Miracle-dz/UniFAR-FTUs huggingface dataset:
On Average-Case Hardness of Higher-Order Model Checking

We study a mixture between the average case and worst case complexities of higher-order model checking, the problem of deciding whether the tree generated by a given λ Y-term (or equivalently, a higher-order recursion scheme) satisfies the property expressed by a given tree automaton. Higher-order model checking has recently been studied extensively in the context of higher-order program verification. Although the worst-case complexity of the problem is k-EXPTIME complete for order-k terms, various higher-order model checkers have been developed that run efficiently for typical inputs, and program verification tools have been constructed on top of them. One may, therefore, hope that higher-order model checking can be solved efficiently in the average case, despite the worst-case complexity. We provide a negative result, by showing that, under certain assumptions, for almost every term, the higher-order model checking problem specialized for the term is k-EXPTIME hard with respect to the size of automata. The proof is based on a novel intersection type system that characterizes terms that do not contain any useless subterms.
Implementation and sustainability of a medication reconciliation toolkit: A mixed methods evaluation.

PURPOSE MARQUIS (Multi-Center Medication Reconciliation Quality Improvement Study) provided participating hospitals with a toolkit to assist in developing robust medication reconciliation programs. Here we describe hospitals' implementation of the MARQUIS toolkit, barriers and facilitators, and important factors that may enhance the spread and sustainability of the toolkit. METHODS We used a mixed methods, quantitative-qualitative study design. We invited site leaders of the 5 hospitals that participated in MARQUIS to complete a Web-based survey and phone interview. The Consolidated Framework for Implementation Research guided question development. We analyzed the collected data using descriptive statistics (for survey responses) and thematic content analysis (for interview results). RESULTS Site leaders from each MARQUIS hospital participated. They reported that MARQUIS toolkit implementation augmented their hospitals' existing but limited medication reconciliation practices. Survey results indicated executive leadership support for toolkit implementation but limited institutional support for hiring staff (reported by 20% of respondents) and/or budgetary support for implementation (reported by 60% of respondents). Most participating hospitals (80%) shifted staff responsibilities to support medication reconciliation. Interview findings showed that inner setting (ie, organizational setting) and process factors (eg, designation of champions) both inhibited and facilitated implementation. Hospitals adopted a variety of toolkit interventions (eg, discharge medication counseling) using a range of implementation strategies, including development of educational tools and tip sheets for staff members and electronic health record templates. CONCLUSION Despite limited institutional support, hospitals can successfully implement, spread, and sustain the MARQUIS toolkit by shifting staff responsibilities, adding pharmacy staff, and using a variety of strategies to facilitate implementation. Although leadership support and resources for data collection and dissemination facilitated implementation, limited staff buy-in and competing priorities may hinder implementation.
Basic fibroblast growth factor improves cellular immunological functions in mice

Basic fibroblast growth factor (bFGF, FGF-2) is a multifunctional growth factor that has been proved to have important roles in various tissues. Background researches revealed that biological functions of B and T lymphocytes producing bFGF and its receptors were regulated by the cytokine, which implied that bFGF may participate in immune defense. In order to investigate the effects of bFGF on immune functions, the present paper employed mice administrated with bFGF to detect phagocytosis of macrophages, activity of natural killer cell and number of antibody-producing cells in vivo as well as proliferation of spleen cells in vitro. Results showed that the four detected parameters were all significantly upregulated in bFGFtreated mice, which suggested an active role of bFGF occurring in cellular immunity of mice. Moreover, the increment of plaques formed by antibody-producing cells implied that bFGF also has a positive effect upon humoral immunity.
Compatibility investigation for a new antituberculotic fixed dose combination with an adequate drug delivery

