Miracle-dz/UniFAR-FTUs huggingface dataset:
Steady-State Policy Synthesis in Multichain Markov Decision Processes

The formal synthesis of automated or autonomous agents has elicited strong interest from the artificial intelligence community in recent years. This problem space broadly entails the derivation of decision-making policies for agents acting in an environment such that a formal specification of behavior is satisfied. Popular formalisms for such specifications include the quintessential Linear Temporal Logic (LTL) and Computation Tree Logic (CTL) which reason over infinite sequences and trees, respectively, of states. However, the related and relevant problem of reasoning over the frequency with which states are visited infinitely and enforcing behavioral specifications on the same has received little attention. That problem, known as Steady-State Policy Synthesis (SSPS) or steady-state control, is the focus of this paper. Prior related work has been mostly confined to unichain Markov Decision Processes (MDPs), while a tractable solution to the general multichain setting heretofore remains elusive. In this paper, we provide a solution to the latter within the context of multichain MDPs over a class of policies that account for all possible transitions in the given MDP. The solution policy is derived from a novel linear program (LP) that encodes constraints on the limiting distributions of the Markov chain induced by said policy. We establish a one-to-one correspondence between the feasible solutions of the LP and the stationary distributions of the induced Markov chains. The derived policy is shown to maximize the reward among the constrained class of stationary policies and to satisfy the specification constraints even when it does not exercise all possible transitions.
Tight Approximation for Proportional Approval Voting

In approval-based multiwinner elections, we are given a set of voters, a set of candidates, and, for each voter, a set of candidates approved by the voter. The goal is to find a committee of size k that maximizes the total utility of the voters. In this paper, we study approximability of Thiele rules, which are known to be NP-hard to solve exactly. We provide a tight polynomial time approximation algorithm for a natural class of geometrically dominant weights that includes such voting rules as Proportional Approval Voting or p-Geometric. The algorithm is relatively simple: first we solve a linear program and then we round a solution by employing a framework called pipage rounding due to Ageev and Sviridenko (2004) and Calinescu et al. (2011). We provide a matching lower bound via a reduction from the Label Cover problem. Moreover, assuming a conjecture called Gap-ETH, we show that better approximation ratio cannot be obtained even in time f(k)*pow(n,o(k)).
Registration of 'NI04421' Hard Red Winter Wheat

Water for irrigation is a major constraint in the Great Plains, and it is expected that the proportion of irrigated crop land to grow irrigated wheat (Triticum aestivum L.), which requires less water than other crops, will increase to conserve irrigation water. ‘NI04421’ (Reg. No. CV-1064, PI 659690) hard red winter wheat (Triticum aestivum L.) was developed cooperatively by the Nebraska Agricultural Experiment Station and the USDA-ARS and released in 2010 by the developing institutions and the Wyoming Agricultural Experiment Station. NI04421 was released primarily for its superior performance under irrigation and rainfed conditions in western Nebraska and eastern Wyoming. NI04421 was selected from the cross NE96644/Wahoo (sib) where the pedigree of NE96644 is ‘Odesskaya P’/‘Cody’//‘Pavon 76’/*3 ‘Scout 66’. The cross was made in the spring of 1998. NI04421 was selected using a modifi ed bulk-breeding method as an F 3:4 line (F 3 -derived line in the F 4 generation) in 2002, and in 2004 was assigned experimental line number NI04421. After extensive testing, it was released in July 2010.
Analysis of Q-learning with Adaptation and Momentum Restart for Gradient Descent

Existing convergence analyses of Q-learning mostly focus on the vanilla stochastic gradient descent (SGD) type of updates. Despite the Adaptive Moment Estimation (Adam) has been commonly used for practical Q-learning algorithms, there has not been any convergence guarantee provided for Q-learning with such type of updates. In this paper, we first characterize the convergence rate for Q-AMSGrad, which is the Q-learning algorithm with AMSGrad update (a commonly adopted alternative of Adam for theoretical analysis). To further improve the performance, we propose to incorporate the momentum restart scheme to Q-AMSGrad, resulting in the so-called Q-AMSGradR algorithm. The convergence rate of Q-AMSGradR is also established. Our experiments on a linear quadratic regulator problem demonstrate that the two proposed Q-learning algorithms outperform the vanilla Q-learning with SGD updates. The two algorithms also exhibit significantly better performance than the DQN learning method over a batch of Atari 2600 games.
Small Molecule-Functionalized Hyperbranched Polyglycerol Dendrimer for Inhibiting Protein Aggregation.

Amyloid protein aggregation is responsible for variety of neurodegenerative diseases and anti-amyloidogenic small molecules are identified for inhibiting such protein aggregation at extra/intracellular space. We show that nanoparticle form of small molecules offer better anti-amyloidogenic performance via enhanced bioavailability and multivalent binding with protein. Here we report hyperbranched polyglycerol dendrimer terminated with anti-amyloidogenic small molecules such as gallate, tyrosine and trehalose and their potential in inhibiting lysozyme/huntingtin protein aggregation under intra/extracellular space. The synthesized functional dendrimers are ~5 nm in size having average molecular weight of ~2000 Da and they are highly biocompatible in nature. We found that functional dendrimers are efficient in micromolar dose with respect to molecular forms that are effective at millimolar concentration. It is observed that trehalose-terminated dendrimer is more effective in inhibiting protein aggregation whereas gallate-terminated dendrimer is more effective in disintegrating mature protein fibrils. This approach can be used to design functional dendrimers as potential nanodrug for treatment of various neurodegenerative diseases.
PRPS-Associated Disorders and the Drosophila Model of Arts Syndrome

