bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstraction-Refinement for Hierarchical Probabilistic Models
Authors: Junges Sebastian , Spaan Matthijs T. J. 
Published: August 2022

AbstractMarkov decision processes are a ubiquitous formalism for modelling systems with non-deterministic and probabilistic behavior. Verification of these models is subject to the famous state space explosion problem. We alleviate this problem by exploiting a hierarchical structure with repetitive parts. This structure not only occurs naturally in robotics, but also in probabilistic programs describing, e.g., network protocols. Such programs often repeatedly call a subroutine with similar behavior. In this paper, we focus on a local case, in which the subroutines have a limited effect on the overall system state. The key ideas to accelerate analysis of such programs are (1) to treat the behavior of the subroutine as uncertain and only remove this uncertainty by a detailed analysis if needed, and (2) to abstract similar subroutines into a parametric template, and then analyse this template. These two ideas are embedded into an abstraction-refinement loop that analyses hierarchical MDPs. A prototypical implementation shows the efficacy of the approach.
Automatic Detection of Epileptic Seizures with Recurrent and Convolutional Neural Networks
Authors: Carrión Salvador , López-Chilet Álvaro , Martínez-Bernia Javier , Coll-Alonso Joan , Chorro-Juan Daniel , Gómez Jon Ander 
Published: August 2022

AbstractComputer-aided diagnosis based on intelligent systems is an effective strategy to improve the efficiency of healthcare systems while reducing their costs. In this work, the epilepsy detection task is approached in two different ways, recurrent and convolutional neural networks, within a patient-specific scheme. Additionally, a detector function and its effects on seizure detection performance are presented. Our results suggest that it is possible to detect seizures from scalp EEGs with acceptable results for some patients, and that the DeepHealth framework is a proper deep learning software for medical research.
Evaluierung
Authors: Kirchner Aljoscha 
Published: August 2022

ZusammenfassungDie in dieser Arbeit entwickelte modellbasierte Entwicklungsmethode wurde mittels zweier verschiedener Techniken evaluiert. Zum einen fand die Evaluierung des Einflusses der modellbasierten Entwicklungsmethode auf die SoC-Entwicklung, wie nachfolgend in Abschnitt 6.1 beschrieben, durch Interviews statt. Zum anderen wurde der als Ergebnis der modellgetriebenen Automatisierung erhaltene Code auf Korrektheit und Performance-Eigenschaften mittels Co-Simulation getestet und mit dem manuell implementierten Code verglichen.
Neuronal-specific septin-3 binds Atg8/LC3B, accumulates and localizes to autophagosomes during induced autophagy
Authors: Tóth Vilmos , Vadászi Henrietta , Ravasz Lilla , Mittli Dániel , Mátyás Dominik , Molnár Tamás , Micsonai András , Szaniszló Tamás , Lőrincz Péter , Kovács Réka Á. , Juhász Tünde , Beke-Somfai Tamás , Juhász Gábor , Györffy Balázs András , Kékesi Katalin A. , Kardos József 
Published: August 2022

AbstractIn synapses that show signs of local apoptosis and mitochondrial stress and undergo neuro-immunological synapse pruning, an increase in the levels of the presynaptic protein, neuronal-specific septin-3 can be observed. Septin-3 is a member of the septin GTPase family with the ability to form multimers and contribute to the cytoskeleton. However, the function of septin-3 remains elusive. Here, we provide evidence that septin-3 is capable of binding the most-studied autophagy protein Atg8 homolog microtubule-associated protein 1 light chain 3B (LC3B), besides another homolog, GABA receptor-associated protein-like 2 (GABARAPL2). Moreover, we demonstrate that colocalization of septin-3 and LC3B increases upon chemical autophagy induction in primary neuronal cells. Septin-3 is accumulated in primary neurons upon autophagy enhancement or blockade, similar to autophagy proteins. Using electron microscopy, we also show that septin-3 localizes to LC3B positive membranes and can be found at mitochondria. However, colocalization results of septin-3 and the early mitophagy marker PTEN-induced kinase 1 (PINK1) do not support that binding of septin-3 to mitochondria is mitophagy related. We conclude that septin-3 correlates with synaptic/neuronal autophagy, binds Atg8 and localizes to autophagic membranes that can be enhanced with chemical autophagy induction. Based on our results, elevated septin-3 levels might indicate enhanced or impeded autophagy in neurons.
Economic analysis using higher-frequency time series: challenges for seasonal adjustment
Authors: Ollech Daniel , Bundesbank Deutsche 
Published: August 2022

