julilili42/papers huggingface dataset:
Exploring the metabolic profiling ofA. baumanniifor antimicrobial development using genome-scale modelling
2023-09-15

ABSTRACT With the emergence of multidrug-resistant bacteria, the World Health Organization published a catalog of microorganisms urgently needing new antibiotics, with the carbapenem-resistant Acinetobacter baumannii designated as “critical”. Such isolates, frequently detected in healthcare settings, pose a global pandemic threat. One way to facilitate a systemic view of bacterial metabolism and allow the development of new therapeutics is to apply constraint-based modelling. Here, we developed a versatile workflow to build high-quality and simulation-ready genome-scale metabolic models. We applied our workflow to create a novel metabolic model for A. baumannii and validated its predictive capabilities using experimental nutrient utilization and gene essentiality data. Our analysis showed that our model i ACB23LX could recapitulate cellular metabolic phenotypes observed during in vitro experiments, while positive biomass production rates were observed and experimentally validated in various growth media. We further defined a minimal set of compounds that increase A. baumannii ‘s cellular biomass and identified putative essential genes with no human counterparts, offering novel candidates for future antimicrobial development. Finally, we assembled and curated the first collection of reconstructions for distinct A. baumannii strains and analysed their growth characteristics. The presented models are in a standardised and well-curated format, enhancing their usability for multi-strain network reconstruction.
Planar BN-Doped Nanographenes on Reactive Metal Surfaces: A Promising Pathway for the Preparation of BN-Doped Graphene Layers
2023-09-15

Boron nitride (BN)-substituted nanographene molecules are currently the focus of interest because the substitution of C–C units by isoelectronic and isosteric BN units is a straightforward way for tuning of their electronic properties. We investigated interface properties of BN-doped B3N3-hexa-peri-hexabenzocoronene (BN-HBC) and B3N3-hexabenzotriphenylene (BN-HBP) on metals with different reactivities using photoelectron spectroscopy (PES). As a reference, HBC was studied on Au(111), Cu(111), and Ni(111) by PES and scanning tunneling microscopy. The substitution of the inner benzene ring of HBC by a borazine core changes the nature of the interaction in the case of more reactive Cu(111) and Ni(111) substrates. Whereas for the planar BN-HBC, chemical interaction occurs mainly via outer C atoms, the inner BN ring is affected in the case of the nonplanar BN-HBP. The stability of the inner ring is expected to be a prerequisite for a successful preparation of well-defined, large-area, BN-doped graphene layers from bottom-up synthesis.
The reawakening of the sleeping X-ray pulsar XTE J1946+274
2023-09-15

We report on a series of outbursts of the high-mass X-ray binary XTE J1946+274 in 2010/2011 observed with INTEGRAL, RXTE, and Swift. We discuss possible mechanisms resulting in the extraordinary outburst behavior of this source. The X-ray spectra can be described by standard phenomenological models, enhanced by an absorption feature of unknown origin at about 10 keV and a narrow iron Kα fluorescence line at 6.4 keV, which are variable in flux and pulse phase. We find possible evidence for a cyclotron resonance scattering feature at about 25 keV at the 93% level. The presence of a strong cyclotron line at 35 keV seen in data from the source’s 1998 outburst that was confirmed by a reanalysis of these data can be excluded. This result indicates that the cyclotron line feature in XTE J1946+274 is variable between individual outbursts.
THE Be/X-RAY BINARY SWIFT J1626.6−5156 AS A VARIABLE CYCLOTRON LINE SOURCE
2023-09-15

Swift J1626.6−5156 is a Be/X-ray binary that was in outburst from 2005 December until 2008 November. We have examined Rossi X-ray Timing Explorer/Proportional Counter Array (PCA) and High Energy X-ray Timing Explorer spectra of three long observations of this source taken early in its outburst, when the PCA 2–20 keV count rate was &gt;70 counts s−1 PCU−1, as well as several combined observations from different stages of the outburst. The spectra are best fit with an absorbed cutoff power law with a ∼6.4 keV iron emission line and a Gaussian optical depth absorption line at ∼10 keV. We present strong evidence that this absorption-like feature is a cyclotron resonance scattering feature, making Swift J1626.6−5156 a new candidate cyclotron line source. The redshifted energy of ∼10 keV implies a magnetic field strength of ∼8.6(1 + z) × 1011 G in the region of the accretion column close to the magnetic poles where the cyclotron line is produced. Analysis of phase-averaged spectra spanning the duration of the outburst suggests a possible positive correlation between the fundamental cyclotron energy and source luminosity. Phase-resolved spectroscopy from a long observation reveals a variable cyclotron line energy, with phase dependence similar to a variety of other pulsars, as well as the first harmonic of the fundamental cyclotron line.
Prevention or Promotion? Predicting Author's Regulatory Focus
2023-09-15

