bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation of Critical GIRK Subunit Residues Disrupts N- and C-Termini Association and Channel Function
Authors: Sarac Radmila , Hou Ping , Hurley Karen M. , Hriciste David , Cohen Noam A. , Nelson Deborah J.
Published: February 2005

The subfamily of G-protein-linked inwardly rectifying potassium channels (GIRKs) is coupled to G-protein receptors throughout the CNS and in the heart. We used mutational analysis to address the role of a specific hydrophobic region of the GIRK1 subunit. Deletion of the GIRK1 C-terminal residues 330-384, as well as the point mutation I331R, resulted in a decrease in channel function when coexpressed with GIRK4 in oocytes and in COS-7 cells. Surface protein expression of GIRK1 I331R coexpressed with GIRK4 was comparable with wild type, indicating that subunits assemble and are correctly localized to the membrane. Subsequent mutation of homologous residues in both the GIRK4 subunit and Kir2.1 (Gβγ-independent inward rectifier) also resulted in a decrease in channel function. Intracellular domain associations resulted in the coimmunoprecipitation of the GIRK1 N and C termini and GIRK4 N and C termini. The point mutation I331R in the GIRK1 C terminus or L337R in the GIRK4 C terminus decreased the association between the N and C termini. Mutation of a GIRK1 N-terminal hydrophobic residue, predicted structurally to interact with the C-terminal domain, also resulted in a decrease in channel function and termini association. We hypothesize that the hydrophobic nature of this GIRK1 subunit region is critical for interaction between adjacent termini and is permissive for channel gating. In addition, the homologous mutation in cytoplasmic domains of Kir2.1 (L330R) did not disrupt association, suggesting that the overall structural integrity of this region is critical for inward rectifier function.
Phospholipase D1-Promoted Release of Tissue Plasminogen Activator Facilitates Neurite Outgrowth
Authors: Zhang Yan , Kanaho Yasunori , Frohman Michael A. , Tsirka Stella E.
Published: February 2005

Temporal lobe epilepsy (TLE) is the most common form of epilepsy, affecting ∼1-2% of the population. Seizure events resulting from TLE are characterized by aberrant hippocampal mossy fiber sprouting and plastic responses that affect brain function. Seizure susceptibility is modulated by the enzyme tissue plasminogen activator (tPA), the normal physiological role of which includes promotion of synaptic reorganization in the mossy fiber pathway by initiating a proteolytic cascade that cleaves extracellular matrix components and influences neurite extension. tPA is concentrated at and selectively secreted from growth cones during excitatory events. However, the mechanisms underlying tPA release during seizure-induced synaptogenesis are not well understood. We examine here potential roles for the signaling enzyme phospholipase D1 (PLD1), which promotes regulated exocytosis in non-CNS cell types, and which we previously demonstrated increases in expression in hippocampal neurons during seizure-induced mossy fiber sprouting. We now show that overexpression of wild-type PLD1 in cultured neurons promotes tPA release and tPA-dependent neurite extension, whereas overexpression of an inactive PLD1 allele or pharmacological inhibition of PLD1 inhibits tPA release. Similarly, viral delivery of wild-type PLD1 into the hippocampus facilitates tPA secretion and mossy fiber sprouting in a seizure-inducing model, whereas the inactive PLD1 allele inhibits tPA release and elicits blunted and abnormal mossy fiber extension similar to that observed for tPA-/-mice. Together, these findings secretion and thus mossy fiber extension in the setting of elevated suggest that PLD1 functions endogenously to regulate tPA-/-neuronal stimulation, such as that seen in TLE.
Mechanism and Kinetics of Organostibine-Mediated Living Radical Polymerization of Styrene
Authors: Kwak Yungwan , Goto Atsushi , Fukuda Takeshi , Yamago Shigeru , Ray Biswajit
Published: February 2005

The polymerization of styrene with a polystyrene-dimethylstibanyl (PS-SbMe2) adduct as a mediator and azobis(isobutyronitrile) (AIBN) as a conventional radical initiator was kinetically studied. PS-SbMe2 had no detectable effect on the polymerization rate R
p, which was virtually the same as that of the conventional (stibanyl-free) system. The pseudo-first-order activation rate constant k
act was proportional to R
p, meaning that degenerative (exchange) chain transfer is the only important activation mechanism, in the examined range of temperature (40–100 °C). The exchange rate constant k
ex was sufficiently large at these temperatures, explaining why this polymerization can afford low-polydispersity polymers. The k
ex was about twice as large as that for polystyrene-methyltellanyl (PS-TeMe). This rationalizes the better polydispersity controllability in the PS-SbMe2 system than in the PS-TeMe system. The activation energy of k
ex was 22.6 kJ mol−1, which is smaller than that (27.8 kJ mol−1) for polystyrene-iodide (PS-I) and slightly larger than that (21.0 kJ mol−1) for polystyrene-dithioacetate (PS-SCSMe).
Theoretical Validation of Single-Pulse Pulsed-Laser Polymerization as a Method for Investigating Chain-Length-Dependent Termination
Authors: Smith Gregory B. , Russell Gregory T.
Published: February 2005

