bluuebunny/crossref_metadata_2025_split huggingface dataset:
Force‐regulated chaperone activity of BiP/ERdj3 is opposite to their homologs DnaK/DnaJ
Authors: Banerjee Souradeep , Chowdhury Debojyoti , Chakraborty Soham , Haldar Shubhasis 
Published: June 2024

AbstractPolypeptide chains experience mechanical tension while translocating through cellular tunnels, which are subsequently folded by molecular chaperones. However, interactions between tunnel‐associated chaperones and these emerging polypeptides under force is not completely understood. Our investigation focused on mechanical chaperone activity of two tunnel‐associated chaperones, BiP and ERdj3 both with and without mechanical constraints and comparing them with their cytoplasmic homologs: DnaK and DnaJ. While BiP/ERdj3 have been observed to exhibit robust foldase activity under force, DnaK/DnaJ showed holdase function. Importantly, the tunnel‐associated chaperones (BiP/ERdj3) transitioned to a holdase state in the absence of force, indicating a force‐dependent chaperone behavior. This chaperone‐driven folding event in the tunnel generated an additional mechanical energy of up to 54 zJ, potentially aiding protein translocation. Our findings align with strain theory, where chaperones with higher intrinsic deformability act as mechanical foldases (BiP, ERdj3), while those with lower deformability serve as holdases (DnaK and DnaJ). This study thus elucidates the differential mechanically regulated chaperoning activity and introduces a novel perspective on co‐translocational protein folding.
Ligation of multiple protein domains using orthogonal inteins with non‐native splice junctions
Authors: Romero‐Casañas Alejandro , García‐Lizarribar Andrea , Castro Jessica , Vilanova Maria , Benito Antoni , Ribó Marc 
Published: June 2024

AbstractProtein splicing is a self‐catalyzed process in which an internal protein domain (the intein) is excised from its flanking sequences, linking them together with a canonical peptide bond. Trans‐inteins are separated in two different precursor polypeptide chains that must assemble to catalytically self‐excise and ligate the corresponding flanking exteins to join even when expressed separately either in vitro or in vivo. They are very interesting to construct full proteins from separate domains because their common small size favors chemical synthesis approaches. Therefore, trans‐inteins have multiple applications such as protein modification and purification, structural characterization of protein domains or production of intein‐based biosensors, among others. For many of these applications, when using more than one trans‐intein, orthogonality between them is a critical issue to ensure the proper ligation of the exteins. Here, we confirm the orthogonality (lack of cross‐reactivity) of four different trans‐ or split inteins, gp41‐1, gp41‐8, IMPDH‐1 and NrdJ‐1 both in vivo and in vitro, and built different constructs that allow for the sequential fusion of up to four protein fragments into one final spliced product. We have characterized the splicing efficiency of these constructs. All harbor non‐native extein residues at the splice junction between the trans‐intein and the neighboring exteins, except for the essential Ser + 1. Our results show that it is possible to ligate four different protein domains using inteins gp41‐1, IMPDH‐1 and NrdJ‐1 with non‐native extein residues to obtain a final four‐domain spliced product with a not negligible yield that keeps its native sequence.
Learning to Read Connections—Sensitivity to Collocation Frequency Links Vocabulary Size and Reading Comprehension in Middle Childhood
Authors: Schmitterer Alexandra M. A. , Gawrilow Caterina , Friedrich Claudia 
Published: June 2024