Abstract The compatibility of formulation components is crucial for safe and high-quality medicines. To detect the potential for incompatibility and to assess formulation stability, it is beneficial to conduct a compatibility study during the drug development phase. The therapy of tuberculosis normally consists of two or more medicines taken together. Consequently, different antituberculotic fixed-dose combination (FDC) formulations have been developed. Isoniazid is first-line medicine and present in several FDCs. Low bioavailability due to the active substances’ incompatibility in acidic medium was reported for some of these FDC forms. Rifabutin, also a first-line antituberculotic, is available in the market as a single component formulation. This study presents compatibility testing of these two active substances for a new FDC and evaluates the impact of the most common solid dosage forms’ excipients on the stability of two active substances. The potential for interaction between the formulation components was analyzed by the UHPLC method. One degradation product and one interaction product were observed and further characterized by high-resolution mass spectrometry. Still, significant degradation of two active substances, such as reported in marketed FDC formulations was not detected for this combination. The stability and drug delivery of the proposed combination were confirmed by the dissolution test in acidic medium.
A REVIEW O PHYTOCHEMICAL AD PHARMACOLOGICAL PROFILE OF EUPHORBIA TIRUCALLI

Summary Euphorbia tirucalli is an ornamental plant commonly known as Aveloz. The plant belongs to Euphorbiaceae family. The species of Euphorbiaceae is extensively used as a folk remedy by local population of many countries to cure numerous diseases such as cancer, diabetes, diarrhoea, heart diseases, hemorrhages, hepatitis, jaundice, malaria, ophthalmic diseases, rheumatism and scabies etc., E. tirucalli is studied extensively by advanced scientific techniques and various bioactive constituents have been isolated from different parts of the plant and analyzed pharmacologically. The plant is reported for hepatoprotective, antimicrobial, antioxidant, insecticidal, larvicidal, molluscicide and antiarthritic activity. The medicinal properties of this plant indicate it as a valuable source of medicinal compound. This study is overall information concerning the ethnobotany, phytochemistry, pharmacology and biological activities of E. tirucalli.
Does Microscopic Extrathyroidal Extension Confer a Higher Risk of Recurrence in Patients With Well-Differentiated Thyroid Cancer?

ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA © Endocrine Society 2020. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Received 3 September 2019. Accepted 31 May 2020. First Published Online 29 June 2020. Corrected and Typeset 10 July 2020. Does Microscopic Extrathyroidal Extension Confer a Higher Risk of Recurrence in Patients With Well-Differentiated Thyroid Cancer?
Bulk Spin Torque‐Driven Perpendicular Magnetization Switching in L10 FePt Single Layer

Due to its inherent superior perpendicular magnetocrystalline anisotropy, the FePt in L10 phase enables magnetic storage and memory devices with ultrahigh capacity. However, reversing the FePt magnetic state, and therefore encoding information, has proven to be extremely difficult. Here, it is demonstrated that an electric current can exert a large spin torque on an L10 FePt magnet, ultimately leading to reversible magnetization switching. The spin torque monotonically increases with increasing FePt thickness, exhibiting a bulk characteristic. Meanwhile, the spin torque effective fields and switching efficiency increase as the FePt approaches higher chemical ordering with stronger spin–orbit coupling. The symmetry breaking that generates spin torque within L10 FePt is shown to arise from an inherent structural gradient along the film normal direction. By artificially reversing the structural gradient, an opposite spin torque effect in L10 FePt is demonstrated. At last, the role of the disorder gradient in generating a substantial torque in a single ferromagnet is supported by theoretical calculations. These results will push forward the frontier of material systems for generating spin torques and will have a transformative impact on magnetic storage and spin memory devices with simple architecture, ultrahigh density, and readily application.
Influence of the accumulation of phosphate and magnesium ions in the yeast cells on the ethanol productivity in batch ethanol fermentation

The accumulation of phosphate and magnesium in the yeast cells is not necessary to assure the ethanol productivity of batch ethanol fermentations. To avoid the decrease of the ethanol productivity it was sufficient to use a fermentation medium containing calculated concentrations of phosphorus and magnesium sources in order to maintain practically constant the phosphorus and magnesium initial contents of the biomass during the fermentation.
Interactions Between Predator Kairomone and Food Level Complicate the Ecological Interpretation of Daphnia Laboratory Results