AbstractThe COVID-19 pandemic has increased the need for timely and granular information to assess the state of the economy in real time. Weekly and daily indices have been constructed using higher-frequency data to address this need. Yet the seasonal and calendar adjustment of the underlying time series is challenging. Here, we analyse the features and idiosyncracies of such time series relevant in the context of seasonal adjustment. Drawing on a set of time series for Germany—namely hourly electricity consumption, the daily truck toll mileage, and weekly Google Trends data—used in many countries to assess economic development during the pandemic, we discuss obstacles, difficulties, and adjustment options. Furthermore, we develop a taxonomy of the central features of seasonal higher-frequency time series.
On cryptographic properties of cubic and splitting Boolean functions
Authors: Musukwa Augustine , Sala Massimiliano , Villa Irene , Zaninelli Marco 
Published: August 2022

AbstractThe weight, balancedness and nonlinearity are important properties of Boolean functions, but they can be difficult to determine in general. In this paper, we study how to compute them for two classes of functions where these problems are more tractable. In particular, we study functions of degree three and the so-called “splitting” functions. The latter are functions that can be written as the sum of two functions defined over disjoint sets of variables. We show how, for splitting functions, studying these properties reduces to the study of simpler functions. We provide then a procedure to compute the weight of a cubic Boolean function. We show computationally that, for a cubic Boolean function with limited number of terms, this procedure is on average significantly more efficient than some other methods.
Metabolic profiling as a powerful tool for the analysis of cellular alterations caused by 20 mycotoxins in HepG2 cells
Authors: Gerdemann Andrea , Behrens Matthias , Esselen Melanie , Humpf Hans-Ulrich 
Published: August 2022

AbstractMycotoxins are secondary fungal metabolites which exhibit toxic effects in low concentrations. Several mycotoxins are described as carcinogenic or immunosuppressive, but their underlying modes of action especially on molecular level have not yet been entirely elucidated. Metabolic profiling as part of the omics methods is a powerful tool to study the toxicity and the mode of action of xenobiotics. The use of hydrophilic interaction chromatography in combination with targeted mass spectrometric detection enables the selective and sensitive analysis of more than 100 polar and ionic metabolites and allows the evaluation of metabolic alterations caused by xenobiotics such as mycotoxins. For metabolic profiling, the hepato-cellular carcinoma cell line HepG2 was treated with sub-cytotoxic concentrations of 20 mycotoxins. Moniliformin and citrinin significantly affected target elements of the citric acid cycle, but also influenced glycolytic pathways and energy metabolism. Penitrem A, zearalenone, and T2 toxin mainly interfered with the urea cycle and the amino acid homeostasis. The formation of reactive oxygen species seemed to be influenced by T2 toxin and gliotoxin. Glycolysis was altered by ochratoxin A and DNA synthesis was affected by several mycotoxins. The observed effects were not limited to these metabolic reactions as the metabolic pathways are closely interrelated. In general, metabolic profiling proved to be a highly sensitive tool for hazard identification in comparison to single-target cytotoxicity assays as metabolic alterations were already observed at sub-toxic concentrations. Metabolic profiling could therefore be a powerful tool for the overall evaluation of the toxic properties of xenobiotics.
Effect of alginate-based coating charged with hydroxyapatite and quercetin on colour, firmness, sugars and volatile compounds of fresh cut papaya during cold storage
Authors: Malvano Francesca , Corona Onofrio , Pham Phuong Ly , Cinquanta Luciano , Pollon Matteo , Bambina Paola , Farina Vittorio , Albanese Donatella 
Published: August 2022

AbstractActive alginate-based coatings with quercetin glycoside and complexes of hydroxyapatite/quercetin-glycoside were used to study the shelf life of fresh cut papaya stored at 6 °C. Hydroxyapatite was used as a carrier for the release of the bioactive compound. The parameters considered affecting the quality of the fruit during storage were weight loss, color, texture, sugars and volatile compounds. Active coatings with hydroxyapatite and quercetin glycoside proved a higher capacity to slow down the degradation phenomena studied, showing less weight loss, a lower reduction in glucose and fructose, as well as better firmness, than the other samples after 14 days of cold storage. Benzyl isothiocyanate, the characteristic odor compound of papaya fruit, ranged from approximately 10.0 μg/kg in fresh cut fruit to approximately 7.50 μg/kg in samples coated by alginate with hydroxyapatite/quercetin and 3.6 μg/kg in the fresh cut papaya without coating after 14 days of cold storage. The trials also indicated greater effectiveness of alginate coatings alone and with quercetin-glucoside in preserving the color of freshly cut papaya.
Characterization of proteins from the 3N5M family reveals an operationally stable amine transaminase
Authors: Kollipara Manideep , Matzel Philipp , Sowa Miriam , Brott Stefan , Bornscheuer Uwe , Höhne Matthias 
Published: August 2022

