bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6
Authors: Park So Hyeon , Jeong Sun Ju , Ha Sung Chul 
Published: February 2023

AbstractThe Maf polymorphic toxin system is involved in conflict between strains found in pathogenic Neisseria species such as Neisseria meningitidis and Neisseria gonorrhoeae. The genes encoding the Maf polymorphic toxin system are found in specific genomic islands called maf genomic islands (MGIs). In the MGIs, the MafB and MafI encode toxin and immunity proteins, respectively. Although the C-terminal region of MafB (MafB-CT) is specific for toxic activity, the underlying enzymatic activity that renders MafB-CT toxic is unknown in many MafB proteins due to lack of homology with domain of known function. Here we present the crystal structure of the MafB2-CTMGI-2B16B6/MafI2MGI-2B16B6 complex from N. meningitidis B16B6. MafB2-CTMGI-2B16B6 displays an RNase A fold similar to mouse RNase 1, although the sequence identity is only ~ 14.0%. MafB2-CTMGI-2B16B6 forms a 1:1 complex with MafI2MGI-2B16B6 with a Kd value of ~ 40 nM. The complementary charge interaction of MafI2MGI-2B16B6 with the substrate binding surface of MafB2-CTMGI-2B16B6 suggests that MafI2MGI-2B16B6 inhibits MafB2-CTMGI-2B16B6 by blocking access of RNA to the catalytic site. An in vitro enzymatic assay showed that MafB2-CTMGI-2B16B6 has ribonuclease activity. Mutagenesis and cell toxicity assays demonstrated that His335, His402 and His409 are important for the toxic activity of MafB2-CTMGI-2B16B6, suggesting that these residues are critical for its ribonuclease activity. These data provide structural and biochemical evidence that the origin of the toxic activity of MafB2MGI-2B16B6 is the enzymatic activity degrading ribonucleotides.
MRI-based deep learning can discriminate between temporal lobe epilepsy, Alzheimer’s disease, and healthy controls
Authors: Chang Allen J. , Roth Rebecca , Bougioukli Eleni , Ruber Theodor , Keller Simon S. , Drane Daniel L. , Gross Robert E. , Welsh James , Abrol Anees , Calhoun Vince , Karakis Ioannis , Kaestner Erik , Weber Bernd , McDonald Carrie , Gleichgerrcht Ezequiel , Bonilha Leonardo ,   Alzheimer’s Disease Neuroimaging Initiative
Published: February 2023

AbstractBackgroundRadiological identification of temporal lobe epilepsy (TLE) is crucial for diagnosis and treatment planning. TLE neuroimaging abnormalities are pervasive at the group level, but they can be subtle and difficult to identify by visual inspection of individual scans, prompting applications of artificial intelligence (AI) assisted technologies.MethodWe assessed the ability of a convolutional neural network (CNN) algorithm to classify TLE vs. patients with AD vs. healthy controls using T1-weighted magnetic resonance imaging (MRI) scans. We used feature visualization techniques to identify regions the CNN employed to differentiate disease types.ResultsWe show the following classification results: healthy control accuracy = 81.54% (SD = 1.77%), precision = 0.81 (SD = 0.02), recall = 0.85 (SD = 0.03), and F1-score = 0.83 (SD = 0.02); TLE accuracy = 90.45% (SD = 1.59%), precision = 0.86 (SD = 0.03), recall = 0.86 (SD = 0.04), and F1-score = 0.85 (SD = 0.04); and AD accuracy = 88.52% (SD = 1.27%), precision = 0.64 (SD = 0.05), recall = 0.53 (SD = 0.07), and F1 score = 0.58 (0.05). The high accuracy in identification of TLE was remarkable, considering that only 47% of the cohort had deemed to be lesional based on MRI alone. Model predictions were also considerably better than random permutation classifications (p < 0.01) and were independent of age effects.ConclusionsAI (CNN deep learning) can classify and distinguish TLE, underscoring its potential utility for future computer-aided radiological assessments of epilepsy, especially for patients who do not exhibit easily identifiable TLE associated MRI features (e.g., hippocampal sclerosis).
Problems in applying Soft OR methods to climate actions: lessons from two cases of governmental use
Authors: Leong Ching , Soon Damien W. X. , Ong Corinne , Howlett Michael 
Published: February 2023