Ideally, single-pulse pulsed-laser polymerization (SP PLP) experiments are marked by a simple relation between time and radical chain length. Thus time-resolved data from such experiments have the potential to directly reflect the chain-length dependence of the termination reaction. However this capability is hostage to various assumptions. These are investigated by performing a series of theory vs. theory comparisons. On the one hand, assumption-free simulations of the kinetics of SP PLP experiments are carried out. The results thus generated are compared with the predictions of equations derived by making assumptions. In this way it is possible to gauge the rectitude of data-analysis methods based on the equations. In turn, the following assumptions are investigated: (1) That of radicals being of length 0 at time 0; (2) That of all radicals terminating at the same rate at any instant; (3) That of transfer being negligible; (4) That of termination being described by a simple power-law; and (5) That of propagation being chain-length independent in rate. All these assumptions are probed in relation to analysis of SP PLP kinetic data, while assumptions (1) and (4) are looked at in relation to the analysis of molecular weight distributions. While some surprising findings do emerge, for the most part it is found that data-analysis methods are reasonably robust, even if they will generally result in underestimation of the true strength of the chain-length dependence of termination. Further, it is possible to make these methods even more accurate by adopting some refinements that are recommended. In general the outstanding potential of SP PLP experiments for investigating the chain-length dependence of the termination reaction is validated.
Speeded Detection of a Tone Embedded in a Quasi-isochronous Sequence: Effects of a Task-Irrelevant Temporal Irregularity
Authors: Penel Amandine , Riess Jones Mari
Published: February 2005

One reason why music features temporal regularities is that they elicit expectancies about when an event will occur, focusing a listener�s attention around certain points in time. Evidence comes from phoneme monitoring tasks (using reaction times, J. G. Martin, 1979) and pitch and time judgment tasks (using accuracy measures, M. R. Jones, H. Moynihan, N. MacKenzie,& J. Puente, 2002; E. W. Large & M. R. Jones, 1999). Reaction times were faster and accuracy was higher for rhythmically expected elements than for unexpected elements. By contrast, A. Penel and M. R. Jones (2004) recently reported an inversely related finding: faster reaction times for rhythmically unexpected tones, which they labeled a temporal capture effect. The present research examines expectancy versus capture phenomena by using a speeded detection task in which listeners must respond to a lower pitched target located within monotone and isochronous sequences. One interonset interval was shortened or lengthened independently of the target�s position. Temporal irregularities tended to trigger false alarms, suggesting capture effects. Patterns of reaction times showed expectancy effects when the temporally perturbed event preceded the target, but these effects seemed to decrease with time in the sequence. When the target itself was temporally perturbed, some capture was observed, but only when the target came early in the sequence. We conclude that Martin�s (1979) expectancy effects in phoneme monitoring were coarticulatory rather than rhythmical.
Influences of Temporal Fluctuation on Infant Attention
Authors: Nakata Takayuki , Mitani Chisato
Published: February 2005

We examined infants� attention to sound sequences as a function of the regularity of timing and the relative familiarity of the sequences (first five trials and last five trials). Infants� attention to the regular and irregular sequences was assessed by a means of a preferential looking (listening) procedure. Infants 6�8 months of age listened longer to the regular sound sequences, but only during the last five trials. Infants 9�11 months of age did not show evidence of differential listening on the basis of sequence regularity, but their attention waned from earlier to later trials.
Consensus statement on the management of the GH-treated adolescent in the transition to adult care
Authors: Clayton P E , Cuneo R C , Juul A , Monson J P , Shalet S M , Tauber M
Published: February 2005

The European Society for Paediatric Endocrinology held a consensus workshop in Manchester, UK in December 2003 to discuss issues relating to the care of GH-treated patients in the transition from paediatric to adult life. Clinicians experienced in the care of paediatric and adult patients on GH treatment, from a wide range of countries, as well as medical representatives from the pharmaceutical manufacturers of GH participated.
A direct approach to the estimation of the origin of oestrogens and androgens in elderly men by comparison with hormone levels in postmenopausal women
Authors: de Ronde Willem , Hofman Albert , Pols Huibert A P , de Jong Frank H
Published: February 2005

Objective: The origin of oestrogens in men is only partly understood. From infusion studies with radioactively labelled hormones, we know that oestradiol (E2) and oestrone (E1) are either directly secreted by the testes and adrenal glands or peripherally produced from testicular or adrenal androgens.

Design and methods: We determined E2, E1, androstenedione, testosterone and dehydroepiandroster-one sulphate (DHEAS) in 292 elderly men and 367 postmenopausal women. We considered post-menopausal women as men without testes, assuming that the postmenopausal ovary is not endocrinologically active and that the testes do not contribute to circulating levels of DHEAS. Subjects were stratified by DHEAS levels to adjust for differences in DHEAS levels between sexes. For men and women separately, mean levels of E2, E1, androstenedione and testosterone were calculated per DHEAS stratum. The relative direct and indirect contributions of the testes to steroid levels in men were calculated by the formula [(Cm −Cf)/Cm] × 100%, in fwhich Cm and Cf represent the mean concentrations of the steroid in men and women respectively.

Results: The relative contributions (%) of the testes to hormone levels per DHEAS stratum (<2, 2–4, 4–6 and >6 μmol/l) respectively were, for E2, 72%, 60%, 52% and 44%; for E1, 54%, 47%, 35% and 34%; for androstenedione, 14%, 4%, 12% and 0%; and, for testosterone, 88%, 88%, 87% and 83%.

