Miracle-dz/UniFAR-FTUs huggingface dataset:
Large‐scale evidence for microbial response and associated carbon release after permafrost thaw

Permafrost thaw could trigger the release of greenhouse gases through microbial decomposition of the large quantities of carbon (C) stored within frozen soils. However, accurate evaluation of soil C emissions from thawing permafrost is still a big challenge, partly due to our inadequate understanding about the response of microbial communities and their linkage with soil C release upon permafrost thaw. Based on a large‐scale permafrost sampling across 24 sites on the Tibetan Plateau, we employed meta‐genomic technologies (GeoChip and Illumina MiSeq sequencing) to explore the impacts of permafrost thaw (permafrost samples were incubated for 11 days at 5°C) on microbial taxonomic and functional communities, and then conducted a laboratory incubation to investigate the linkage of microbial taxonomic and functional diversity with soil C release after permafrost thaw. We found that bacterial and fungal α diversity decreased, but functional gene diversity and the normalized relative abundance of C degradation genes increased after permafrost thaw, reflecting the rapid microbial response to permafrost thaw. Moreover, both the microbial taxonomic and functional community structures differed between the thawed permafrost and formerly frozen soils. Furthermore, soil C release rate over five month incubation was associated with microbial functional diversity and C degradation gene abundances. By contrast, neither microbial taxonomic diversity nor community structure exhibited any significant effects on soil C release over the incubation period. These findings demonstrate that permafrost thaw could accelerate C emissions by altering the function potentials of microbial communities rather than taxonomic diversity, highlighting the crucial role of microbial functional genes in mediating the responses of permafrost C cycle to climate warming.
Knowledge reuse in software projects: Retrieving software development Q&A posts based on project task similarity

Software developers need to cope with a massive amount of knowledge throughout the typical life cycle of modern projects. This knowledge includes expertise related to the software development phases (e.g., programming, testing) using a wide variety of methods and tools, including development methodologies (e.g., waterfall, agile), software tools (e.g., Eclipse), programming languages (e.g., Java, SQL), and deployment strategies (e.g., Docker, Jenkins). However, there is no explicit integration of these various types of knowledge with software development projects so that developers can avoid having to search over and over for similar and recurrent solutions to tasks and reuse this knowledge. Specifically, Q&A sites such as Stack Overflow are used by developers to share software development knowledge through posts published in several categories, but there is no link between these posts and the tasks developers perform. In this paper, we present an approach that (i) allows developers to associate project tasks with Stack Overflow posts, and (ii) recommends which Stack Overflow posts might be reused based on task similarity. We analyze an industry dataset, which contains project tasks associated with Stack Overflow posts, looking for the similarity of project tasks that reuse a Stack Overflow post. The approach indicates that when a software developer is performing a task, and this task is similar to another task that has been associated with a post, the same post can be recommended to the developer and possibly reused. We believe that this approach can significantly advance the state of the art of software knowledge reuse by supporting novel knowledge-project associations.
Current View of Diagnosing Small Fiber Neuropathy

Small fiber neuropathy (SFN) is a disorder of the small myelinated Aδ-fibers and unmyelinated C-fibers [5, 6]. SFN might affect small sensory fibers, autonomic fibers or both, resulting in sensory changes, autonomic dysfunction or combined symptoms [7]. As a consequence, the symptoms are potentially numerous and have a large impact on quality of life [8]. Since diagnostic methods for SFN are numerous and its pathophysiology complex, this extensive review focusses on categorizing all aspects of SFN as disease and its diagnosis. In this review, sensitivity in combination with specificity of different diagnostic methods are described using the areas under the curve. In the end, a diagnostic work-flow is suggested based on different phenotypes of SFN.
Targeted Protein Degradation Phenotypic Studies Using HaloTag CRISPR/Cas9 Endogenous Tagging Coupled with HaloPROTAC3