AbstractThe field of Soft Operational Research (Soft OR) has emerged from the attempt to address contextually rich, multi-actor ‘wicked’ problems that are not amenable to traditional ‘hard’ operational research techniques, which often rely on mathematical modelling. This study assesses the use of Soft OR techniques in climate change policymaking. Since climate change problems are classical wicked problems, many assume that Soft OR would be in high demand in developing climate change policy. And the review of the use of these techniques conducted here does find that in the cases where Soft OR methods have been used by academics and other non-governmental actors, they have consistently provided useful results for policymaking. It is puzzling therefore that there is little evidence of governments using Soft OR application in this area. We study two cases of explicit (in Bristol UK) and implicit use (Rhode Island, US) of such techniques by governments to explain why this is so. We argue that notwithstanding the challenges the two cases reveal in their application, Soft OR nevertheless has much to offer policymakers in the arena of climate change policymaking and deserve more attention and use.
Interpretation of Misarticulated Words by Children With and Without Speech Sound Disorders
Authors: Krueger Breanna I. , Beers Hally , Frankenberry Jacob 
Published: February 2023

Purpose:
Children with speech sound disorders (SSDs) often struggle with forming early representations for phonemes and words, which could impact their speech production as well as their lexical access. This difficulty may limit their ability to accurately identify nonexemplar productions of words, such as developmental misarticulations produced by peers. The purpose of this study was to examine word interpretation of misarticulated words by children with SSD.

Method:
Seventeen monolingual English-speaking preschoolers were assessed for language, phonological processing, and articulation skills. Participants heard three types of words: accurate productions (e.g., “leaf”), common misarticulated productions (e.g., “weaf”), uncommon misarticulated productions (e.g., “yeaf”), and unrelated nonwords (e.g., “gim”). Children were presented with these words aurally and asked to select the picture that matched what they heard—either a real object or a blank square.

Results:
The proportion of real object picture selections was calculated for each word type and compared within subjects. The findings indicate that children with SSD reliably associated common misarticulated words with pictured objects more frequently than they did in the uncommon misarticulation condition. These results were compared between subjects to typically developing (TD) peers' responses using a one-way analysis of variance. The results indicate that children with SSD identified common substitutions as real object pictures more often than TD peers.

Conclusion:
The results of this study suggest that children with SSD are sensitive to the commonness of misarticulations; however, they accept common substitutions as real object pictures significantly more often than TD peers.
Efecto de la temperatura y la poda tardía sobre la fisiología y calidad del cv. Merlot en el Valle Central de Chile
Authors: Salazar-Parra Carolina , Macias José , Reyes Marisol , Peppi Cecilia 
Published: February 2023

La Poda tardía (PT) ha surgido como una herramienta que podría apoyar la adaptación de la viticultura frente al cambio climático, pudiendo retrasar la maduración y reducir el desequilibro en la madurez entre los azucares, ácidos y compuestos fenológicos, producidos por el incremento de temperatura (T). El objetivo del estudio fue evaluar la PT en cv. Merlot del Valle Central de Chile, en 2 condiciones de temperatura: Ambiente; Elevada y 3 momentos de poda: Invierno; Brotación; Brotes 2-4 cm. Se realizó un seguimiento fenológico, determinación de intercambio gaseoso y crecimiento. Al momento de la cosecha se valoró la calidad de la fruta (brix, acidez, pH) y la concentración de antocianinas.
El aumento de T produjo un incremento de la temperatura de hojas por sobre 30ºC, además de caídas en la AN, gs y WUEF, y disminuyo significativamente el rendimiento por planta. Los tratamientos en T elevada presentaron una cosecha adelantada y menor concentración de antocianinas, independiente de la poda, no logrando contrarrestar los efectos de la T. En condiciones de T actual la poda fue capaz de retrasar la cosecha en al menos una semana, sumado a un incremento del 10% de la concentración de antocianinas en piel.
Influencia de la reducción del grado alcohólico en los vinos de crianza biológica sobre sus características físico-químicas y sensoriales. Primeros resultados
Authors: Lasanta Cristina , Muñoz-Castells Raquel , Gómez Juan , Moreno Juan 
Published: February 2023