Conclusions: We conclude that in elderly men dependent on DHEAS levels, 44–72% of E2 and 34–54% of E1 originate directly or indirectly from the testes.
Estrogen responsiveness of bone formation in vitro and altered bone phenotype in aged estrogen receptor-α-deficient male and female mice
Authors: Parikka Vilhelmiina , Peng ZhiQi , Hentunen Teuvo , Risteli Juha , Elo Teresa , Väänänen H Kalervo , Härkönen Pirkko
Published: February 2005

Objective: Although the beneficial effects of estrogen on bone are well known, the roles of estrogen receptors (ERs) in mediating these effects are not fully understood.

Methods: To study the effects of long-term ERα deficiency, bone phenotype was studied in aged ERα knockout (ERKO) mice. In addition, ERKO osteoclasts and osteoblasts were culturedin vitro.

Design and results: Histomorphometric analysis showed that the trabecular bone volume and thickness were significantly increased and the rate of bone formation enhanced in both male and female ERKO mice in comparison to the wild-type animals. In ERKO males, however, the bones were thinner and their maximal bending strengths decreased. Consistent with previous reports, the bones of knockout mice, especially of female mice, were shorter than those of wild-type mice. In addition, the growth plates were totally absent in the tibiae of aged ERKO females, whereas the growth plate cartilages were detectable in wild-type females as well as in all the males. Analysis of cultured bone marrow cells from 10- to 12-week-old mice demonstrated that 17β-estradiol could stimulate osteoblastic differentiation of bone marrow cells derived from ERKO mice relatively to the same extent as those derived from wild-type mice. This was demonstrated by increases in synthesis of type I collagen, activity of alkaline phosphatase and accumulation of calcium in cultures. Total protein content was, however, reduced in ERKO osteoblast cultures.

Conclusions: These results show altered bone phenotype in ERKO mice and demonstrate the stimulatory effect of estrogen on osteoblasts even in the absence of full-length ERα.
Insulin-secretion abnormalities and clinical deterioration related to impaired glucose tolerance in cystic fibrosis
Authors: Tofé Santiago , Moreno José C , Máiz Luis , Alonso Milagros , Escobar Héctor , Barrio Raquel
Published: February 2005

Objective: To evaluate insulin-secretion kinetics and insulin sensitivity in cystic fibrosis (CF) patients with normal glucose tolerance (CF-NGT), impaired glucose tolerance (CF-IGT) or CF-related diabetes (CFRD), and the potential effects of moderate hyperglycemia on clinical and nutritional status.

Design and methods: Cross-sectional study including 50 outpatients with CF. Patients underwent both oral (OGGT) and intravenous (IVGTT) glucose tolerance tests in order to assess insulin secretion and peripheral insulin sensitivity. Homeostasis assessment model and OGGT were used to investigate insulin sensitivity. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) were measured to evaluate pulmonary function. Body mass index (BMI) was determined to assess nutritional status.

Results: Insulin secretion was significantly decreased (and delayed at OGTT) in the CFRD group (n = 9) versus the CF-IGT group (n = 10) and the CF-IGT versus the CF-NGT group (n = 31). Insulin sensitivity was significantly different in the CF-IGT and CFRD groups versus the CF-NGT group. FEV1, FVC and BMI presented a significant linear correlation with plasma glucose value at 120 min at OGTT and were significantly lower in both CF-IGT and CFRD versus the CF-NGT group, whereas no differences were found between the CF-IGT and CFRD groups.

Conclusions: CF patients with IGT present diminished insulin secretion and increased peripheral insulin resistance, correlating with a worse clinical status, undernutrition and impaired pulmonary function. These findings open the question of whether early treatment of mild alterations of glucose metabolism with insulin secretagogues or short-action insulin may lead to improvement of clinical status in CF patients.
Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells
Authors: Borg S A , Kerry K E , Royds J A , Battersby R D , Jones T H
Published: February 2005

Objectives: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion.

Methods: Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1α and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging.

Results: VEGF was detected in conditioned medium of HP75 cells (900±52 pg/ml) and in 82% of tumours tested (range 26–16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume,P= 0.056; VEGF,P< 0.001 (Pvalues based on Spearman’s test)) and IL1α produced (volume,P< 0.005; VEGF,P< 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1α, but not IL6, significantly increased VEGF production.

Conclusions: The significant associations between VEGF and the levels of IL6 and IL1α suggest an important role for these cytokines in the development of these tumours.
l-Tri-iodothyronine is a major determinant of resting energy expenditure in underweight patients with anorexia nervosa and during weight gain
Authors: Onur Simone , Haas Verena , Bosy-Westphal Anja , Hauer Maren , Paul Thomas , Nutzinger Detlev , Klein Harald , Müller Manfred J
Published: February 2005

Objective: We aimed to define the effect of l-3,5,3′-tri-iodothyronine (T3) on metabolic adaptation in underweight patients with anorexia nervosa (AN) as well as during weight gain.

Methods: This involved clinical investigation of 28 underweight patients with AN, who were compared with 49 normal-weight controls. A subgroup of 17 patients was followed during weight gain. Resting energy expenditure was measured by indirect calorimetry. Body composition was measured by anthropometry as well as bioelectrical impedance analysis. Energy intake (EI) was assessed by a 3-day dietary record. Plasma concentrations of thyroid hormones (thyroxine (T4), T3 and thyrotropin (TSH)) were analyzed by enzyme immunoassays.

