Miracle-dz/UniFAR-FTUs huggingface dataset:
An Improved Sketching Algorithm for Edit Distance

We provide improved upper bounds for the simultaneous sketching complexity of edit distance. Consider two parties, Alice with input x ∈ Σ n and Bob with input y ∈ Σ n , that share public randomness and are given a promise that the edit distance ed ( x, y ) between their two strings is at most some given value k . Alice must send a message sx and Bob must send sy to a third party Charlie, who does not know the inputs but shares the same public randomness and also knows k . Charlie must output ed ( x, y ) precisely as well as a sequence of ed ( x, y ) edits required to transform x into y . The goal is to minimize the lengths | sx | , | sy | of the messages sent. The protocol of Belazzougui and Zhang (FOCS 2016), building upon the random walk method of Chakraborty, Goldenberg, and Koucký (STOC 2016), achieves a maximum message length of ˜ O ( k 8 ) bits, where ˜ O ( · ) hides poly(log n ) factors. In this work we build upon Belazzougui and Zhang’s protocol and provide an improved analysis demonstrating that a slight modification of their construction achieves a bound of ˜ O ( k 3 ).
A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration

Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of four brain regions (temporal, frontal, entorhinal cortex, and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age-, and AD-associated epigenetic profiles. In one of these datasets it was also possible to distinguish 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiles. We showed that DNAm differences between males and females tend to be shared between the four brain regions, while aging differently affects cortical regions compared to cerebellum. We found that the proportion of sex-dependent probes whose methylation is modified also during aging is higher than expected, but that differences between males and females tend to be maintained, with only a few probes showing age-by-sex interaction. We did not find significant overlaps between AD- and sex-associated probes, nor disease-by-sex interaction effects. On the contrary, we found that AD-related epigenetic modifications are significantly enriched in probes whose DNAm varies with age and that there is a high concordance between the direction of changes (hyper or hypo-methylation) in aging and AD, supporting accelerated epigenetic aging in the disease. In summary, our results suggest that age-associated DNAm patterns concur to the epigenetic deregulation observed in AD, providing new insights on how advanced age enables neurodegeneration.
ESBL and AmpC β-Lactamase Encoding Genes in E. coli From Pig and Pig Farm Workers in Vietnam and Their Association With Mobile Genetic Elements

Animals are considered important sources of ESBL/AmpC-producing bacteria in humans. We analyzed indications of transfer of ESBL/AmpC genes between pigs and pig farmers in Vietnam by analyzing whole genome sequences of 114 ESBL/AmpC-producing E. coli isolated from the two hosts, and performed conjugation experiments and plasmid profiling to confirm that such transfer could have happened. ESBL-encoding genes detected in pigs and pig farmers included blaCTX–M-55, blaCTX-M-27, blaCTX-M-65, blaCTX-M-15, blaCTX-M-14, blaCTX-M-3, blaCTX-M-24, and blaCARB-2, and AmpC β-lactamases included blaCMY-2, blaDHA-1, and blaCMY-42. The most frequent ESBL gene, blaCTX-M-55, was carried on plasmid with replicons types IncF, IncX, IncH, IncN, IncR, and IncP. The insertion transposases downstream of the blaCTX-M-55 gene were different in plasmids carried by different strains. The second most detected gene, blaCTX-M-27, is found in a stable genetic arrangement with the same flanking transposons seen across strains, and the gene was located on similar conjugal IncF plasmid types, suggesting a horizontal spread of these plasmids. In three strains, we observed a novel blaCTX-M-27 harboring IncF type of plasmid which had not been reported before. Its closest reference in NCBI was the non-ESBL Salmonella Typhimurium plasmid pB71 that might have experienced an insertion of blaCTX-M-27. Our data also point to an emergence of plasmids co-carrying ESBL genes, mcr genes, quinolones and other antimicrobials resistance determinants, and such plasmids require special attention. Plasmids phylogeny confirmed that the blaCTX-M-55 encoding plasmids varied considerably, while those encoding blaCTX-M-27 were closely related. Plasmids harboring both ESBL genes were confirmed to be conjugative and not to differ in transfer efficacy. The isolates carrying the plasmids, even those with plasmids of similar types, showed wide genetic variation with high number of SNPs, suggesting horizontal spread of plasmids into different clonal lines. Their virulence profiles did not confirm to known pathotypes, suggesting that unrelated commensals are a main reservoir for ESBL and AmpC β-lactamases in both humans and pigs. Overall, despite evidence of transferability of plasmids in the analyzed strains, our findings do not support that ESBL-producing E. coli from pigs or their ESBL/AmpC encoding plasmids are commonly spread to workers in close contact with the animals.
The Contact Allergen NiSO4 Triggers a Distinct Molecular Response in Primary Human Dendritic Cells Compared to Bacterial LPS

