julilili42/papers huggingface dataset:
The processing of pseudoword form and meaning in production and comprehension: A computational modeling approach using Linear Discriminative Learning
2020-02-19

Pseudowords have long served as key tools in psycholinguistic investigations of the lexicon. A common assumption underlying the use of pseudowords is that they are devoid of meaning: Comparing words and pseudowords may then shed light on how meaningful linguistic elements are processed differently from meaningless sound strings.However, pseudowords may in fact carry meaning. On the basis of a computational model of lexical processing, Linear Discriminative Learning (LDL Baayen et al., 2019), we compute numeric vectors representing the semantics of pseudowords. We demonstrate that quantitative measures gauging the semantic neighborhoods of pseudowords predict reaction times in the Massive Auditory Lexical Decision (MALD) database (Tucker et al., 2018). We also show that the model successfully predicts the acoustic durations of pseudowords. Importantly, model predictions hinge on the hypothesis that the mechanisms underlying speech production and comprehension interact. Thus, pseudowords emerge as an outstanding tool for gauging the resonance between production and comprehension.Many pseudowords in the MALD database contain inflectional suffixes. Unlike many contemporary models, LDL captures the semantic commonalities of forms sharing inflectional exponents without using the linguistic construct of morphemes. We discuss methodological and theoretical implications for models of lexical processing and morphological theory. The results of this study, complementing those on real words reported in Baayen et al. (2019), thus provide further evidence for the usefulness of LDL both as a cognitive model of the mental lexicon, and as a tool for generating new quantitative measures that are predictive for human lexical processing.
Phase III study of pembrolizumab (pembro) plus enzalutamide (enza) versus placebo plus enza for metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-641.
2020-02-19

TPS258 Background: The mechanisms of action of pembro, a PD-1 inhibitor, and enza, an androgen receptor inhibitor, may be synergistic in the treatment of patients (pts) with mCRPC. The phase 1b/2 KEYNOTE-365 (NCT02861573) study showed antitumor activity with pembro + enza in pts with mCRPC pretreated with abiraterone acetate. A phase 2 study (NCT02312557) of enza-pretreated patients with mCRPC showed that some pts had a profound and durable anticancer response to pembro + enza. Methods: KEYNOTE-641 (NCT03834493) is a randomized, double-blind, phase 3 trial to evaluate efficacy and safety of pembro + enza versus placebo + enza in pts with mCRPC. An estimated 1200 patients will be randomly assigned 1:1 to receive enza 160 mg/day + pembro 200 mg IV Q3W or enza 160 mg/day + placebo. Treatment will be stratified by prior abiraterone acetate treatment (yes/no), metastases location (bone only/liver/other), and prior docetaxel treatment for metastatic hormone-sensitive prostate cancer (yes/no). Adults (≥18 years) with histologically or cytologically confirmed mCRPC who experienced biochemical or radiographic progression, ECOG PS 0/1, and adequate organ function are eligible. Pts will be required to provide tissue for biomarker analysis. Intolerance to or progression while receiving prior abiraterone acetate therapy is permitted, but not required. Prior chemotherapy for mCRPC, checkpoint inhibition, or any treatment with a second-generation androgen receptor inhibitor is prohibited. Responses will be assessed by CT/MRI and radionuclide bone imaging per PCWG3-modified RECIST v1.1 Q9W during the first year and Q12W thereafter. Treatment will continue until progression, unacceptable toxicity, or consent withdrawal, with up to 2 years of pembro/placebo. Dual primary end points are OS and rPFS by blinded independent central review. Secondary end points are time to subsequent anticancer therapy or death, ORR, DOR, PSA response rate, PSA undetectable rate, time to PSA progression, time to pain progression, time to soft tissue progression, time to symptomatic skeletal-related event, and safety. Accrual began July 28, 2019. Clinical trial information: NCT03834493.
The endometrial transcription landscape of MRKH syndrome
2020-02-19

Abstract The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue. In order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome. Differential and co-expression analyses of the data identified cellular processes and candidate genes that converge on a core network of interconnected regulators that emerge as pivotal for the perturbed expression space. With these results and browsable access to the rich data through an online tool we seek to accelerate research to unravel the underlying biology of this syndrome.
Analysis of clinical outcomes according to response status in prospective clinical trials of atezolizumab (atezo) in pretreated locally advanced/metastatic urothelial carcinoma (mUC).
2020-02-19

