Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of crustal strength fields on the patterns and rates of fluvial incision

Gradients in the bedrock strength field are increasingly recognized as integral to the rates and patterns of landscape evolution. To explore this influence, we incorporate data from fault strength profiles into a landscape evolution model, under the assumption that erodibility of rock is proportional to the inverse square root of cohesion for bedrock rivers incised by bedload abrasion. Our model calculations illustrate how patterns in the crustal strength field can play a dominant role in local fluvial erosion rates and consequently the development of fluvial network patterns. Fluvial incision within weak zones can be orders of magnitude faster than that for resistant bedrock. The large difference in erosion rate leads to the formation of a straight, high‐order channel with short, orthogonal tributaries of low order. In comparison, channels incising into homogeneous strength fields produce dendritic drainage patterns with no directional dependence associated with erodibility gradients. Channels that cross the strength gradient experience local variations in knickpoint migration rate and the development of stationary knickpoints. Structurally confined channels can shift laterally if they incise into weak zones with a shallow dip angle, and this effect is strongly dependent on the magnitude of the strength difference, the dip angle, and the symmetry and thickness of the weak zone. The influence of the strength field on drainage network patterns becomes less apparent for erodibility gradients that approach homogeneity. There are multiple natural examples with drainage network patterns similar to those seen in our numerical experiments.
Genetically encoded transcriptional plasticity underlies stress adaptation in Mycobacterium tuberculosis

Abstract Transcriptional regulation is a critical adaptive mechanism that allows bacteria to respond to changing environments, yet the concept of transcriptional plasticity (TP) remains largely unexplored. In this study, we investigate the genome-wide TP profiles of Mycobacterium tuberculosis ( Mtb ) genes by analyzing 894 RNA sequencing samples derived from 73 different environmental conditions. Our data reveal that Mtb genes exhibit significant TP variation that correlates with gene function and gene essentiality. We also found that critical genetic features, such as gene length, GC content, and operon size independently impose constraints on TP, beyond trans-regulation. By extending our analysis to include two other Mycobacterium species -- M. smegmatis and M. abscessus -- we demonstrate a striking conservation of the TP landscape. This study provides a comprehensive understanding of the TP exhibited by mycobacteria genes, shedding light on this significant, yet understudied, genetic feature encoded in bacterial genomes.
DEMETER satellite observations of lightning‐induced electron precipitation

DEMETER spacecraft detects short bursts of lightning‐induced electron precipitation (LEP) simultaneously with newly‐injected upgoing whistlers, and sometimes also with once‐reflected (from conjugate hemisphere) whistlers. For the first time causative lightning discharges are definitively geo‐located for some LEP bursts aboard a satellite. The LEP bursts occur within <1 s of the causative lightning and consist of 100–300 keV electrons. First in‐situ observations of large regions of enhanced background precipitation are presented. The regions are apparently produced and maintained by high rate of lightning within a localized thunderstorm.
Predictive value of DOT1L mutations for clinical outcomes in non‐small‐cell lung cancer patients receiving immune checkpoint inhibitor therapy

In this study, we present findings that highlight the role of baseline Disruptor of telomeric silencing 1-like ( DOT1L ) mutations as a promising biomarker to identify stage IIIb/IV non-small-cell lung cancer (NSCLC) patients who might demonstrate potential clinical benefit under immune checkpoint inhibitor (ICI) therapies. NSCLC patients often present advanced/metastatic disease upon diagnosis
Ubiquitination detection techniques

