Artificial Intelligence Applied to Battery Research: Hype or Reality?

This is a critical review of artificial intelligence/machine learning (AI/ML) methods applied to battery research. It aims at providing a comprehensive, authoritative, and critical, yet easily understandable, review of general interest to the battery community. It addresses the concepts, approaches, tools, outcomes, and challenges of using AI/ML as an accelerator for the design and optimization of the next generation of batteries─a current hot topic. It intends to create both accessibility of these tools to the chemistry and electrochemical energy sciences communities and completeness in terms of the different battery R&D aspects covered.

Perinatal Protein Restriction Impacts Nuclear O-GalNAc Glycosylation in Cells of Liver and Brain Structures of the Rat.

BACKGROUND: Post-translational modifications are key factors in the modulation of nuclear protein functions controlling cell physiology and an individual's health. OBJECTIVES: This study examined the influence of protein restriction during the perinatal period on the nuclear O-N-acetylgalactosamine (O-GalNAc) glycosylation of cells from the liver and parts of the brain in the rat. METHODS: Pregnant Wistar rats were divided into 2 groups on day 14 of pregnancy and fed ad libitum 1 of 2 isocaloric diets containing 24% (well-fed) or 8% (protein-restricted diet) casein until the end of the experiment. Male pups were studied after weaning at 30 d of life. Animals and their organ/tissues (liver, cerebral cortex, cerebellum and hippocampus) were weighed. Cell nuclei were purified, and the presence in nucleus and cytoplasm of all factors required for the initiation of O-GalNAc glycan biosynthesis, i.e., the sugar donor (UDP-GalNAc), enzyme activity (ppGalNAc-transferase) and the glycosylation product (O-GalNAc glycans), were evaluated by western blotting, fluorescent microscopy, enzyme activity, enzyme-lectin sorbent assay and mass spectrometry. RESULTS: The perinatal protein deficit reduced progeny weight, as well as the cerebral cortex and cerebellum weight. UDP-GalNAc levels in the cytoplasm and nuclei of the liver, the cerebral cortex, cerebellum, or hippocampus were not affected by the perinatal dietary protein deficits. However, this deficiency affected the ppGalNAc-transferase activity localized in the cerebral cortex and hippocampus cytoplasm as well as in the liver nucleus, thus reducing the "writing" ppGalNAc-transferase activity of O-GalNAc glycans. In addition, liver nucleoplasm from protein-restricted offspring revealed a significant reduction in the expression of O-GalNAc glycans on important nuclear proteins. CONCLUSIONS: Our results report an association between the consumption of a protein-restricted diet by the dam and her progeny with the modulation in the offspring' liver nuclei O-GalNAc glycosylation, which may ultimately regulate nuclear protein functions.

Carbonyl-Based Redox-Active Compounds as Organic Electrodes for Batteries: Escape from Middle-High Redox Potentials and Further Improvement?

Extracting─from the vast space of organic compounds─the best electrode candidates for achieving energy material breakthrough requires the identification of the microscopic causes and origins of various macroscopic features, including notably electrochemical and conduction properties. As a first guess of their capabilities, molecular DFT calculations and quantum theory of atoms in molecules (QTAIM)-derived indicators were applied to explore the family of pyrano[3,2-b]pyran-2,6-dione (PPD, i.e., A0) compounds, expanded to A0 fused with various kinds of rings (benzene, fluorinated benzene, thiophene, and merged thiophene/benzene). A glimpse of up-to-now elusive key incidences of introducing oxygen in vicinity to the carbonyl redox center within 6MRs─as embedded in the A0 core central unit common to all A-type compounds─has been gained. Furthermore, the main driving force toward achieving modulated low redox potential/band gaps thanks to fusing the aromatic rings for the A compound series was discovered.

Management of groin hernias detected by ultrasound: a comprehensive study.