People differ fundamentally in what motivates them to pursue a goal and how they approach it. For instance, some people seek growth and show eagerness, whereas others prefer security and are vigilant. The concept of regulatory focus is employed in psychology, to explain and predict this goal-directed behavior of humans underpinned by two unique motivational systems – the promotion and the prevention system. Traditionally, text analysis methods using closed-vocabularies are employed to assess the distinctive linguistic patterns associated with the two systems. From an NLP perspective, automatically detecting the regulatory focus of individuals from text provides valuable insights into the behavioral inclinations of the author, finding its applications in areas like marketing or health communication. However, the concept never made an impactful debut in computational linguistics research. To bridge this gap we introduce the novel task of regulatory focus classification from text and present two complementary German datasets – (1) experimentally generated event descriptions and (2) manually annotated short social media texts used for evaluating the generalizability of models on real-world data. First, we conduct a correlation analysis to verify if the linguistic footprints of regulatory focus reported in psychology studies are observable and to what extent in our datasets. For automatic classification, we compare closed-vocabulary-based analyses with a state-of-the-art BERT-based text classification model and observe that the latter outperforms lexicon-based approaches on experimental data and is notably better on out-of-domain Twitter data.
A morphometric analysis of the retinal arterioles with adaptive optics imaging in RPE65‐associated retinal dystrophy after treatment with voretigene neparvovec
2023-09-16

Abstract Purpose To investigate the changes in retinal arterial architecture after treatment with voretigene neparvovec in patients with retinal dystrophy caused by bi‐allelic mutations in the RPE65 gene. Methods Sixteen eyes treated with voretigene neparvovec at the University Eye Clinic in Tuebingen, Germany, underwent adaptive optics ophthalmoscopy (AO) imaging at baseline and 2 weeks, 1, 3, 6 and 12 months after treatment. Follow‐up was performed in six eyes of four patients. For each eye, five different positions at arterial vessels were selected and the wall‐to‐lumen ratio (WLR), the lumen diameter (LD) and the wall cross‐sectional area (WCSA) were measured by the manufacturer's software over the observational period. Results Vast retinal atrophy dominated all gained AO images. WLR fluctuated in the observation period without statistically significant change. LD and WCSA changed significantly after 2 weeks from the baseline examination and returned to values similar to baseline thereafter. There were no signs of inflammation such as macrophages or perivascular accumulated fluid visible. Conclusion AO imaging of the retinal vessels in RPE65‐ associated retinal dystrophies (IRD) is challenging. There was no change in the retinal arterial vasculature over the observation period of 12 months that would indicate inflammatory changes. Decrease of the LD and WCSA shortly after treatment might be caused by the perioperative prednisolone intake. AO of retinal vessels can be used as a diagnostic module to complement monitoring the disease and effects of genetic treatments if the acquisition is possible in selected cases.
Microbial degradation of plant toxins
2023-09-17

Abstract Plants produce a variety of secondary metabolites in response to biotic and abiotic stresses. Although they have many functions, a subclass of toxic secondary metabolites mainly serve plants as deterring agents against herbivores, insects, or pathogens. Microorganisms present in divergent ecological niches, such as soil, water, or insect and rumen gut systems have been found capable of detoxifying these metabolites. As a result of detoxification, microbes gain growth nutrients and benefit their herbivory host via detoxifying symbiosis. Here, we review current knowledge on microbial degradation of toxic alkaloids, glucosinolates, terpenes, and polyphenols with an emphasis on the genes and enzymes involved in breakdown pathways. We highlight that the insect‐associated microbes might find application in biotechnology and become targets for an alternative microbial pest control strategy.
Exploring the Translational Gap of a Novel Class of Escherichia coli IspE Inhibitors
2023-09-17