The effect of food concentration on the phenotypic response of life history traits to two predator kairomones was investigated in Daphnia. For the experiment, one clone of Daphnia galeata was used as the prey organism and solutions containing infochemicals (kairomones) of Chaoborus (phantom midge) and Perca (perch) simulated the presence of potential predators. The combined effect of food level and predator kairomone on phenotypic plasticity of Daphnia life history is complex. At low food levels, the responses in life history traits to kairomones are enhanced. For example, in the Perca treatment, this leads to a younger age at first reproduction. The presence of Chaoborus kairomone decreases survival so that death often occurs before reproduction is reached. This results in a strong decrease in the intrinsic rate of population increase and might contribute to the pronounced summer decline of some Daphnia populations during periods of food shortage.
Upregulation of Alzheimer's Disease Amyloid-β Protein Precursor in Astrocytes Both in vitro and in vivo.

BACKGROUND The amyloid cascade hypothesis of Alzheimer's disease (AD) posits that amyloid-β (Aβ) protein accumulation underlies the pathogenesis of the disease by leading to the formation of amyloid plaques, a pathologic hallmark of AD. Aβ is a proteolytic product of amyloid-β protein precursor (AβPP; APP), which is expressed in both neurons and astrocytes. Although considerable evidence shows that astrocytes may play critical roles in the pathogenesis of AD, the longitudinal changes of amyloid plaques in relationship to AβPP expression in astrocytes and cellular consequences are largely unknown. OBJECTIVE Here, we aimed to investigate astrocyte-related pathological changes of Aβ and AβPP using immunohistochemistry and biochemical studies in both animal and cell models. METHODS/RESULTS Weutilized 5XFAD transgenic mice and found age-dependent upregulation of AβPP in astrocytes demonstrated with astrocytic reactive properties, which followed appearance of amyloid plaques in the brain. We also observed that AβPP proteins presented well-defined punctate immuno reactivity in young animals, whereas AβPP staining showed disrupted structures surrounding amyloid plaques in older mice. Moreover, we utilized astrocyte cell models and showed that pretreatment of Aβ42 resulted in downstream astrocyte autonomous changes, including up regulation in AβPP and BACE1 levels, as well as prolonged amyloidogenesis that could be reduced by pharmacological inhibition of BACE1. CONCLUSION Collectively, our results show that age-dependent AβPP up regulation in astrocytes is a key feature in AD, which will not only provide novel insights for understanding AD progression, but also may offer new therapeutic strategies for treating AD.
NELL2 Function in Axon Development of Hippocampal Neurons

Neurons have multiple dendrites and single axon. This neuronal polarity is gradually established during early processes of neuronal differentiation: generation of multiple neurites (stages 1-2); differentiation (stage 3) and maturation (stages 4-5) of an axon and dendrites. In this study, we demonstrated that the neuron-specific n-glycosylated protein NELL2 is important for neuronal polarization and axon growth using cultured rat embryonic hippocampal neurons. Endogenous NELL2 expression was gradually increased in parallel with the progression of developmental stages of hippocampal neurons, and overexpression of NELL2 stimulated neuronal polarization and axon growth. In line with these results, knockdown of NELL2 expression resulted in deterioration of neuronal development, including inhibition of neuronal development progression, decreased axon growth and increased axon branching. Inhibitor against extracellular signal-regulated kinase (ERK) dramatically inhibited NELL2-induced progression of neuronal development and axon growth. These results suggest that NELL2 is an important regulator for the morphological development for neuronal polarization and axon growth.
A Probabilistic Higher-Order Fixpoint Logic

