Miracle-dz/UniFAR-FTUs huggingface dataset:
In situ reaction kinetic analysis of dental restorative materials

The objective of this study was to evaluate in situ structural and thermal changes of dental restorative materials at periodical time intervals. The commercial materials included zinc oxide eugenol (ZOE), zinc phosphate type I (ZnPO 4 ), glass ionomer cement type II (GIC) and resin-based nano-omposite (Filtek Z350 XT). These materials were processed according to manufacturer’s instructions. For the structural analysis Fourier transform infrared spectroscopy (FTIR) was used at high resolution. TGA was used to evaluate thermal weight-loss. The FTIR spectra were collected at periodic time intervals. FTIR spectra showed that with time passing all materials exhibited an increase in peak intensities and a new appearance of shoulders and shifting of peaks for example, ZnPO 4 (P-O), ZOE (C═O, C═N, C-O-C), GIC (COO – , C-H, Si-OH), composites (C═O, C═C, C═N, C-N-H). The peaks were replaced by bands and these bands became broader with time interval. Composites showed a degree of conversion and new peaks corresponded to the cross-linking of polymer composites. TGA analysis showed that significant changes in weight loss of set materials were observed after 24 h, where ZOE showed continuous changes in thermal degradation. The spectral changes and thermal degradation with time interval elucidated in situ setting behaviour and understanding of their bonding compatibility with tooth structure and change in relation to time.
Rhythmic Accessibility to Sequential Working Memory in a Theta Phase-Dependent Manner

Takuya Ideriha1* and Junichi Ushiyama2,3,4* 1Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa, Japan 5 2Faculty of Environment and Information Studies, Keio University, Fujisawa, Kanagawa, Japan 3Department of Rehabilitation Medicine, Keio University School of Medicine, Keio University, Tokyo, Japan 4Lead contact *Correspondence: ushiyama@sfc.keio. ac.jp (J.U.), ide3.ko@keio.jp (T.I.) 10
Proautoimmune Allele of Tyrosine Phosphatase, PTPN22, Enhances Tumor Immunity

Key Points PEP-619WW mice have superior control of immunogenic tumors. PEP-619WW mice had increased tumor-infiltrating lymphocytes. Tumor-infiltrating lymphocytes have a more activated phenotype in PEP-619WW mice. The 1858C>T allele of the tyrosine phosphatase PTPN22 (causing amino acid substitution R620W in encoded protein lymphoid tyrosine phosphatase) is present in 5–10% of the North American population and is strongly associated with numerous autoimmune diseases. Although much research has been done to define how this allele potentiates autoimmunity, the influence PTPN22 and its proautoimmune allele have in tumor immunity is poorly defined. To interrogate the role this allele may have in the antitumor immune response, we used CRISPR/Cas9 to generate mice in which the ortholog of lymphoid tyrosine phosphatase, PEST domain–enriched protein (PEP), is mutated at position 619 to produce the relevant proautoimmune mutation (R619W). Results of this study show that mice homozygous for this alteration (PEP-619WW) resist tumor growth as compared with wild-type mice. Consistent with these results, tumors from PEP-619WW mice have more CD45 infiltrates containing more activated CD8 T cells and CD4 T cells. In addition, there are more conventional dendritic cell type 1 (cDC1) cells and fewer myeloid-derived suppressor cells in tumors from PEP-619WW mice. Interestingly, the tumor-infiltrating PEP-619WW cDC1 cells have decreased PD-L1 expression compared with cDC1 cells from PEP-wild-type mice. Taken together, our data show that the proautoimmune allele of Ptpn22 drives a strong antitumor response in innate and adaptive immune cells resulting in superior control of tumors.
Auditory mismatch responses are differentially sensitive to changes in muscarinic acetylcholine versus dopamine receptor function

The auditory mismatch negativity (MMN) has been proposed as a biomarker of NMDA receptor (NMDAR) dysfunction in schizophrenia. Pathophysiological theories suggest that such dysfunction might be partially caused by aberrant interactions of different modulatory neurotransmitters with NMDARs, which could explain heterogeneity among patients with schizophrenia and their treatment response. Understanding the differential impact of different neuromodulators on readouts of NMDAR function is therefore of high clinical relevance. Here, we report results from two studies (N=81 each) which systematically tested whether the MMN is sensitive to diminishing and enhancing cholinergic vs. dopaminergic function. Both studies used a double-blind, placebo-controlled between-subject design and monitored individual drug plasma levels. Using a novel variant of the auditory oddball paradigm, we contrasted phases with stable versus volatile probabilities of tone switches. In the first study, we found that the muscarinic acetylcholine receptor antagonist biperiden reduced and/or delayed mismatch responses, particularly during stable phases of the experiment, whereas this effect was absent for amisulpride, a dopamine D2/D3 receptor antagonist. The direct comparison between biperiden and amisulpride indicated a significant drug × mismatch interaction. In the second study, neither elevating acetylcholine nor dopamine levels via administration of galantamine and levodopa, respectively, exerted significant effects on MMN. Overall, our results indicate differential sensitivity of the MMN to changes in cholinergic (muscarinic) versus dopaminergic receptor function. This finding may prove useful for developments of future tools for predicting individual treatment responses in disorders that show abnormal MMN, such as schizophrenia.
Optogenetic manipulation of individual or whole population Caenorhabditis elegans worms with an under hundred-dollar tool: the OptoArm

