Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving Actor–Critic Reinforcement Learning via Hamiltonian Monte Carlo Method

The actor–critic reinforcement learning (RL) is widely used in various robotic control tasks. By viewing the actor–critic RL from the perspective of variational inference (VI), the policy network is trained to obtain the approximate posterior of actions, given the optimality criteria. However, in practice, the actor–critic RL may yield suboptimal policy estimates due to the amortization gap and insufficient exploration. In this work, inspired by the previous use of Hamiltonian Monte Carlo (HMC) in VI, we propose to integrate the policy network of actor–critic RL with HMC, which is termed as Hamiltonian policy. As such we propose to evolve actions from the base policy according to HMC, and our proposed method has many benefits. First, HMC can improve the policy distribution to better approximate the posterior and hence reduce the amortization gap. Second, HMC can also guide the exploration more to the regions of action spaces with higher Q values, enhancing the exploration efficiency. Further, instead of directly applying HMC into RL, we propose a new leapfrog operator to simulate the Hamiltonian dynamics. Finally, in safe RL problems, we find that the proposed method can not only improve the achieved return, but also reduce safety constraint violations by discarding potentially unsafe actions. With comprehensive empirical experiments on continuous control baselines, including MuJoCo and PyBullet Roboschool, we show that the proposed approach is a data-efficient and easy-to-implement improvement over previous actor–critic methods.
Comprehensive Genomic Features indicative for Notch Responsiveness

Transcriptional specificity is often determined by transcription factor levels and/or chromatin context. In the Notch signal transduction pathway, transcription factor RBPJ is the central component and directly forms a coactivator complex together with the Notch intracellular domain (NICD). While the RBPJ protein levels remain constant in most tissues, dynamic expression of Notch target genes varies depending on the given cell-type and the Notch activity state. To elucidate dynamic RBPJ binding genome-wide, we investigated RBPJ occupancy by ChIP-Seq making use of Notch-dependent T cells. Surprisingly, only a small set of the total RBPJ sites show a dynamic binding behavior in response to Notch signaling. Compared to static RBPJ sites, dynamic sites differ in regard to their chromatin state, binding strength and enhancer positioning. Dynamic RBPJ sites are predominantly located distal to transcriptional start sites (TSS), while most static sites are found in promoter-proximal regions. Importantly, gene responsiveness is preferentially associated with dynamic RBPJ binding sites and this static and dynamic binding behavior is repeatedly observed in different cell types and species. Based on the above findings we used a machine-learning algorithm to predict Notch responsiveness with high confidence in different cellular contexts. This approach is potentially applicable to other transcription factors regulating signal-induced gene sets. Our results strongly support the notion that the combination of binding strength and enhancer positioning are indicative of Notch responsiveness.
Static and dynamic pressure sensitivity anisotropy of a calcareous shale

Optimizing the productivity of nonconventional, low‐permeability “shale” reservoirs requires detailed knowledge of the mechanical properties of such materials. These rocks' elastic anisotropy is acknowledged but usually ignored due to difficulties in obtaining such information. Here we study in detail the dynamic and static elastic properties of a suite of calcareous mudstones from the nonconventional Duvernay reservoir of Alberta, Canada. The complete set of transversely isotropic elastic constants is obtained from strategically oriented ultrasonic transducers to confining pressures of 90 MPa. Wave speed anisotropies of up to 35% are observed at even the highest confining pressures. Furthermore, the stress sensitivity of the wave speeds, and hence moduli, is itself highly dependent on direction with speeds taken perpendicular to the bedding plane being highly nonlinearly dependent on pressure, whereas those along the bedding plane show, unexpectedly, nearly no pressure dependence. These observations are in qualitative agreement with the preferentially oriented porosity and minerals seen in scanning electron microscope images. These results may be significant to the interpretation of sonic logs and azimuthal amplitude versus offset for principal stress directions, for the concentration of stress within such formations, and for estimation of static engineering moduli from sonic log wave speeds.
Protein structure determination using Riemannian approach