Dendritic cells (DC) play a central role in the pathogenesis of allergic contact dermatitis (ACD), the most prevalent form of immunotoxicity in humans. However, knowledge on allergy-induced DC maturation is still limited and proteomic studies, allowing to unravel molecular effects of allergens, remain scarce. Therefore, we conducted a global proteomic analysis of human monocyte-derived dendritic cells (MoDC) treated with NiSO4, the most prominent cause of ACD and compared proteomic alterations induced by NiSO4 to the bacterial trigger lipopolysaccharide (LPS). Both substances possess a similar toll-like receptor (TLR) 4 binding capacity, allowing to identify allergy-specific effects compared to bacterial activation. MoDCs treated for 24 h with 2.5 μg/ml LPS displayed a robust immunological response, characterized by upregulation of DC activation markers, secretion of pro-inflammatory cytokines and stimulation of T cell proliferation. Similar immunological reactions were observed after treatment with 400 μM NiSO4 but less pronounced. Both substances triggered TLR4 and triggering receptor expressed on myeloid cells (TREM) 1 signaling. However, NiSO4 also activated hypoxic and apoptotic pathways, which might have overshadowed initial signaling. Moreover, our proteomic data support the importance of nuclear factor erythroid 2-related factor 2 (Nrf2) as a key player in sensitization since many Nrf2 targets genes were strongly upregulated on protein and gene level selectively after treatment with NiSO4. Strikingly, NiSO4 stimulation induced cellular cholesterol depletion which was counteracted by the induction of genes and proteins relevant for cholesterol biosynthesis. Our proteomic study allowed for the first time to better characterize some of the fundamental differences between NiSO4 and LPS-triggered activation of MoDCs, providing an essential contribution to the molecular understanding of contact allergy.
Beyond the Early Adopters: Escape Rooms in Science Education

Case studies report enthusiastically on the implementation of escape rooms in science education. This mixed-method study explores beyond the early adopting teacher, as the perceptions of 50 teachers and 270 students were investigated. Escape rooms are time restricted games where participants work together and accomplish a specific goal. The escape rooms’ usability for education in terms of goals, experiences during gameplay, outcomes, and boundary conditions are studied, using multiple data sources: online questionnaires, interviews, classroom observations and movie clips made by students about their experiences. The use of mixed methods and large samples on this topic is a novelty. Results show that teachers of different ages, gender and teaching experience were appealed in particular to the diversity of activities offered that call for multiple skills and teamwork. Students experienced the need to think hard using multiple thinking skills and enjoyed the feeling of autonomy and mastery during gameplay. This is interesting, as an escape room setup is very strict, with few degrees of freedom. According to teachers and students, escape rooms are suitable for processing, rehearsing and formative assessment of science knowledge and skills. However, the time restriction during gameplay appears to be an ambiguous factor in student learning.
On the Source Parameters and Genesis of the 2017, Mw 4 Montesano Earthquake in the Outer Border of the Val d’Agri Oilfield (Italy)