Abstract
Amine transaminases (ATA) convert ketones into optically active amines and are used to prepare active pharmaceutical ingredients and building blocks. Novel ATA can be identified in protein databases due to the extensive knowledge of sequence-function relationships. However, predicting thermo- and operational stability from the amino acid sequence is a persisting challenge and a vital step towards identifying efficient ATA biocatalysts for industrial applications. In this study, we performed a database mining and characterized selected putative enzymes of the β-alanine:pyruvate transaminase cluster (3N5M) — a subfamily with so far only a few described members, whose tetrameric structure was suggested to positively affect operational stability. Four putative transaminases (TA-1: Bilophilia wadsworthia, TA-5: Halomonas elongata, TA-9: Burkholderia cepacia, and TA-10: Burkholderia multivorans) were obtained in a soluble form as tetramers in E. coli. During comparison of these tetrameric with known dimeric transaminases we found that indeed novel ATA with high operational stabilities can be identified in this protein subfamily, but we also found exceptions to the hypothesized correlation that a tetrameric assembly leads to increased stability. The discovered ATA from Burkholderia multivorans features a broad substrate specificity, including isopropylamine acceptance, is highly active (6 U/mg) in the conversion of 1-phenylethylamine with pyruvate and shows a thermostability of up to 70 °C under both, storage and operating conditions. In addition, 50% (v/v) of isopropanol or DMSO can be employed as co-solvents without a destabilizing effect on the enzyme during an incubation time of 16 h at 30 °C.

Key points
• Database mining identified a thermostable amine transaminase in the β-alanine:pyruvate transaminase subfamily.
• The tetrameric transaminase tolerates 50% DMSO and isopropanol under operating conditions at 30 °C.
• A tetrameric structure is not necessarily associated with a higher operational stability

Graphical abstract
Seemingly unrelated clusterwise linear regression for contaminated data
Authors: Perrone Gabriele , Soffritti Gabriele 
Published: August 2022

AbstractClusterwise regression is an approach to regression analysis based on finite mixtures which is generally employed when sample observations come from a population composed of several unknown sub-populations. Whenever the response is continuous, Gaussian clusterwise linear regression models are usually employed. Such models have been recently robustified with respect to the possible presence of mild outliers in the sub-populations. However, in some fields of research, especially in the modelling of multivariate economic data or data from the social sciences, there may be prior information on the specific covariates to be considered in the linear term employed in the prediction of a certain response. As a consequence, covariates may not be the same for all responses. Thus, a novel class of multivariate Gaussian linear clusterwise regression models is proposed. This class provides an extension to mixture-based regression analysis for modelling multivariate and correlated responses in the presence of mild outliers that let the researcher free to use a different vector of covariates for each response. Details about the model identification and maximum likelihood estimation via an expectation-conditional maximisation algorithm are given. The performance of the new models is studied by simulation in comparison with other clusterwise linear regression models. A comparative evaluation of their effectiveness and usefulness is provided through the analysis of a real dataset.
The prognostic value of the ratio of standard uptake value of lymph node to primary tumor before treatment of locally advanced nasopharyngeal carcinoma
Authors: Lou Yunlong , Chen Dandan , Lin Zheng , Sun Jianda , Song Li , Chen Wenzhong , Zhang Ming , Chen Yibiao 
Published: August 2022

Abstract
Background
To evaluate the prognostic value of the ratio of the standard uptake value of the lymph node and primary tumor before the treatment of locally advanced nasopharyngeal carcinoma and examine the prognostic value of the tumor metabolic parameters (SUVmax, MTV, and TLG) of the lymph node and primary tumor of locally advanced nasopharyngeal carcinoma.

Methods
A total of 180 patients with locally advanced nasopharyngeal carcinoma diagnosed pathologically from January 1, 2016 to December 31, 2018 were selected, and the MEDEX system was used to automatically delineate the SUVmax, MTV, and TLG of the lymph node metastases and nasopharyngeal carcinoma primary tumor. In addition, the ratio of LN-SUVmax (SUVmax of the lymph node metastases) to T-SUVmax (SUVmax of the nasopharyngeal carcinoma primary tumor) was calculated, and a ROC curve was drawn to obtain the best cut-off value. Kaplan–Meier and Cox regression models were used for survival and multivariate analyses, respectively.