INTRODUCTION: It remains unclear whether ultrasound-detected hernias (UDH) are the sole cause of pain in patients with groin pain, and clinical examination plays a complementary role. The aim of our study is to describe the evolution of patients with ultrasound detected hernias in terms of development of groin hernia detected by physical examination, pain resolution, and alternative diagnosis. METHODS: An observational, descriptive, longitudinal study of a prospective case series including patients with UDH with groin pain. Follow-up evaluation included the following: follow-up time, side of pain, its evolution, time to resolution, clinical hernia (CH) development, need for surgical resolution, and the presence of postoperative pain and alternative diagnosis. RESULTS: A total of 98 patients with complete follow-up for groin pain and UDH were included. Seven patients (7.1%) developed CH, with a median time to conversion of 8 months. Four of them (4.1% of the total and 57.1% of the ones who developed CH) ended up having surgery. Fifty-three patients (54.1%) resolved their pain in a median time to resolution of 2 months, and 75.5% of them did so spontaneously. The majority of patients with persistent pain (73.3%) were able to lead a normal life and only reported pain with movement. More than half of the patients (53.3%) reached a specific diagnosis. Among those patients who did not develop CH, 39.6% reached an alternative diagnosis, the majority being musculoskeletal pathologies. CONCLUSION: Watchful waiting and a thorough search for other alternative causes of groin pain in UDH and clinically occult hernia would be a reasonable option.

Gaining Insight into the Electrochemical Interface Dynamics in an Organic Redox Flow Battery with a Kinetic Monte Carlo Approach.

Finding low-cost and nontoxic redox couples for organic redox flow batteries is challenging due to unrevealed reaction mechanisms and side reactions. In this study, a 3D kinetic Monte Carlo model to study the electrode-anolyte interface of a methyl viologen-based organic redox flow battery is presented. This model captures various electrode processes, such as ionic displacement and degradation of active materials. The workflow consists of input parameters obtained from density functional theory calculations, a kinetic Monte Carlo algorithm to simulate the discharging process, and an electric double layer model to account for the electric field distribution near the electrode surface. Galvanostatic discharge is simulated at different anolyte concentrations and input current densities, which demonstrate that the model captured the formation of the electrical double layer due to ionic transport. The simulated electrochemical kinetics (potential, charge density) are found to be in agreement with the Nernst equation and the obtained EDL structure corresponded with published molecular dynamics results. The model's flexibility allows further applications of simulating the behavior of different redox couples and makes it possible to consider other molecular-scale phenomena. This study paves the way for computational screening of active species by assessing their potential kinetics in electrochemical environments.

Quorum sensing and stress-activated MAPK signaling repress yeast to hypha transition in the fission yeast Schizosaccharomyces japonicus.

Quorum sensing (QS), a mechanism of microbial communication dependent on cell density, governs developmental decisions in many bacteria and in some pathogenic and non-pathogenic fungi including yeasts. In these simple eukaryotes this response is mediated by the release into the growth medium of quorum-sensing molecules (QSMs) whose concentration increases proportionally to the population density. To date the occurrence of QS is restricted to a few yeast species. We show that a QS mediated by the aromatic alcohols phenylethanol and tryptophol represses the dimorphic yeast to hypha differentiation in the fission yeast S. japonicus in response to an increased population density. In addition, the stress activated MAPK pathway (SAPK), which controls cell cycle progression and adaptation to environmental changes in this organism, constitutively represses yeast to hypha differentiation both at transcriptional and post-translational levels. Moreover, deletion of its main effectors Sty1 MAPK and Atf1 transcription factor partially suppressed the QS-dependent block of hyphal development under inducing conditions. RNAseq analysis showed that the expression of nrg1+, which encodes a putative ortholog of the transcription factor Nrg1 that represses yeast to hypha dimorphism in C. albicans, is downregulated both by QS and the SAPK pathway. Remarkably, Nrg1 may act in S. japonicus as an activator of hyphal differentiation instead of being a repressor. S. japonicus emerges as an attractive and amenable model organism to explore the QS mechanisms that regulate cellular differentiation in fungi.

Correction: Quorum sensing and stress-activated MAPK signaling repress yeast to hypha transition in the fission yeast Schizosaccharomyces japonicus.

[This corrects the article DOI: 10.1371/journal.pgen.1008192.].

CHAMPION: Chalmers hierarchical atomic, molecular, polymeric and ionic analysis toolkit.

We present CHAMPION (Chalmers hierarchical atomic, molecular, polymeric, and ionic analysis toolkit): a software developed to automatically detect time-dependent bonds between atoms based on their dynamics, classify the local graph topology around them, and analyze the physicochemical properties of these topologies by statistical physics. In stark contrast to methodologies where bonds are detected based on static conditions such as cut-off distances, CHAMPION considers pairs of atoms to be bound only if they move together and act as a bound pair over time. Furthermore, the time-dependent global bond graph is possible to split into dynamically shifting connected components or subgraphs around a certain chemical motif and thereby allow the physicochemical properties of each such topology to be analyzed by statistical physics. Applicable to condensed matter and liquids in general, and electrolytes in particular, this allows both quantitative and qualitative descriptions of local structure, as well as dynamical processes such as speciation and diffusion. We present here a detailed overview of CHAMPION, including its underlying methodology, implementation, and capabilities.