Ubiquitination is an intricately regulated post-translational modification that involves the covalent attachment of ubiquitin to a substrate protein. The complex dynamic nature of the ubiquitination process regulates diverse cellular functions including targeting proteins for degradation, cell cycle, deoxyribonucleic acid (DNA) damage repair, and numerous cell signaling pathways. Ubiquitination also serves as a crucial mechanism in protein quality control. Dysregulation in ubiquitination could result in lethal disease conditions such as cancers and neurodegenerative diseases. Therefore, the ubiquitination cascade has become an attractive target for therapeutic interventions. Enormous efforts have been made to detect ubiquitination involving different detection techniques to better grasp the underlying molecular mechanisms of ubiquitination. This review discusses a wide range of techniques stretching from the simplest assays to real-time assays. This includes western blotting/immunoblotting, fluorescence assays, chemiluminescence assays, spectrophotometric assays, and nanopore sensing assays. This review compares these applications, and the inherent advantages and limitations.
The efficacy of natural bioactive compounds against prostate cancer: Molecular targets and synergistic activities

Globally, prostate cancer (PCa) is regarded as a challenging health issue, and the number of PCa patients continues to rise despite the availability of effective treatments in recent decades. The current therapy with chemotherapeutic drugs has been largely ineffective due to multidrug resistance and the conventional treatment has restricted drug accessibility to malignant tissues, necessitating a higher dosage resulting in increased cytotoxicity. Plant‐derived bioactive compounds have recently attracted a great deal of attention in the field of PCa treatment due to their potent effects on several molecular targets and synergistic effects with anti‐PCa drugs. This review emphasizes the molecular mechanism of phytochemicals on PCa cells, the synergistic effects of compound‐drug interactions, and stem cell targeting for PCa treatment. Some potential compounds, such as curcumin, phenethyl‐isothiocyanate, fisetin, baicalein, berberine, lutein, and many others, exert an anti‐PCa effect via inhibiting proliferation, metastasis, cell cycle progression, and normal apoptosis pathways. In addition, multiple studies have demonstrated that the isolated natural compounds: d‐limonene, paeonol, lanreotide, artesunate, and bicalutamide have potential synergistic effects. Further, a significant number of natural compounds effectively target PCa stem cells. However, further high‐quality studies are needed to firmly establish the clinical efficacy of these phytochemicals against PCa.
Development and validation of real-time recombinase polymerase amplification-based assays for detecting HPV16 and HPV18 DNA

ABSTRACT Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. Persistent human papillomavirus (HPV) infection is the principal cause of cervical cancer, with HPV16 and HPV18 accounting for about 70% of cases worldwide. Cervical screening is an effective secondary measure for preventing cervical cancer. Testing for HPV DNA is becoming increasingly important in cervical cancer screening. The existing PCR-based HPV detection technology has several disadvantages: the assays are time-consuming, and sophisticated equipment is required to control the temperature cycles. These drawbacks have led to the development of detection technologies based on isothermal amplification. Here, we present real-time recombinase polymerase amplification (RPA-exo)-based assays for single genotyping of either the E7 or the L1 segment of HPV16 or HPV18. These assays were highly sensitive, able to detect HPV in all clinical samples with Ct values below 34, and yielded results within 25 min. A dual-detection system capable of detecting both HPV16 and HPV18 in a single reaction was also developed based on the L1 gene. It has a limit of detection of approximately 10,000 copies of each genotype per reaction. The assays were validated with DNA extracted from 36 biopsy specimens and 42 exfoliated cell samples from 43 patients with cervical lesions at different stages. The RPA-exo system is a promising clinical detection platform with the advantages of yielding results rapidly and operating at a constant temperature, while being cost-effective and easy to use. IMPORTANCE HPV DNA screening is an effective approach for the prevention of cervical cancer. The novel real-time recombinase polymerase amplification-based HPV detection systems we developed constitute an improvement over the HPV detection methods currently used in clinical practice and should help to extend cervical cancer screening in the future, particularly in point-of-care test settings. HPV DNA screening is an effective approach for the prevention of cervical cancer. The novel real-time recombinase polymerase amplification-based HPV detection systems we developed constitute an improvement over the HPV detection methods currently used in clinical practice and should help to extend cervical cancer screening in the future, particularly in point-of-care test settings.
A methodology for assessing ensemble experiments