Results
The median follow-up period for participants was 32 (4–62) months. Univariate analysis showed that age (P = 0.013), LN-SUVmax (P = 0.001), LN-TLG (P = 0.007) and NTR (P = 0.001) were factors influencing the overall survival (OS). Factors affecting local progression-free survival (LPFS) were LN-SUVmax (P = 0.005), LN-TLG (P = 0.003) and NTR (P = 0.020), while clinical stage (P = 0.023), LN-SUVmax (P = 0.007), LN-TLG (P = 0.006), and NTR (P = 0.032) were factors affecting distant metastasis-free survival (DMFS). Multivariate analysis showed that NTR was an independent influencing factor of OS (HR 3.00, 95% CI 1.06–8.4, P = 0.038), LPFS (HR 3.08, 95% CI 1.27–7.50, P = 0.013), and DMFS (HR 1.84, 95% CI 0.99–3.42, P = 0.054). Taking OS as the main observation point, the best cut-off point of NTR was 0.95. Kaplan–Meier results showed that the 3-year OS (97.0% vs 85.4%, χ2 = 11.25, P = 0.001), 3-year LPFS (91.3% vs 82.1%, χ2 = 4.035, P = 0.045), and 3-year DMFS (92.3% vs 87.9%, χ2 = 4.576, P = 0.032) of patients with NTR < 0.95 were higher than those with NTR > 0.95.

Conclusions
High NTR before treatment indicates a poor prognosis for patients with nasopharyngeal carcinoma. This can serve as a reference value for the reasonable treatment and prognosis monitoring of such patients.
Sandwiching dense random regular graphs between binomial random graphs
Authors: Gao Pu , Isaev Mikhail , McKay Brendan D. 
Published: August 2022

AbstractKim and Vu made the following conjecture (Advances in Mathematics, 2004): if $$d\gg \log n$$

d
≫
log
n

, then the random d-regular graph $${\mathscr {G}}(n,d)$$

G
(
n
,
d
)

can asymptotically almost surely be “sandwiched” between $${\mathscr {G}}(n,p_1)$$

G
(
n
,

p
1

)

and $${\mathscr {G}}(n,p_2)$$

G
(
n
,

p
2

)

where $$p_1$$

p
1

and $$p_2$$

p
2

are both $$(1+o(1))d/n$$

(
1
+
o
(
1
)
)
d
/
n

. They proved this conjecture for $$\log n\ll d\leqslant n^{1/3-o(1)}$$

log
n
≪
d
⩽

n

1
/
3
-
o
(
1
)

, with a defect in the sandwiching: $${\mathscr {G}}(n,d)$$

G
(
n
,
d
)

contains $${\mathscr {G}}(n,p_1)$$

G
(
n
,

p
1

)

perfectly, but is not completely contained in $${\mathscr {G}}(n,p_2)$$

G
(
n
,

p
2

)

. The embedding $${\mathscr {G}}(n,p_1) \subseteq {\mathscr {G}}(n,d)$$

G

(
n
,

p
1

)

⊆
G

(
n
,
d
)

was improved by Dudek, Frieze, Ruciński and Šileikis to $$d=o(n)$$

d
=
o
(
n
)

. In this paper, we prove Kim–Vu’s sandwich conjecture, with perfect containment on both sides, for all d where $$\min \{d, n-d\}\gg n/\sqrt{\log n}$$

min

{
d
,
n
-
d
}

≫
n
/

log
n

. The sandwich theorem allows translation of many results from $${\mathscr {G}}(n,p)$$

G
(
n
,
p
)

to $${\mathscr {G}}(n,d)$$

G
(
n
,
d
)

such as Hamiltonicity, the chromatic number, the diameter, etc. It also allows translation of threshold functions of phase transitions from $${\mathscr {G}}(n,p)$$

G
(
n
,
p
)

to bond percolation of $${\mathscr {G}}(n,d)$$

G
(
n
,
d
)

. In addition to sandwiching regular graphs, our results cover graphs whose degrees are asymptotically equal. The proofs rely on estimates for the probability of small subgraph appearances in a random factor of a pseudorandom graph, which is of independent interest.
Die zeitliche Dimension des Broad Consent
Authors: Wiertz Svenja 
Published: August 2022

