Miracle-dz/UniFAR-FTUs huggingface dataset:
Curiosity eliminates the exploration-exploitation dilemma

In this paper we offer an unconventional perspective on the exploration-exploitation dilemma. We offer this because exploratory behavior in animals can have two different explanations. If environmental rewards are expected by the animal, then exploration is cast as a search for those rewards (1–6). Rewards are how most studies of exploration are framed (2). If instead, there is no reason to expect rewards from the environment, then exploration is a search for information, or curiosity (7–13). Exploitation has one definition, taking the most rewarding action. It is always the opposite of exploration. An open problem is to unify these opposites, exploration with exploitation. But past attempts at such a union have focused on exploration-for-rewards which in turn leads to the explorationexploitation dilemma, which is an intractable mathematical problem (14–19). We illustrate this in Figure 1a. Here we offer an alternative approach by unifying exploitation with pure curiosity instead. We illustrate this in Figure 1b. We will prove this take on a union is tractable. We are interested in curiosity because it is a universal drive, though the definition of what curiosity is remains open. Curiosity can be triggered by an incongruity, or novelty and surprise, or by a gap in knowledge, a prediction error, or by the potential usefulness of some knowledge (9, 20–28). Here we will take an even more general position than these definitions. We argue that curiosity can be recognized by an animal pursuing learning for learning’s sake. Even though this definition is both abstract and recursive, we show it lends itself to a precise mathematical form. Curiosity the drive is as strong as the drive for collecting environmental rewards, if not stronger (7, 9, 11, 12, 25, 29– 32). Furthermore, in studies with artificial agents curiosity-like algorithms are highly effective at solving difficult optimization problems (8, 33–40). In other words, we are interested because curiosity is universal and because it works. This paper consists of a mathematical study of information Fig. 1. Two views of exploration and exploitation. a. The dilemma: either exploit an action with a known reward (e.g., return to the previous flower) or explore other actions on the chance they will return a better outcome. The central challenge here is that the outcome of exploration is uncertain, intractable, and filled with questions. b. Our alternative view of the dilemma, with two goals: either exploit rewards or explore to maximize information value, with a curious search of the environment. The solution we propose to this alternative view is to pursue either information value, or reward value, depending on which is expected to be larger. In other words, we set information and reward on equal terms and propose a greedy solution to choose between them. Artist credit : Richard Grant.
1,3,4-OXADIAZOLE: A THERAPEUTICAL EMERGING SCAFFOLD

Abstrac t-The five-membered heterocyclic ring oxadiazole symbolizes the significance of a structural key in pharmaceutical and medicinal chemistry. Four distinct isomers of oxadiazole exist 1,2,3-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole and 1,2,4-oxadiazole. Due to their extensive spectrum of chemical and biological properties, the 1,3,4-oxadiazole and 1,2,4-oxadiazole are better and are extensively investigated by researchers. The aromatic heterocyclic 1,3,4-oxadiazole has two nitrogen and one oxygen in its nucleus. The nucleus of the 1,3,4-oxadiazole is a biological scaffold with a wide range of pharmacological activities such as anti-cancer, anti-inflammation, analgesic, anti-HIV, anti-bacterial, anti-hypertensive, anti-tubercular, ant-microbial, anti-helminthic, anti-oxidant, anti-diabetic, anti-viral, anti-parkinsonian and anti-convulsant etc. The 1,3,4-oxadiazole scaffold is present in many marketed formulations such as nitrofuran derivative (Furamizole) which has potent anti-bacterial activity, Raltegravir as an anti-viral treatment, Nesapidil as an anti-hypertensive and Zobitentan as an anti-cancer medication. The 1,3,4-oxadiazole nucleus drew researchers from around the world to work in this field of developing new drugs. The present review summarized some pharmacological activities and various synthesis routes for 2
Changes in the vertical distribution of ozone over Canada from ozonesondes: 1980-2001