Optogenetic tools have revolutionized the study of neuronal circuits in Caenorhabditis elegans. The expression of light-sensitive ion channels or pumps under specific promotors allows researchers to modify the behavior of excitable cells. Several optogenetic systems have been developed to spatially and temporally photoactivate light-sensitive actuators in C. elegans. Nevertheless, their high costs and low flexibility have limited wide access to optogenetics. Here, we developed an inexpensive, easy-to-build, and adjustable optogenetics device for use on different microscopes and worm trackers, called the OptoArm. The OptoArm allows for single- and multiple-worm illumination and is adaptable in terms of light intensity, lighting profiles and light-color. We demonstrate the OptoArm’s power in a population-based study on contributions of motor circuit cells to age-related motility decline. We find that functional decline of cholinergic neurons mirrors motor decline, while GABAergic neurons and muscle cells are relatively age-resilient, suggesting that rate-limiting cells exist and determine neuronal circuit aging.
Investigating temperature effects on coastal microbial populations and trophic interactions with 16S and 18S rRNA metabarcoding

Temperature is a universal driver of microbial life, with rising sea surface temperatures expected to differentially influence the physiology, biodiversity, and distribution of bacteria and plankton. The impact of ocean warming on microbial interactions remains unclear, despite the importance of these relationships for ecosystem functioning. We employed weekly to monthly 18S and 16S rRNA gene amplicon metabarcoding over a full year (33 d) in a subtropical estuary, investigating microbial population dynamics and network interactions with respect to a temperature gradient (9–31°C). Certain microbes (e.g., Acidimicrobiia, Nitrososphaeria, and Syndiniales) increased in relative abundance with rising temperatures (Spearman ρ > 0.69), whereas other groups (e.g., Alpha- and Gammaproteobacteria, Bacillariophyta, and Dinophyceae) slightly decreased, became saturated, or remained stable. With network analysis, we observed an increase in 18S– 18S interactions in warm (23–31°C) vs. cold (<23°C) temperatures, largely involving Syndiniales, Bacillariophyta, and Dinophyceae ASVs. Bacteria ASVs were more connected to other microbes (higher degree and centrality) and became more prominent in the cold network, highlighted by well-established cross-domain relationships (e.g., diatom–bacteria) and positive interactions among bacteria (e.g., SAR11 and Rhodobacterales). These efforts highlight the types of interactions that may be more common under changing temperatures, with implications for modeling biogeochemistry and assessing ecosystem health.
3D models of Alzheimer’s disease patient microglia recapitulate disease phenotype and show differential drug responses compared to 2D

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation is a major contributor to neurodegeneration and hence, microglia, the brain’s resident immune cells, are an attractive target for potentially more effective therapeutic strategies. However, there is no current in vitro model system that faithfully recapitulates patient-specific microglial characteristics. To address this shortcoming, we developed novel 3D models of monocyte-derived microglia-like cells (MDMi) from AD patients. MDMi in 3D exhibited mature microglial features, including a highly branched morphology and enhanced bonafide microglial marker expression compared to 2D. Moreover, AD MDMi in 3D co-cultures with neuro-glial cells showed altered cell-to-cell interactions, growth factor and cytokine secretion profiles and responses to amyloid-β. Drug screening assays in 3D AD MDMi revealed different cytokine responses compared to 2D. Our study demonstrates disease- and drug-specific responses in 3D MDMi models that are not apparent in 2D and presents a new 3D platform for more effective and personalised drug testing.
Complementarities, firm strategies and environmental innovations: empirical evidence for a district based manufacturing system

Abstract Innovation is a key factor in firms achieving better environmental performance, to the extent that it helps to increase the materials/energy efficiency of production processes and reduces the emissions/effluents associated with outputs. The study has two main aims. First, by testing a set of hypotheses, to provide new evidence on the influence of a wide array of innovation drivers. Second, to examine the hypothesis of a complementary relationship regarding the adoption of different environmental innovations and a set of associated innovation drivers. The investigation shows that the more general structural characteristics of the firm appear to matter less than eco auditing, R&D and policy related costs. As far as adoption of different eco innovations is concerned, the analysis shows that firms that innovate tend to pursue different environmental innovations simultaneously. At the level of innovation drivers, it appears that the complementarity, though predominant across the various pairings of drivers, presents an evidence, which is dependent on the typology of innovation and the specific analysed innovation drivers Thus, though relevant for explaining innovation dynamics, and crucial in terms of informing management and policy efforts, complementarity is not the complete panacea to the complexity of the environmental innovation system, from either the management or the policy action point of view.
Timing of increased temperature sensitivity coincides with nervous system development in winter moth embryos