To assess the role of a protein, protein loss phenotypic studies can be used, most commonly through mutagenesis RNAi or CRISPR knockout. Such studies have been critical for the understanding of protein function and the identification of putative therapeutic targets for numerous human disease states. However, these methodological approaches present challenges because they are not easily reversible, and if an essential gene is targeted, an associated loss of cell viability can potentially hinder further studies. Here we present a reversible and conditional live‐cell knockout strategy that is applicable to numerous proteins. This modular protein‐tagging approach regulates target loss at the protein, rather than the genomic, level through the use of HaloPROTAC3, which specifically degrades HaloTag fusion proteins via recruitment of the VHL E3 ligase component. To enable HaloTag‐mediated degradation of endogenous proteins, we provide protocols for HaloTag genomic insertion at the protein N or C terminus via CRISPR/Cas9 and use of HaloTag fluorescent ligands to enrich edited cells via Fluorescence‐Activated Cell Sorting (FACS). Using these approaches, endogenous HaloTag fusion proteins present in various subcellular locations can be degraded by HaloPROTAC3. As detecting the degradation of endogenous targets is challenging, the 11‐amino‐acid peptide tag HiBiT is added to the HaloTag fusion to allows the sensitive luminescence detection of HaloTag fusion levels without the use of antibodies. Lastly, we demonstrate, through comparison of HaloPROTAC3 degradation with that of another fusion tag PROTAC, dTAG‐13, that HaloPROTAC3 has a faster degradation rate and similar extent of degradation. © 2020 The Authors.
X-Ray Study on the Binding Properties of Cu 2 O and Ag 2 O Crystals

Crystallographical properties of the chemically prepared powder samples of Ag 2 O and Cu 2 O were investigated by an X-ray diffractometer, in relation to their bonding characters. The lattice constant is 4.720±0.004A for Ag 2 O and 4.268±0.001A for Cu 2 O. The thermal expansion coefficient of the lattice is 1.9×10 -6 for Cu 2 O. The root-mean-square amplitude of the thermal lattice vibration is determined as 0.26A for Cu 2 O and 0.40A for Ag 2 O at room temperature. The mean lattice strain is 1.4% for Ag 2 O and 0.15% for Cu 2 O, respectively. The thermal decomposition of Ag 2 O was also observed. The obtained results suggest that the binding force between metallic and oxygen atoms is much weaker in Ag 2 O than in Cu 2 O, which can not be expected from the purely ionic model for the present crystals.
Motor function recovery: deciphering a regenerative niche at the neuromuscular synapse

The coordinated movement of many organisms relies on efficient nerve–muscle communication at the neuromuscular junction (NMJ), a peripheral synapse composed of a presynaptic motor axon terminal, a postsynaptic muscle specialization, and non‐myelinating terminal Schwann cells. NMJ dysfunctions are caused by traumatic spinal cord or peripheral nerve injuries as well as by severe motor pathologies. Compared to the central nervous system, the peripheral nervous system displays remarkable regenerating abilities; however, this capacity is limited by the denervation time frame and depends on the establishment of permissive regenerative niches. At the injury site, detailed information is available regarding the cells, molecules, and mechanisms involved in nerve regeneration and repair. However, a regenerative niche at the final functional step of peripheral motor innervation, i.e. at the mature neuromuscular synapse, has not been deciphered. In this review, we integrate classic and recent evidence describing the cells and molecules that could orchestrate a dynamic ecosystem to accomplish successful NMJ regeneration. We propose that such a regenerative niche must ensure at least two fundamental steps for successful NMJ regeneration: the proper arrival of incoming regenerating axons to denervated postsynaptic muscle domains, and the resilience of those postsynaptic domains, in morphological and functional terms. We here describe and combine the main cellular and molecular responses involved in each of these steps as potential targets to help successful NMJ regeneration.
Elevated serum miR‐3129‐5p contributes to the progression of coronary heart disease via targeting mTOR

