a challenging problem. We state this joint problem as a co-clustering problem that is principled and tractable by existing algorithms. We demonstrate the effectiveness of this approach by combining bottom-up motion segmentation by grouping of point trajectories with high-level multiple object tracking by clustering of bounding boxes. We show that solving the joint problem is beneficial at the low-level, in terms of the FBMS59 motion segmentation benchmark, and at the high-level, in terms of the Multiple Object Tracking benchmarks MOT15, MOT16 and the MOT17 challenge, and is state-of-the-art in some metrics.
Rule-based learning for eye movement type detection
2018-10-16

Eye movements hold information about human perception, intention, and cognitive state. Various algorithms have been proposed to identify and distinguish eye movements, particularly fixations, saccades, and smooth pursuits. A major drawback of existing algorithms is that they rely on accurate and constant sampling rates, error free recordings, and impend straightforward adaptation to new movements, such as microsaccades, since they are designed for certain eye movement detection. We propose a novel rule-based machine learning approach to create detectors on annotated or simulated data. It is capable of learning diverse types of eye movements as well as automatically detecting pupil detection errors in the raw gaze data. Additionally, our approach is capable of using any sampling rate, even with fluctuations. Our approach consists of learning several interdependent thresholds and previous type classifications and combines them into sets of detectors automatically. We evaluated our approach against the state-of-the-art algorithms on publicly available datasets. Our approach is integrated in the newest version of EyeTrace which can be downloaded at http://www.ti.uni-tuebingen.de/Eyetrace.1751.0.html.
Histogram of oriented velocities for eye movement detection
2018-10-16

Research in various fields including psychology, cognition, and medical science deal with eye tracking data to extract information about the intention and cognitive state of a subject. For the extraction of this information, the detection of eye movement types is an important task. Modern eye tracking data is noisy and most of the state-of-the-art algorithms are not developed for all types of eye movements since they are still under research. We propose a novel feature for eye movement detection, which is called histogram of oriented velocities. The construction of the feature is similar to the well known histogram of oriented gradients from computer vision. Since the detector is trained using machine learning, it can always be extended to new eye movement types. We evaluate our feature against the state-of-the-art on publicly available data. The evaluation includes different machine learning approaches such as support vector machines, regression trees, and k nearest neighbors. We evaluate our feature together with the machine learning approaches for different parameter sets. We provide a matlab script for the computation and evaluation as well as an integration in EyeTrace which can be downloaded at http://www.ti.uni-tuebingen.de/Eyetrace.1751.0.html.
Transparent Graphene/PEDOT:PSS Microelectrodes for Electro‐ and Optophysiology
2018-10-16

Abstract Conventional opaque electrodes in microelectrode array (MEA) technology obstruct the view of cells in their immediate vicinity (e.g., ≈50 μm) from which the strongest extracellular action potentials are recorded. This limitation has been overcome by transparent graphene electrodes which allow for optical access essential for novel applications such as optogenetics and calcium imaging. Downscaling, necessary for high resolution single‐unit electrophysiological recordings, has been a significant challenge due to inferior electrochemical impedance and correspondingly lower signal‐to‐noise ratio. Here, the combination of graphene with the conductive polymer poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) as a transparent microelectrode material for in vitro MEAs is presented and their application with optical imaging and electrophysiology is demonstrated. Optimal graphene/PEDOT:PSS microelectrodes display transparencies of 84% over the visible spectrum and impedance magnitude of (166 ± 13) kΩ at 1 kHz. The balance of transparency and 1 kHz impedance can be tuned from ≈90% and 700 kΩ to 50% and 42 kΩ.
LRBA Deficiency in a Patient With a Novel Homozygous Mutation Due to Chromosome 4 Segmental Uniparental Isodisomy
2018-10-16

LRBA deficiency was first described in 2012 as an autosomal recessive disorder caused by biallelic mutations in the <i>LRBA</i> gene (OMIM #614700). It was initially characterized as producing early-onset hypogammaglobulinemia, autoimmune manifestations, susceptibility to inflammatory bowel disease, and recurrent infection. However, further reports expanded this phenotype (including patients without hypogammaglobulinemia) and described LRBA deficiency as a clinically variable syndrome with a wide spectrum of clinical manifestations. We present the case of a female patient who presented with type 1 diabetes, psoriasis, oral thrush, and enlarged liver and spleen at the age of 8 months. She later experienced recurrent bacterial and viral infections, including pneumococcal meningitis and Epstein Barr viremia. She underwent two consecutive stem cell transplants at the age of 8 and 9 years, and ultimately died. Samples from the patient and her parents were subjected to whole exome sequencing, which revealed a homozygous 1-bp insertion in exon 23 of the patient's <i>LRBA</i> gene, resulting in frameshift and premature stop codon. The patient's healthy mother was heterozygous for the mutation and her father tested wild-type. This finding suggested that either one copy of the paternal chromosome 4 bore a deletion including the <i>LRBA</i> locus, or the patient inherited two copies of the mutant maternal <i>LRBA</i> allele. The patient's sequencing data showed a 1-Mb loss of heterozygosity region in chromosome 4, including the <i>LRBA</i> gene. Comparative genomic hybridization array of the patient's and father's genomic DNA yielded normal findings, ruling out genomic copy number abnormalities. Here, we present the first case of LRBA deficiency due to a uniparental disomy (UPD). In contrast to classical Mendelian inheritance, UPD involves inheritance of 2 copies of a chromosomal region from only 1 parent. Specifically, our patient carried a small segmental isodisomy of maternal origin affecting 1 Mb of chromosome 4.
Switching Between Bicyclic and Linear Peptides — The Sulfhydryl-Specific Linker TPSMB Enables Reversible Cyclization of Peptides
2018-10-16

Phage display-selected bicyclic peptides have already shown their great potential for the development as bioactive modulators of therapeutic targets. They can provide enhanced proteolytic stability and improved membrane permeability. Molecular design of new linker molecules has led to a variety of new synthetic approaches for the generation of chemically constrained cyclic peptides. This diversity can be useful for the development of novel peptide-based therapeutic, diagnostic, and scientific tools. Herein, we introduce 1,3,5-tris((pyridin-2-yldisulfanyl)methyl)benzene (TPSMB) as a planar, trivalent, sulfhydryl-specific linker that facilitates reversible cyclization and linearization via disulfide bond formation and cleavage of bicyclic peptides of the format CX<sub>n</sub>CX<sub>n</sub>C, where X is any proteinogenic amino acid except cysteine. The rapid and highly sulfhydryl-specific reaction of TPSMB under physiological conditions is demonstrated by selecting bicyclic peptide binders against c-Jun N-terminal kinase 3 (JNK3) as a model target. While model peptides remain stably cyclized for several hours in presence of typical blood levels of glutathione <i>in vitro</i>, high cytosolic concentrations of glutathione linearize these peptides completely within 1 h. We propose that reversible linkers can be useful tools for several technical applications where target affinity depends on the bicyclic structure of the peptide.