AbstractThe collocation frequency of words in the language environment contributes to early vocabulary development. Vocabulary size, in turn, predicts children's reading comprehension skills later in development. Both collocation frequency and reading comprehension have been connected to inferential reasoning at different time points in development. Here, it was hypothesized that 8‐year‐old children's (N = 147; 76 female) sensitivity to collocation frequency would be related to vocabulary size and reading comprehension skills of varying complexity. Participants completed an auditory thematic judgment task to assess their sensitivity to collocation frequency (response accuracy or speed). In the task, children were presented with a short sentence containing a reference word (e.g., “John sees the cloud.”) and asked to judge which of two subsequent words best fit the sentence (e.g., “rain” or “lip”). Semantic relatedness between reference words and test words was operationalized in three levels (strong, weak, and distant) based on a corpus‐based analysis of collocation frequency. Multilevel and mediation analyses confirmed that thematic judgment responses were related to corpus‐based measures of collocation frequency and were associated with vocabulary size and reading comprehension skills at the sentence and text level. Furthermore, thematic judgment predicted vocabulary size and reading comprehension when the relation of decoding and reading comprehension was taken into account. The study highlights sensitivity to collocation frequency as a link between early language comprehension development (i.e., lexical retrieval and inferential reasoning) and reading comprehension in middle childhood. It also integrates theoretical approaches from computational network or distributional semantics studies and behavioral experimental studies.
Photodynamic therapy promotes hypoxia‐activated nitrogen mustard drug release
Authors: Wang Ran , He Maomao , Zhang Zongwei , Qiu Tian , Xi Yue , Zeng Xiaolong , Fan Jiangli , Sun Wen , Peng Xiaojun 
Published: June 2024

AbstractPhotodynamic therapy (PDT) has become a promising method for tumor treatment due to its non‐invasive and high spatiotemporal selectivity. However, PDT is still hindered by reactive oxygen species deficiency, because solid tumors feature a hypoxic microenvironment. PDT combined with hypoxia‐activated chemotherapy drugs can effectively induce tumor death, overcoming the limitations of the sole PDT for the fight against hypoxia. Herein, we designed a nanosystem (PCe6AZOM) that enhances the release of hypoxia‐activated drugs (AZOM) by PDT. Under hypoxic conditions, the azo bond of AZOM is cleaved by azo reductase, releasing highly cytotoxic AZOM and resulting in a significant increase in intratumor drug concentration. Meanwhile, the commercial photosensitizer Ce6 can aggravate the oxygen‐poor state during the PDT process and further cause more AZOM release. Moreover, the cascade reactions in the nanosystem could activate singlet oxygen and enhance drug release through 660 nm light laser irradiation, contributing to more effective induction of tumor apoptosis and tumor growth retardation in vitro and in vivo.
The role of nonlocality on low and high frequency behaviors of functionally graded sandwich nanoplates
Authors: Ghazwani Mofareh Hassan , Alnujaie Ali , Eltaher Mohamed A. , Van Vinh Pham 
Published: June 2024

AbstractThe role of nonlocality on low and high frequency behaviors and modes of the functionally graded (FG) sandwich nanoplates is investigated in this study for the first time using simple nonlocal higher‐order shear deformation theory (HSDT). The simple HSDT consists of only four unknowns in its equation of the displacement field. The nonlocal elasticity theory is used to consider the small‐scale effects on the behaviors of the nanoplates. The governing equations of motion are established by applying Hamilton's principle, then Navier's solution technique is employed to solve these equations to achieve the free vibration behaviors of the FG sandwich nanoplates. The vibrations of the nanoplates under both low and high frequency conditions are investigated, but the high frequency vibration of the nanoplates is discussed extensively. The influences of the geometrical dimensions, material gradient index, and nonlocal parameter on the high frequency vibration of the FG nanoplates are also considered and discussed comprehensively.
Semilinear damped wave equations on the Heisenberg group with initial data from Sobolev spaces of negative order
Authors: Dasgupta Aparajita , Kumar Vishvesh , Mondal Shyam Swarup , Ruzhansky Michael 
Published: June 2024

AbstractIn this paper, we focus on studying the Cauchy problem for semilinear damped wave equations involving the sub-Laplacian $$\mathcal {L}$$
L
on the Heisenberg group $$\mathbb {H}^n$$

H

n

with power type nonlinearity $$|u|^p$$

|
u
|

p

and initial data taken from Sobolev spaces of negative order homogeneous Sobolev space $$\dot{H}^{-\gamma }_{\mathcal {L}}(\mathbb {H}^n), \gamma >0$$

H
˙

L

-
γ

(

H

n

)

,
γ
>
0

, on $$\mathbb {H}^n$$

H

n

. In particular, in the framework of Sobolev spaces of negative order, we prove that the critical exponent is the exponent $$p_{\text {crit}}(Q, \gamma )=1+\frac{4}{Q+2\gamma },$$

p
crit

(
Q
,
γ
)