ZusammenfassungDie informierte Einwilligung von Teilnehmer:innen gilt in vielen Fällen als Voraussetzung auch für die rein datenbasierte medizinische Forschung. In diesem Kontext wird ein Modell der breiten Einwilligung (Broad Consent) diskutiert. In Deutschland hat die Medizininformatik-Initiative einen konkreten Vorschlag für deutsche Kliniken ausgearbeitet, der eine Gültigkeit der Einwilligung für einen Zeitraum von 30 Jahren vorsieht. Der vorliegende Artikel diskutiert vor diesem Hintergrund die Frage, wie der Anspruch der Informiertheit in dieser zeitlichen Perspektive einzuordnen ist. Die Praxis der Einwilligung wird dabei so verstanden, dass sie auf die Verwirklichung von Wohlergehen, persönlicher Souveränität und Vertrauen ausgerichtet ist. Eine anzunehmende Informationsasymmetrie zwischen Forschungsteilnehmenden, Forschenden, und datenspeichernden Institutionen wird dabei als spezifisches Kontextmerkmal herausgestellt. Um dieser Informationsasymmetrie in angemessener Weise zu begegnen, so die These, ist eine kontinuierliche Weitergabe von verständlich aufbereiteten Informationen an Forschungsteilnehmende notwendig, um die Wahrnehmung persönlicher Souveränität zu ermöglichen.
Complexity and clinical significance of drug–drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT)
Authors: Tsoukalas Nikolaos , Brito-Dellan Norman , Font Carme , Butler Taylor , Rojas-Hernandez Cristhiam M. , Butler Thomas , Escalante Carmen ,   on behalf of the MASCC Hemostasis Study Group
Published: August 2022

AbstractCancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug–drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncology drugs are extensively used, more attention should be given to monitoring potential DDIs to minimize risks. Recognition of DDIs is of utmost importance in an era of rapid developments in cancer treatments and introduction of novel treatments and protocols. When managing cancer-associated thrombosis (CAT), the concomitant use of a DOAC and a moderate or strong modulator (inhibitor or inducer) of CYP3A4 or a P-glycoprotein (P-gp) is most likely to be associated with significant DDIs. Therefore, LMWHs remain the first-line option for the long-term management of CAT under these circumstances and physicians must consider utilizing LMWHs as first line. This review describes the risk of DDIs and their potential impact and outcomes in patients with cancer associated thrombosis (CAT) receiving anticoagulation.
Glucocerebrosidase mutations and Parkinson disease
Authors: Vieira Sophia R. L. , Schapira Anthony H. V. 
Published: August 2022

AbstractThe discovery of glucocerebrosidase (GBA1) mutations as the greatest numerical genetic risk factor for the development of Parkinson disease (PD) resulted in a paradigm shift within the research landscape. Efforts to elucidate the mechanisms behind GBA1-associated PD have highlighted shared pathways in idiopathic PD including the loss and gain-of-function hypotheses, endoplasmic reticulum stress, lipid metabolism, neuroinflammation, mitochondrial dysfunction and altered autophagy–lysosomal pathway responsible for degradation of aggregated and misfolded a-synuclein. GBA1-associated PD exhibits subtle differences in phenotype and disease progression compared to idiopathic counterparts notably an earlier age of onset, faster motor decline and greater frequency of non-motor symptoms (which also constitute a significant aspect of the prodromal phase of the disease). GBA1-targeted therapies have been developed and are being investigated in clinical trials. The most notable are Ambroxol, a small molecule chaperone, and Venglustat, a blood–brain-barrier-penetrant substrate reduction therapy agent. It is imperative that further studies clarify the aetiology of GBA1-associated PD, enabling the development of a greater abundance of targeted therapies in this new era of precision medicine.
An optimal investor-state dispute settlement mechanism
Authors: Stähler Frank 
Published: August 2022

AbstractMany investment treaties include investor-state dispute settlement (ISDS) provisions which are supposed to protect a foreign investor against opportunistic behavior of a host country. This paper scrutinizes the optimal design of ISDS provisions that solve the holdup problem. It shows that an efficient investor protection mechanism requires an arbitrator as established in investment treaties. However, this arbitrator does neither have to learn nor to evaluate the circumstances of the dispute. Furthermore, any ISDS compensation from the government to the investor should not be based on reductions in investor profits but on the host country’s welfare effects.