Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural insights into specific recognition of PTENα/β-NTE by WDR5 in cancer progression

PTENα/β, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the crystal structure of PTENα-NTE in complex with WDR5, which reveal that PTENα specifically binds to the WIN site of WDR5 through a novel binding motif specifically found in the NTE domain of PTENα/β. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as therapeutic agents for PTENα/β associated cancers. These findings not only shed light on the important role of the PTENα/β-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.
Concurrent threats and extinction risk in a long-lived, highly fecund vertebrate with parental care

Detecting declines and quantifying extinction risk of long-lived, highly fecund vertebrates including fishes, reptiles, and amphibians, can be challenging. In addition to the false notion that large clutches always buffer against population declines, the imperiled status of long-lived species can often be masked by extinction debt, wherein adults persist on the landscape for several years after populations cease to be viable. Here we develop a demographic model for the Eastern Hellbender (Cryptobranchus alleganiensis), an imperiled aquatic salamander with paternal care. We examined the individual and interactive effects of three of the leading threats hypothesized to contribute to the species’ demise: habitat loss due to siltation, high rates of nest failure, and excess adult mortality caused by fishing and harvest. We parameterized the model using data on their life history and reproductive ecology to model the fates of individual nests and address multiple sources of density-dependent mortality under both deterministic and stochastic environmental conditions. Our model suggests that high rates of nest failure observed in the field are sufficient to drive hellbender populations towards a geriatric age distribution and eventually to localized extinction, but that this process takes decades. Moreover, the combination of limited nest site availability due to siltation, nest failure, and stochastic adult mortality can interact to increase the likelihood and pace of extinction, which was particularly evident under stochastic scenarios. Density-dependence in larval survival and recruitment can severely hamper a population’s ability to recover from declines. Our model helps to identify tipping points beyond which extinction becomes certain and management interventions become necessary. Our approach can be generalized to understand the interactive effects of various threats to the extinction risk of other long-lived vertebrates. As we face unprecedented rates of environmental change, holistic approaches incorporating multiple concurrent threats and their impacts on different aspects of life history will be necessary to proactively conserve long-lived species.
Interaction with IP6K1 supports pyrophosphorylation of substrate proteins by the inositol pyrophosphate 5-IP7

Inositol pyrophosphates (PP-IPs) are a sub-family of water soluble inositol phosphates that possess one or more diphosphate groups. PP-IPs can transfer their β-phosphate group to a phosphorylated Ser residue to generate pyrophosphorylated Ser. This unique post-translational modification occurs on Ser residues that lie in acidic stretches within an intrinsically disordered protein sequence. Serine pyrophosphorylation is dependent on the presence of Mg2+ ions, but does not require an enzyme for catalysis. The mechanisms by which cells can regulate this enzyme-independent modification are still unknown. Here, we show that IP6K1, an enzyme responsible for the synthesis of the PP-IP 5-IP7, interacts with several proteins that undergo 5-IP7 mediated pyrophosphorylation, and with CK2, a protein kinase that phosphorylates Ser residues prior to pyrophosphorylation. We characterized the interaction of IP6K1 with AP3B1, the β subunit of the AP3 adaptor protein complex, which is a known pyrophosphorylation substrate. We observe the formation of a protein complex between IP6K1, AP3B1, and the catalytic α-subunit of CK2, and show that disrupting IP6K1 binding to AP3B1 lowers its in vivo pyrophosphorylation. We propose that assembly of a substrate-CK2-IP6K complex would allow for coordinated pre-phosphorylation and pyrophosphorylation of the target serine residue, and provide a mechanism to regulate this enzyme-independent modification.
EnsembleSeq: A workflow towards real-time, rapid and simultaneous multi-kingdom amplicon sequencing for holistic and cost-effective microbiome research at scale