The protein nuclear magnetic resonance (NMR) structure determination is one of the most extensively studied problems due to its increasing importance in biological function analysis. We adopt a novel method, based on one of the matrix completion (MC) techniques–the Riemannian approach, to solve the protein structure determination problem. We formulate the protein structure in terms of low-rank matrix which can be solved by an optimization problem in the Riemannian spectrahedron manifold whose objective function has been delimited with the derived boundary condition. Two efficient algorithms in Riemannian approach-the trust-region (Tr) algorithm and the conjugate gradient (Cg) algorithm are used to reconstruct protein structures. We first use the two algorithms in a toy model and show that the Tr algorithm is more robust. Afterwards, we rebuild the protein structure from the NOE distance information deposited in NMR Restraints Grid (http://restraintsgrid.bmrb.wisc.edu/NRG/MRGridServlet). A dataset with both X-ray crystallographic structure and NMR structure deposited in Protein Data Bank (PDB) is used to statistically evaluate the performance of our method. By comparing both our rebuilt structures and NMR counterparts with the “standard” X-ray structures, we conclude that our rebuilt structures have similar (sometimes even smaller) RMSDs relative to “standard” X-ray structures in contrast with the reference NMR structures. Besides, we also validate our method by comparing the Z-scores between our rebuilt structures with reference structures using Protein Structure Validation Software suit. All the validation scores indicate that the Riemannian approach in MC techniques is valid in reconstructing the protein structures from NOE distance information. The software based on Riemannian approach is freely available at https://github.com/xubiaopeng/Protein_Recon_MCRiemman. Author summary Matrix Completion is a technique widely used in many aspects, such as the global positioning in sensor networks, collaborative filtering in recommendation system for many companies and face recognition, etc. In biology, distance geometry used to be a popular method for reconstructing protein structures related to NMR experiment. However, due to the low quality of the reconstructed results, those methods were replaced by other dynamic methods such as ARIA, CYANA and UNIO. Recently, a new MC technique named Riemannian approach is introduced and proved mathematically, which promotes us to apply it in protein structure determination from NMR measurements. In this paper, by combining the Riemannian approach and some post-processing procedures together, we reconstruct the protein structures from the incomplete distance information measured by NMR. By evaluating our results and comparing with the corresponding PDB NMR deposits, we show that the current Riemannian approach method is valid and at least comparable with (if not better than) the state-of-art methods in NMR structure determination.
G1 length dictates heterochromatin landscape

Stem cells have lower facultative heterochromatin as defined by trimethylation of histone H3 lysine 27 (H3K27me3) compared to differentiated cells, however, the underlying mechanism for this observation has been unknown. Because H3K27me3 levels are diluted two-fold in every round of replication and then restored through the rest of the cycle, we reasoned that the cell cycle length could determine the time available for setting total H3K27me3 levels. Here, we demonstrate that a fast cell cycle sets low levels of H3K27me3 in serum-grown murine embryonic stem cells (mESCs). Extending the G1 phase leads to an increase in global H3K27me3 in mESCs due to the formation of de novo Polycomb domains, and the length of the G1/S block correlates with the extent of gain in H3K27me3, arguing that levels of the modification depend on the time available between successive rounds of replication. Similarly, accelerating the cell cycle in HEK293 cells decreases H3K27me3 levels. Finally, we applied this principle in tumor cells that, due to the dominant negative effect of the sub-stoichiometric H3K27M mutant, have reduced H3K27me3. Here, extending G1 using Palbociclib increased H3K27me3 levels, pointing to an unexpected means to rescue the effect of oncohistones. Our results suggest cell cycle length as a universal mechanism to modulate heterochromatin formation and, thus, cellular identity.
Permanent deconstruction of intracellular primary cilia in differentiating granule cell neurons

Primary cilia on granule cell neuron progenitors in the developing cerebellum detect sonic hedgehog to facilitate proliferation. Following differentiation, cerebellar granule cells become the most abundant neuronal cell type in the brain. While essential during early developmental stages, the fate of granule cell cilia is unknown. Here, we provide nanoscopic resolution of ciliary dynamics in situ by studying developmental changes in granule cell cilia using large-scale electron microscopy volumes and immunostaining of mouse cerebella. We found that many granule cell primary cilia were intracellular and concealed from the external environment. Cilia were disassembed in differentiating granule cell neurons in a process we call cilia deconstruction that was distinct from pre-mitotic cilia resorption in proliferating progenitors. In differentiating granule cells, ciliary loss involved unique disassembly intermediates, and, as maturation progressed, mother centriolar docking at the plasma membrane. Cilia did not reform from the docked centrioles, rather, in adult mice granule cell neurons remained unciliated. Many neurons in other brain regions require cilia to regulate function and connectivity. In contrast, our results show that granule cell progenitors had concealed cilia that underwent deconstruction potentially to prevent mitogenic hedgehog responsiveness. The ciliary deconstruction mechanism we describe could be paradigmatic of cilia removal during differentiation in other tissues.
Auditory Aversive Generalization Learning Prompts Threat-Specific Changes in Alpha-Band Activity