=
1
+

4

Q
+
2
γ

,

for $$\gamma \in (0, \frac{Q}{2})$$

γ
∈
(
0
,

Q
2

)

, where $$Q:=2n+2$$

Q
:
=
2
n
+
2

is the homogeneous dimension of $$\mathbb {H}^n$$

H

n

. More precisely, we establish

A global-in-time existence of small data Sobolev solutions of lower regularity for $$p>p_{\text {crit}}(Q, \gamma )$$

p
>

p
crit

(
Q
,
γ
)

in the energy evolution space;

A finite time blow-up of weak solutions for $$1<p<p_{\text {crit}}(Q, \gamma )$$

1
<
p
<

p
crit

(
Q
,
γ
)

under certain conditions on the initial data by using the test function method.

Furthermore, to precisely characterize the blow-up time, we derive sharp upper bound and lower bound estimates for the lifespan in the subcritical case.
An inf-sup approach to $$C_0$$-semigroup generation for an interactive composite structure-Stokes PDE dynamics
Authors: Geredeli Pelin G. 
Published: June 2024

AbstractIn this work, we investigate the existence and uniqueness properties of a composite structure (multilayered)–fluid interaction PDE system which arises in multi-physics problems, and particularly in biofluidic applications related to the mammalian blood transportation process. The PDE system under consideration consists of the interactive coupling of 3D Stokes flow and 3D elastic dynamics which gives rise to an additional 2D elastic equation on the boundary interface between these 3D PDE systems. By means of a nonstandard mixed variational formulation, we show that the PDE system generates a $$C_0$$

C
0

-semigroup on the associated finite energy space of data. In this work, the presence of the pressure term in the 3D Stokes equation adds a great challenge to our analysis. To overcome this difficulty, we follow a methodology which is based on the necessarily non-Leray-based elimination of the associated pressure term, via appropriate nonlocal operators. Moreover, while we express the fluid solution variable via decoupling of the Stokes equation, we construct the elastic solution variables by solving a mixed variational formulation via a Babuska–Brezzi approach.
The necroptosis cell death pathway drives neurodegeneration in Alzheimer’s disease
Authors: Balusu Sriram , De Strooper Bart 
Published: June 2024

AbstractAlthough apoptosis, pyroptosis, and ferroptosis have been implicated in AD, none fully explains the extensive neuronal loss observed in AD brains. Recent evidence shows that necroptosis is abundant in AD, that necroptosis is closely linked to the appearance of Tau pathology, and that necroptosis markers accumulate in granulovacuolar neurodegeneration vesicles (GVD). We review here the neuron-specific activation of the granulovacuolar mediated neuronal-necroptosis pathway, the potential AD-relevant triggers upstream of this pathway, and the interaction of the necrosome with the endo-lysosomal pathway, possibly providing links to Tau pathology. In addition, we underscore the therapeutic potential of inhibiting necroptosis in neurodegenerative diseases such as AD, as this presents a novel avenue for drug development targeting neuronal loss to preserve cognitive abilities. Such an approach seems particularly relevant when combined with amyloid-lowering drugs.
Repeated cognitive assessments show stable function over time in patients with ALS
Authors: Öijerstedt Linn , Foucher Juliette , Lovik Anikó , Yazdani Solmaz , Juto Alexander , Kläppe Ulf , Fang Fang , Ingre Caroline 
Published: June 2024

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a multisystem disorder with not only motor symptoms but also extra-motor features including cognitive impairment. The most common cognitive profile observed in patients with ALS includes deficits in executive function, language, and social cognition. However, longitudinal studies on cognitive changes over time in ALS are sparse. We aimed to investigate the presence and nature of cognitive impairment at the time of ALS diagnosis and its association with survival as well as explore longitudinal cognitive change.

Method
Patients (n = 216) were recruited at the Karolinska University Hospital in Stockholm, Sweden. Follow-up visits (n = 307 in total) were performed every 6 months. Cognitive impairment was assessed using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and/or Montreal Cognitive Assessment (MoCA).