On October 27, 2017, an Mw 4 earthquake occurred close to the municipality of Montesano sulla Marcellana, less than 10 km external to the concession of the largest European onshore hydrocarbon reservoir—the Val d’Agri oilfield (Southern Italy). Being a weak event located outside the extended monitoring domain of the industrial concession, the relevance of this earthquake and the possible links with the hydrocarbon exploitation were not extensively discussed. Actually, the analysis of shallow seismic events close to subsurface exploitation domains plays a significant role in the definition of key parameters in order to discriminate between natural, triggered, and induced seismicity, especially in tectonically active regions. The study of weak-to-moderate earthquakes can improve the characterization of the potentially destructive seismic hazard of this particular area, already struck by M > 6.5 episodes in the past. In this work, we analyze the source parameters of this Mw 4 earthquake by applying advanced seismological techniques to estimate the uncertainties derived from the moment tensor inversion and identify plausible directivity effects. The moment tensor is dominated by a NW–SE oriented normal faulting with a centroid depth of 14 km. A single ML 2.1 aftershock was recorded and used as the empirical Green’s function to calculate the apparent source time function for the mainshock. Apparent durations (in the range 0.11–0.21 s, obtained from S-waves) define an azimuthal pattern, which reveals an asymmetric bilateral rupture with 70% of the rupture propagation in the N310°W direction, suggesting a rupture plane dipping to the SW. Our results tally with the activation of a deeper fault segment associated with the Eastern Agri Fault System close to the basement as the origin of the Montesano earthquake. Finally, the Coulomb stress rate induced by depletion of the oilfield is calculated to quantify the trigger potential estimated for the Montesano earthquake yielding relatively low probabilities below 10%. Our analyses point toward the conclusion that the Mw 4 event was more likely due to the local natural tectonic stress, rather than induced or triggered by the long-term hydrocarbon extraction in the Val d’Agri oilfield.
Atomic Power in Forks: A Super-Logarithmic Lower Bound for Implementing Butterfly Networks in the Nonatomic Binary Fork-Join Model

We prove an Ω(log n log log n ) lower bound for the span of implementing the n input, log n -depth FFT circuit (also known as butterﬂy network) in the nonatomic binary fork-join model. In this model, memory-access synchronizations occur only through fork operations, which spawn two child threads, and join operations, which resume a parent thread when its child threads terminate. Our bound is asymptotically tight for the nonatomic binary fork-join model, which has been of interest of late, due to its conceptual ele-gance and ability to capture asynchrony. Our bound implies super-logarithmic lower bound in the nonatomic binary fork-join model for implementing the butterﬂy merging networks used, e.g., in Batcher’s bitonic and odd-even mergesort networks. This lower bound also implies an asymptotic separation result for the atomic and nonatomic versions of the fork-join model, since, as we point out, FFT circuits can be implemented in the atomic binary fork-join model with span equal to their circuit depth.
Soil Moisture Estimation and Its Influencing Factors Based on Temporal Stability on a Semiarid Sloped Forestland

Soil water content (SWC) plays a crucial role in the hydrological cycle and ecological restoration in arid and semi-arid areas. Studying the temporal stability of SWC spatial distribution is a requirement for the dynamic monitoring of SWC and the optimization of water resource management. The SWC in a Pinus tabulaeformis Carr. forest on the slope of the Loess Plateau of China were analyzed in five soil layers (0–100 cm with an interval of 20 cm) in the rainy and dry seasons from July 2014 to November 2017. The mean SWC was estimated and the main factors affecting the temporal stability of the SWC were further analyzed. Results showed that the SWC had strong temporal stability during the two seasons for several consecutive years. The temporal stability of SWC and the number of representative locations varied with season and depth. The elevation, soil total phosphorus (STP), clay, silt, or sand content of the representative locations approached the corresponding mean value of the study area. A single representative location accurately represented the mean SWC for the five depths in the rainy and dry seasons (RMSE <2%; rainy season: 0.81 < R 2 < 0.94; dry season: 0.63 < R 2 < 0.83; p < 0.01). The mean relative difference (MRD) and the relative difference standard deviation (SDRD) changed with the seasons and were significantly correlated with elevation, root density, and sand and silt content in two seasons (p < 0.05). Elevation, root density, and sand content were the main factors influencing the change of SWC temporal stability in different seasons. The results provide scientific guidance to monitor SWC by using a small number of locations and enrich our understanding of the factors affecting the temporal stability of SWC in the rainy and dry seasons of the Loess Plateau of China.
Alpine Newts (Ichthyosaura alpestris) Avoid Habitats Previously Used by Parasite-Exposed Conspecifics

