julilili42/papers huggingface dataset:
Self-Tuning Extended Kalman Filter Parameters to Identify Ankle's Third-Order Mechanics
2020-08-07

Abstract The estimation of human ankle's mechanical impedance is an important tool for modeling human balance. This work presents the implementation of a parameter-estimation approach based on a state-augmented extended Kalman filter (AEKF) to infer the ankle's mechanical impedance during quiet standing. However, the AEKF filter is sensitive to the initialization of the noise covariance matrices. In order to avoid a time-consuming trial-and-error method and to obtain a better estimation performance, a genetic algorithm (GA) is proposed to best tune the measurement noise (Rk) and process noise covariances (Q) of the extended Kalman filter (EKF). Results using simulated data show the efficacy of the proposed algorithm for parameter-estimation of a third-order biomechanical model. Experimental validation of these results is also presented. They suggest that age is an influencing factor in the human balance.
Clinical Validation of Kinematic Assessments of Post-Stroke Upper Limb Movements with a Multi-Joint Arm Exoskeleton
2020-08-07

Abstract Background : Robotic and gravity-balancing exoskeletons, originally designed for the rehabilitation training of neurological patients, are now being increasingly applied in objective and fine-grained sensor-based assessments of upper limb function. However, gravity compensation, inertia and damping properties of the exoskeleton interfere with the natural sensorimotor interaction, proprioceptive and visual feedback during movement execution. This may endanger the validity of the kinematic assessments in relation to the clinical outcome measures that they were supposed to reflect. Here, we applied Methods : In a proof of concept study involving nineteen severely impaired chronic stroke patients, we assessed sensor-based kinematic data acquired with a multi-joint arm exoskeleton and compared it to the clinical outcome measure Upper Extremity Fugl-Meyer Assessment (UE-FMA) scale. During this assessment, real-time movement feedback of the system’s seven degrees of freedom was provided with a biomorphic 3D virtual representation of the upper limb, including the proximal component of the arm. To align posture and to minimize the exoskeleton-patient interaction, the same position (neutral zero) with a distance of 90 degrees between forearm and upper arm was taken as the starting position for all assessments. Within self-contained tasks, we assessed separately and subsequently the range of motion/spatial posture of four single joints (i.e., joint angles of wrist, elbow, arm, and shoulder movement) and the closing and opening of the hand with a pressure sensor placed in the handle. Results : A strong correlation was observed between wrist and elbow movements within the kinematic parameters (r &gt; 0.7, p&lt;0.003; Bonferroni corrected). A multiple regression model predicted the UE-FMA significantly (F (5, 13) = 12.22, p &lt; 0.0005, adj. R 2 = 0.83). Both shoulder rotation and grip pressure added significantly (p &lt; 0.05) to the prediction with the standardized coefficients β of 0.55 and 0.38, respectively. Conclusions : Exoskeleton-based evaluation of single-joint movements and grip force facilitates the assessment of upper limb kinematics after stroke with high structural and convergent validity. Proximal and distal measures may contribute independently to the prediction of the clinical status.
Invited Editorial: Despite COVID-19, Influenza Must Not Be Relegated to “Only the Sniffles”
2020-08-07

As the current COVID-19 pandemic continues to rage worldwide, it has emerged that the 2019–2020 influenza season has been milder and shorter than usual in the northern hemisphere, presumably due to enforced social distancing [...]
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing
2020-08-08

Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org ). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long‐term PPI use, particularly at higher plasma concentrations.
An Update on Molecular Tools for Genetic Engineering of Actinomycetes—The Source of Important Antibiotics and Other Valuable Compounds
2020-08-08

The first antibiotic-producing actinomycete (Streptomyces antibioticus) was described by Waksman and Woodruff in 1940. This discovery initiated the “actinomycetes era”, in which several species were identified and demonstrated to be a great source of bioactive compounds. However, the remarkable group of microorganisms and their potential for the production of bioactive agents were only partially exploited. This is caused by the fact that the growth of many actinomycetes cannot be reproduced on artificial media at laboratory conditions. In addition, sequencing, genome mining and bioactivity screening disclosed that numerous biosynthetic gene clusters (BGCs), encoded in actinomycetes genomes are not expressed and thus, the respective potential products remain uncharacterized. Therefore, a lot of effort was put into the development of technologies that facilitate the access to actinomycetes genomes and activation of their biosynthetic pathways. In this review, we mainly focus on molecular tools and methods for genetic engineering of actinomycetes that have emerged in the field in the past five years (2015–2020). In addition, we highlight examples of successful application of the recently developed technologies in genetic engineering of actinomycetes for activation and/or improvement of the biosynthesis of secondary metabolites.
Infratentorial IDH-mutant astrocytoma is a distinct subtype
2020-08-10