492 Background: Atezo is an approved therapy for mUC based on the IMvigor210 (IM210) and IMvigor211 (IM211) phase 2 and 3 trials. The single-arm phase 3b SAUL study in a broader patient (pt) population showed consistent efficacy and safety. The value of complete response to immunotherapy is well recognized, but less is known about the benefit of partial response (PR) or stable disease (SD). We performed post hoc analyses of outcomes in pts with PR/SD in atezo trials. Methods: Pts with mUC received atezo 1200 mg q3w until disease progression (PD) or unacceptable toxicity. Baseline characteristics, efficacy and safety were analyzed in pts achieving PR or SD in IM210 cohort 2 (2nd line), IM211 (atezo and chemotherapy [CT] arms analyzed separately) and SAUL. Data cutoffs were 5/5/15, 3/13/17 and 9/16/18, respectively. Results: The analysis population included 229 PR and 583 SD pts (183 and 421, respectively, treated with atezo); ~40% of pts had 0 Bellmunt risk factors. Baseline characteristics were generally similar between trials. PD-L1 IC 2/3 was more common in PR than SD pts in atezo-treated (41% vs 26%) and CT-treated (37% vs 23%) pts. Median time to best response (PR or SD) was 2.1 mo across trials and treatments. In PR pts, disease control (DC) and overall survival (OS) durations were longer with atezo than CT (Table). Durations of DC and OS were shorter in SD than PR pts; OS was numerically longer with atezo than with CT in the SD population. Presence of more Bellmunt risk factors was associated with worse OS with CT but showed only a weak (SD pts) or no (PR pts) association in atezo-treated pts. Conclusions: Pts achieving a PR or SD have meaningful OS expectancy; pts with PR on atezo have sustained DC. Clinical trial information: NCT02108652 ; NCT02302807 ; NCT02928406 . [Table: see text]
Nuclear structure dependence of the coherent (μ-,e-) conversion matrix elements
2020-02-19

Coherent rates for the neutrinoless muon to electron conversion. (μ-, e-) in the presence of nuclei, are studied throughout the periodic table. The relevant ground state to ground state transition matrix elements are obtained in the context of the quasi-particle RPA. The results are discussed in view of the existing experimental data extracted at TRIUMF and PSI for 48Ti and 208Pb nuclei and compared with: (i) the single particle shell model results calculated with a determinantal ground state wave function and (ii) the results deduced in a local density approximation.
Simple models including energy and spike constraints reproduce complex activity patterns and metabolic disruptions
2020-02-19

Abstract In this work, we introduce new phenomenological neuronal models ( e LIF and mAdExp) that account for energy supply and demand in the cell as well as the inactivation of spike generation how these interact with subthreshold and spiking dynamics. Including these constraints, the new models reproduce a broad range of biologically-relevant behaviors that are identified to be crucial in many neurological disorders, but were not captured by commonly used phenomenological models. Because of their low dimensionality e LIF and mAdExp open the possibility of future large-scale simulations for more realistic studies of brain circuits involved in neuronal disorders. The new models enable both more accurate modeling and the possibility to study energy-associated disorders over the whole time-course of disease progression instead of only comparing the initially healthy status with the final diseased state. These models, therefore, provide new theoretical and computational methods to assess the opportunities of early diagnostics and the potential of energy-centered approaches to improve therapies. Author summary Neurons, even “at rest”, require a constant supply of energy to function. They cannot sustain high-frequency activity over long periods because of regulatory mechanisms, such as adaptation or sodium channels inactivation, and metabolic limitations. These limitations are especially severe in many neuronal disorders, where energy can become insufficient and make the neuronal response change drastically, leading to increased burstiness, network oscillations, or seizures. Capturing such behaviors and impact of energy constraints on them is an essential prerequisite to study disorders such as Parkinson’s disease and epilepsy. However, energy and spiking constraints are not present in any of the standard neuronal models used in computational neuroscience. Here we introduce models that provide a simple and scalable way to account for these features, enabling large-scale theoretical and computational studies of neurological disorders and activity patterns that could not be captured by previously used models. These models provide a way to study energy-associated disorders over the whole time-course of disease progression, and they enable a better assessment of energy-centered approaches to improve therapies.
From cyanobacteria to Archaeplastida: new evolutionary insights into PII signalling in the plant kingdom
2020-02-20