Climate change is rapidly altering the environment and many species will need to genetically adapt their seasonal timing to keep up with these changes. Insect development rate is largely influenced by temperature, but we know little about the mechanisms underlying temperature sensitivity of development. Here we investigate seasonal timing of egg hatching in the winter moth, one of the few species which has been found to genetically adapt to climate change, likely through selection on temperature sensitivity of egg development rate. To study when during development winter moth embryos are most sensitive to changes in ambient temperature, we gave eggs an increase or decrease in temperature at different moments during their development. We measured their developmental progression and timing of egg hatching, and used fluorescence microscopy to construct a timeline of embryonic development for the winter moth. We found that egg development rate responded more strongly to temperature once embryos were in the fully extended germband stage. This is the phylotypic stage at which all insect embryos have developed a rudimentary nervous system. Furthermore, at this stage timing of ecdysone signaling determines developmental progression, which could act as an environment dependent gateway. Intriguingly, this may suggest that, from the phylotypic stage onward, insect embryos can start to integrate internal and environmental stimuli to actively regulate important developmental processes. As we found evidence that there is genetic variation for temperature sensitivity of egg development rate in our study population, such regulation could be a target of selection imposed by climate change.
Population differences in the length and early‐life dynamics of telomeres among European pied flycatchers

Telomere length and shortening rate are increasingly used as biomarkers for long-term costs in ecological and evolutionary studies because of their relationships with survival and fitness. Both early-life conditions and growth, and later-life stressors can create variation in telomere shortening rate. Studies on between-population telomere length and dynamics are scarce, despite the expectation that populations exposed to varying environmental constraints would present divergent telomere length patterns. The pied flycatcher (Ficedula hypoleuca) is a passerine bird breeding across Eurasia (from Spain to western Siberia) and migrating through the Iberian Peninsula to spend the non-breeding period in sub-Saharan Africa. Thus, different populations show marked differences in migration distance. We studied the large-scale variation of telomere length and early-life dynamics in the pied flycatcher by comparing six European populations across a north-south gradient (Finland, Estonia, England, and Spain) and considered the effects of migration distance and nestling growth. There were clear population differences in telomere length, with English birds having the longest telomeres, followed by Spanish and lastly by Estonian and Finnish birds. Telomere length did not thus show consistent latitudinal variation and was not linearly linked to differences in migration distance. Early-life telomere shortening rate tended to vary between populations. Fast growth was associated with shorter telomeres in the early life, but faster nestling growth affected telomeres more negatively in northern than southern populations. While the sources of between-population differences in telomere-related biology remain to be more intensively studied, our study illustrates the need to expand telomere studies at the between-population level.
Peer presence increases adolescents’ prosocial behavior by speeding the evaluation of rewards for others

Peer presence can elicit maladaptive adolescent decision-making, potentially by increasing sensitivity to the rewards one receives. It remains unknown whether peer presence also increases adolescents’ sensitivity to others’ rewards, which could have an adaptive effect in contexts allowing pro-social behaviors. Here, we combine social utility modeling and real-time decision process modeling to characterize how peer presence alters adolescents’ processing of self and other rewards. We found that adolescents behaved selfishly when privately allocating rewards for themselves and a peer in an incentive-compatible task. In peer presence, however, adolescents became more altruistic. Real-time estimates of reward processing collected using computer mouse tracking showed that altruistic behavior was associated with relatively earlier processing of peer-rewards relative to self-rewards, such that peer presence sped peer-reward processing without altering self-reward processing. Our results indicate a causal mechanism through which peer presence prompts greater prosocial behavior by altering how adolescents process prosocial outcomes.
Dopamine and reward-related vigor in younger and older human participants

Vigor reflects how motivated one is to respond to a stimulus. We previously showed that humans are more vigorous when more reward is available on average, and that this relationship is modulated by the dopamine precursor levodopa. Dopamine signalling and probabilistic reward learning degrade with age, so the relationship between vigor and reward should change with age. We test this and assess whether the relationship between vigor and reward correlates with D1 dopamine receptor availability measured using Positron Emission Tomography. We measured response times of 30 older and 30 younger subjects during an oddball discrimination task where rewards varied systematically between trial. Reward rate had a similar impact on the vigor of both groups. We observed a weak positive association across subjects between ventral striatal dopamine receptor availability and effect of average reward rate on response time, which was in the opposite direction to our prediction. Overall, the effect of reward on response vigor is similar between younger and older humans and is weakly sensitive to dopamine D1 receptor availability.
Anti-fibrotic activity of an antimicrobial peptide in a Drosophila model