[1] Measurements of the vertical profile of ozone concentration using balloon-borne ECC ozonesondes have been made weekly since 1980 at several sites in Canada (Edmonton, Goose Bay, Churchill, and Resolute), since 1987 at Alert, and since 1992 at Eureka. Previous analyses of ozone trends over Canada have shown strong negative trends in tropospheric ozone. We present here a new analysis of trends in the vertical distribution of ozone with data up to the end of 2001. In addition, more detailed attention is paid to some potential sources of bias: total ozone correction, background current correction, and time-of-launch (diurnal) variation. For the 1980–2001 period the overall linear trends are primarily negative, both in tropospheric and stratospheric ozone. However, when the data for 1991–2001 only are considered, the trends are positive, even in the lower stratosphere. When the time series are compared with previously reported trends (to 1993), it is evident that ozone has rebounded at all levels below about 63 hPa. These differences do not appear to be related to changes in tropopause height, as the average height of the tropopause (as measured over the ozonesonde stations) has not changed over either the 22-year or the 11-year period. Nevertheless, comparison with another dynamical indicator, the wintertime frequency of occurrence of laminae in the ozone profile, suggests that this rebound may be partly a result of small changes in the atmospheric circulation, rather than a recovery of the ozone layer from halocarbon-induced depletion. The long-term trends in average tropospheric ozone concentrations over Canada are similar to corresponding lower stratospheric trends, and tropospheric ozone levels show significant correlation with lower stratospheric ozone amounts.
Mechanical Signals Inhibit Growth of a Grafted Tumor In Vivo: Proof of Concept

In the past ten years, many studies have shown that malignant tissue has been “normalized” in vitro using mechanical signals. We apply the principles of physical oncology (or mechanobiology) in vivo to show the effect of a “constraint field” on tumor growth. The human breast cancer cell line, MDA MB 231, admixed with ferric nanoparticles was grafted subcutaneously in Nude mice. The magnetizable particles rapidly surrounded the growing tumor. Two permanent magnets located on either side of the tumor created a gradient of magnetic field. Magnetic energy is transformed into mechanical energy by the particles acting as “bioactuators”, applying a constraint field and, by consequence, biomechanical stress to the tumor. This biomechanical treatment was applied 2 hours/day during 21 days, from Day 18 to Day 39 following tumor implantation. The study lasted 74 days. Palpable tumor was measured two times a week. There was a significant in vivo difference between the median volume of treated tumors and untreated controls in the mice measured up to D 74 (D 59 + population): (529 [346; 966] mm3 vs 1334 [256; 2106] mm3; p=0.015), treated mice having smaller tumors. The difference was not statistically significant in the group of mice measured at least to D 59 (D 59 population). On ex vivo examination, the surface of the tumor mass, measured on histologic sections, was less in the treated group, G1, than in the control groups: G2 (nanoparticles, no magnetic field), G3 (magnetic field, no nanoparticles), G4 (no nanoparticles, no magnetic field) in the D 59 population (Median left surface was significantly lower in G1 (5.6 [3.0; 42.4] mm2, p=0.005) than in G2 (20.8 [4.9; 34.3]), G3 (16.5 [13.2; 23.2]) and G4 (14.8 [1.8; 55.5]); Median right surface was significantly lower in G1 (4.7 [1.9; 29.2] mm2, p=0.015) than in G2 (25.0 [5.2; 55.0]), G3 (18.0 [14.6; 35.2]) and G4 (12.5 [1.5; 51.8]). There was no statistically significant difference in the day 59+ population. This is the first demonstration of the effect of stress on tumor growth in vivo suggesting that biomechanical intervention may have a high translational potential as a therapy in locally advanced tumors like pancreatic cancer or primary hepatic carcinoma for which no effective therapy is currently available.
Lithospheric-scale analogue modelling of collision zones with a pre-existing weak zone