Summary The PII superfamily consists of signal transduction proteins found in all domains of life. Canonical PII proteins sense the cellular energy state through the competitive binding of ATP and ADP, and carbon/nitrogen balance through 2‐oxoglutarate binding. The ancestor of Archaeplastida inherited its PII signal transduction protein from an ancestral cyanobacterial endosymbiont. Over the course of evolution, plant PII proteins acquired a glutamine‐sensing C‐terminal extension, subsequently present in all Chloroplastida PII proteins. The PII proteins of various algal strains (red, green and nonphotosynthetic algae) have been systematically investigated with respect to their sensory and regulatory properties. Comparisons of the PII proteins from different phyla of oxygenic phototrophs (cyanobacteria, red algae, Chlorophyta and higher plants) have yielded insights into their evolutionary conservation vs adaptive properties. The highly conserved role of the controlling enzyme of arginine biosynthesis, N ‐acetyl‐ l ‐glutamate kinase (NAGK), as a main PII‐interactor has been demonstrated across oxygenic phototrophs of cyanobacteria and Archaeplastida. In addition, the PII signalling system of red algae has been identified as an evolutionary intermediate between that of Cyanobacteria and Chloroplastida. In this review, we consider recent advances in understanding metabolic signalling by PII proteins of the plant kingdom.
Prognostic factors in 161 patients with mucosal melanoma: a study of German Central Malignant Melanoma Registry
2020-02-20

Abstract Background Mucosal melanoma is a rare malignancy which represents approximately 1% of all melanomas. It is shown that mucosal melanomas have a different biology and less favourable prognosis than its cutaneous counterpart. Objectives Predictive and prognostic factors of survival for mucosal melanoma have not yet been elucidated. The aim of this study was to investigate risk factors affecting the course of mucosal melanoma patients followed in our clinic. Methods One hundred and sixty‐one patients with mucosal melanoma prospectively documented in the German Central Malignant Melanoma Registry ( CMMR ) were included in this study. Gender, age, localization, stage at first medical examination, tumour thickness and mutational status were documented. The American Joint Committee on Cancer ( AJCC ), 7th edition was used to define tumour stage. Kaplan–Meier survival curves were evaluated compared with the log‐rank test. Multivariate Cox proportional hazard models were used to identify significant independent prognostic factors. Results According to the localization, patients were categorized in 44.7% oral–nasal, 28.6% genital, 20.5% anorectal and 6.2% visceral. Genital mucosal melanomas had the most favourable 5‐year OS rate (58.6%) followed by visceral (58.3%) and oral–nasal (39.3%). Anorectal melanomas had the worst OS time (median: 21 ± 4.8 months) and 5‐year survival rate (22.7%). Patients &lt;60 years had a better survival than the older group ( P = 0.013). Tumour stage at the time of the first medical examination was also a significant factor for survival ( P = 0.001). Gender and mutational status were found to have no effect on survival. Age (&lt;60 years vs. ≥60 years; HR = 2.1) and stage at first medical examination (Stage I vs. Stage IV ; HR = 8.2) are shown to be significant independent prognostic factors on multivariate Cox regression analysis, but not localization. Conclusion In this study, we observed that older age and advanced stage have significant negative effects on the survival of mucosal melanoma. Thus, the AJCC staging system is applicable for mucosal melanoma.
Retinal image analysis for eye safety evaluations of products emitting optical radiation
2020-02-20

Optical systems emitting radiation in the visible and near infrared wavelength range represent a potential hazard for the retina of the human eye. This can result in irreparable damages due to photochemical, photothermal, photomechanical or thermomechanical interactions. To perform an eye safety evaluation a distinction must be made between coherent light sources and broadband light sources. For both types of light sources the corresponding safety standards, namely the IEC 60825-1:2014 and the IEC 62471:2006, provide accessible emission limits which depend on the angular subtense of the apparent source. This parameter is not a characteristic of the light source but must be determined by the irradiance distribution of the retinal image in case of coherent radiation and by the spectral radiance distribution of the retinal image in case of broadband radiation. This investigation introduces software-based methods investigating the retinal image in order to calculate the angular subtense of the apparent source. The results can be used to perform an eye safety evaluation in conformity with the laser safety standard IEC 60825-1:2014 as well as with the lamp safety standard IEC 62471:2006. However, the procedures given by the standards are not clearly defined. For this reason different implementations are discussed and compared to each other for a broad variety of exemplary retinal images.
In search of a Paleolithic Silk Road in Kazakhstan
2020-02-20

Paleoanthropological data suggest that the Late Pleistocene was a time of population contact and possibly dispersal in Central Asia. Geographic and paleoclimatic data suggest that a natural corridor through Kazakhstan linked areas to the north and east (Siberia, China) to those further to the west and south (Uzbekistan), much akin to a Paleolithic Silk Road. We review the known Pleistocene archaeology and paleoclimatic setting of this region and provide a geoarchaeological framework for contextualizing preliminary survey results of the PALAEOSILKROAD project’s first three seasons of fieldwork. We discuss some systematic biases in three geomorphic and sedimentary archives: karst, loess, and spring deposits, specifying ways in which these biases might determine the kinds of data that are extractable by systematic survey. In particular, we caution about the possibility of future systematic biases in chronology that could come about as a result of the type of geomorphic context in which the sites are recovered. We conclude with recommendations for future work in the area.
High standing genetic variation in an invasive plant allows immediate evolutionary response to climate warming
2020-02-20