Abstract Discovery of novel antibiotics needs multidisciplinary approaches to gain target enzyme and bacterial activities while aiming for selectivity over mammalian cells. Here, we report a multiparameter optimisation of a fragment‐like hit that was identified through a structure‐based virtual‐screening campaign on Escherichia coli IspE crystal structure. Subsequent medicinal‐chemistry design resulted in a novel class of E. coli IspE inhibitors, exhibiting activity also against the more pathogenic bacteria Pseudomonas aeruginosa and Acinetobacter baumannii . While cytotoxicity remains a challenge for the series, it provides new insights on the molecular properties for balancing enzymatic target and bacterial activities simultaneously as well as new starting points for the development of IspE inhibitors with a predicted new mode of action.
An experimental test of the Big-Fish-Little-Pond Effect using an immersive virtual reality classroom
2023-09-17

Abstract Academic self-concept plays a central role in successful learning and is substantially shaped by social comparisons. Research on the so-called Big-Fish-Little-Pond Effect (BFLPE) has yielded a highly robust and generalizable pattern of negative effects of higher class/school average achievement on students’ self-concept when controlling for individual achievement. However, most BFLPE studies have not provided information about the causes behind or the mechanisms underlying the proposed effects. To address this, we used a fully immersive virtual reality (IVR) classroom to experimentally test the extent to which students recognized performance-related classroom behavior as implicit social comparison information and how these perceptions explained differences in students’ self-concepts. Participants ( N = 381 sixth-grade students) experienced an authentic yet standardized IVR teaching situation with virtual classmates who exhibited different performance levels (operationalized as 20% vs. 35% vs. 65% vs. 80% of classmates raising their hands). Hand-raising behavior had a significant positive effect on students’ perceptions of the class’ performance level ( d 20% vs. 65% = 0.60; d 20% vs. 80% = 1.24). In line with the BFLPE, results showed a negative effect of higher performing classmates on students’ situational self-concept ( d 20% vs. 80% = 0.30). Students’ perceptions of the class’ performance level fully explained the effect of classmates’ hand-raising behavior on students’ situational self-concept. The study’s experimental approach provided new insights into the emergence of social comparison effects in the classroom, highlighting the major role of students’ perceptions of their classmates’ performance-related behavior, and moreover demonstrated the general potential of using IVR in classroom research.
mTOR signaling and Alzheimer's disease: What we know and where we are?
2023-09-18

Abstract Despite the great body of research done on Alzheimer's disease, the underlying mechanisms have not been vividly investigated. To date, the accumulation of amyloid‐beta plaques and tau tangles constitutes the hallmark of the disease; however, dysregulation of the mammalian target of rapamycin (mTOR) seems to be significantly involved in the pathogenesis of the disease as well. mTOR, as a serine–threonine protein kinase, was previously known for controlling many cellular functions such as cell size, autophagy, and metabolism. In this regard, mammalian target of rapamycin complex 1 (mTORC1) may leave anti‐aging impacts by robustly inhibiting autophagy, a mechanism that inhibits the accumulation of damaged protein aggregate and dysfunctional organelles. Formation and aggregation of neurofibrillary tangles and amyloid‐beta plaques seem to be significantly regulated by mTOR signaling. Understanding the underlying mechanisms and connection between mTOR signaling and AD may suggest conducting clinical trials assessing the efficacy of rapamycin, as an mTOR inhibitor drug, in managing AD or may help develop other medications. In this literature review, we aim to elaborate mTOR signaling network mainly in the brain, point to gaps of knowledge, and define how and in which ways mTOR signaling can be connected with AD pathogenesis and symptoms.
Challenges of neural interfaces for stroke motor rehabilitation
2023-09-18