Boosting Rechargeable Batteries R&D by Multiscale Modeling: Myth or Reality?

This review addresses concepts, approaches, tools, and outcomes of multiscale modeling used to design and optimize the current and next generation rechargeable battery cells. Different kinds of multiscale models are discussed and demystified with a particular emphasis on methodological aspects. The outcome is compared both to results of other modeling strategies as well as to the vast pool of experimental data available. Finally, the main challenges remaining and future developments are discussed.

Differential functional regulation of protein kinase C (PKC) orthologs in fission yeast.

The two PKC orthologs Pck1 and Pck2 in the fission yeast Schizosaccharomyces pombe operate in a redundant fashion to control essential functions, including morphogenesis and cell wall biosynthesis, as well as the activity of the cell integrity pathway and its core element, the MAPK Pmk1. We show here that, despite the strong structural similarity and functional redundancy of these two enzymes, the mechanisms regulating their maturation, activation, and stabilization have a remarkably distinct biological impact on both kinases. We found that, in contrast to Pck2, putative in vivo phosphorylation of Pck1 within the conserved activation loop, turn, and hydrophobic motifs is essential for Pck1 stability and biological functions. Constitutive Pck activation promoted dephosphorylation and destabilization of Pck2, whereas it enhanced Pck1 levels to interfere with proper downstream signaling to the cell integrity pathway via Pck2. Importantly, although catalytic activity was essential for Pck1 function, Pck2 remained partially functional independent of its catalytic activity. Our findings suggest that early divergence from a common ancestor in fission yeast involved important changes in the mechanisms regulating catalytic activation and stability of PKC family members to allow for flexible and dynamic control of downstream functions, including MAPK signaling.

Multiple layers of regulation influence cell integrity control by the PKC ortholog Pck2 in fission yeast.

The fission yeast protein kinase C (PKC) ortholog Pck2 controls cell wall synthesis and is a major upstream activator of the cell integrity pathway (CIP) and its core component, the MAP kinase Pmk1 (also known as Spm1), in response to environmental stimuli. We show that in vivo phosphorylation of Pck2 at the conserved T842 activation loop during growth and in response to different stresses is mediated by the phosphoinositide-dependent kinase (PDK) ortholog Ksg1 and an autophosphorylation mechanism. However, T842 phosphorylation is not essential for Pmk1 activation, and putative phosphorylation at T846 might play an additional role in Pck2 catalytic activation and downstream signaling. These events, together with turn motif autophosphorylation at T984 and binding to small GTPases Rho1 and/or Rho2, stabilize Pck2 and render it competent to exert its biological functions. Remarkably, the target of rapamycin complex 2 (TORC2) does not participate in the catalytic activation of Pck2, but instead contributes to de novo Pck2 synthesis, which is essential to activate the CIP in response to cell wall damage or glucose exhaustion. These results unveil a novel mechanism whereby TOR regulates PKC function at a translational level, and they add a new regulatory layer to MAPK signaling cascades.

Structural and surface coverage effects on CO oxidation reaction over carbon-supported Pt nanoparticles studied by quadrupole mass spectrometry and diffuse reflectance FTIR spectroscopy.

The CO oxidation reaction on carbon-supported Pt nanoparticles (average size of 2.8 to 7.7 nm) was studied under flowing conditions at atmospheric pressure and temperatures between 300 and 353 K by coupling quadrupole mass spectrometry (QMS) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The Pt loading was varied between 20 and 60 wt%. Gases diluted in He (0.5 mol%) were used together with Ar as a tracer. Reactions with CO and O2 introduced separately onto the samples were studied by QMS, applying successive step changes of the reaction mixtures. Variations in the rate of the reactions were observed and correlated with changes of the calculated coverage of the Pt surface by CO and/or O adspecies at varying steps of the experiment. The transient reaction of CO(g) with adsorbed O (Oad) was fast and mass transport-limited while that of O2(g) with adsorbed CO (COad) was sluggish. Following the same experimental procedures, FTIR spectra of adsorbed CO after varying steps were recorded, confirming the variations of COad and Oad as determined by QMS and indicating changes in the CO distribution over varying types of Pt surface sites. The influence of the adlayer composition (co-adsorption of COad and Oad), the particle size/structure and some possible surface reconstruction effects on the CO oxidation rate were evidenced and discussed. The structure of the Pt nanoparticles supported on carbon appears as an important factor for the efficiency of the so-called O2 bleeding as a CO mitigation strategy in polymer electrolyte membrane fuel cells.

Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating Wee1 kinase.

Cytokinesis involves temporally and spatially coordinated action of the cell cycle, cytoskeletal and membrane systems to achieve separation of daughter cells. The septation initiation network (SIN) and mitotic exit network (MEN) signaling pathways regulate cytokinesis and mitotic exit in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. Previously, we have shown that in fission yeast, the nucleolar protein Dnt1 negatively regulates the SIN pathway in a manner that is independent of the Cdc14-family phosphatase Clp1/Flp1, but how Dnt1 modulates this pathway has remained elusive. By contrast, it is clear that its budding yeast relative, Net1/Cfi1, regulates the homologous MEN signaling pathway by sequestering Cdc14 phosphatase in the nucleolus before mitotic exit. In this study, we show that dnt1(+) positively regulates G2/M transition during the cell cycle. By conducting epistasis analyses to measure cell length at septation in double mutant (for dnt1 and genes involved in G2/M control) cells, we found a link between dnt1(+) and wee1(+). Furthermore, we showed that elevated protein levels of the mitotic inhibitor Wee1 kinase and the corresponding attenuation in Cdk1 activity is responsible for the rescuing effect of dnt1Δ on SIN mutants. Finally, our data also suggest that Dnt1 modulates Wee1 activity in parallel with SCF-mediated Wee1 degradation. Therefore, this study reveals an unexpected missing link between the nucleolar protein Dnt1 and the SIN signaling pathway, which is mediated by the Cdk1 regulator Wee1 kinase. Our findings also define a novel mode of regulation of Wee1 and Cdk1, which is important for integration of the signals controlling the SIN pathway in fission yeast.

Coverage-dependent thermodynamic analysis of the formation of water and hydrogen peroxide on a platinum model catalyst.

Understanding the selectivity of the oxygen reduction reaction, especially the formation of water versus hydrogen peroxide in fuel cells, is an ongoing challenge in electrochemistry, surface science and catalysis. In this study, we propose a comprehensive thermodynamic analysis of the reaction intermediates for the formation of water on Pt(111). Density functional theory calculations of all the elementary steps linking hydroxyl and hydroperoxyl surface species with water and hydrogen peroxide have been performed at low (1/12 ML, ML = monolayer) and high (1/4 ML) coverages. The reaction energy variation for the two competing elementary events (molecular oxygen dissociation and hydroperoxyl formation) is strongly coverage-dependent. For the direct dissociation, an increase is observed at low coverage with respect to the usual high coverage picture. The stability of the reaction intermediates is investigated from thermodynamic diagrams. At 353 K and a total pressure of 1 atm, water and hydroxyl surface species are expected to compete for adsorption on Pt(111).

Binder-Free Cnt Cathodes for Li-O2 Batteries with More Than One Life.

Li-O2 batteries (LOB) performance degradation ultimately occurs through the accumulation of discharge products and irreversible clogging of the porous electrode during the cycling. Electrode binder degradation in the presence of reduced oxygen species can result in additional coating of the conductive surface, exacerbating capacity fading. Herein, a facile method to fabricate free-standing is established, binder-free electrodes for LOBs in which multi-wall carbon nanotubes form cross-linked networks exhibiting high porosity, conductivity, and flexibility. These electrodes demonstrate high reproducibility upon cycling in LOBs. After cell death, efficient and inexpensive methods to wash away the accumulated discharge products are demonstrated, as reconditioning method. The second life usage of these electrodes is validated, without noticeable loss of performance. These findings aim to assist in the development of greener high energy density batteries while reducing manufacturing and recycling costs.

Sleeve gastrectomy as a bridge to maternity in a patient with obesity, infertility and tetraplegia. A case report.