The current study aims to explore the miRNA changes that occur in the serum of patients with coronary heart disease (CHD) and healthy controls using a microarray technique, thereby exploring the potential biomarkers in the diagnosis of CHD and the underlying mechanism. Clinical data were reviewed, and venous blood samples were collected from 66 cases of CHD and 58 cases of healthy controls. MicroRNA‐wide expression profiling identified 16 miRNAs that were aberrantly decreased by ~2‐fold in the serum of patients with CHD compared to that of healthy controls. RT‐PCR analysis indicated that the expression of miR‐3129‐5p was increased the most in patients with CHD compared with that of controls. Moreover, serum miR‐3129‐5p was found to be highest in the severe stenosis group, followed by the moderate stenosis group and mild stenosis group. ROC analysis showed that serum miR‐3129‐5p could differentiate patients with CHD from controls. Further study showed that mTOR was a target gene of miR‐3129‐5p. Western blot assays demonstrated that miR‐3129‐5p significantly suppressed the phosphorylation of S6 but increased LC3II/LC3I and Beclin1 levels. Consistently, GFP‐LC3 and TEM assays indicated that miR‐3129 increased autophagy puncta in H9C2 cells. More importantly, silencing mTOR significantly decreased the expression of p‐S6 but increased LC3II/LC3I and Beclin expression even in H9C2 cells transfected with miR‐3129‐5p inhibitor, indicating that miR‐3129‐5p‐induced cell autophagy was mediated via mTOR in H9C2 cells. In summary, elevated serum miR‐3129‐5p contributes to CHD by targeting mTOR signaling and may be a therapeutic target in the treatment of CHD.
An Evacuation Simulation for Hazard Analysis of Isolation at Sea during Passenger Ship Heeling

The Crisis Management Manual is essential for safe and rapid evacuation in the event of an accident. However, the disaster response measures in the current ship evacuation manual are not systematic and are simple and impractical. In particular, the current instructions when the ship is heeling call for evacuation to the highest deck, in the opposite direction. This advice is dangerous, however, because it is isolated to a specific space, due to the walking limit angle according to the angle of heel during evacuation. This study focuses on the MV Sewol ferry accident on 16 April 2014, to evaluate the risk of isolation at sea when evacuating to the highest deck opposite in the direction of heeling when the ship was sinking. According to the initial angle of heel and various angular velocities, hazard maps were created for each safety factor to predict the risks for each situation, by performing a comprehensive evaluation of the safe and dangerous situations when evacuating to the highest deck. The problems and limitations of the current evacuation manuals and systems were identified, and the necessity of a new evacuation solution was presented.
Design and Theoretical Analysis of a Dual-Polarized Quasi D-Shaped Plasmonic PCF Microsensor for Back-to-Back Measurement of Refractive Index and Temperature

We present a new quasi D-shaped plasmonic photonic crystal fiber (PCF) microsensor with dual polarization for back-to-back measurement of refractive index (RI) and temperature. The PCF structure of the microsensor is form birefringent and supports two orthogonal polarizations for independent probing of both RI and temperature variations. Thin layers of tantalum pentoxide (Ta<sub>2</sub>O<sub>5</sub>) and gold (Au) are applied to the side-polished plane to form the RI sensing section. Furthermore, four micro air holes in the lower part of its outer cladding ring are gold-coated and selectively infiltrated with a temperature-sensitive liquid. A detailed investigation and numerical analyses of the coupling characteristics and sensing responses are presented using the finite element method (FEM) with a circular perfectly matched layer (PML). The RI metrics show a maximum wavelength sensitivity of 5000 nm/RIU and a maximum amplitude sensitivity of 266.54 RIU<sup>−1</sup> from 1.35 to 1.46 RI range in the specified operating wavelength range of 1.25-<inline-formula> <tex-math notation="LaTeX">$1.65~\mu \text{m}$ </tex-math></inline-formula>. The corresponding RI resolution is <inline-formula> <tex-math notation="LaTeX">$2.0\times 10^{-5}$ </tex-math></inline-formula> RIU. For the temperature sensing metrics, a maximum amplitude sensitivity of <inline-formula> <tex-math notation="LaTeX">$4.8\times 10^{-2}\,\,^\circ \text{C}^{-1}$ </tex-math></inline-formula>, a maximum wavelength sensitivity of 3.0 nm/°C, and a maximum resolution of <inline-formula> <tex-math notation="LaTeX">$3.33\times 10^{-2}\,\,^{\circ }\text{C}$ </tex-math></inline-formula> from −50°C to 50°C is achieved. With appropriate instrumentation incorporating a polarization selector, the microsensor can double as a real-time simultaneous multiparameter sensor. Applications for the proposed microsensor can be found in molecular science, medical measurement and analysis, terrestrial environmental engineering and data assessment, aquatic ecosystem investigations, pharmaceutical and alimentary process control and validation, cryogenic studies, and several others.
YAP and TAZ regulate Schwann cell proliferation and differentiation during peripheral nerve regeneration