More than 85% of stroke survivors suffer from different degrees of disability for the rest of their lives. They will require support that can vary from occasional to full time assistance. These conditions are also associated to an enormous economic impact for their families and health care systems. Current rehabilitation treatments have limited efficacy and their long-term effect is controversial. Here we review different challenges related to the design and development of neural interfaces for rehabilitative purposes. We analyze current bibliographic evidence of the effect of neuro-feedback in functional motor rehabilitation of stroke patients. We highlight the potential of these systems to reconnect brain and muscles. We also describe all aspects that should be taken into account to restore motor control. Our aim with this work is to help researchers designing interfaces that demonstrate and validate neuromodulation strategies to enforce a contingent and functional neural linkage between the central and the peripheral nervous system. We thus give clues to design systems that can improve or/and re-activate neuroplastic mechanisms and open a new recovery window for stroke patients.
Discrete Trivalent Lanthanide Isobutylaluminates in Isoprene Polymerization: Elucidation of Cationized Active Species
2023-09-18

Triisobutylaluminum (TIBA) is a main component applied in industrial Ziegler-type mixed catalysts for conjugated diene polymerization. Despite this importance, discrete crystalline trivalent lanthanide tetraisobutylaluminates have not yet been examined in polymerization. The present study revealed that discrete complexes Ln[N(SiMe3)2](HAliBu3)(AliBu4) (Ln = La, Pr, Nd, Gd) promote highly stereoselective isoprene polymerization with >99% cis selectivity. Mechanistic studies with borate cocatalysts, supported by single crystal X-ray diffraction, and NMR spectroscopy, disclose the formation of dicationic neodymium complex [Nd{N(SiMe3)2}(PhNMe2)2][B(C6F5)4]2 from the binary system Nd[N(SiMe3)2](HAliBu3)(AliBu4)/[PhNMe2H][B(C6F5)4]. Complex [Nd{N(SiMe3)2}(PhNMe2)2][B(C6F5)4]2 engages in single-component isoprene polymerization.
Online Interaction Turns the Congeniality Bias Into an Uncongeniality Bias
2023-09-18

Online phenomena like echo chambers and polarization are believed to be driven by humans’ penchant to selectively expose themselves to attitudinally congenial content. However, if like-minded content were the only predictor of online behavior, heated debate and flaming on the Internet would hardly occur. Research has overlooked how online behavior changes when people are given an opportunity to reply to dissenters. Three experiments (total N = 320; convenience student samples from Germany) and an internal meta-analysis show that in a discussion-forum setting where participants can reply to earlier comments larger cognitive conflict between participant attitude and comment attitude predicts higher likelihood to respond ( uncongeniality bias). When the discussion climate was friendly (vs. oppositional) to the views of participants, the uncongeniality bias was more pronounced and was also associated with attitude polarization. These results suggest that belief polarization on social media may not only be driven by congeniality but also by conflict.
SGLT2 inhibitors decrease overhydration and proteasuria in patients with chronic kidney disease: a longitudinal observational study
2023-09-18

Abstract Background SGLT2 inhibitors are used to reduce the risk of progression of chronic kidney disease (CKD). In patients with type 2 diabetes, they have been found to reduce extracellular volume. Given the high prevalence of extracellular volume expansion and overhydration in CKD, we investigated whether SGLT2 inhibitors might correct these disturbances in CKD patients. Methods CKD patients who started treatment with an SGLT2 inhibitor were investigated in this prospective observational study for 6 months. Body composition and fluid status were measured by bioimpedance spectroscopy. In addition, spot urine samples were analyzed for albuminuria, glucosuria and urinary aprotinin-sensitive serine protease activity. Results 42 patients (29% with diabetic/hypertensive CKD, 31% with IgA nephropathy; 88% dapagliflozin 10 mg, 10% dapagliflozin 5 mg, 2% empagliflozin 20 mg; median eGFR 46 mL/min/1.73m2 and albuminuria 1911 mg/g creatinine) participated in the study. Median glucosuria increased to 14 (10–19) g/g creatinine. At baseline, patients displayed overhydration (OH) with + 0.4 (-0.2–2.2) L/1.73m2 which decreased by 0.5 (0.1–1.2) L/1.73m2 after 6 months. Decrease of OH correlated with higher OH at BL, decrease of albuminuria, glucosuria and urinary aprotinin-sensitive protease activity. Adipose tissue mass was not significantly reduced after 6 months. Conclusions SGLT2 inhibitors reduce overhydration in patients with CKD, which is pronounced in the presence of high albuminuria, glucosuria and urinary aprotinin-sensitive protease activity. Trial Registration The study was registered at the German Clinical Trials Register (DRKS00028560).
Simulation Tool for Optical Systems: Evaluating and Optimizing Autofocals and Beyond
2023-09-18