A bstract Predicting plant distributions under climate change is constrained by our limited understanding of potential rapid adaptive evolution. In an experimental evolution study with the invasive common ragweed, we subjected replicated populations of the same initial genetic composition to simulated climate warming. Pooled DNA sequencing of parental and offspring populations showed that warming populations experienced a greater loss of genetic diversity, and greater genetic divergence from their parents, than control populations. In a common environment, offspring from warming populations showed more convergent phenotypes in seven out of nine plant traits, with later flowering and larger biomass, than plants from control populations. For both traits, we also found a significant higher ratio of phenotypic to genetic differentiation across generations for warming than for control populations, indicating stronger selection under warming conditions. Our findings demonstrate that ragweed populations can rapidly evolve in response to climate change within a single generation.
The effects of NMDA receptor blockade on TMS-evoked EEG potentials from prefrontal and parietal cortex
2020-02-21

Abstract Measuring the brain’s response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers unique insights into the cortical circuits activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (NMDA receptor antagonist) or placebo across two sessions in a double-blinded pseudo-randomised crossover design. At baseline, there were amplitude differences between PFC and PAR TEPs across a wide time range (15–250 ms), however the signals were correlated after ~80 ms, suggesting early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. Early TEP peaks were not reliably altered following dextromethorphan compared to placebo, although findings were less clear for later peaks, and low frequency resting oscillations were reduced in power. Our findings suggest that early TEP peaks (&lt;80 ms) from PFC and PAR reflect stimulation site specific activity that is largely insensitive to changes in NMDA receptor-mediated neurotransmission.
Higher Order Corrections to the Mean-Field Description of the Dynamics of Interacting Bosons
2020-02-21

Abstract In this paper, we introduce a novel method for deriving higher order corrections to the mean-field description of the dynamics of interacting bosons. More precisely, we consider the dynamics of N <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>d</mml:mi></mml:math> -dimensional bosons for large N . The bosons initially form a Bose–Einstein condensate and interact with each other via a pair potential of the form <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mrow><mml:mo>(</mml:mo><mml:mi>N</mml:mi><mml:mo>-</mml:mo><mml:mn>1</mml:mn><mml:mo>)</mml:mo></mml:mrow><mml:mrow><mml:mo>-</mml:mo><mml:mn>1</mml:mn></mml:mrow></mml:msup><mml:msup><mml:mi>N</mml:mi><mml:mrow><mml:mi>d</mml:mi><mml:mi>β</mml:mi></mml:mrow></mml:msup><mml:mi>v</mml:mi><mml:mrow><mml:mo>(</mml:mo><mml:msup><mml:mi>N</mml:mi><mml:mi>β</mml:mi></mml:msup><mml:mo>·</mml:mo><mml:mo>)</mml:mo></mml:mrow></mml:mrow></mml:math> for <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>β</mml:mi><mml:mo>∈</mml:mo><mml:mo>[</mml:mo><mml:mn>0</mml:mn><mml:mo>,</mml:mo><mml:mfrac><mml:mn>1</mml:mn><mml:mrow><mml:mn>4</mml:mn><mml:mi>d</mml:mi></mml:mrow></mml:mfrac><mml:mo>)</mml:mo></mml:mrow></mml:math> . We derive a sequence of N -body functions which approximate the true many-body dynamics in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mi>L</mml:mi><mml:mn>2</mml:mn></mml:msup><mml:mrow><mml:mo>(</mml:mo><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mi>dN</mml:mi></mml:mrow></mml:msup><mml:mo>)</mml:mo></mml:mrow></mml:mrow></mml:math> -norm to arbitrary precision in powers of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mi>N</mml:mi><mml:mrow><mml:mo>-</mml:mo><mml:mn>1</mml:mn></mml:mrow></mml:msup></mml:math> . The approximating functions are constructed as Duhamel expansions of finite order in terms of the first quantised analogue of a Bogoliubov time evolution.
Justifying Kubo’s formula for gapped systems at zero temperature: A brief review and some new results
2020-02-21

We first review the problem of a rigorous justification of Kubo’s formula for transport coefficients in gapped extended Hamiltonian quantum systems at zero temperature. In particular, the theoretical understanding of the quantum Hall effect rests on the validity of Kubo’s formula for such systems, a connection that we review briefly as well. We then highlight an approach to linear response theory based on non-equilibrium almost-stationary states (NEASS) and on a corresponding adiabatic theorem for such systems that was recently proposed and worked out by one of us in [51] for interacting fermionic systems on finite lattices. In the second part of our paper, we show how to lift the results of [51] to infinite systems by taking a thermodynamic limit.