We introduce PHFL, a probabilistic extension of higher-order fixpoint logic, which can also be regarded as a higher-order extension of probabilistic temporal logics such as PCTL and the $\mu^p$-calculus. We show that PHFL is strictly more expressive than the $\mu^p$-calculus, and that the PHFL model-checking problem for finite Markov chains is undecidable even for the $\mu$-only, order-1 fragment of PHFL. Furthermore the full PHFL is far more expressive: we give a translation from Lubarsky's $\mu$-arithmetic to PHFL, which implies that PHFL model checking is $\Pi^1_1$-hard and $\Sigma^1_1$-hard. As a positive result, we characterize a decidable fragment of the PHFL model-checking problems using a novel type system.
Red blood cell-mediated S-nitrosohemoglobin-dependent vasodilation: lessons learned from a β-globin Cys93 knock-in mouse.

SIGNIFICANCE RBC mediated vasodilation plays an important role in oxygen delivery. This occurs through hemoglobin actions, at least in significant part, to convert heme-bound NO (in T/Deoxy-state hemoglobin) into vasodilator S-nitrosothiol (SNO) (in R/Oxy-state hemoglobin), convey SNO through the bloodstream, and release it in tissues to increase blood flow. The coupling of hemoglobin R-T state allostery, both to NO conversion into SNO and to SNO release (along with oxygen) under hypoxia supports the model of a 3-gas respiratory cycle (O2/NO/CO2). Recent Advances: Oxygenation of tissues is dependent on a single, strictly conserved Cys residue in hemoglobin (βCys93). Hemoglobin couples SNO formation/release at βCys93 to O2 binding/release at hemes ('thermodynamic linkage'). Mice bearing βCys93Ala hemoglobin unable to generate SNO-βCys93 establish that SNO-hemoglobin is important for R-T allostery-regulated vasodilation by RBCs that couples blood flow to tissue oxygenation. CRITICAL ISSUES The model for RBC-mediated vasodilation originally proposed by Stamler and colleagues in 1996 has been largely validated: SNO-βCys93 forms in vivo, dilates blood vessels and is hypoxia-regulated, and RBCs actuate vasodilation proportionate to hypoxia. Numerous compensations in βCys93Ala animals to alleviate tissue hypoxia (discussed herein) are predicted to preserve vasodilatory responses of RBCs, but impair linkage to R/T transition in hemoglobin. This is borne out by loss of responsivity of mutant RBCs to oxygen, impaired blood flow responses to hypoxia, and tissue ischemia in βCys93-mutant animals. FUTURE DIRECTIONS SNO-hemoglobin mediates hypoxic vasodilation in the respiratory cycle. This fundamental physiology promises new insights in vascular diseases and blood disorders.
Understanding Side-Effect Intentionality Asymmetries: Meaning, Morality, or Attitudes and Defaults?

People frequently label harmful (but not helpful) side effects as intentional. One proposed explanation for this asymmetry is that moral considerations fundamentally affect how people think about and apply the concept of intentional action. We propose something else: People interpret the meaning of questions about intentionally harming versus helping in fundamentally different ways. Four experiments substantially support this hypothesis. When presented with helpful (but not harmful) side effects, people interpret questions concerning intentional helping as literally asking whether helping is the agents’ intentional action or believe questions are asking about why agents acted. Presented with harmful (but not helpful) side effects, people interpret the question as asking whether agents intentionally acted, knowing this would lead to harm. Differences in participants’ definitions consistently helped to explain intentionality responses. These findings cast doubt on whether side-effect intentionality asymmetries are informative regarding people’s core understanding and application of the concept of intentional action.
Lateralization of attention in adults with ADHD: Evidence of pseudoneglect