Diffuse IDH-mutant astrocytic tumors are rarely diagnosed in the cerebellum or brainstem. In this multi-institutional study, we characterized a series of primary infratentorial IDH-mutant astrocytic tumors with respect to clinical and molecular parameters. We report that about 80% of IDH mutations in these tumors are of non-IDH1-R132H variants which are rare in supratentorial astrocytomas. Most frequently, IDH1-R132C/G and IDH2-R172S/G mutations were present. Moreover, the frequencies of ATRX-loss and MGMT promoter methylation, which are typically associated with IDH mutations in supratentorial astrocytic tumors, were significantly lower in the infratentorial compartment. Gene panel sequencing revealed two samples with IDH1-R132C/H3F3A-K27M co-mutations. Genome-wide DNA methylation as well as chromosomal copy number profiling provided further evidence for a molecular distinctiveness of infratentorial IDH-mutant astrocytomas. Clinical outcome of patients with infratentorial IDH-mutant astrocytomas is significantly better than that of patients with diffuse midline gliomas, H3K27M-mutant (p < 0.005) and significantly worse than that of patients with supratentorial IDH-mutant astrocytomas (p = 0.028). The presented data highlight the very existence and distinctiveness of infratentorial IDH-mutant astrocytomas that have important implications for diagnostics and prognostication. They imply that molecular testing is critical for detection of these tumors, since many of these tumors cannot be identified by immunohistochemistry applied for the mutated IDH1-R132H protein or loss of ATRX.
Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome
2020-08-10

Abstract Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin‐2 ( SYT2 ), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant‐negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS‐disease gene and expands its clinical and genetic spectrum to include recessive loss‐of‐function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications.
Interplay between Glass Formation and Liquid–Liquid Phase Separation Revealed by the Scattering Invariant
2020-08-10

The interplay of the glass transition with liquid-liquid phase separation (LLPS) is a subject of intense debate. We use the scattering invariant <i>Q</i> to probe how approaching the glass transition affects the shape of LLPS boundaries in the temperature/volume fraction plane. Two protein systems featuring kinetic arrest with a lower and an upper critical solution temperature phase behavior, respectively, are studied varying the quench depth. Using <i>Q</i> we noninvasively identify system-dependent differences for the effect of glass formation on the LLPS boundary. The glassy dense phase appears to enter the coexistence region for the albumin-YCl<sub>3</sub> system, whereas it follows the equilibrium binodal for the γ-globulin-PEG system.
A Hitchhiker’s Guide to Particle Sizing Techniques
2020-08-10

Accurate characterization of particle size and particle size distributions is mandatory in nanotechnology and a broad range of colloidal sciences. The size of colloidal particles can be determined using various techniques in direct and reciprocal space, including electron microscopy and static and dynamic light scattering. Differential dynamic microscopy was introduced recently and offers a new alternative. In this paper we present a systematic study of particle size determination using various techniques. We compare the results and highlight advantages and disadvantages. Unexpectedly we find that differential dynamic microscopy offers the unique possibility to determine the particle size in highly turbid samples.
Growth Expectations, Undue Optimism, and Short-Run Fluctuations
2020-08-10

Abstract This paper proposes a two-step procedure in order to identify belief shocks—shocks to expectations about the current state of the economy. First, we use the Survey of Professional Forecasters to measure nowcast errors about contemporaneous output growth. Second, we extract belief shocks from nowcast errors, once by regressing them on existing measures of structural shocks and once by imposing sign restrictions on a VAR model. Using both approaches, we find that belief shocks trigger similar adjustment dynamics and a high degree of co-movement across macroeconomic variables. Belief shocks account for about onethird of short-run output fluctuations.
Gut Microbiota, Probiotics and Psychological States and Behaviors after Bariatric Surgery—A Systematic Review of Their Interrelation
2020-08-10