Climate simulations and forecast experiments of increasingly large ensemble size are being performed to assess the predictive skill of a dynamic model on seasonal and longer timescales. Especially in the cases of ensemble climate simulation or forecast forced by observed or predicted sea surface temperatures, the model is expected to maximize potential predictability due to boundary forcing and to minimize internal variability generated from dynamic instability. In the light of small predictive skill in extratropics from boundary forcing, one must evaluate skill of the ensemble mean quantity against intersample variability or spread of the individual ensemble member. On the other hand, certain dominant signals in climate variability, such as E1 Nino-Southern Oscillation, have been documented. Predictability for these major signals is the hope of seasonal and climate forecasting using a dynamic model. It may be unrealistic to anticipate a model being able to simulate or forecast the full spectra of climate variability. The question is how to evaluate a model's performance in capturing the dominant climate signals in ensemble experiments with increasingly large sample size. These issues have motivated us to develop a compact methodology for assessing climate experiments with large ensemble size. This method treats the ensemble mean as signal and intersample variability as spread or noise in a common framework. Hence not only dominant signals from boundary forcing can be isolated, but also sensitivity of these signals to the forcing can be assessed. Other potential applications of the method to climate simulation and forecasting are also discussed.
Fostering the Dense Packing of Halide Perovskite Quantum Dots through Binary-Disperse Mixing

Due to their versatile applications, perovskite quantum dot (PQD)-based optoelectrical devices have garnered significant research attention. However, the fundamental packing behavior of PQDs in thin films and its impact on the device performance remain relatively unexplored. Drawing inspiration from theoretical models concerning packing density with size mixtures, this study presents an effective strategy, namely, binary-disperse mixing, aimed at enhancing the packing density of PQD films. Comprehensive grazing-incidence small-angle X-ray characterization suggested that the PQD film consists of three phases: two monosize phases and one binary mixing phase. The volume fraction and population of the binary-size phase can be tuned by mixing an appropriate amount of large and small PQDs. Furthermore, we performed multi-length-scale all-atom and coarse-grained molecular dynamics simulations to elucidate the distribution and conformation of organic surface ligands, highlighting their influence on PQD packing. Notably, the mixing of two PQDs of different sizes promotes closer face-to-face contact. The densely packed binary-disperse film exhibited largely suppressed trap-assisted recombination, much longer carrier lifetime, and thereby improved power conversion efficiency. Hence, this study provides fundamental understanding of the packing mechanism of perovskite quantum dots and highlights the significance of packing density for PQD-based solar cells.
Predicting regional somatic mutation rates using DNA motifs

How the locus-specificity of epigenetic modifications is regulated remains an unanswered question. A contributing mechanism is that epigenetic enzymes are recruited to specific loci by DNA binding factors recognizing particular sequence motifs (referred to as epi-motifs). Using these motifs to predict biological outputs depending on local epigenetic state such as somatic mutation rates would confirm their functionality. Here, we used DNA motifs including known TF motifs and epi-motifs as a surrogate of epigenetic signals to predict somatic mutation rates in 13 cancers at an average 23kbp resolution. We implemented an interpretable neural network model, called contextual regression, to successfully learn the universal relationship between mutations and DNA motifs, and uncovered motifs that are most impactful on the regional mutation rates such as TP53 and epi-motifs associated with H3K9me3. Furthermore, we identified genomic regions with significantly higher mutation rates than the expected values in each individual tumor and demonstrated that such cancer-related regions can accurately predict cancer types. Interestingly, we found that the same mutation signatures often have different contributions to cancer-related and cancer-independent regions, and we also identified the motifs with the most contribution to each mutation signature.
Estimation of aquifer recharge by means of atmospheric chloride deposition balance in the soil