Results: When compared with normal-weight women, underweight patients with AN had reduced fat mass (FM) (−71.3%), fat-free mass (FFM) (−13.1%), resting energy expenditure (REE) (−21.8%), T3- (−33.4%) and T4-concentrations (−19.8%) at unchanged TSH. REE remained reduced after adjustment for FFM (−24.6%). T3 showed a close association with REE. This association remained after adjustment of REE for FFM. Treatment of underweight AN patients resulted in a mean weight gain of 8.3 kg. This was mainly explained by an increase in FM with small or no changes in FFM. REE and T3 also increased (+9.3% and +33.3% respectively) at unchanged TSH and T4. There was a highly significant association between weight gain-induced changes in T3 and changes in adjusted REE (r = 0.78, P < 0.001, based on Pearson’s correlation). An increase in plasma T3 concentrations of 1.8 pmol/l could explain an increase in REE of 0.6 MJ/day (that is, a 32% increase in T3 was associated with a 13% increase in REE).

Conclusions: Our data provide evidence that the low T3 concentrations add to metabolic adaptation in underweight patients with AN. During weight gain, increases in T3 are associated with increases in REE, which is independent of FFM. Both results are evidence for a physiologic role of T3 in modulation of energy expenditure in humans.
Management of Food Allergies and Food-Related Anaphylaxis
Authors: Iglesia Edward G. A. , Kwan Mildred , Virkud Yamini V. , Iweala Onyinye I.
Published: February 2024

Importance

An estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US. IgE-mediated food allergies may cause anaphylaxis and death. A delayed, IgE-mediated allergic response to the food-carbohydrate galactose-α-1,3-galactose (alpha-gal) in mammalian meat affects an estimated 96 000 to 450 000 individuals in the US and is currently a leading cause of food-related anaphylaxis in adults.

Observations

In the US, 9 foods account for more than 90% of IgE-mediated food allergies—crustacean shellfish, dairy, peanut, tree nuts, fin fish, egg, wheat, soy, and sesame. Peanut is the leading food-related cause of fatal and near-fatal anaphylaxis in the US, followed by tree nuts and shellfish. The fatality rate from anaphylaxis due to food in the US is estimated to be 0.04 per million per year. Alpha-gal syndrome, which is associated with tick bites, is a rising cause of IgE-mediated food anaphylaxis. The seroprevalence of sensitization to alpha-gal ranges from 20% to 31% in the southeastern US. Self-injectable epinephrine is the first-line treatment for food-related anaphylaxis. The cornerstone of IgE-food allergy management is avoidance of the culprit food allergen. There are emerging immunotherapies to desensitize to one or more foods, with one current US Food and Drug Administration–approved oral immunotherapy product for treatment of peanut allergy.

Conclusions and Relevance

IgE-mediated food allergies, including delayed IgE-mediated allergic responses to red meat in alpha-gal syndrome, are common in the US, and may cause anaphylaxis and rarely, death. IgE-mediated anaphylaxis to food requires prompt treatment with epinephrine injection. Both food-protein allergy and alpha-gal syndrome management require avoiding allergenic foods, whereas alpha-gal syndrome also requires avoiding tick bites.
Osmotic stress induces the formation of migrasome‐like vesicles
Authors: Yoshikawa Koki , Saito Shogo , Kadonosono Tetsuya , Tanaka Masayoshi , Okochi Mina
Published: February 2024

Migrasomes are extracellular vesicles that form on the retraction fibers of migrating cells. In this study, we report the formation of migrasome‐like vesicles enriched in tetraspanin 4 and containing cytoplasmic components in response to hypoosmotic stress. When migrating cells were subjected to hypoosmotic stress, vesicles with a size distribution of 0.5 to 2 μm formed on the retraction fibers, and vanished in a few minutes. The vesicles are rich in cholesterol, and their number was reduced when cells were pretreated with lipoprotein‐deficient serum. The formation of migrasome‐like vesicles upon hypoosmotic stress may provide biophysical cues regarding the cellular response to this external stimulus in cells and tissues.
AI‐EDGE: An NSF AI institute for future edge networks and distributed intelligence
Authors: Ju Peizhong , Li Chengzhang , Liang Yingbin , Shroff Ness
Published: February 2024

This paper highlights the overall endeavors of the NSF AI Institute for Future Edge Networks and Distributed Intelligence (AI‐EDGE) to create a research, education, knowledge transfer, and workforce development environment for developing technological leadership in next‐generation edge networks (6G and beyond) and artificial intelligence (AI). The research objectives of AI‐EDGE are twofold: “AI for Networks” and “Networks for AI.” The former develops new foundational AI techniques to revolutionize technologies for next‐generation edge networks, while the latter develops advanced networking techniques to enhance distributed and interconnected AI capabilities at edge devices. These research investigations are conducted across eight symbiotic thrust areas that work together to address the main challenges towards those goals. Such a synergistic approach ensures a virtuous research cycle so that advances in one area will accelerate advances in the other, thereby paving the way for a new generation of networks that are not only intelligent but also efficient, secure, self‐healing, and capable of solving large‐scale distributed AI challenges. This paper also outlines the institute's endeavors in education and workforce development, as well as broadening participation and enforcing collaboration.
Physical scene understanding
Authors: Wu Jiajun
Published: February 2024