Abstract Lithospheric-scale analogue experiments have been conducted to investigate the influence of strength heterogeneities on the distribution and mode of crustal-scale deformation, on the resulting geometry of the deformed area, and on its topographic expression. Strength heterogeneities were incorporated by varying the strength of the crust and upper mantle analogue layers and by implementing a weak plate or part-of-a-plate between two stronger ones. Three (brittle crust/viscous crust/strong viscous upper mantle) and four (brittle crust/viscous crust/brittle upper mantle/strong viscous upper mantle) layer models were confined by a weak silicone layer on one side in order to contain but not oppose lateral extrusion. Experimental results show that relative strength contrasts between converging plates and intervening weak plates control the location and the shape of deformation sites taken as ‘collision orogens’. If the contrast is small, internal deformation of the strong plates through fore- and backthrusting occurs early in the deformation history. However, the bulk system is dominated by buckling that nucleates on the weak plate whose antiformal topography is highest; model Moho of the bordering stronger plates is deepest under these conditions. If the contrast is large, deformation remains localized within the weak plate for a larger amount of shortening and develops a root zone below a narrow deformation belt, which coincides with the locus of maximum topography. Implementing a buoyant, low-viscosity layer above the model Moho of the weak plate favours the development of asymmetric model orogens notwithstanding the initial symmetric setup. Once the asymmetry is established strain remains localized in thrust faults and ductile shear zones documenting foreland directed displacement of the model orogen. Such laterally and vertically irregular configurations have applications in continent-continent collision settings such as the Eastern Alps. First-order mechanical boundary conditions recognized from modelling to be favourable to the post early Oligocene tectonics of the Eastern Alps include: (1) subtle rather than high-strength contrasts between the Adriatic indentor and the strongly deformed region comprising Penninic and Austroalpine units to the north of it; (2) decoupling of Penninic continental upper crust from its substratum to allow for crustal-scale buckling of the Tauern Window; (3) weak mechanical behaviour of the European lower crust during collision to account for its constant thickness along the TRANSALP deep seismic transect; and (4) the direct continuation of the basal detachment underlying the fold and thrust belt in the hangingwall of the European plate with a wide ductile shear zone in the core of the orogen, which separates the European from the Adriatic plate.
Case report: Whole-exome sequencing identifies a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and sudden cardiac death

Background Desmin is an intermediate filament protein that plays a critical role in the stabilization of the sarcomeres and cell contacts in the cardiac intercalated disk. Mutated DES gene can cause hereditary cardiomyopathy with heterogeneous phenotypes, while the underlying molecular mechanisms requires further investigation. Methods We described a Chinese family present with cardiomyopathy and sudden cardiac death (SCD). Whole-exome sequencing (WES) and bioinformatics strategies were employed to explore the genetic entity of this family. Results An unknown heterozygote missense variant (c.1300G > A; p. E434K) of DES gene was identified. The mutation cosegregates in this family. The mutation was predicted as pathogenic and was absent in our 200 healthy controls. Conclusion We identified a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and SCD. Our study not only provided a new case for the study of the relationship between DES mutations and hereditary cardiomyopathy but also broadened the spectrum of DES mutations.
The Science o f Human Information Seeking

The following copyright notice is a publisher requirement: This book chapter has been published in The Drive for Knowledge: The Science of Human Information Seeking edited by Irene Cogliati Dezza, Eric Schulz and Charley M. Wu, https://doi.org/10.1017/9781009026949. This version is free to view and download for private research and study only. Not for re-distribution or re-use. © 2022 Cambridge University Press
Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol

Introduction Primary sclerosing cholangitis (PSC) is a progressive inflammatory liver disease characterised by relentless liver fibrosis and a high unmet need for new therapies. Preventing fibrosis represents an important area of interest in the development of vital new drugs. Vascular adhesion protein-1 (VAP-1) drives inflammation in liver disease, and provision of an antibody against VAP-1 blunts fibrosis in murine models of liver injury. Methods and analysis BUTEO is a single-arm, two-stage, open-label, multi-centre, phase II clinical trial. Up to 59 patients will receive treatment with anti-VAP monoclonal antibody, BTT1023, over a 78-day treatment period. Adults with PSC and a serum alkaline phosphatase (ALP) of at least 1.5 times the upper limit of normal will be included. Our primary outcome measure is a reduction in ALP by >25% from baseline to Day 99. Secondary outcome measures include safety and tolerability, changes pre therapy/post therapy in circulating serum VAP-1 as well as imaging findings. The first patient participant was recruited on 08 September 2015. Ethics and dissemination This protocol has been approved by the Research Ethics Committee (REC, reference 14/EM/1272). The first REC approval date was 06 January 2015 with three subsequent approved amendments. This article refers to protocol V3.0, dated 16 March 2016. Results will be disseminated via peer-reviewed publication and presentation at international conferences. Trial registration The trial is registered with the European Medicines agency (EudraCT: 2014-002393-37), the National Institute for Health Research (Portfolio ID: 18051) and ISRCTN: 11233255. The clinicaltrials.gov identifier is NCT02239211. Pre-results.
Cognitive Linguistics

Because they involve individual-level cognitive processes, psychological explanations of linguistic phenomena are in principle testable against individual behaviour. The present study draws on patterns of individual variation in corpus data to test explanations of productivity. Linguistic patterns are predicted to become more productive with higher type frequencies and lower token frequencies. This is because the formation of abstract mental representations is encouraged by varied types but counteracted by automation of highfrequency types. The predictions are tested for English -ly and -ness-derivation, as used by 698 individual journalists in the New York Times Annotated Corpus and 171 members of Parliament in the Hansard Corpus. Linear regression is used to model individual variation in productivity, in relation to type and token frequency, as well as several other predictor variables. While the expected effects are observed, there is also robust evidence of an interaction effect between type and token frequency, indicating that productivity is highest for patterns with many types and not-too-infrequent tokens. This fits best with a view of entrenchment as both a conservative and creative force in language. Further, some variation remains irreducibly individual and is not explained by currently known predictors of productivity.
Catchment export of carbon, nitrogen, and phosphorus across an agro‐urban land use gradient, Swan‐Canning River system, southwestern Australia

[1] Coastal regions in many regions of the world are under increasing pressure from the expansion of agriculture and urbanization associated with elevated N and P loading and eutrophication of coastal estuaries. I compared how mixed land use catchments deliver dissolved and particulate forms of C, N, and P in streamflow to the Swan-Canning estuary that bisects Perth, Western Australia. Dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) composed the majority of the total C and N load, particulate C and N fluxes were minor, and P fluxes were evenly split between soluble reactive phosphorus and particulate/organic P. In contrast to current biogeochemical theory, DON export was dominant in urban and agricultural catchments in the low-gradient environment of the Swan Coastal Plain, whereas NO3 export was a greater factor in higher-gradient, forested catchments on the urban fringe. This trend suggests that hydrologic conditions that supported coastal wetlands prior to human development may still promote DON mobilization as well as dissolved inorganic nitrogen loss along hydrologic flow paths. Substantial variability in export of C, N, and P across catchments highlights the unique hydrologic properties of Australian catchments. Areal C, N, and P export was significantly related to catchment runoff which was lowest in a catchment with inland drainage, but greatest in urban catchments with impervious surfaces and shallow groundwater. The effective delivery of DOC and DON to aquatic ecosystems in urbanizing coastal catchments underscores the importance of restoration efforts that address hydrologic retention as well as the source and bioavailability of dissolved organic matter.
Socially Shared Metacognitive Regulation in Asynchronous CSCL in Science: Functions, Evolution and Participation