En estat estacionari, la deposicio de clorur atmosferic sobre el terreny permet estimar la recarrega mitjana en els aquifers a llarg termini quan el contingut mitja de clorurs de l'aigua de recarrega es conegut. Es un metode senzill, ben conegut, pero no sense dificultats teoriques i practiques, malgrat que el seu potencial, sovint, no s'aplica. En circumstancies favora- bles els resultats obtinguts son fiables i permeten estimar-ne la incertesa. El contingut en clorurs de la recarrega es pot deduir del mostreig de la part superior del nivell freatic. El metode i la seva millora han estat l'objectiu de recerca i d'aplicacio en diversos aquifers i en tot el territori espanyol, com a part de projectes de recerca aplicada i de tesis doctorals lligades al Grup d'Hidrologia Subterrania del Departament d'Enginyeria del Terreny, Cartografica i Geofisica, de la Universitat Politecnica de Catalunya (UPC). En el cas d'aquifers que descarreguen en brolladors o son explotats mitjancant pous profunds, la mescla vertical de l'aigua recarregada a diverses altures es important, de manera que la recarrega estimada a partir del balanc de clorurs pot ser notablement sobrevalorada i cal fer-hi correccions. El metode es pot comparar favorablement amb els altres metodes per a avaluar la recarrega, encara que cadascun proporciona estimacions de la recarrega diferents, que s'han de considerar en el context apropiat de lloc i temps.
Asymmetric Evolution of Protein Domains in the Leucine-Rich Repeat Receptor-Like Kinase Family of Plant Signaling Proteins

Abstract The coding sequences of developmental genes are expected to be deeply conserved, with cis-regulatory change driving the modulation of gene function. In contrast, proteins with roles in defense are expected to evolve rapidly, in molecular arms races with pathogens. However, some gene families include both developmental and defense genes. In these families, does the tempo and mode of evolution differ between genes with divergent functions, despite shared ancestry and structure? The leucine-rich repeat receptor-like kinase (LRR-RLKs) protein family includes members with roles in plant development and defense, thus providing an ideal system for answering this question. LRR-RLKs are receptors that traverse plasma membranes. LRR domains bind extracellular ligands; RLK domains initiate intracellular signaling cascades in response to ligand binding. In LRR-RLKs with roles in defense, LRR domains evolve faster than RLK domains. To determine whether this asymmetry extends to LRR-RLKs that function primarily in development, we assessed evolutionary rates and tested for selection acting on 11 subfamilies of LRR-RLKs, using deeply sampled protein trees. To assess functional evolution, we performed heterologous complementation assays in Arabidopsis thaliana (Arabidopsis). We found that the LRR domains of all tested LRR-RLK proteins evolved faster than their cognate RLK domains. All tested subfamilies of LRR-RLKs had strikingly similar patterns of molecular evolution, despite divergent functions. Heterologous transformation experiments revealed that multiple mechanisms likely contribute to the evolution of LRR-RLK function, including escape from adaptive conflict. Our results indicate specific and distinct evolutionary pressures acting on LRR versus RLK domains, despite diverse organismal roles for LRR-RLK proteins.
Comparison of cutaneous adverse events between second-generation tyrosine kinase inhibitors and imatinib for chronic myeloid leukemia: a systematic review and meta-analysis

Abstract Background Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In this study, we aimed to compare the risks of cutaneous adverse events between imatinib- and second-generation TKI-treated patients with CML. Material and Methods Paired reviewers independently obtained studies from PubMed, Embase, and Cochrane Library published until 15 March 2022. The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. Two independent reviewers screened the results and selected articles on cutaneous adverse events. RevMan 5.4 and the Cochrane Collaboration tool were used to perform the meta-analysis and risk of bias assessment. Results and Conclusion Eleven trials involving 4502 patients were analyzed in this study. Patients treated with second-generation TKIs were significantly more likely to experience cutaneous adverse events than those treated with imatinib with a relative risk (RR) of 1.62 (95% confidence interval [CI], [1.25–2.09]). Except dasatinib (RR [95% CI], 1.39 [0.75–2.56]), the risk of adverse events was more with second-generation TKIs than with imatinib as follows: nilotinib (2.11 [1.53–2.90]), bosutinib (1.41 [1.07–1.86]), and radotinib (1.87 [1.33–2.63]). Rash was the most common cutaneous adverse event that was observed in 21.6% of cases across all grades, followed by pruritus (5.7%) and alopecia (4.3%). In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs.
Bag of World Anchors for Instant Large-Scale Localization