Many organisms avoid habitats posing risks of parasitism. Parasites are not generally conspicuous, however, which raises the question of what cues individuals use to detect parasitism risk. Here, we provide evidence in alpine newts (Ichthyosaura alpestris) that non-visual cues from parasite-exposed conspecifics inform habitat avoidance. Alpine newts breed in aquatic habitats and occasionally move among adjacent terrestrial habitat during breeding seasons. We completed experiments with newts whereby individuals had access to both habitats, and the aquatic habitats varied in prior occupancy by conspecifics with different histories of exposure to the parasitic skin fungus, Batrachochytrium dendrobatidis (Bd). Continuous filming of newt activity for 2 days provided little evidence that prior use of aquatic habitats by conspecifics, regardless of their Bd exposure history, immediately influenced newt habitat use. However, newts that encountered aquatic habitats used specifically by Bd-exposed conspecifics on day 1 spent less time aquatic on day 2, whereas other newts did not alter habitat use. Responses could have been elicited by cues generated by Bd stages on the conspecifics or, perhaps more likely, cues emitted by the conspecifics themselves. In either case, these observations suggest that newts use non-visual cues sourced from exposed conspecifics to detect Bd risk and that those cues cause newts to avoid aquatic habitats. Bd may therefore influence host behavior in early phases of interactions, and possibly before any contact with infectious stages is made, creating potential for non-consumptive effects.
Opposing Effects of TGFβ and BMP in the Pulmonary Vasculature in Congenital Diaphragmatic Hernia

Background: Pulmonary hypertension is the major cause of morbidity and mortality in congenital diaphragmatic hernia (CDH). Mutations in several genes that encode signaling molecules of the transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) pathways have previously been associated with CDH. Since studies on the activation of these pathways in CDH are scarce, and have yielded inconsistent conclusions, the downstream activity of both pathways was assessed in the nitrofen-CDH rat model. Methods and Results: Pregnant Sprague-Dawley rats were treated with nitrofen at embryonic day (E) 9.5 to induce CDH in offspring. At E21, lungs were screened for the expression of key factors of both signaling pathways, at both the mRNA transcript and protein levels. Subsequently, paying particular attention to the pulmonary vasculature, increased phosphorylation of SMAD2, and decreased phosphorylation of Smad5 was noted in the muscular walls of small pulmonary vessels, by immunohistochemistry. This was accompanied by increased proliferation of constituent cells of the smooth muscle layer of these vessels. Conclusions: Increased activation of the TGFβ pathway and decreased activation of the BMP pathway in the pulmonary vasculature of rats with experimentally-induced CDH, suggesting that the deregulated of these important signaling pathways may underlie the development of pulmonary hypertension in CDH.
Experimental study of hydrogen plasma breakdown in a 2.45 GHz microwave discharge

Temporal evolution of microwave-plasma coupling, vacuum ultraviolet (VUV) light emission and plasma electron temperature and density is reported for a 2.45 GHz microwave hydrogen discharge pulsed at 50 Hz. Directional couplers, a VUV spectrometer and a Langmuir probe are used for the diagnostics of the plasma breakdown. A 5–10 µs transient peak of light emission exceeding the steady-state intensity by a factor of 3.3 is observed in coincidence with an abrupt drop in the microwave electric field. Observed light emission intensities combined with cross section data indicate that the electron temperature during the breakdown transient exceeds the steady-state value of 4–6 eV by a factor ⩾3, which is in good agreement with the Langmuir probe data. The estimated magnitude of the electron temperature transient corresponds well with the microwave-plasma coupling characteristics, indicating a drop of 30–40% in the electric field strength due to plasma damping.
Soluble Sema4D in Plasma of Head and Neck Squamous Cell Carcinoma Patients Is Associated With Underlying Non-Inflamed Tumor Profile