The gastrointestinal (GI) microbiota plays an important role in health and disease, including brain function and behavior. Bariatric surgery (BS) has been reported to result in various changes in the GI microbiota, therefore demanding the investigation of the impact of GI microbiota on treatment success. The goal of this systematic review was to assess the effects of BS on the microbiota composition in humans and other vertebrates, whether probiotics influence postoperative health, and whether microbiota and psychological and behavioral factors interact. A search was conducted using PubMed and Web of Science to find relevant studies with respect to the GI microbiota and probiotics after BS, and later screened for psychological and behavioral parameters. Studies were classified into groups and subgroups to provide a clear overview of the outcomes. Microbiota changes were further assessed for whether they were specific to BS in humans through the comparison to sham operated controls in other vertebrate studies. Changes in alpha diversity appear not to be specific, whereas dissimilarity in overall microbial community structure, and increases in the abundance of the phylum Proteobacteria and Akkermansia spp. within the phylum Verrucomicrobia after surgery were observed in both human and other vertebrates studies and may be specific to BS in humans. Human probiotic studies differed regarding probiotic strains and dosages, however it appeared that probiotic interventions were not superior to a placebo for quality of life scores or weight loss after BS. The relationship between GI microbiota and psychological diseases in this context is unclear due to insufficient available data.
Proof Compression and NP Versus PSPACE II
2020-08-10

We upgrade [3] to a complete proof of the conjecture NP = PSPACE that is known as one of the fundamental open problems in the mathematical theory of computational complexity; this proof is based on [2]. Since minimal propositional logic is known to be PSPACE complete, while PSPACE to include NP, it suffices to show that every valid purely implicational formula ρ has a proof whose weight (= total number of symbols) and time complexity of the provability involved are both polynomial in the weight of ρ. As is [3], we use proof theoretic approach. Recall that in [3] we considered any valid ρ in question that had (by the definition of validity) a “short” tree-like proof π in the Hudelmaier-style cutfree sequent calculus for minimal logic. The “shortness” means that the height of π and the total weight of different formulas occurring in it are both polynomial in the weight of ρ. However, the size (= total number of nodes), and hence also the weight, of π could be exponential in that of ρ. To overcome this trouble we embedded π into Prawitz’s proof system of natural deductions containing single formulas, instead of sequents. As in π, the height and the total weight of different formulas of the resulting tree-like natural deduction ∂1 were polynomial, although the size of ∂1 still could be exponential, in the weight of ρ. In our next, crucial move, ∂1 was deterministically compressed into a “small”, although multipremise, dag-like deduction ∂ whose horizontal levels contained only mutually different formulas, which made the whole weight polynomial in that of ρ. However, ∂ required a more complicated verification of the underlying provability of ρ. In this paper we present a nondeterministic compression of ∂ into a desired standard dag-like deduction ∂0 that deterministically proves ρ in time and space polynomial in the weight of ρ.2 Together with [3] this completes the proof of NP = PSPACE.Natural deductions are essential for our proof. Tree-to-dag horizontal compression of π merging equal sequents, instead of formulas, is (possible but) not sufficient, since the total number of different sequents in π might be exponential in the weight of ρ – even assuming that all formulas occurring in sequents are subformulas of ρ. On the other hand, we need Hudelmaier’s cutfree sequent calculus in order to control both the height and total weight of different formulas of the initial tree-like proof π, since standard Prawitz’s normalization although providing natural deductions with the subformula property does not preserve polynomial heights. It is not clear yet if we can omit references to π even in the proof of the weaker result NP = coNP.
A methodology for psycho-biological assessment of stress in software engineering
2020-08-10

Stress pervades our everyday life to the point of being considered the scourge of the modern industrial world. The effects of stress on knowledge workers causes, in short term, performance fluctuations, decline of concentration, bad sensorimotor coordination, and an increased error rate, while long term exposure to stress leads to issues such as dissatisfaction, resignation, depression and general psychosomatic ailment and disease. Software developers are known to be stressed workers. Stress has been suggested to have detrimental effects on team morale and motivation, communication and cooperation-dependent work, software quality, maintainability, and requirements management. There is a need to effectively assess, monitor, and reduce stress for software developers. While there is substantial psycho-social and medical research on stress and its measurement, we notice that the transfer of these methods and practices to software engineering has not been fully made. For this reason, we engage in an interdisciplinary endeavor between researchers in software engineering and medical and social sciences towards a better understanding of stress effects while developing software. This article offers two main contributions. First, we provide an overview of supported theories of stress and the many ways to assess stress in individuals. Second, we propose a robust methodology to detect and measure stress in controlled experiments that is tailored to software engineering research. We also evaluate the methodology by implementing it on an experiment, which we first pilot and then replicate in its enhanced form, and report on the results with lessons learned. With this work, we hope to stimulate research on stress in software engineering and inspire future research that is backed up by supported theories and employs psychometrically validated measures.
Early Alpine occupation backdates westward human migration in Late Glacial Europe
2020-08-10