YAP and TAZ are effectors of the Hippo pathway that controls multicellular development by integrating chemical and mechanical signals. Peripheral nervous system development depends on the Hippo pathway. We previously showed that loss of YAP and TAZ impairs the development of peripheral nerve as well as Schwann cell myelination. The role of the Hippo pathway in peripheral nerve regeneration has just started to be explored. After injury, Schwann cells adopt new identities to promote regeneration by converting to a repair‐promoting phenotype. While the reprogramming of Schwann cells to repair cells has been well characterized, the maintenance of such repair phenotype cannot be sustained for a very long period, which limits nerve repair in human. First, we show that short or long‐term myelin maintenance is not affected by defect in YAP and TAZ expression. Using crush nerve injury and conditional mutagenesis in mice, we also show that YAP and TAZ are regulators of repair Schwann cell proliferation and differentiation. We found that YAP and TAZ are required in repair Schwann cells for their redifferentiation into myelinating Schwann cell following crush injury. In this present study, we describe how the Hippo pathway and YAP and TAZ regulate remyelination over time during peripheral nerve regeneration.
Changes in Intestinal Permeability Ex Vivo and Immune Cell Activation by Three Commonly Used Emulsifiers

Food additives such as emulsifiers are used in increasing quantities in the food industry. The aim of this study was to compare three different emulsifiers (polysorbate 80 (P80), carboxymethyl cellulose (CMC), and β-lactoglobulin (β-lac) with regards to their effect on the stimulation of immune cells and intestinal permeability. The immune stimulatory effects were studied in the myeloid cell line MUTZ-3-cells, while the change in intestinal permeability was studied in the Caco-2 cell line and ex vivo in the Ussing chamber system using small intestinal fragments from rats. The tested concentrations of the emulsifiers ranged from 0.02% up to 1%, which are concentrations commonly used in the food industry. The results showed that P80 affected both the myeloid cells and the intestinal permeability more than CMC (p < 0.05) and β-lac (p < 0.05) at the highest concentration. CMC was found to neither affect the permeability in the intestine nor the MUTZ-3 cells, while β-lac changed the permeability in the total part of the small intestine in rats. These findings indicate that P80 might be more cytotoxic compared to the other two emulsifiers.
A lithium peroxide precursor on the α-MnO2 (100) surface

α-MnO2 is an active electrocatalyst for the cathode of lithium–air batteries, where the main reaction is the reversible formation of lithium peroxide. In this work we study the adsorption of lithium and oxygen on the low-energy (100) surface by atomistic simulations based on the density functional theory, in order to understand the first steps of lithium peroxide formation. Oxygen prefers to adsorb in molecular form both in the presence and in the absence of co-adsorbed lithium. This represents a marked difference with respect to other manganese oxides, where oxygen dissociation takes place, and we argue that this might be of advantage in the formation and dissolution of lithium peroxide. By studying the formation energies of Li2O2-like species at the surface we have identified the most probable precursor for the formation of Li2O2 nanoparticles on this surface. The possible consequences of these findings for the functionality of the battery are discussed.
Antibody profiling of patients with prostate cancer reveals differences in antibody signatures among disease stages