In this work, we present a novel scene description to perform large-scale localization using only geometric constraints. Our work extends compact world anchors with a search data structure to efficiently perform localization and pose estimation of mobile augmented reality devices across multiple platforms (e.g., HoloLens 2, iPad). The algorithm uses a bag-of-words approach to characterize distinct scenes (e.g., rooms). Since the individual scene representations rely on compact geometric (rather than appearance-based) features, the resulting search structure is very lightweight and fast, lending itself to deployment on mobile devices. We present a set of experiments demonstrating the accuracy, performance and scalability of our novel localization method. In addition, we describe several use cases demonstrating how efficient cross-platform localization facilitates sharing of augmented reality experiences.
Extragenic suppression of an HSV-1 UL34 nuclear egress mutant reveals role for pUS9 as an inhibitor of epithelial cell-to-cell spread

ABSTRACT The herpes simplex virus pUL34 component of the nuclear egress complex functions in both nuclear egress and cell-to-cell spread. A R158A/R161A double substitution in pUL34 has been shown to strongly inhibit both nuclear egress and spread. Selection for extragenic suppressors of UL34R158A/R161A on the background of a virus that expresses monomeric red fluorescent protein-tagged pUL35 yielded two viruses , SUP7 and SUP9, that both replicated and spread much better than the parental virus. The two viruses carried both unique and common genetic changes. The most striking unique genetic change was a large rearrangement of the US region of SUP7 resulting in duplication of ICP22 and deletion of part of US3 and all of US9-12. The two common genetic changes were a frame shift that eliminated expression of pUL35, and mutations that either eliminated or diminished expression of pUS9. The mutations in pUL35 significantly improved replication but had only a small effect on spread. We observed that mutations that diminish or eliminate detectable pUS9 expression significantly improved spread on Vero cells of viruses that were impaired in the spread function of either pUL34 or pUL51, but did not enhance spread of an otherwise wild-type virus. A similar enhancement was observed on U2OS, but not HaCaT cells, suggesting that the spread-inhibitory function of pUS9 differs between cell lines. IMPORTANCE Herpesviruses are able to disseminate in infected hosts despite development of a strong immune response. Their ability to do this relies on a specialized process called cell-to-cell spread in which newly assembled virus particles are trafficked to plasma membrane surfaces that abut adjacent uninfected cells. The mechanism of cell-to-cell spread is obscure, and little is known about whether or how it is regulated in different cells. We show here that a viral protein with a well-characterized role in promoting spread from neurons has an opposite, inhibitory role in other cells. Herpesviruses are able to disseminate in infected hosts despite development of a strong immune response. Their ability to do this relies on a specialized process called cell-to-cell spread in which newly assembled virus particles are trafficked to plasma membrane surfaces that abut adjacent uninfected cells. The mechanism of cell-to-cell spread is obscure, and little is known about whether or how it is regulated in different cells. We show here that a viral protein with a well-characterized role in promoting spread from neurons has an opposite, inhibitory role in other cells.
Interpolating Solutions of the Helmholtz Equation With Compressed Sensing

We present an algorithm which allows us to model wavefields with frequency-domain methods using a much smaller number of frequencies than that typically required by the classical sampling theory in order to obtain an alias-free result. The foundation of the algorithm is the recent results on the compressed sensing, which state that data can be successfully recovered from an incomplete measurement if the data is sufficiently sparse. Results from numerical experiment show that only 30% of the total frequency spectrum is need to capture the full wavefield information when working in the hard 2D synthetic Marmousi model.