Current AI systems still fail to match the flexibility, robustness, and generalizability of human intelligence: how even a young child can manipulate objects to achieve goals of their own invention or in cooperation, or can learn the essentials of a complex new task within minutes. We need AI with such embodied intelligence: transforming raw sensory inputs to rapidly build a rich understanding of the world for seeing, finding, and constructing things, achieving goals, and communicating with others. This problem of physical scene understanding is challenging because it requires a holistic interpretation of scenes, objects, and humans, including their geometry, physics, functionality, semantics, and modes of interaction, building upon studies across vision, learning, graphics, robotics, and AI. My research aims to address this problem by integrating bottom‐up recognition models, deep networks, and inference algorithms with top‐down structured graphical models, simulation engines, and probabilistic programs.
NIH Toolbox performance of persons with Parkinson's disease according to GBA1 and STN‐DBS status
Authors: Almelegy Ahmad , Gunda Srujanesh , Buyske Steven , Rosenbaum Marc , Sani Sepehr , Afshari Mitra , Metman Leo V. , Goetz Christopher G. , Hall Deborah , Mouradian M. Maral , Pal Gian
Published: February 2024

Objective

Mutations in the glucocerebrosidase (GBA1) gene and subthalamic nucleus deep brain stimulation (STN‐DBS) are independently associated with cognitive dysfunction in persons with Parkinson's disease (PwP). We hypothesized that PwP with both GBA1 mutations and STN‐DBS are at greater risk of cognitive dysfunction than PwP with only GBA1 mutations or STN‐DBS, or neither. In this study, we determined the pattern of cognitive dysfunction in PwP based on GBA1 mutation status and STN‐DBS treatment.

Methods

PwP who are GBA1 mutation carriers with or without DBS (GBA1+DBS+, GBA1+DBS−), and noncarriers with or without DBS (GBA1−DBS+, GBA1−DBS−) were included. Using the NIH Toolbox, cross‐sectional differences in response inhibition, processing speed, and episodic memory were compared using analysis of variance with adjustment for relevant covariates.

Results

Data were available for 9 GBA1+DBS+, 14 GBA1+DBS−, 17 GBA1−DBS+, and 26 GBA1−DBS− PwP. In this cross‐sectional study, after adjusting for covariates, we found that performance on the Flanker test (measure of response inhibition) was lower in GBA1+DBS+ PwP compared with GBA1−DBS+ PwP (P = 0.030).

Interpretation

PwP who carry GBA1 mutations and have STN‐DBS have greater impaired response inhibition compared with PwP with STN‐DBS but without GBA1 mutations. Longitudinal data, including preoperative scores, are required to definitively determine whether GBA1 mutation carriers respond differently to STN‐DBS, particularly in the domain of response inhibition.
Effects of Zn/Ca Alloying on the Second Phase, Corrosion Behavior, and Mg–Air Battery Anodic Performance of Mg–1Sn‐Based Alloys
Authors: Le Taihe , Mao Pingli , Hu Wenyi , Le Qichi
Published: February 2024

To improve the corrosion behavior and discharge performance of Mg–1Sn‐based Mg–air battery anodes, Zn/Ca alloying elements are added in the alloys to modify the type and morphology of the formed second phases. Scanning electron microscope is used to observe the microstructure, and X‐ray diffraction is used to identify the phases formed. Immersion, electrochemistry techniques, and Mg–air battery tests are used to characterize the corrosion and discharge performance of the alloys. The results indicate that the addition of Ca rather than Zn has better effects in improving the corrosion resistance and discharge performance of Mg–1Sn‐based alloys. The second‐phase combination improves the corrosion resistance and electrochemical activity of Mg–1Sn‐based alloys in the following order: Mg2Ca and CaMgSn phases (Mg–1Sn–1Ca alloy) > Ca2Mg6Zn3 and CaMgSn phases (Mg–1Sn–1Zn–1Ca alloy) > the net‐shape Mg4Zn7 + Mg2Sn phases (Mg–1Sn–1Zn alloy) > Mg2Sn phase (Mg–1Sn alloy). In addition, Mg–1Sn–1Zn–1Ca alloy exhibits the highest anodic efficiency, specific capacity, and specific energy among four alloys, i.e., 54.3 , 1197.6 mA h g−1, and 1366.1 mW h g−1, respectively, at a current density of 20 mA cm−2.
When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor‐Like Microcapsules
Authors: Antonelli Yasmin , Krüger René , Buehler Adrian , Monavari Mahshid , Fuentes‐Chandía Miguel , Colombo Federico , Palmisano Ralf , Boßerhoff Anja K. , Kappelmann‐Fenzl Melanie , Schödel Johannes , Boccaccini Aldo R. , Selhuber‐Unkel Christine , Letort Gaelle , Leal‐Egaña Aldo
Published: February 2024

Biofabrication techniques enable the performance of bioinspired three‐dimensional (3D) matrices resembling primary tumors. To validate their reliability, embedded cells may express complex biophysical responses. Among others, the emergence of tumor heterogeneity and the generation of Polyploid Giant Cancer Cells (PGCC), as a result of the mechanical stress, are two of the most challenging hallmarks to resemble in vitro. Here, these phenomena are studied in cells cultured on two‐dimensional (2D) flasks, in 3D spheroids, or immobilized within 3D polymer‐based tumor‐like microcapsules. These results show that cells cultured in 3D microcapsules exhibited an enhanced biomechanical heterogeneity, a higher number of PGCC, and an increased exertion of cell‐matrix attachment forces with respect to the other two experimental conditions. Additionally, cells isolated from tumor‐like microcapsules redistribute and align the cytoplasmatic protein Caveolin‐1, and upregulate markers involved in cell proliferation (i.e., Ki67), metastasis (i.e., TGF‐β1, TGF‐β‐R2), and epithelial to mesenchymal transition, to name a few. These hallmarks are barely described in the past as a result of the confinement and mechanical stress. Thus, in this work it is demonstrated that both the mechanical stress and confinement are required to stimulate cell polyploidy and biomechanical heterogeneity, which can be easily addressed by immobilizing breast cancer cells in tumor‐like microcapsules.
Defect Anchoring [S–Ni–P] Interfacial Channel Regulating Charge Migration for Efficient Photoelectrochemical Water Splitting
Authors: Wang Cheng , Chen Wei , Sun Shengdong , Zhang Hui , Zhou Hang , Li Shikuo
Published: February 2024