Background Previous studies of prostate cancer autoantibodies have largely focused on diagnostic applications. So far, there have been no reports attempting to more comprehensively profile the landscape of prostate cancer-associated antibodies. Specifically, it is unknown whether the quantity of antibodies or the types of proteins recognized change with disease progression. Methods A peptide microarray spanning the amino acid sequences of the gene products of 1611 prostate cancer-associated genes was synthesized. Serum samples from healthy male volunteers (n=15) and patients with prostate cancer (n=85) were used to probe the array. These samples included patients with various clinical stages of disease: newly diagnosed localized prostate cancer (n=15), castration-sensitive non-metastatic prostate cancer (nmCSPC, n=40), castration-resistant non-metastatic prostate cancer (n=15) and castration-resistant metastatic disease (n=15). The patients with nmCSPC received treatment with either standard androgen deprivation therapy (ADT) or an antitumor DNA vaccine encoding prostatic acid phosphatase. Serial sera samples from these individuals were also used to probe the array, to secondarily determine whether this approach could be used to detect treatment-related changes. Results We demonstrated that this peptide array yielded highly reproducible measurements of serum IgG levels. We found that the overall number of antibody responses did not increase with disease burden. However, the composition of recognized proteins shifted with clinical stage of disease. Our analysis revealed that the largest difference was between patients with castration-sensitive and castration-resistant disease. Patients with castration-resistant disease recognized more proteins associated with nucleic acid binding and gene regulation compared with men in other groups. Our longitudinal data showed that treatments can elicit antibodies detectable by this array, and notably vaccine-treated patients developed increased responses to more proteins over the course of treatment than did ADT-treated patients. Conclusions This study represents the largest survey of prostate cancer-associated antibodies to date. We have been able to characterize the classes of proteins recognized by patients and determine how they change with disease burden. Our findings further demonstrate the potential of this platform for measuring antigen spread and studying responses to immunomodulatory therapies.
PD-L1 Expression in Mismatch Repair-deficient Endometrial Carcinoma and Tumor-associated Immune Cells: Differences Between MLH1 Methylated and Nonmethylated Subgroups

Supplemental Digital Content is available in the text. Mismatch repair (MMR)-deficient endometrial carcinomas show increased programmed cell death-ligand 1 (PD-L1) expression compared with MMR-intact endometrial carcinomas, but there are limited data regarding PD-L1 expression between sporadic and inherited carcinomas exhibiting MMR loss. Most of the studies investigating PD-L1 expression in endometrial carcinoma have used tissue microarrays and did not examine all tumor blocks. In this study, we analyzed the expression of PD-L1 in resection specimens of 176 consecutive endometrial carcinomas using all tumor blocks; we compared PD-L1 expression in MMR-deficient endometrial carcinomas, including the MLH1 and PMS2-loss subgroup, and the other MMR-loss subgroups (MSH2 and MSH6, isolated PMS2, and isolated MSH6), with the MMR-intact subgroup. MLH1 methylation was performed in tumors with MLH1 and PMS2 loss. Tumor cell (TC) and tumor-associated immune cell (IC) PD-L1 positivity with a 1% cutoff was observed in 21% (n=37) and 66.5% (n=117) of cases, respectively, and with a 5% cutoff in 5.1% (n=9) and 39.8% (n=70) of cases, respectively. MMR protein deficiency was a statistically significant parameter associated with IC PD-L1 positivity, with 1% and 5% cutoffs on multivariate analysis [odds ratio (OR)=5.236, 95% confidence interval (CI)=2.075-13.211, P=0.001, and OR=3.702, 95% CI=1.759-7.791, P=0.001, respectively]. The multivariate analysis showed that IC PD-L1 positivity, using both 1% and 5% cutoffs, was significantly associated with the MLH1 and PMS2 loss compared with the MMR protein-intact subgroup (MLH1 and PMS2 loss for 1% cutoff: OR=5.104, 95% CI=1.876–13.881, P=0.001, and for 5% cutoff: OR=3.322, 95% CI=1.540–7.166, P=0.002). Squamous differentiation was an independent predictor for TC PD-L1 positivity, with a 5% cutoff (OR=6.102, 95% CI=1.280–10.096, P=0.026). Larger tumor size was an independent predictive factor for IC PD-L1 positivity with a 1% cutoff (OR=6.757, 95% CI=1.569–29.109, P=0.010). Overall, 48 (92.3%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 1% cutoff, and 34 (65.4%) of 52 MLH1 methylated tumors showed IC PD-L1 positivity with 5% cutoff. Our results show a higher rate of IC PD-L1 positivity than in previous studies. This is likely due in part to the use of all tumor blocks. MLH1 and PMS2 loss was an independent predictive factor for IC PD-L1 positivity, with both 1% and 5% cutoffs. Using univariate analysis, we observed decreased disease-free survival for IC PD-L1 positivity ≥5%. Our study results should now be tested and proven in larger cohorts, with longer follow-up data.