Las Denominaciones de Origen Protegidas Jerez-Xérez-Sherry, Manzanilla Sanlúcar de Barrameda y Montilla-Moriles son de las más antiguas de España. En ellas se elaboran los vinos tipo Fino y Manzanilla mediante una etapa de crianza biológica bajo velo de Flor durante varios años. Estos vinos, que presentan características organolépticas específicas, tienen establecido una graduación alcohólica mínima del 15% (14,5% en el caso de los vinos Finos sin alcohol añadido en la DO Montilla-Moriles).
Los gustos de los consumidores van cambiando y cada vez hay una mayor preocupación por la salud, por lo que la tendencia actual es la de consumir bebidas alcohólicas con un contenido en alcohol moderado. En el presente trabajo, se ha estudiado la viabilidad de elaborar vinos tipo Fino y Manzanilla con un grado alcohólico más reducido. Los primeros resultados nos indican que es viable elaborar esta tipología de vinos con un menor contenido en alcohol, manteniendo la elaboración tradicional y calidad de estos vinos, aunque es un proceso que habrá que seguir estudiando a largo plazo.
Wer sollte die pädiatrischen Wirbelsäulenpathologien (Tumore, Deformitäten, Trauma) operieren?
Der Wirbelsäulenchirurg, oder der Kinderorthopäde, – Neurochirurg?
Authors: Jeszenszky Dezsö 
Published: February 2023

ZusammenfassungSeit Jahrzehnten besteht in chirurgischen Kreisen ein Kompetenzgerangel bezüglich der Behandlung von Wirbelsäulenpathologien, insbesondere bei pädiatrischen Patienten. Zum Wohle unserer Patienten braucht es einen ausgebildeten Wirbelsäulenchirurg nach der Facharztweiterbildung Orthopädie/Unfallchirurgie oder Neurochirurgie. Eine entsprechende Spezialisierung mit operativer Erfahrung in allen Segmenten der Wirbelsäule und fachlicher Kenntnis in der Versorgung der kindlichen und wachsenden Wirbelsäule werden eine optimale Patientenversorgung in der Zukunft gewährleisten.
Operative Versorgung der Typ 2 Dens Fraktur bei >80 j – Pro
Authors: Arand Markus 
Published: February 2023

ZusammenfassungTyp 2 Frakturen des Dens axis bei mobilen und rüstigen Patienten >80 Jahren und bei frailty-Patienten sind in der Regel operativ zu stabilisieren. In der Literatur spiegelt sich ein Wandel weg von der konservativen und hin zu der operativen Stabilisation wieder, nachdem Metaanalysen und die Aufarbeitung großer Datenbanken für das operative Verfahren eine geringere Mortalität zeigen. Die eigene prospektive Erfassung 2012–2022 von 55 konsekutiv operierten Patienten zeigt eine Frühmortalität von 15% und liegt damit auch im Trend der Literatur. 16 (29%) der Patienten wurden über einen dorsalen Zugang occipitozervikal und ein Patient (2%) C1–C3 stabilisiert, in dieser Gruppe war die Inzidenz von translatorischen Instabilitäten C1–C2 und begleitende instabile Atlas- und Massa lateralis-Frakturen C2 deutlich höher, wie auch die Frühmortalität (38%). Bei 37 Patienten (67%) wurde die Osteosynthese/Stabilisation über einen ventralen Zugang bei einfacherer Frakturmorphologie vorgenommen (15×1 Schraube, 8×2 Schrauben und 14 C2–C1 transartikulär beidseits) mit einer Frühmortalität von 5%, aber einer höheren Komplikationsrate für Schluckstörungen und implantatassoziierte Komplikationen. Moribunde Patienten, ohne Aussicht auf Mobilität sollten konservativ im Sinne of „best supportive care“ behandelt werden.
The relationship between investment intensity and profitability measures from the perspective of foreign investors
Authors: AL Ani Mawih Kareem , Chavali Kavita 
Published: February 2023

AbstractInvestment intensity is the level of investment in fixed assets that affects a company’s long-term growth prospects. In order to make good investment decisions, investors pay more attention to achieving a high level of investment intensity. This study examines the impact of two non-GAAP measures of profitability—earnings before interest, tax, depreciation, and amortization and earnings before interest and tax—on investment intensity in Gulf Cooperation Council (GCC) member countries. The study also examines the preference for two non-GAAP measures of profitability from the perspective of foreign investors. The study conducts panel data regressions using 205 firm observations covering the period 2010–2019 to examine the relationship between earnings before interest, tax, depreciation and amortization, earnings before interest and tax, and investment intensity. The study used various statistical estimators to overcome the heterogeneity and endogeneity problems of panel data and employed many diagnostic tests to increase robustness. The study finds that earnings before interest, tax, depreciation and amortization are positively and significantly associated with investment intensity in all GCC countries, but earnings before interest and tax are negatively associated with investment intensity in these countries. The results indicate that foreign investors prefer to use earnings before interest, tax, depreciation, and amortization to make decisions about investment intensity. The main implication of the study is that capital market regulators and foreign investors should use earnings before interest, tax, depreciation, and amortization information as a guideline to improve investment intensity decisions and achieve a better allocation of resources in capital markets.
Stability and energy identity for Yang–Mills–Higgs pairs
Authors: Han Xiaoli , Jin Xishen , Wen Yang 
Published: February 2023