The end of the Last Glacial Maximum (LGM) in Europe (~16.5 ka ago) set in motion major changes in human culture and population structure 1 . In Southern Europe, Early Epigravettian material culture was replaced by Late Epigravettian art and technology about 18-17 ka ago at the beginning of southern Alpine deglaciation, although available genetic evidence from individuals who lived ~14 ka ago 2–5 opened up questions on the impact of migrations on this cultural transition only after that date. Here we generate new genomic data from a human mandible uncovered at the Late Epigravettian site of Riparo Tagliente (Veneto, Italy), that we directly dated to 16,980-16,510 cal BP (2σ). This individual, affected by a low-prevalence dental pathology named focal osseous dysplasia, attests that the very emergence of Late Epigravettian material culture in Italy was already associated with migration and genetic replacement of the Gravettian-related ancestry. In doing so, we push back by at least 3,000 years the date of the diffusion in Southern Europe of a genetic component linked to Balkan/Anatolian refugia, previously believed to have spread during the later Bølling/Allerød warming event (~14 ka ago 4,6 ). Our results suggest that demic diffusion from a genetically diverse population may have substantially contributed to cultural changes in LGM and post-LGM Southern Europe, independently from abrupt shifts to warmer and more favourable conditions.
Non-invasive brain-spine interface: continuous brain control of trans-spinal magnetic stimulation using EEG
2020-08-10

Abstract Brain-controlled neuromodulation therapies have emerged as a promising tool to promote functional recovery in patients with motor disabilities. This neuromodulatory strategy is exploited by brain-machine interfaces and could be used for restoring lower limb muscle activity or alleviating gait deficits. Towards a non-invasive approach for leg neurorehabilitation, we present a set-up that combines acquisition of electroencephalographic (EEG) activity to volitionally control trans-spinal magnetic stimulation (ts-MS). We engineered, for the first time, a non-invasive brain-spine interface (BSI) to contingently connect motor cortical activation during leg motor imagery with the activation of leg muscles via ts-MS. This novel brain-controlled stimulation was validated with 10 healthy participants who underwent one session including different ts-MS conditions. After a short screening of their cortical activation during lower limb motor imagery, the participants used the closed-loop system at different stimulation intensities and scored system usability and comfort. We demonstrate the efficiency and robustness of the developed system to remove online stimulation artifacts from EEG regardless of ts-MS intensity used. All the participants reported absence of pain due to ts-MS and good usability. Our results also revealed that ts-MS controlled afferent and efferent intensity-dependent modulation of the nervous system. The here presented system represents a novel non-invasive means to neuromodulate peripheral nerve activity of lower limb using brain-controlled spinal stimulation.
Peer Review #2 of "A methodology for psycho-biological assessment of stress in software engineering (v0.1)"
2020-08-10

Stress pervades our everyday life to the point of being considered the scourge of the modern industrial world.The effects of stress on knowledge workers causes, in short term, performance fluctuations, decline of concentration, bad sensorimotor coordination, and an increased error rate, while long term exposure to stress leads to issues such as dissatisfaction, resignation, depression and general psychosomatic ailment and disease.Software developers are known to be stressed workers.Stress has been suggested to have detrimental effects on team morale and motivation, communication and cooperationdependent work, software quality, maintainability, and requirements management.There is a need to effectively assess, monitor, and reduce stress for software developers.While there is substantial psycho-social and medical research on stress and its measurement, we notice that the transfer of these methods and practices to software engineering has not been fully made.For this reason, we engage in an interdisciplinary endeavour between researchers in software engineering and medical and social sciences towards a better understanding of stress effects while developing software.This paper offers two main contributions.First, we provide an overview of supported theories of stress and the many ways to assess stress in individuals.Second, we propose a robust methodology to detect and measure stress in controlled experiments that is tailored to software engineering research.We also evaluate the methodology by implementing it on an experiment, which we first pilot and then replicate in its enhanced form, and report on the results with lessons learned.With this work, we hope to stimulate research on stress in software engineering and inspire future research that is backed up by supported theories and employs psychometrically validated measures.