Background Bacterial communities are often concomitantly present with numerous microorganisms in the human body and other natural environments. Amplicon based microbiome studies have generally paid a skewed attention, that too at a rather shallow genus level resolution, to the highly abundant bacteriome, with interest now forking towards the other microorganisms, particularly fungi. Given the generally sparse abundance of other microbes in the total microbiome, simultaneous sequencing of amplicons targeting multiple microbial kingdoms could be possible even with full multiplexing. Guiding studies are currently needed for performing and monitoring multi-kingdom-amplicon sequencing and data capture at scale. Method Full length bacterial 16S rRNA gene and entire fungal ITS region amplification was performed for human saliva samples (n=96, including negative and positive controls). Combined amplicon DNA libraries were prepared for nanopore sequencing using a major fraction of 16S molecules and a minor fraction of ITS amplicons. Sequencing was performed in a single run of an R10.4. 1 flowcell employing the latest V14 chemistry. An approach for real time monitoring of the species saturation using dynamic rarefaction was designed as a guiding determinant of optimal run time. Results Real-time saturation monitoring for both bacterial and fungal species enabled the completion of sequencing within 30 hours, utilizing less than 60% of the total nanopores. ∼5 million HQ taxonomically assigned reads were generated (∼4.2 million bacterial and 0.7 million fungal), providing a wider (beyond bacteriome) snapshot of human oral microbiota at species level resolution. Among the more than 400 bacterial and 240 fungal species identified in the studied samples, the species of Streptococcus (e.g. S. mitis, S. oralis) and Candida (e.g. C. albicans, C. tropicalis) were observed to be the dominating microbes in the oral cavity, respectively. This conformed well with the previous reports of the human oral microbiota. Conclusion Ensembleseq provides a proof-of-concept towards identification of both fungal and bacterial species simultaneously in a single fully multiplexed nanopore sequencing run in a time and resource effective manner. Details of this workflow are provided to enable large scale application for a holistic species level microbiome study.
Seasonal fluctuations in the bone microstructure of Sciurus vulgaris fuscoater humeri: a case study using phenomics on µCT-scans

Sciurus vulgaris Linnaeus, 1758, the red squirrel, is a small, mostly arboreally living rodent, spread across the Palearctic. It is mostly vegetarian, feeding on plants, fungi and seeds, and is less active in the winter months, but does not hibernate. In this lateral study, the humeri of the subspecies Sciurus vulgaris fuscoater, the Central European red squirrel, were analysed to uncover potential intraspecific variation between individuals found in different seasons. The µCT-scans were obtained with a resolution of 26 microns. Five bone parameters were calculated and statistically evaluated with regards to seasonal variations: total volume, bone volume, endocortical surface, cortical thickness, and average trabecular thickness. Bone volume, trabecular thickness and endocortical thickness correlate with bone size, whereas cortical thickness does not. Seasonal differences were observed between the warmer summer and autumn months versus the colder winter and spring months for all parameters. We, speculatively, relate the observed seasonal variation to nutrient intake, notably calcium. These results offer a deeper understanding of intraindividual variation in red squirrels, that may be useful in further ecological, taxonomic, and paleontological research.
Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis

Nucleolar ribosomal DNA (rDNA) repeats control ribosome manufacturing. rDNA harbors a ribosomal RNA (rRNA) gene and an intergenic spacer (IGS). RNA polymerase (Pol) I transcribes rRNA genes yielding the rRNA components of ribosomes. Pol II at the IGS induces rRNA production by preventing Pol I from excessively synthesizing IGS non-coding RNAs (ncRNAs) that can disrupt nucleoli. At the IGS, Pol II regulatory processes and whether Pol I function can be beneficial remain unknown. Here, we identify IGS Pol II regulators, uncovering nucleolar optimization via IGS Pol I. Compartment-enriched proximity-dependent biotin identification (compBioID) showed enrichment of the TATA-less promoter-binding TBPL1 and transcription regulator PAF1 with IGS Pol II. TBPL1 localizes to TCT motifs, driving Pol II and Pol I and maintaining its baseline ncRNA levels. PAF1 promotes Pol II elongation, preventing unscheduled R-loops that hyper-restrain IGS Pol I and its ncRNAs. PAF1 or TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. In PAF1-deficient cells, repressing unscheduled IGS R-loops rescues nucleolar organization and rRNA production. Depleting IGS Pol I-dependent ncRNAs is sufficient to compromise nucleoli. We present the interactome of nucleolar Pol II and show its control by TBPL1 and PAF1 ensures IGS Pol I ncRNAs maintaining nucleolar structure and operation.
Device for contactless current generation, in particular bicycle dynamo, vehicle lighting system and bicycle

A device for contactless current generation, in particular bicycle dynamo, on a rotatable counter element, in particular wheel rim, with at least one movably mounted rotor element (2) having at least one magnet (3), and at least one coil (7), in the at least one winding of which a current can be induced by the magnet (3), which moves together with the rotor element (2), said current being usable to operate a consumer, wherein the rotor element (2) is movable by magnetic interaction with the counter element (1), characterized in that the rotor element (2) and the counter element (1) have different axial profiles, and, in an operative position, the rotor element (2) is designed to generate at least one magnetic field (6a, 6b) on the basis of an eddy current in the conductive counter element (1), which forms an uninterrupted circular path, in such a manner that, by means of continuous relative movement between the counter element (2) and rotor element (1), eddy current fields which are continuously opposed to one another and have oppositely polled magnetic fields (6a, 6b) to one another are induced in the counter element and the rotor element (2) is thus moved together with the counter element (1) with an eddy current gearing being formed. Furthermore, the invention relates to a vehicle lighting system and to a bicycle, each with a corresponding device for current generation.
Shale Gas Boom Affecting the Relationship Between LPG and Oil Prices