In this paper, we study the properties of the critical points of Yang–Mills–Higgs functional, which are called Yang–Mills–Higgs pairs. We first consider the properties of weakly stable Yang–Mills–Higgs pairs on a vector bundle over Sn (n ≥ 4). When n ≥ 4, we prove that the norm of its Higgs field is 1 and the connection is actually Yang–Mills. More precisely, its curvature vanishes when n ≥ 5. We also use the bubble-neck decomposition to prove the energy identity of a sequence of Yang–Mills–Higgs pairs over a four-dimensional compact manifold with uniformly bounded energy. We show there is a subsequence that converges smoothly to a Yang–Mills–Higgs pair up to gauge modulo finitely many four-dimensional spheres with Yang–Mills connections.
Effects of flexibility in coarse-grained models for bovine serum albumin and immunoglobulin G
Authors: Hirschmann Frank , Lopez Hender , Roosen-Runge Felix , Seydel Tilo , Schreiber Frank , Oettel Martin 
Published: February 2023

We construct a coarse-grained, structure-based, low-resolution, 6-bead flexible model of bovine serum albumin (BSA, PDB: 4F5S), which is a popular example of a globular protein in biophysical research. The model is obtained via direct Boltzmann inversion using all-atom simulations of a single molecule, and its particular form is selected from a large pool of 6-bead coarse-grained models using two suitable metrics that quantify the agreement in the distribution of collective coordinates between all-atom and coarse-grained Brownian dynamics simulations of solutions in the dilute limit. For immunoglobulin G (IgG), a similar structure-based 12-bead model has been introduced in the literature [Chaudhri et al., J. Phys. Chem. B 116, 8045 (2012)] and is employed here to compare findings for the compact BSA molecule and the more anisotropic IgG molecule. We define several modified coarse-grained models of BSA and IgG, which differ in their internal constraints and thus account for a variation of flexibility. We study denser solutions of the coarse-grained models with purely repulsive molecules (achievable by suitable salt conditions) and address the effect of packing and flexibility on dynamic and static behavior. Translational and rotational self-diffusivity is enhanced for more elastic models. Finally, we discuss a number of effective sphere sizes for the BSA molecule, which can be defined from its static and dynamic properties. Here, it is found that the effective sphere diameters lie between 4.9 and 6.1 nm, corresponding to a relative spread of about ±10% around a mean of 5.5 nm.
Ionization energies and ionization-induced structural changes in 2-phenylethylamine and its monohydrate
Authors: Yifrach Yair , Rahimi Rami , Baraban Joshua H. , Bar Ilana 
Published: February 2023

We report the resonance-enhanced two-photon ionization combined with various detection approaches and quantum chemical calculations of biologically relevant neurotransmitter prototypes, the most stable conformer of 2-phenylethylamine (PEA), and its monohydrate, PEA-H2O, to reveal the possible interactions between the phenyl ring and amino group in the neutral and ionic species. Extracting the ionization energies (IEs) and appearance energy was achieved by measuring the photoionization and photodissociation efficiency curves of the PEA parent and photofragment ions, together with velocity and kinetic energy-broadened spatial map images of photoelectrons. We obtained coinciding upper bounds for the IEs for PEA and PEA-H2O of 8.63 ± 0.03 and 8.62 ± 0.04 eV, within the range predicted by quantum calculations. The computed electrostatic potential maps show charge separation, corresponding to a negative charge on phenyl and a positive charge on the ethylamino side chain in the neutral PEA and its monohydrate; in the cations, the charge distributions naturally become positive. The significant changes in geometries upon ionization include switching of the amino group orientation from pyramidal to nearly planar in the monomer but not in the monohydrate, lengthening of the N–H⋯π hydrogen bond (HB) in both species, Cα–Cβ bond in the side chain of the PEA+ monomer, and the intermolecular O–H⋯N HB in PEA-H2O cations, leading to distinct exit channels.
Analytical model for ionic current dominated corrosion of nanoelectrodes in metalized films: Frequency and electric stress
Authors: Li Hua , Qiu Tian , Li Zheng , Lin Fuchang , Zhang Qin 
Published: February 2023