Regulating bulk charge carrier transfer and surface catalytic reaction kinetics is thought a big challenge to photoelectrochemical (PEC) water splitting. Herein, the dual sites of CoNiP are delicately introduced into ZnIn2S4 (RZIS‐CoNiP) nanosheet arrays via a defect anchoring method. The paving [S─Ni─P] interfacial bond like a “bridge” can greatly reduce the phase resistance, improve the charge separation and migration, and promote the surface oxygen evolution reaction (OER) reaction. As expected, the optimized RZIS‐CoNiP photoanode achieved a maximum photocurrent density of 4.77 mA cm−2 at 1.23 V versus reversible hydrogen electrode (RHE) in neutral electrolyte solution without the presence of any sacrificial agents, which is ≈12 times higher than that of the pristine ZnIn2S4 under AM 1.5G illumination. And the amount of oxygen evolution for the RZIS‐CoNiP photoanode is as high as 21.9 µmol in 3 h. Transient spectroscopy measurements and density functional theory (DFT) calculations in situ discovered the mechanism of defect anchoring [S─Ni─P] bond on regulating charge transfer and surface reaction processes. This work provides a feasible anchoring interface route through defect engineering to regulate charge carrier transfer for PEC water splitting.
Defect Engineering in Nanocatalysts: From Design and Synthesis to Applications
Authors: Muhammad Pir , Zada Amir , Rashid Jamshaid , Hanif Sumaira , Gao Yanan , Li Chenchen , Li Yuanyuan , Fan Kelong , Wang Yanli
Published: February 2024

Defect engineering is an emerging technology for tailoring nanomaterials' characteristics and catalytic performance in various applications. Recently, defect‐engineered nanoparticles have emerged as highly researched materials in catalytic applications because of their exceptional redox reaction capabilities and physicochemical and optical properties. The properties of nanomaterials can be readily adjusted by controlling the nature and concentration of defects within the nanoparticles, avoiding the need for intricate design strategies. This review investigates defect engineering in nanocatalysts, including the design, fabrication, and applications. Initially, the various categories and strategies of nanomaterial defects and their impacts on the nanocatalysts' electronic and surface properties, catalytic activity, selectivity, and stability are summarized. Then, the catalytic processes and their uses, including gas sensing, hydrogen (H2) evolutions, water splitting, reductions of carbon dioxide (CO2) and nitrogen to value‐aided products, pollutant degradation, and biomedical (oncotherapy, antibacterial and wound healing, and biomolecular sensing) applications are discussed. Finally, the limitations in defect engineering and the prospective paths for allowing the logical design and optimization of nanocatalytic materials for long‐term and efficient applications are also examined. This comprehensive review gives unique insights into the current state of defect engineering in nanocatalysts and inspires future research on exploiting shortcomings to improve and customize catalytic performance.
IL‐37 Modulates Myocardial Calcium Handling via the p‐STAT3/SERCA2a Axis in HF‐Related Engineered Human Heart Tissue
Authors: Yin Dan , Liu Yong , Xue Bingqing , Ding Rui , Wang Gang , Xia Shutao , Zhang Donghui
Published: February 2024

Interleukin‐37 (IL‐37) is a potent anti‐inflammatory cytokine belonging to the IL‐1 family. This study investigates the regulatory mechanism and reparative effects of IL‐37 on HF‐related human induced pluripotent stem cells derived cardiomyocytes (hiPSC‐CMs) and engineered human heart tissue subjected to hypoxia and H2O2 treatment. The contractile force and Ca2+ conduction capacity of the tissue are assessed using a stretching platform and high‐resolution fluorescence imaging system. This investigation reveals that IL‐37 treatment significantly enhances cell viability, calcium transient levels, contractile force, and Ca2+ conduction capacity in HF‐related hiPSC‐CMs and engineered human heart tissue. Notably, IL‐37 facilitates the upregulation of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) through enhancing nuclear p‐STAT3 levels. This effect is mediated by the binding of p‐STAT3 to the SERCA2a promoter, providing a novel insight on the reparative potential of IL‐37 in HF. IL‐37 demonstrates its ability to enhance systolic function by modulating myocardial calcium handling via the p‐STAT3/SERCA2a axis in HF‐related engineered human heart tissue (as shown in schematic diagram).
Transformable Supramolecular Self‐Assembled Peptides for Cascade Self‐Enhanced Ferroptosis Primed Cancer Immunotherapy
Authors: Wang He , Jiao Di , Feng Dexiang , Liu Qian , Huang Yuhua , Hou Jianquan , Ding Dan , Zhang Weijie
Published: February 2024