Traumatic spinal cord injury (SCI) is a major cause of severe and permanent disability in young adults. Overweight and obesity are commonly observed among patients affected with SCI, with reports of a prevalence of over 60 and 30% respectively. Case report: A 34 year-old woman suffering from tetraplegia after sustaining a traumatic injury to C5-C6 at age 23 as a result of a motor vehicle accident was presented to our hospital's multidisciplinary bariatric team due to class II obesity. At the time of presentation to the team, eleven years after the accident, her BMI was calculated to be 39 Kg/m2 (weight 97 kg, height 1.57 meters). She was diagnosed with infertility while seeking pregnancy, and referred to our bariatric unit for weight loss. In addition, she had overcome the physical limitations of her injury, had a regular job and was engaged in regular physical activities such as swimming. In May 2017, she underwent laparoscopic sleeve gastrectomy (LSG) without complications and was discharged on postoperative day 2. 17 months following LSG, with a normal BMI, she became naturally pregnant. She had emergency cesarean at 35 weeks due to pneumonia but both patient and child recovered without sequelae. Currently, 4 years after surgery she maintains 37.11% total weight loss (weight 61 kg). She reports having a better quality of life with fewer medical intercurrencies. Conclusions: Patients with SCI and obesity, particularly women seeking to conceive, may be benefited by being referred to bariatric teams for assessment and treatment to improve results associated with sustained weight reduction.

Biological significance of nuclear localization of mitogen-activated protein kinase Pmk1 in fission yeast.

Mitogen-activated protein kinase (MAPK) signaling pathways play a fundamental role in the response of eukaryotic cells to environmental changes. Also, much evidence shows that the stimulus-dependent nuclear targeting of this class of regulatory kinases is crucial for adequate regulation of distinct cellular events. In the fission yeast Schizosaccharomyces pombe, the cell integrity MAPK pathway, whose central element is the MAPK Pmk1, regulates multiple processes such as cell wall integrity, vacuole fusion, cytokinesis, and ionic homeostasis. In non-stressed cells Pmk1 is constitutively localized in both cytoplasm and nucleus, and its localization pattern appears unaffected by its activation status or in response to stress, thus questioning the biological significance of the presence of this MAPK into the nucleus. We have addressed this issue by characterizing mutants expressing Pmk1 versions excluded from the cell nucleus and anchored to the plasma membrane in different genetic backgrounds. Although nuclear Pmk1 partially regulates cell wall integrity at a transcriptional level, membrane-tethered Pmk1 performs many of the biological functions assigned to wild type MAPK like regulation of chloride homeostasis, vacuole fusion, and cellular separation. However, we found that down-regulation of nuclear Pmk1 by MAPK phosphatases induced by the stress activated protein kinase pathway is important for the fine modulation of extranuclear Pmk1 activity. These results highlight the importance of the control of MAPK activity at subcellular level.

Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation.

BACKGROUND: Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase. The cell integrity Pmk1 pathway is another MAPK cascade that regulates various processes in fission yeast, including cell wall construction, cytokinesis, and ionic homeostasis. Pmk1 pathway also becomes strongly activated in response to glucose deprivation but its role during glucose exhaustion and ensuing adaptation to respiratory metabolism is currently unknown. RESULTS: We found that Pmk1 activation in the absence of glucose takes place only after complete depletion of this carbon source and that such activation is not related to an endogenous oxidative stress. Notably, Pmk1 MAPK activation relies on de novo protein synthesis, is independent on known upstream activators of the pathway like Rho2 GTPase, and involves PKC ortholog Pck2. Also, the Glucose/cAMP pathway is required operative for full activation of the Pmk1 signaling cascade. Mutants lacking Pmk1 displayed a partial growth defect in respiratory media which was not observed in the presence of glucose. This phenotype was accompanied by a decreased and delayed expression of transcription factor Atf1 and target genes fbp1+ and pyp2+. Intriguingly, the kinetics of Sty1 activation in Pmk1-less cells was clearly altered during growth adaptation to non-fermentable carbon sources. CONCLUSIONS: Unknown upstream elements mediate Pck2-dependent signal transduction of glucose withdrawal to the cell integrity MAPK pathway. This signaling cascade reinforces the adaptive response of fission yeast to such nutritional stress by enhancing the activity of the SAPK pathway.

Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

BACKGROUND: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. AIM: To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. DESIGN: Prospective multicenter study. PATIENTS: In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. INTERVENTION: Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. OUTCOME: Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. RESULTS: The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). CONCLUSIONS: Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.