<title>Abstract</title> The development and evaluation of autofocal glasses require robust and efficient tools for assessing their performance in various real-world scenarios. This study presents a novel virtual reality (VR) simulation tool designed to evaluate the control algorithms of autofocal glasses. The tool incorporates a matching task involving Landolt rings and Sloan letters presented on different screens at varying distances and a NASA Task Load Index (TLX) questionnaire to assess participants’ subjective workload and convenience. By employing this experimental design, we aimed to gain insights into the effectiveness and efficiency of the evaluated control algorithms for autofocals within our VR-based simulation tool. Our results indicate that the developed VR simulation tool provides a valuable platform for assessing the performance of autofocal glasses in a controlled environment, ultimately contributing to the development of more efficient and user-friendly autofocal glasses.
Classical homocystinuria presenting with transient basal ganglia pathology and dystonia
2023-09-18

Abstract Classical homocystinuria is caused by pathogenic variants in the CBS gene leading to a deficiency of the vitamin B6‐dependent enzyme cystathionine beta synthase. The disease is typically associated with high blood homocysteine concentrations. Clinical features include developmental delay/intellectual disability, psychiatric problems, thromboembolism, lens dislocation, and marfanoid habitus. We report on a child with classical homocystinuria presenting with acute episodes of dystonia and symmetrical basal ganglia abnormalities mimicking a mitochondrial disease. After starting treatment with vitamin B6, homocysteine levels rapidly normalized and dystonic episodes did not re‐occur. Moreover, brain‐imaging findings almost completely disappeared. The case illustrates that homocystinuria should be considered as a treatable differential diagnosis of dystonia.
The forgotten militant and his enduring mission: Zing-Yang Kuo and his extraordinary years in behavioral neuroembryology (1929–1939)
2023-09-18

Zing-Yang Kuo (1898-1970), hailed as China's behaviorist psychologist, earned "Out-Watsons Mr. Watson" in the international anti-instinct movement. His contributions to the field on behavioral neuroembryology (1929-1939) are often overlooked in comparison to his achievements in psychology. We retrieved the titles of all of Kuo's publications from 1929 to 1939 and examined those related to his research on the origins and development of embryonic behavioral ontogeny and the neural basis of embryonic behavior. Remarkably, Kuo concurrently focused on embryos during the same period as North American neuroembryologists. He maintained an independent stance in the debate over the sequence of behavioral ontogeny, represented by the embryonic neuroscientists Coghill and Windle, and critically pointed out limitations in research on both sides of the debate. Drawing from his experiments with chicken embryos, Kuo proposed the theory of behavioral epigenesis, which attempted to end the nature-nurture dichotomy and promote the transformation of the research path of behavioral embryology from elementary physiological anatomy toward a deep "comprehensive science." Kuo's achievements directly laid the foundation for the interdisciplinary field of developmental psychobiology, constructing a new conceptual framework for the systematic analysis of behavioral development and promoting the establishment and development of a new approach to epiphenotype epigenetics.
Magnetic equilibria of relativistic axisymmetric stars: The impact of flow constants
2023-09-18

Symmetries and conservation laws associated with the ideal Einstein-Euler system, for stationary and axisymmetric stars, can be utilized to define a set of flow constants. These quantities are conserved along flow lines in the sense that their gradients are orthogonal to the four-velocity. They are also conserved along surfaces of constant magnetic flux, making them powerful tools to identify general features of neutron star equilibria. One important corollary of their existence is that mixed poloidal-toroidal fields are inconsistent with the absence of meridional flows except in some singular sense, a surprising but powerful result first proven by Bekenstein and Oron. In this work, we revisit the flow constant formalism to rederive this result together with several new ones concerning both nonlinear and perturbative magnetic equilibria. Our investigation is supplemented by some numerical solutions for multipolar magnetic fields on top of a Tolman-VII background, where strict power-counting of the flow constants is used to ensure a self-consistent treatment.