Immunotherapy has received widespread attention for its effective and long‐term tumor‐eliminating ability. However, for immunogenic “cold” tumors, such as prostate cancer (PCa), the low immunogenicity of the tumor itself is a serious obstacle to efficacy. Here, this work reports a strategy to enhance PCa immunogenicity by triggering cascade self‐enhanced ferroptosis in tumor cells, turning the tumor from “cold” to “hot”. This work develops a transformable self‐assembled peptide TEP‐FFG‐CRApY with alkaline phosphatase (ALP) responsiveness and glutathione peroxidase 4 (GPX4) protein targeting. TEP‐FFG‐CRApY self‐assembles into nanoparticles under aqueous conditions and transforms into nanofibers in response to ALP during endosome/lysosome uptake into tumor cells, promoting lysosomal membrane permeabilization (LMP). On the one hand, the released TEP‐FFG‐CRAY nanofibers target GPX4 and selectively degrade the GPX4 protein under the light irradiation, inducing ferroptosis; on the other hand, the large amount of leaked Fe2+ further cascade to amplify the ferroptosis through the Fenton reaction. TEP‐FFG‐CRApY‐induced immunogenic ferroptosis improves tumor cell immunogenicity by promoting the maturation of dendritic cells (DCs) and increasing intratumor T‐cell infiltration. More importantly, recovered T cells further enhance ferroptosis by secreting large amounts of interferon‐gamma (IFN‐γ). This work provides a novel strategy for the molecular design of synergistic molecularly targeted therapy for immunogenic “cold” tumors.
Full‐Space Janus Meta‐Lens for Shared‐Aperture Transmission‐Reflection‐Independent Focusing of Electromagnetic Wave
Authors: Dong Shufang , Qu Kai , Hu Qi , Wang Shaojie , Chen Ke , Feng Yijun
Published: February 2024

Janus metasurfaces emerge as a promising platform for implementing multiple wave functionalities by fully exploiting the inherent propagation direction of electromagnetic waves. Their out‐of‐plane asymmetric structures enable different wave functions depending on the propagation direction. Herein, a multiplexed Janus metasurface is proposed, which operates in the microwave region to flexibly manipulate the transmission and reflection wavefronts for same linearly polarized (LP) incidence propagating along the two opposite directions. A meta‐lens is constructed to validate the concept of full‐space shared‐aperture transmission‐reflection‐independent focusing of electromagnetic (EM) waves, exhibiting four distinct focusing performances. Experiments are conducted in the microwave region that agree well with the simulation results. The proposed full‐space Janus metasurface may provide a platform for asymmetric imaging, multichannel information processing, and encrypted communication.
Bearing Fault Diagnosis based on Convolution Neural Network with Logistic Chaotic Map
Authors: Zhang Fangfang , Chen Luobing , Dai Yiyang , Kou Lei , Ji Peng , Liu Yuanhong
Published: February 2024

Bearing is the most basic component of motor, and prone to failure. Bearing fault diagnosis is paramount for improving the reliability and safety in motor‐drive systems. Therefore, convolutional neural network (CNN) is proposed with Logistic chaotic map and its corresponding fault diagnosis approach, which can effectively advance the accuracy of bearing fault diagnosis. Specifically, the Logistic chaotic map and Sigmoid function are combined into a non‐monotonic excitation function, which is employed to the full connection layer of the CNN. The proposed chaotic CNN can solve two issues that the conventional neural network inclines to get the local minimum value and the gradient of Sigmoid excitation function disappears. It is applied to fault data from the center of Western Reserve University and from the American Society for Mechanical Failure Prevention technology (in noiseless and noisy conditions). The results indicate the diagnosis accuracy of the algorithm outperforms other classical bearing diagnosis algorithms. Moreover, the chaotic CNN exhibits better anti‐noise performance.
DNALI1 Promotes Neurodegeneration after Traumatic Brain Injury via Inhibition of Autophagosome‐Lysosome Fusion
Authors: Ding Xulong , Cao Shuqiang , Wang Qing , Du Bin , Lu Kefeng , Qi Shiqian , Cheng Ying , Tuo Qing‐zhang , Liang Weibo , Lei Peng
Published: February 2024

Traumatic brain injury (TBI) leads to progressive neurodegeneration that may be caused by chronic traumatic encephalopathy (CTE). However, the precise mechanism remains unclear. Herein, the study identifies a crucial protein, axonemal dynein light intermediate polypeptide 1 (DNALI1), and elucidated its potential pathogenic role in post‐TBI neurodegeneration. The DNALI1 gene is systematically screened through analyses of Aging, Dementia, and TBI studies, confirming its elevated expression both in vitro and in vivo. Moreover, it is observed that altered DNALI1 expression under normal conditions has no discernible effect. However, upon overexpression, DNALI1 inhibits autophagosome‐lysosome fusion, reduces autophagic flux, and exacerbates cell death under pathological conditions. DNALI1 silencing significantly enhances autophagic flux and alleviates neurodegeneration in a CTE model. These findings highlight DNALI1 as a potential key target for preventing TBI‐related neurodegeneration.
Understanding clerkship experiences in emergency medicine and their potential influence on specialty selection: A qualitative study
Authors: Diaz Rosemarie , Balgord Sarah , Klekowski Nicole , Farthing Alexandra S. , Escolero Sylvia Guadalupe , DeCloux Korynne , Burkhardt John C. , Haggins Adrianne N. , Hopson Laura R.
Published: February 2024

Objectives

The specialty of emergency medicine (EM) is experiencing a significant decrease in student interest. In addition, women are historically underrepresented within the specialty at all levels of training and practice. We sought to understand how clinical experiences and perceptions of EM influence specialty selection by medical students, particularly women.