Results
Cognitive impairment was observed in 38% of the patients at the time of ALS diagnosis, and the majority of these patients had deficits in executive function and/or language. Patients with cognitive impairment at the time of diagnosis had a more rapid decline in ALSFRS-R at 12- and 18-months follow-up, and a shorter survival. Cognitive function was stable during the first 2 years after diagnosis, and did not follow the trajectories of decline in motor functions.

Conclusion
Cognitive impairment in ALS was associated with a faster decline of motor functions, and shorter survival. However, cognitive function did not deteriorate over time. Cognitive assessment is essential for the patients and caregivers to understand the phenotypic expression of ALS.
Cultivation modes affect the morphology, biochemical composition, and antioxidant and anti-inflammatory properties of the green microalga Neochloris oleoabundans
Authors: Baldisserotto C. , Gessi S. , Ferraretto E. , Merighi S. , Ardondi L. , Giacò P. , Ferroni L. , Nigro M. , Travagli A. , Pancaldi S. 
Published: June 2024

AbstractMicroalgae are considered promising sustainable sources of natural bioactive compounds to be used in biotechnological sectors. In recent years, attention is increasingly given to the search of microalgae-derived compounds with antioxidant and anti-inflammatory properties for nutraceutical or pharmacological issues. In this context, attention is usually focused on the composition and bioactivity of algae or their extracts, while less interest is driven to their biological features, for example, those related to morphology and cultivation conditions. In addition, specific studies on the antioxidant and anti-inflammatory properties of microalgae mainly concern Chlorella or Spirulina. The present work was focused on the characterization of the Chlorophyta Neochloris oleoabundans under two combinations of cultivation modes: autotrophy and glucose-induced mixotrophy, each followed by starvation. Biomass for morphological and biochemical characterization, as well as for extract preparation, was harvested at the end of each cultivation phase. Analyses indicated a different content of the most important classes of bioactive compounds with antioxidant/anti-inflammatory properties (lipids, exo-polysaccharides, pigments, total phenolics, and proteins). In particular, the most promising condition able to prompt the production of antioxidant algal biomass with anti-inflammatory properties was the mixotrophic one. Under mixotrophy, beside an elevated algal biomass production, a strong photosynthetic metabolism with high appression of thylakoid membranes and characteristics of high photo-protection from oxidative damage was observed and linked to the overproduction of exo-polysaccharides and lipids rather than pigments. Overall, mixotrophy appears a good choice to produce natural bioactive extracts, potentially well tolerated by human metabolism and environmentally sustainable.
Approximate ground truth generation for semantic labeling of historical documents with minimal human effort
Authors: Rahal Najoua , Vögtlin Lars , Ingold Rolf 
Published: June 2024

AbstractDeep learning approaches have shown high performance for layout analysis of historical documents, provided that enough labeled data is available. This is not an issue for generic tasks such as image binarization, text graphics separation, or text line and text block detection but can become an impediment for more specialized tasks specific to one or a few books only. This paper addresses layout analysis of medieval books with rich and complex layouts, for which no labeled data is initially available. The proposed strategy consists of training an initial model with artificial data created to reflect the rules a deep neural network should learn. Then, the model is iteratively fine-tuned by mixing the artificial data with real data obtained by previous predictions, post-processed, and manually selected by an expert user. Such a strategy needs less human effort than manual ground truthing. The approach is qualitatively and quantitatively assessed and shows that the system converges to an accurate model that finally produces approximate ground truth stable and good enough to train a final model to solve the targeted task with high accuracy.
Estimation of optimal adherence threshold for tumor necrosis factor inhibitors in rheumatoid arthritis
Authors: Harris Jennifer Toth , Yang Yi , Bentley John P. , Chen Yixin , Ramachandran Sujith 
Published: June 2024

Abstract
Introduction
Optimal adherence thresholds can vary across medications and disease states. The objective of the study was to determine the optimal threshold of the proportion of days covered (PDC) for tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA).