Pairing a neutral stimulus with aversive outcomes prompts neurophysiological and autonomic changes in response to the conditioned stimulus (CS+), compared to cues that signal safety (CS-). One of these changes—selective amplitude reduction of parietal alpha-band oscillations— has been reliably linked to processing of visual CS+. It is however unclear to what extent auditory conditioned cues prompt similar changes, how these changes evolve as learning progresses, and how alpha reduction in the auditory domain generalizes to similar stimuli. To address these questions, fifty-five participants listened to three sine wave tones, with either the highest or lowest pitch (CS+) being associated with a noxious white noise burst. A threat specific (CS+) reduction in occipital-parietal alpha-band power was observed similar to changes expected for visual stimuli. No evidence for aversive generalization to the tone most similar to the CS+ was observed in terms of alpha-band power changes, aversiveness ratings, or pupil dilation. By-trial analyses found that selective alpha-band changes continued to increase as aversive conditioning continued, beyond when participants reported awareness of the contingencies. The results support a theoretical model in which selective alpha power represents a cross-modal index of continuous aversive learning, accompanied by sustained sensory discrimination of conditioned threat from safety cues.
Gamified city for 6th graders : The effect of gameful experience on students’ 21st century readiness in Finland

Teachers are continuously challenged with questions of how to meaningfully convey skills of modern society, i.e., 21st century, to young children. Increasingly, gameful methods and playful learning environments are employed in formal education to enhance teaching. This paper examines a physical learning environment of Yrityskylä in Finland, which simulates a city where students act as employees and consumers through various gameful methods. We investigate the relation of 6th grade (12-year-old) students’ (N = 253) skill and attitude formation based on 21st century framework before and after attending the learning environment. Through Partial Least Squares (PLS) Structural Equation Modeling (SEM), the results show a positive association between gameful experience and all examined 21st century skills dimensions. Whilst it is important to consider the novelty effect and holistic nature of the school day spent in the gamified learning environment, our findings nevertheless indicate the potentiality such a day can have on young students.
A 30-Min Nucleic Acid Ampli ﬁ cation Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy

Background: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid ampli ﬁ cation test (NAAT)-based CT cartridge, delivering results in 30 min. Methods: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/ RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested “ fresh ” within 10 days of collection, or “ frozen ” at − 80 °C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. Results: CT prevalence was 7.2% (51/709) overall. Sensitivity, speci ﬁ city, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Con ﬁ dence Interval (CI): 86.5 – 99.5), 97.7% (95%CI: 96.3 – 98.7), 76.6% (95%CI: 64.3 – 86.2) and 99.7% (95%CI: 98.9 – 100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. Conclusions: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable speci ﬁ c treatment, initiation of partner noti ﬁ cation and appropriately intensive health promotion at the point of care. © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
Tritesting in Battor, Ghana: an integrated cervical precancer screening strategy to mitigate the challenges of multiple screening visits and loss to follow-up