Liquefied petroleum gases (LPGs) together with other natural gas liquids (NGLs) have played an important role in the current U.S. shale gas boom. Depressed gas prices in recent years have made pure natural gas operations less profitable. The result is that liquids components in gas production have become increasingly important in ensuring the profitability of shale gas operations. In this paper we investigate whether the shale gas expansion, which has led to an increase in associated LPG production, has also affected the historically strong relationship between LPG and oil prices. Revealing the strength and stability of the LPG/oil relationship is relevant when it comes to the future profitability and development of the U.S. natural gas sector. Our results suggest that the LPG/oil relationship has weakened in recent years with a move towards cheaper liquids relative to oil. This is consistent with developments in the natural gas sector with increased liquids production. A consequence is that U.S. natural gas operations cannot automatically rely on high liquids prices to ensure profitability.
Comparison of the perioperative parameters between computer navigation and fluoroscopy guidance for pedicle screw placement

Abstract Background: Computer navigation technology is gradually applied to the placement of pedicle screws, but its security and effectiveness still lack of high-quality evidence-based medical evidence. In this study, we will perform a systematic review of previously published randomized controlled trials to investigate the accuracy and effectiveness of computer navigation vsersus fluoroscopy guidance for pedicle screw placement. Methods: All study protocols adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed (MEDLINE), The excerpta medica database, Web of Science (science and social science citation index), The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, WanFang, Chinese Biomedical Literature Database will be searched for relevant articles up to 18 April, 2020. We will include randomized controlled trials of computer navigation and fluoroscopy guidance for pedicle screw placement. The Cochrane Handbook (v6) will be used for assessment of study bias and reliability, and a meta-analysis will be performed using STATA 16.0. The main outcome will be the proportion of accurate implanted screws. Additional outcomes including: overall complication rate, radiation dosage, length of surgery, length of stay, estimated blood loss. Results: The quality of the assessments will be assessed through Grading of Recommendations Assessment, Development, and Evaluation. Data will be disseminated through publications in peer-reviewed journals. Conclusion: We will evaluate the accuracy and other perioperative parameters between computer navigation and fluoroscopy guidance for pedicle screw placement. Trial registration number: PROSPERO 2020 CRD42020172087.
The association between Ki-67 expression and the clinical pathological characteristics of colorectal cancer

Abstract Background: This study will explore the association between Ki-67 expression and clinical pathological characteristics (CPC) of colorectal cancer (CC). Methods: We will search relevant studies from electronic databases (Cochrane Library, PUBMED, EMBASE, Scopus, Cumulative Index to Nursing and Allied Health Literature, China Biology Medicine, and China National Knowledge Infrastructure) from beginning to April 1, 2020 without language and publication time limitations. We will consider all case-controlled studies (CCSs) or randomized controlled studies (RCSs) investigating the association between Ki-67 expression and CPC of CC. We will appraise study quality of CCSs by Newcastle–Ottawa Scale, and RCSs by Cochrane risk of bias tool. Statistical analysis will be carried out by Review Manager 5.3 software. Results: The present study will explore the association between Ki-67 expression and CPC of CC. Conclusion: Its findings may summarize scientific evidence of the association between Ki-67 expression and CPC of CC, and may provide helpful evidence for clinical practice. Systematic review registration: PROSPERO CRD42020173795.
The Role of Financial Speculation in Driving the Price of Crude Oil

Abstract As financial firms have increased their positions in the oil futures market during the past ten years, oil prices have increased dramatically as well. The coincidence of these two events has led some observers to argue that financial speculation caused the oil-price increases. Yet several arguments cast doubt on the validity of this claim. For example, although the quantity of oil implied by the number ofopen futures contracts is much larger than U.S. daily oil consumption, comparing these two statistics is misleading because not all paper oil is immediately deliverable. In addition, changes in financial firms’ positions do not predict oil-price changes, but oil-price changes predict changes in positions. Other explanations for the oil-price increases include macroeconomic fundamentals such as increased demand from emerging Asia. Of these explanations, the most consistent with the facts relates the oil-price increases to a series of positive demand shocks emanating from emerging Asia.
Semiconductor terahertz spatial modulators with high modulation depth and resolution for imaging applications