Methods
Patients with RA initiating self-administered TNF inhibitors were identified using 2012–18 Medicare fee-for-service claims. Time-varying PDC was calculated every day for the preceding 90 days during follow-up. Oral and injected glucocorticoid use, hospitalizations, emergency room (ER) visits, serious infections, and a composite of these were measured as outcomes. Time to first occurrence of each outcome as a function of time-varying PDC for TNF inhibitors was evaluated using Cox regression. Incident/dynamic time-dependent receiver operating characteristic curves and Youden’s J index were used to obtain the optimal PDC threshold for outcomes at 365 days.

Results
Of the 1190 patients who met the study inclusion criteria, almost 75% (865 patients) experienced at least one of the outcomes. Increasing PDC by 10% was significantly associated with decreased risks of the composite outcome (HR 0.98, 95% CI 0.96–1.00), oral glucocorticoid use (HR 0.93, 95% CI 0.91–0.96), and hospitalization (HR 0.96, 95% CI 0.94–0.99) but an increased risk of ER visits (HR 1.04, 95% 1.01–1.07). Optimal PDC thresholds for the composite outcome, oral glucocorticoid use, and hospitalization were 0.64, 0.59, and 0.56, respectively.

Conclusions
Increased PDC was associated with a decreased risk of adverse outcomes, except ER visits. The optimal PDC for TNF inhibitors in Medicare patients with RA based on clinical outcomes was about 60%.

Key Points• The optimal proportion of days covered threshold for tumor necrosis factor inhibitors at 365 days based on clinical outcomes was found to be about 60%, which is lower than the traditional 80% used to define adherence.• Increased adherence was associated with decreased risks of oral glucocorticoid use, hospitalization, and the composite outcome. However, it was also associated with an increased risk of emergency room visits.• The mean time-varying 90-day proportion of days covered decreased throughout the study starting 92% at day 1 of follow-up to 62% at day 365.
Energy abundance, the geographical distribution of manufacturing, and international trade
Authors: Elliott Robert J. R. , Sun Puyang , Zhu Tong 
Published: June 2024

AbstractOne of the main challenges of the current energy transition is how countries can deliver a low-carbon future while at the same time ensuring they can meet an ever growing demand for energy. This paper investigates how the spatial distribution of endowments of energy resources influences the location of firms and their subsequent exports. Employing a pseudo-endowment approach, we measure energy abundance using province-sector-year input data for Chinese provinces from 2006 to 2010. Our results suggest that energy abundance has a positive and significant impact on the location of industrial production, especially for energy intensive sectors. Nonetheless, the impact of energy abundance on trade flows is much smaller than on production shares, in terms of both the magnitude and significance. Further analysis explores how an uneven distribution of new coal mines, fuel prices, and policy-driven shocks affect the location of production and trade. Our study contributes to understanding the economic consequences of the energy transition, particularly regarding the phase-out of traditional energy sources such as coal and its impact on firm location and trade flows.
Regional ionospheric correction generation for GNSS PPP-RTK: theoretical analyses and a new interpolation method
Authors: Zhang Wenhao , Wang Jinling , Khodabandeh Amir 
Published: June 2024

AbstractThe regional ionospheric corrections have become one of the critical parts of Precise Point Positioning (PPP)-based Real-Time-Kinematic (RTK) services to achieve fast positioning convergence. Several methods for regional ionospheric corrections supporting PPP-RTK have been developed and implemented over recent years, but little attention is given to the theoretical foundation of existing ionospheric correction methods and their performance comparison to find an optimal method in some sense. The optimality criterion of such methods should not only be based on the precision of the ionospheric correction itself, but also on its broadcasting strategies, and implementation aspects. This contribution studies ionospheric correction generation methods within the best linear unbiased predictor (BLUP) framework. Comparing the accuracy performances of the methods, we demonstrate that the Kriging method with trend, as a special case of BLUP, is the most appropriate method for large-scale networks (above 500 km). A strategy for the evaluation of the uncertainty of the grid-interpolated ionospheric corrections is also developed. In contrast to other empirical methods, this new method is rigorous in the sense that it avoids the underestimation of the uncertainty of predicted ionospheric corrections, especially when reference stations are close to a grid point.