Background Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detecting cervical precancer; however, increasing reports of high-risk HPV (hr-HPV)-negative cases of cervical intraepithelial neoplasia (CIN) and even malignancy motivate the use of combined testing. We present our experience with ‘tritesting’, defined as the performance of HPV DNA testing, cytology and visual inspection in a single session at the Cervical Cancer Prevention and Training Centre, Ghana. We further determined the prevalence rates of hr-HPV infection, abnormal cytology and cervical lesions among women screened using tritesting. Methods This descriptive retrospective cross-sectional study assessed all women screened via tritesting between April 2019 to April 2023. HPV DNA testing was performed using the Sansure MA-6000, GeneXpert or AmpFire platforms. Visual inspection was performed using enhanced visual assessment mobile colposcopy or visual inspection with acetic acid. Liquid-based cytology was performed using cervical samples taken with a Cervex-Brush® and fixed in PreservCyt, while samples for conventional cytology were taken using an Ayre spatula and cytobrush. Results Among 236 women screened (mean age, 39.1 years (standard deviation, 10.9)), the overall prevalence rates of hr-HPV infection and cervical lesions were 17.8% (95% confidence interval (CI), 13.1–23.3) and 11.9% (95% CI, 8.0–16.7), respectively. Cytology yielded findings of atypical squamous cells of undetermined significance or worse in 2.5% (95% CI, 0.9–5.5) of women. Histopathology following loop electrosurgical excision procedure revealed CIN I (tritest positive) and CIN III (hr-HPV-positive, visual inspection ‘positive’, cytology-negative) in one woman each. Factors independently associated with hr-HPV infection among ‘tritested’ women were age ≥ 39 years, tertiary level of education and current contraceptive use. Twenty-seven out of 39 hr-HPV-positive women (69.2%; 95% CI, 52.4–83.0) showed a type 3 transformation zone and would have needed to be recalled for a cytologic sample to be taken in a ‘see and triage’ approach with HPV DNA testing and a visual inspection method. Conclusion This study brings tritesting into the spotlight, as an alternative to other methods, particularly for women who prefer this due to the advantage of a single visit to a health facility and being more cost-effective, if they have to travel long distances to access cervical screening services.
Playing the Admissions Game: Student Reactions to Increasing College Competition.

Gaining entrance to a four-year college or university, particularly a selective institution, has become increasingly competitive over the last several decades. We document this phenomenon and show how it has varied across different parts of the student ability distribution and across region, with the most pronounced increases in competition being found among higher-ability students and in the Northeast. Additionally, we explore how the college preparatory behavior of high school seniors has changed in response to the growth in competition. We also discuss the theoretical implications of increased competition on longer-term measures of learning and achievement and attempt to test them empirically; the evidence and related literature, while limited, suggests little long-term benefit.
Nber Working Paper Series the Asset Cost of Poor Health

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Formation and Loss of Light Absorbance by Phenolic Aqueous SOA by OH and an Organic Triplet Excited State

phases with oxidants - such as hydroxyl radical ( ● OH) and organic triplet excited states ( 3 C*) - to form light-absorbing 15 secondary organic aerosol (SOA). These reactions in atmospheric aqueous phases, such as cloud/fog drops and aerosol liquid water (ALW), form aqueous SOA (aqSOA), i.e., low-volatility, high molecular weight products. While these are important routes of aqSOA formation, the light absorption and lifetimes of the BrC formed are poorly characterized. To study these aspects, we monitored the formation and loss of light absorption by aqSOA produced by reactions of six highly substituted phenols with ● OH and 3 C*. While the parent phenols absorb very little tropospheric sunlight, they are oxidized to aqSOA that 20 can absorb significant amounts of sunlight. The extent of light absorption by the aqSOA depends on both the ArOH precursor and oxidant: more light-absorbing aqSOA is formed from more highly substituted phenols and from triplet reactions rather than ● OH. Under laboratory conditions, continued reactions with ● OH diminish sunlight absorption by aqSOA on timescales of hours, while continued reactions with 3 C* reduce light absorption much more slowly. Estimated lifetimes of light-absorbing phenolic aqSOA range from 3 to 13 hours in cloud
Characterization of Selected Soybean Germplasm through Fatty Acid and Oil Composition using Near-Infrared Spectroscopy

: Soybean belongs to legumes and is said to be one of the best sources of oil and fats. The objective of this research was to identify specific and individual accession among the fifty soybean accessions collected from Plants Genetics Research Institute (PGRI) Islamabad for oil contents and fatty acids profile using near-infrared reflectance spectroscopy. The amount of oil content in 50 soybean accessions was recorded in the range of 13.816-23.40 % among which accessions 017421, 17423, 17430, 17435, and 17459 were found with the highest percentage of 23.4 %, 22.80 %, 22.214 %, 22.105 %, and 22.08 % respectively. The values of fatty acid content in these accessions for palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), linoleic acid (18:2) and linolenic acid (18:3) ranged between 10.077-18.48%, 1.95-5.88 %, 18.204-30.12 %, 22.756-53.879 % and 4.714-9.96 % respectively. Soybean accessions observed higher for oil content are recommended for cultivation; where it is grown for oil production. Based on essential fatty acids contents, accessions 017418 and 017420 are recommended for a future breeding program to improve human health. Due to the variability identified in the present research, it is critical to select single Soybean accession having all the traits for further breeding programs until a specific trait is chosen.