Fibrotic lesions accompany several pathological conditions including tumors. We show that expression of a dominant-active form of the Ras oncogene in Drosophila salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apico-basal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide Drosomycin (Drs), which also restores secretory activity of the SGs. In addition to ECM components, both Drs and F-actin localize to fibrotic lesions.
No evidence for a special role of language in feature-based categorization

The relationship between language and human thought is the subject of long-standing debate. One specific claim implicates language in feature-based categorization. According to this view, language resources facilitate object categorization based on a certain feature (e.g., color). Specifically, it is hypothesized that verbal labels help maintain focus on a relevant categorization criterion and reduce interference from irrelevant features. As a result, language impairment is expected to affect categorization of items grouped according to a single feature (low-dimensional categories, e.g., ‘Things that are yellow’), where many irrelevant features need to be inhibited, more than categorization of items that share many features (high-dimensional categories, e.g., ‘Animals’), where few irrelevant features need to be inhibited. In two behavioral studies with individuals with aphasia, we failed to find consistent support for the role of language in low-dimensional categorization. We also collected fMRI data from healthy adults and observed little activity in language-responsive brain regions during both low-dimensional and high-dimensional categorization. Combined, these results demonstrate that the language system is not implicated in object categorization. Our work adds to the growing evidence that, although language may assist in accessing task-relevant information (e.g., instructions), many cognitive tasks in adult brains proceed without recruiting the language system.
Mid-infrared diode lasers for free-space optical communications

In this work we report on a specially optimized type-I InAsSb/InAsSbP double heterostructure (DH) ridge laser grown by liquid phase epitaxy (LPE). To remove residual impurities and reduce Shockley-Read recombination, the active region was purified using a Gd gettering technique. In addition free carrier absorption loss was minimized by the introduction of two undoped quaternary layers with the same composition of the cladding layers either side of the active region. The inserted layers also helped alleviate inter-diffusion of unwanted dopants towards the active region during or after growth and reduced current leakage of the device. The diode lasers operate readily in pulsed mode at elevated temperatures and emit near 3.45 μm at 170 K with a threshold current density as low as 118 A/cm2 at 85 K. Compared to the conventional 3-layer DH laser, the optimized 5-layer structure with reduced optical loss can raise the maximum lasing temperature by 95 K to ~210 K.
Burrowing crabs and physical factors hasten marsh recovery at panne edges

Salt marsh loss is projected to increase as sea-level rise accelerates with global climate change. Salt marsh loss occurs along both lateral creek and channel edges and in the marsh interior, when pannes expand and coalesce. Often, edge loss is attributed to erosive processes whereas dieback in the marsh interior is linked to excessive inundation or deposition of wrack. We conducted a two-year field experiment (2016-2018) in a central California estuary, where, immediately preceding our study, marsh dieback at creek edges and panne expansion occurred during a period of severe drought and an overlapping warm water event. Our study explored how an abundant burrowing crab, shown to have strong negative effects on marsh biomass near creek edges, affects panne dynamics. We also explored which panne attributes best predicted their dynamics. Overall, we found that pannes contracted during the study period, but with variable rates of marsh recovery across pannes. Our model incorporating both physical and biological factors explained 86% of the variation in panne contraction. The model revealed a positive effect of crab activity, sediment accretion, and a composite of depth and elevation on panne contraction, and a negative effect of panne size and distance to nearest panne. The positive crab effects detected in pannes contrast with negative effects we had earlier detected near creek edges, highlighting the context-dependence of top-down and bioturbation effects in marshes. As global change continues and the magnitude and frequency of disturbances increases, understanding the dynamics of marsh loss in the marsh interior as well as creek banks will be critical for the management of these coastal habitats.
Transcription Factor NF-κB Unravels Nucleosomes

NF-κB is a transcription factor responsible for activating hundreds of genes in mammalian organisms. To accomplish its function, NF-κB must interact with DNA occupied by nucleosomes, but how this interaction occurs is unclear. Here we used Atomic Force Microscopy to characterize complexes of NF-κB with nucleosomes assembled on different DNA templates. The assembly of NF-κB-nucleosome complexes leads to a substantial decrease of DNA wrapping efficiency. Mapping of the nucleosomes did not reveal displacement of under-wrapped nucleosomes from their original position, suggesting that unravelling involves dissociation of one or both flanks of the nucleosomes. We discovered two binding modes of NF-κB associated with nucleosome unraveling - NF-κB bound to the nucleosome core and to the DNA flanks and propose models explaining the interaction of NF-κB with the nucleosome. We speculate that NF-κB can function as a pioneer factor enhancing its ability to facilitate rapid transcriptional response to cell stress.