Semaphorin 4D (Sema4D) is a glycoprotein that is expressed by several tumors and immune cells. It can function as a membrane bound protein or as a cleaved soluble protein (sSema4D). We sought to investigate the translational potential of plasma sSema4D as an immune marker in plasma of patients with head and neck squamous cell carcinoma (HNSCC). Paired peripheral blood and tumor tissue samples of 104 patients with HNSCC were collected at the same time point to allow for real time analysis. Scoring of the histological inflammatory subtype (HIS) was carried out using Sema4D immunohistochemistry on the tumor tissue. sSema4D was detected in plasma using direct ELISA assay. Defining elevated sSema4D as values above the 95th percentile in healthy controls, our data showed that sSema4D levels in plasma were elevated in 25.0% (95% CI, 16.7–34.9%) of the patients with HNSCC and showed significant association with HIS immune excluded (HIS-IE) (p = 0.007), Sema4D+ve tumor cells (TCs) (p = 0.018) and PD-L1+ve immune cells (ICs) (p = 0.038). A multi-variable logistic regression analysis showed that HIS was significantly (P = 0.004) associated with elevated sSema4D, an association not explained by available patient-level factors. Using the IO-360 nanoString platform, differential gene expression (DGE) analysis of 10 HNSCC tumor tissues showed that patients with high sSema4D in plasma (HsS4D) clustered as IFN-γ negative tumor immune signature and were mostly HIS-IE. The IC type in the HsS4D paired tumor tissue was predominantly myeloid, while the lymphoid compartment was higher in the low sSema4D (LsS4D). The Wnt signaling pathway was upregulated in the HsS4D group. Further analysis using the IO-360, 770 gene set, showed significant non-inflamed profile of the HsS4D tumors compared to the LsS4D. In conclusion, our data reveals an association between sSema4D and the histological inflammatory subtype.
Design of a novel Peltier-based cooling device and its use in neutron diffraction data collection of perdeuterated yeast pyrophosphatase

H atoms play a central role in enzymatic mechanisms, but H-atom positions cannot generally be determined by X-ray crystallography. Neutron crystallography, on the other hand, can be used to determine H-atom positions but it is experimentally very challenging. Yeast inorganic pyrophosphatase (PPase) is an essential enzyme that has been studied extensively by X-ray crystallography, yet the details of the catalytic mechanism remain incompletely understood. The temperature instability of PPase crystals has in the past prevented the collection of a neutron diffraction data set. This paper reports how the crystal growth has been optimized in temperature-controlled conditions. To stabilize the crystals during neutron data collection a Peltier cooling device that minimizes the temperature gradient along the capillary has been developed. This device allowed the collection of a full neutron diffraction data set.
Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients

Sickle Cell Anemia (SCA) is the most common genetic disorder around the world. The mutation in the β-globin gene is responsible for a higher hemolysis rate, with further involvement of immunological molecules, especially cytokines, chemokines, growth factors, and anaphylatoxins. These molecules are responsible for inducing and attracting immune cells into circulation, thus contributing to increases in leukocytes and other pro-inflammatory mediators, and can culminate in a vaso-occlusive crisis (VOC). This study aimed to characterize the levels of these molecules in SCA patients in different clinical conditions in order to identify potential hallmarks of inflammation in these patients. An analytical prospective study was conducted using the serum of SCA patients in steady-state (StSt; n = 27) and VOC (n = 22), along with 53 healthy donors (HD). Samples from the VOC group were obtained on admission and on discharge, in the convalescent phase (CV). Levels of chemokines (CXCL8, CXCL10, CL2, CLL3, CCL4, CL5, and CCL11), cytokines (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17A, TNF-α, and IFN-γ) and growth factors (VEGF, FGFb, PDGF-BB, GM-CSF, and G-CSF) were measured using a Luminex assay, and anaphylatoxins (C3a, C4a, and C5a) were measured using Cytometric Bead Array. SCA patients in StSt showed a pro-inflammatory profile, and were indicated as being higher producers of CCL2, IL-1β, IL-12p70, IFN-γ, IL-17A, and GM-CSF, while VOC is highlighted by molecules IL-4 and IL-5, but also IL-2, IL-7, PDGF-BB, and G-CSF. PDGF-BB and IL-1ra seemed to be two important hallmarks for the acute-to-chronic stage, due to their significant decrease after crisis inflammation and statistical difference in VOC and CV groups. These molecules show higher levels and a strong correlation with other molecules in VOC. Furthermore, they remain at higher levels even after crisis recovery, which suggest their importance in the role of inflammation during crisis and participation in immune cell adhesion and activation. These results support a relevant role of cytokines, neutrophil and monocytes, since these may act as markers of VOC inflammation in SCA patients.