The significance of socially shared metacognitive regulation (SSMR) in collaborative learning is gaining momentum. To date, however, there is still a paucity of research of how SSMR is manifested in asynchronous computer-supported collaborative learning (CSCL), and hardly any systematic investigation of SSMR’s functions and evolution across different phases of complex collaborative learning activities. Furthermore, how individual students influence group regulatory effort is not well known and even less how they participate in SSMR over the entire collaborative learning process. The multi-method, in-depth case study presented in this article addresses these gaps by scrutinizing the participation of a small group of students in SSMR in asynchronous computer supported collaborative inquiry learning. The networked discussion, consisting of 640 notes, was used as baseline data. The sets of notes, which formed nine SSMR threads, were identified and their functions analyzed. Several analytical methods, including social network analysis, were used to investigate various aspects of individual participation. The findings show that some SSMR threads lasted over an extended period, and they sometimes intertwined or overlapped. Furthermore, SSMR threads were found to play different functions, mainly inhibiting the perceived inappropriate direction of the ongoing cognitive process. Finally, SSMR was found in all phases of the process – but with some variation. The use of different analytical methods was critical as this provided a variety of complementary insights into students’ participation in SSMR. The value of using multiple, rigorous analytical methods to understand SSMR’s significance over the entire course of an asynchronous CSCL activity is discussed.
The experimental watersheds in Slovenia

Experimental watersheds are critical to the advancement of hydrological science. By setting up three experimental watersheds, Slovenia also obtained its grounds for further development of the science and discipline. In the Dragonja experimental watershed the studies are focused on the afforestation of the watershed in a mediterranean climate, on the Reka river the water balance in a partly karstic area is examined, and on the case of the Glinscica stream the implications of the urban environment are studied. We have obtained valuable experience and tested new measuring equipment on all three experimental watersheds. Measurements and analysis on the experimental watersheds improved the current understanding of hydrological processes. They resulted in several PhD Theses, Master Theses and scientific articles. At the same time the experimental watersheds provide support to the teaching and studying process.
Empirical analysis of the impact of enterprise digital transformation on the composition of the technicist

: The process of digital transformation is gaining importance as a result of the current trend of the expanding digital economy and the rapid expansion of the digital economy.By constructing the index of digital transformation of enterprises through the text of the annual report of listed enterprises, the quasi-benchmark regression method is used to study the influence of the composition of technical personnel of enterprises on digital transformation. The final conclusion of the paper is that the digital transformation of enterprises has a certain impact on the proportion of enterprise technicians in general. In large enterprises, the digital transformation affects the recruitment of technical personnel and thus affects the enterprise structure, while in small and medium-sized enterprises, the degree of digital transformation does not significantly improve the recruitment of technical personnel in enterprises, but has an inhibiting effect.
Primary factors governing hydraulic fractures in heterogeneous stratified porous formations

Some primary material, macrostructural and tectonic features of typical geological formations are identified, insofar as they affect the hydraulic fracturing operation whereby suitably treated fluid is pumped into massive crack(s) underground: the retardation or channeling due to strata interfaces, discontinuities and other heterogeneities is roughly characterized, in the context of fully three-dimensional crack shape evolution, and the initiation from oriented boreholes is discussed in detail. A general-purpose numerical scheme is described, efficiently based on a physically transparent distribution of discontinuity multipoles (or dislocations) and the solution of resulting singular integral equations, which permits precise quantification of these effects: in particular, the barriers provided by adjacent stiffer and tougher strata are properly rationalized and the roles of inelastic slippage, blunting, branching, arrest, and re-initiation are placed in more transparent perspective. Stabilization effects due to alterations of pore-fluid pressure (and hence effective decohering stress), or the flux of formation fluid into the open region near to the crack tip, are described as potentially unfavorable for hydrofrac containment. However, the dominant time-dependent mechanism of frac fluid penetration into the narrow crack aperture attracts most attention: this process is very naturally and tractably incorporated in our comprehensive numerical formulation so that realistic simulation ofmore » actual field operations should be feasible in the near future. « less