Abstract Background. We investigated whether adults with attention-deficit/hyperactivity disorder (ADHD) show pseudoneglect—preferential allocation of attention to the left visual field (LVF) and a resulting slowing of mean reaction times (MRTs) in the right visual field (RVF), characteristic of neurotypical (NT) individuals —and whether lateralization of attention is modulated by presentation speed and incentives. Method. Fast Task, a four-choice reaction-time task where stimuli were presented in LVF or RVF, was used to investigate differences in MRT and reaction time variability (RTV) in adults with ADHD (n = 43) and NT adults (n = 46) between a slow/no-incentive and fast/incentive condition. In the lateralization analyses, pseudoneglect was assessed based on MRT, which was calculated separately for the LVF and RVF for each condition and each study participant. Results. Adults with ADHD had overall slower MRT and increased RTV relative to NT. MRT and RTV improved under the fast/incentive condition. Both groups showed RVF-slowing with no between-group or between-conditions differences in RVF-slowing. Conclusion. Adults with ADHD exhibited pseudoneglect, a NT pattern of lateralization of attention, which was not attenuated by presentation speed and incentives.
The FTO gene is not associated with weight gain during 6 years of observation in population of PURE study in Poland

Introduction: We present the first longitudinal study in Poland analysing the association between fat mass and obesity-associated gene (FTO) polymorphism and changes in anthropometric parameters. Material and methods: 1120 participants of the Prospective Urban Rural (PURE) study in Poland (mean age 53.7 years) were genotyped for FTO gene polymorphism (rs9939609, rs9930506, rs1421085, rs1121980). Anthropometric parameters were measured at three time points (baseline, after three years, and after six years of observation).
Sexual Dimorphism and the Making of Oversized Male Characters in Beetles (Coleoptera)

Abstract Sexual dimorphism and the origin of conspicuous male characters in animals have been a major topic of evolutionary biology. Beetles (Coleoptera) possibly represent the greatest number and diversity of sexually dimorphic species. Yet, their features and the origin of oversized male apparatus are not fully understood. Morphological observations of 349 species and subspecies were used to describe the general features of sexual dimorphism and the development of outstanding male characters at the family, genus, species, and subspecies levels. Although allometrically developed male fighting apparatus is the most conspicuously sexually dimorphic, high male intraspecific variability and negatively allometric hind wings may be equally important biological features of sexually dimorphic beetle species. Male traits in sexually dimorphic species primarily evolved through positive allometry for larger apparatus. Their proportion to body size and actual size might have been further enhanced by concerted selection toward higher allometry and larger body, as evidenced by the highly significant interspecific correlation between the two traits seen within some existing genera. Yet, most oversized male traits may have evolved as a result of strong selection toward a larger body that in turn acts on the previously acquired allometry rather than by ongoing selection toward higher allometry. In some other genera, conspicuous male traits may be retained merely as an allometric inertia of selection toward larger body size even after the positive allometry ceased to be adaptively advantageous.
Treasure Your Exceptions

Understanding various examples of nonMendelian inheritance has always enhanced genetic theory. Cytoplasmic inheritance and numerous cases of preferential segregation, for example, were important for elucidating additional parameters of genetic and cytogenetic behavior. Interestingly, technologies currently being employed in plant genetics studies are uncovering new cases of nonMendelian inheritance, which will undoubtedly further deepen our appreciation for the intricacies of gene expression. A recent symposium brought together about 100 plant geneticists from Japan, the U.S., and Europe to share information in a workshop entitled “Modification of Gene Expression and Non-Mendelian Inheritancel’The workshop was held in Tsukuba, Japan, from January 24 to 26, 1995, and was sponsored by the National lnstitute of Agrobiological Resources of Japan, the Science and Technology Agency of Japan, and the U.S.-Japan Joint Working Leve1 Committee in Science and Technology (U.S. Department of State). Research presented at the workshop coalesced around several general themes, some of which are new and some of which have a long but relatively unsung history in plant genetics. “Homology-dependent” or “repeat-induced” gene silencing, paramutation, epimutation, parenta1 imprinting, and somaclonal variation were topics common to many of the talks. It is increasingly apparent that these phenomena are interrelated in that they reflect the behavior of complex eukaryotic genomes in the context of plant development and reproduction, and, as this workshop madeclear, they all contribute to the numerous examples of non-Mendelian inheritance that abound in the plant kingdom.