Spatial modulation of terahertz waves enabled by the charge carrier generation-recombination dynamics in semiconductor is promising for terahertz compressive sensing imaging since the modulation is broadband, low-loss and of enough speed (tens of thousands of Hertz). However, their performance in terahertz compressive sensing imaging is significantly limited by their inferior modulation depth and resolution. Here, silicon was cut into small pieces and packed closely in arrays to shut off the charge carrier diffusion between them and increase the resolution of the terahertz spatial modulators. A monolayer of gold nanoparticles was coated on the silicon surface to enhance the terahertz modulation depth through the enhanced generation of charge carriers by surface plasma. Through a comparison test, it is found that gold nanoparticle coated small silicon arrays have improved contrast and resolution for terahertz imaging over the uncoated and coated large pieces of silicon, respectively.
Parameter Efficient Multi-task Fine-tuning by Learning to Transfer Token-wise Prompts

Prompt tuning has been proven to be successful on various tasks by incorporating a small number of trainable parameters while freezing large pre-trained language models (PLMs). However, it is still unsettled how to generate more proper prompts for any individual examples and how to extend prompt tuning to multi-task learning scenarios by leveraging cross-task features. To address these challenges, we propose a token-wise prompt tuning (TPT), in which a bank of finer-grained soft prompt tokens is built for multi-task learning by memory network. The tokens are retrieved from the bank against an input example and assembled to an instance-dependent prompt. Extensive experimental results on 14 datasets demonstrated that the models enhanced by our TPT performed far better than full parameter fine-tuned models and achieved state-of-the-art by tuning only 0 . 035% parameters. 1
CCIM: Cross-modal Cross-lingual Interactive Image Translation

Text image machine translation (TIMT) which translates source language text images into target language texts has attracted intensive attention in recent years. Although the end-to-end TIMT model directly generates target translation from encoded text image features with an efficient architecture, it lacks the recognized source language information resulting in a decrease in translation performance. In this paper, we propose a novel Cross-modal Cross-lingual Interactive Model (CCIM) to incorporate source language information by synchronously generating source language and target language results through an interactive attention mechanism between two language de-coders. Extensive experimental results have shown the interactive decoder significantly out-performs end-to-end TIMT models and has faster decoding speed with smaller model size than cascade models. 1
The interaction between demography and harvesting in red grouse

Many animal populations are threatened by human activity, including habitat loss and harvesting but recent advances in population ecology show that the ageand sex-structure are important when aiming to understand population dynamics. However, research on population dynamics often focuses on species that experience relatively little human disturbance and human caused mortality is often assumed not to affect population dynamics. An increasing number of studies shows short-term and long-term evolutionary and ecological consequences of harvesting. This has not only implications for the understanding of population dynamics but also for the management and conservation of species in human-dominated landscapes. This thesis aims to investigate the interaction between the demographic structure and harvesting in a fluctuating species, the red grouse (Lagopus lagopus scoticus) using a combination of empirical and theoretical approaches. The relative roles of agerelated parasite burden, fecundity and shooting in driving population dynamics are assessed, and empirical data are used to parameterise a model examining the effect of harvesting on the population dynamics. The empirical part of the thesis starts with the investigation of the intensity and distribution of the parasitic nematode Trichostrongylus tenuis for three age-classes of red grouse before the breeding season. The intensity of the parasite increased with host age. Parasites in two-year-old grouse were more aggregated than in one-yearold and 3+-year-old grouse. This has implications for population dynamics because the aggregation of parasites within the host influences mortality rates. Females of the oldest age class (3+-years-old) were less fecund than younger grouse and interactions with nesting habitat and year were found to affect female fecundity. The ageand sex-structure of shot birds was compared with the ageand sex-structure of the population before shooting. More old birds were shot at small bag sizes but this bias decreased as more birds were shot. Old males were highly susceptible to shooting at the beginning of the season but susceptibility decreased with number of
GPT Deciphering Fedspeak: Quantifying Dissent Among Hawks and Doves

Markets and policymakers around the world hang on the consequential monetary policy decisions made by the Federal Open Market Committee (FOMC). Publicly available textual documentation of their meetings provides insight into members’ attitudes about the economy. We use GPT-4 to quantify dissent among members on the topic of inflation. We find that transcripts and minutes reflect the diversity of member views about the macroeconomic out-look in a way that is lost or omitted from the public statements. In fact, diverging opinions that shed light upon the committee’s “true” attitudes are almost entirely omitted from the final statements. Hence, we argue that forecasting FOMC sentiment based solely on statements will not sufficiently reflect dissent among the hawks and doves.