Metalized film capacitors in a.c. applications suffer high frequency and high voltage, which will induce electrode corrosion, leading to capacitance degradation. The intrinsic mechanism of the corrosion is oxidation caused by ionic migration in the oxide film formed on the electrode surface. In this work, a D–M–O illustration structure for the nanoelectrode corrosion process is established, and thereby, an analytical model is derived to study the influences of frequency and electric stress on corrosion speed in a quantitative approach. The analytical results well conform to the experimental facts. It is found the corrosion rate rises with frequency and finally tends to reach a saturation value. The electric field in oxide has an exponential-like contribution to the corrosion rate. In the case of aluminum metalized films, the saturation frequency and minimum field required for corrosion initiation are, respectively, 3434 Hz and 0.35 V/nm calculated by the proposed equations.
A soil fungus confers plant resistance against a phytophagous insect by disrupting the symbiotic role of its gut microbiota
Authors: Di Lelio Ilaria , Forni Giobbe , Magoga Giulia , Brunetti Matteo , Bruno Daniele , Becchimanzi Andrea , De Luca Maria G. , Sinno Martina , Barra Eleonora , Bonelli Marco , Frusciante Sarah , Diretto Gianfranco , Digilio Maria C. , Woo Sheridan L. , Tettamanti Gianluca , Rao Rosa , Lorito Matteo , Casartelli Morena , Montagna Matteo , Pennacchio Francesco 
Published: February 2023

Plants generate energy flows through natural food webs, driven by competition for resources among organisms, which are part of a complex network of multitrophic interactions. Here, we demonstrate that the interaction between tomato plants and a phytophagous insect is driven by a hidden interplay between their respective microbiotas. Tomato plants colonized by the soil fungus
Trichoderma afroharzianum
, a beneficial microorganism widely used in agriculture as a biocontrol agent, negatively affects the development and survival of the lepidopteran pest
Spodoptera littoralis
by altering the larval gut microbiota and its nutritional support to the host. Indeed, experiments aimed to restore the functional microbial community in the gut allow a complete rescue. Our results shed light on a novel role played by a soil microorganism in the modulation of plant–insect interaction, setting the stage for a more comprehensive analysis of the impact that biocontrol agents may have on ecological sustainability of agricultural systems.
Structure-guided approach to modulate small molecule binding to a promiscuous ligand-activated protein
Authors: Lin Wenwei , Huber Andrew D. , Poudel Shyaron , Li Yongtao , Seetharaman Jayaraman , Miller Darcie J. , Chen Taosheng 
Published: February 2023

Ligand-binding promiscuity in detoxification systems protects the body from toxicological harm but is a roadblock to drug development due to the difficulty in optimizing small molecules to both retain target potency and avoid metabolic events. Immense effort is invested in evaluating metabolism of molecules to develop safer, more effective treatments, but engineering specificity into or out of promiscuous proteins and their ligands is a challenging task. To better understand the promiscuous nature of detoxification networks, we have used X-ray crystallography to characterize a structural feature of pregnane X receptor (PXR), a nuclear receptor that is activated by diverse molecules (with different structures and sizes) to up-regulate transcription of drug metabolism genes. We found that large ligands expand PXR’s ligand-binding pocket, and the ligand-induced expansion occurs through a specific unfavorable compound-protein clash that likely contributes to reduced binding affinity. Removing the clash by compound modification resulted in more favorable binding modes with significantly enhanced binding affinity. We then engineered the unfavorable ligand-protein clash into a potent, small PXR ligand, resulting in marked reduction in PXR binding and activation. Structural analysis showed that PXR is remodeled, and the modified ligands reposition in the binding pocket to avoid clashes, but the conformational changes result in less favorable binding modes. Thus, ligand-induced binding pocket expansion increases ligand-binding potential of PXR but is an unfavorable event; therefore, drug candidates can be engineered to expand PXR’s ligand-binding pocket and reduce their safety liability due to PXR binding.