Methods

Using a constructivist grounded theory approach, we analyzed semistructured interviews with senior medical students who considered EM as a specialty. We used purposive sampling to recruit from diverse learning environments and represent a variety of experiences. Participants reflected on their specialty selection process and experiences in EM including their perceived acceptance in the work environment.

Results

Twenty‐five medical students from 11 geographically diverse schools participated. A total of 68% (17/25) identified as women. The majority (21/25, 84%) planned on applying to EM residency. We identified four major themes: (1) distressing interpersonal interactions with patients and the ED care team negatively affect students; (2) EM culture includes behaviors that are perceived as exclusionary; (3) beliefs about the attributes of an ideal EM physician and the specialty itself have a gendered nature; and (4) ease of access to mentors, representation, and early exposure to EM environment increased interest in specialty.

Conclusions

Our participants express that EM causes challenges for students to accept the norms of behavior in the field, which is an essential element in joining a group and professional identity formation. In addition, we raise concern that gendered perceptions and language may send exclusionary environmental cues that may negatively impact recruitment of a diverse physician workforce.
Bringing abstract concepts to life: A health humanities–based approach to teaching social determinants of health
Authors: Balhara Kamna S. , Regan Linda , Chopra Eisha , Irvin Nathan
Published: February 2024

Background

To address health inequities, emergency physicians must understand the structural underpinnings of health disparities, including social determinants of health (SDoH), and must critically reflect on the integration of SDoH into clinical practice. SDoH education should include reflective knowledge acquisition, while incorporating systemic sociohistorical forces and individual factors, such as bias, which propagate inequities but are rarely emphasized in graduate medical education (GME). The health humanities (HH), an inclusive transdisciplinary field combining arts, humanities, and social justice, may represent a novel unexplored approach toward incorporating SDoH in GME.

Methods

We sought to implement and evaluate a GME HH‐based curriculum focused on SDoH. An interprofessional team applied Kern's framework to create a longitudinal HH curriculum integrating narrative medicine and visual thinking strategies with evidence‐based practices for addressing SDoH in clinical practice. This curriculum was implemented for 52 residents in an EM program in 2019–2020; sessions were initially held in the classroom and community and then virtually during the COVID‐19 pandemic. Objectives included encouraging (1) critical thinking about SDoH, (2) engagement with patients and communities, (3) self‐reflection, and (4) translation of SDoH to patient care. Descriptive statistics and a constructivist paradigm were applied to results of a postcurriculum survey and focus group, respectively.

Results

A curriculum evaluation survey completed by 32/52 residents (61.5%) revealed agreement (75%–90%) that objectives were met. 93.1% of respondents thought humanities were important in residency training. Qualitative analysis of a focus group with 10 participants revealed additional impacts on individual growth, transformation of departmental culture, and transformation of patient care. Curriculum implementation was inexpensive and relied on interprofessional collaboration.

Conclusions

The HH represent a promising collaborative framework for integrating SDoH in GME and may inspire transformation of learners’ attitudes and practices in EM, though clinical impacts still need to be established.
Evaluation of dredge fines material in manufactured soil blends on soil health parameters
Authors: Lake Loryssa M. , Benson Kaitlyn S. , Basta Nicholas T.
Published: February 2024

Solutions are needed to address increasing concerns over degraded land and global food insecurity. One solution is to design soil blends that can restore soil quality and fertility. Dredge material has many soil‐like properties, which makes it a good candidate for the main component of manufactured soil blends. Questions have arisen over contaminants of concern (heavy metals and polyaromatic hydrocarbons [PAH]) in dredge fines precluding them from reuse. One approach is to remove the fine fraction of dredge to lower the contaminant concentration; however, it may result in a lower quality soil substitute for land reclamation. In this study, soil blends were designed to compare the use of whole dredge to dredge fines (e.g., dredge with silt and clay fraction) and to assess the benefits of compost material, clay, and fertilizer additions. Dredge fines blends led to increases in soil quality, dry matter growth, plant available water, total and active C, potentially mineralizable N, and micronutrients. The addition of compost material led to better soil quality for a vast majority of the tested parameters. Dredge fines were below regulatory standards for contaminants of concern (e.g., carinogenic polyaromatic hydrocarbon and heavy metals), allowing their reuse in soil blends. Removal of fines from dredge decreases the quality of soil blends and should not be removed from dredge material for use as topsoil or in topsoil blends. The 80% (v/v) dredge fines blend with 20% (v/v) additions of compost material resulted in the greatest improvements in the assessed soil health parameters.
State labeling's impact on geographic boundaries of local
Authors: Fife Kathryn , Secor William , Campbell Benjamin
Published: February 2024

Local labeling is an important issue within the horticultural industry as many producers have devoted considerable resources to advertising their products as local. Further, all states have implemented some form of local labeling program to increase local purchasing. As states expand the reach of these programs, the programs begin to compete as awareness and perception move across state lines. Using an online survey to study consumers in the Southeastern United States, we look to identify how state labeling programs are viewed in nearby states. Notably, we assess awareness, perception, and its impact on the local definition of these programs in their “home” state as well as nearby states. Specifically, we evaluate the impact of nine Southeastern state‐level branding programs. Our results indicate that consumers are more aware of their home state's local label, but awareness does exist for other states' labels. We also find that a home state label moves some consumers to a more state‐level local boundary, while seeing another state's label increases the boundary for what is perceived as local [EconLit Citation: Q13].