While a plethora of genetic techniques have been developed over the past century, modifying specific sequences of the fruit fly genome has been a difficult, if not impossible task. clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 truly redefined molecular genetics and provided new tools to model human diseases in Drosophila melanogaster. This is particularly true for genes whose protein sequences are highly conserved. Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme in nucleotide metabolism whose missense mutations are found in several neurological disorders, including Arts syndrome. In addition, PRPS is deregulated in cancer, particularly those that become resistant to cancer therapy. Notably, Drosophila PRPS shares about 90% protein sequence identity with its human orthologs, making it an ideal gene to study via CRISPR/Cas9. In this review, we will summarize recent findings on PRPS mutations in human diseases including cancer and on the molecular mechanisms by which PRPS activity is regulated. We will also discuss potential applications of Drosophila CRISPR/Cas9 to model PRPS-dependent disorders and other metabolic diseases that are associated with nucleotide metabolism.
Soccer heading and subclinical neuropsychiatric symptomatology in professional soccer players

Objectives To evaluate the association between postconcussive symptomatology and heading in professional soccer players, overcoming the bias of self-reported exposure, we evaluated several clinical neuropsychiatric symptoms using questionnaires after a thorough objective follow-up of players’ heading exposure throughout an entire season. Methods We collected heading data for all Israeli Premier League players for an entire season using a web-based platform for performance analysis, which enabled us to quantify the exact number of headers per player. Players filled out questionnaires regarding postconcussion symptoms, depression, anxiety, and sleep disorders. We tested the association between the number of headers and each outcome using a negative binomial regression corrected for the hours played. Results A total of 159 players were included, of whom 79 were considered in the high heading exposure group (49%), defined as more than median number of headings (1.34 per game hour). Among players without any past head injury, those with higher heading exposure were less likely to have postconcussion symptoms compared with players with low heading exposure (relative risk [RR] per heading per hour 0.94, 95% confidence interval [CI] 0.912–0.963). Players with high heading exposure had fewer depression symptoms (RR 0.98, 95% CI 0.961–0.997), anxiety (RR 0.98, 95% CI 0.958–0.997), and sleep disorders (RR 0.98, 95% CI 0.961–0.996). Conclusion Professional soccer players with high heading rate do not display higher postconcussive symptomatology severity. Symptoms among players with low heading exposure might be explained by low resilience, possibly associated with an inferior heading technique. Alternatively, it can reflect heading-avoidant behavior.
Monocyte-Derived Leukemia-Associated Macrophages Facilitate Extramedullary Distribution of T-cell Acute Lymphoblastic Leukemia Cells

This study links monocyte-derived leukemia-associated macrophages with noninfectious inflammation and extramedullary distribution of leukemia cells during leukemia progression, providing new insight into macrophage-based immunotherapy in leukemia. Macrophages play important roles in both physiologic and pathologic processes and arise from successive waves of embryonic and adult hematopoiesis. Monocyte-derived macrophages (MOMF) exert distinct functions under pathologic conditions, and leukemia-associated macrophages (LAM) show considerable diversities in activation and functional phenotype. However, their origin and pathologic roles have not been well elucidated. Here we used wild-type and CCR2−/− mice to study the pathologic roles of monocyte-derived LAM in extramedullary tissues in models of Notch1-induced T-cell acute lymphoblastic leukemia (T-ALL). MOMF existed in the resting liver and spleen. In the spleen, Ly6C+ monocytes gave rise to the Ly6C+ macrophage subset. Furthermore, an increase of monocyte-derived LAM, including the Ly6C+ subset, was detected in the extramedullary tissues in leukemic mice. More monocyte-derived LAM, including Ly6C+ LAM, was detected in the spleens of leukemic mice transplanted with exogeneous mononuclear cells. Moreover, Ly6C+ LAM exhibited increased M1-related characteristics and contributed to sterile inflammation. In CCR2−/− leukemic mice, reduced Ly6C+ LAM, relieved sterile inflammation, and reduced distribution of leukemia cells were detected in extramedullary tissues. In addition, monocyte-derived Ly6C+ LAM expressed high levels of CCL8 and CCL9/10. Blocking CCR1 and CCR2 relieved hepatosplenomegaly and inhibited the extramedullary distribution of leukemia cells in T-ALL mice. Collectively, our findings reveal the multifaceted pathologic roles of monocyte-derived LAM in T-ALL progression. Significance: This study links monocyte-derived leukemia-associated macrophages with noninfectious inflammation and extramedullary distribution of leukemia cells during leukemia progression, providing new insight into macrophage-based immunotherapy in leukemia.
Food and feeding habits of Otolithes cuvieri (Trewavas, 1974) from Ratnagiri, Maharashtra

The present report on food and feeding habits of Otolithes cuvieri is based on the examination of gut contents of 781 fishes within the size range of 83-300 mm collected from Ratnagiri, Maharashtra. Based on index of relative importance values, crustaceans like Acetes spp. and penaeid prawns were found to be the dominant food items followed by fishes, cephalopods and gastropods. Crustaceans were predominant in most of the months. Fishes of smaller lengths preferred only Acetes spp. Dominance of empty stomachs in most of the months as well as in different size groups indicates low feeding intensity of the species.
Effect of switching from acenocoumarol to phenprocoumon on time in therapeutic range and INR variability: A cohort study

Background Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. Aims We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. Methods and results In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2–3, 269 patients in target range 2–3.5 and 98 patients in target range 2.5–3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers’ TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2–3, 2–3.5 and 2.5–3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers’ INRs were much more stable than non-switchers’. Conclusion Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.
Agonists of Orally Expressed TRP Channels Stimulate Salivary Secretion and Modify the Salivary Proteome

Quantitative proteomics revealed sources of variation and differentially secreted proteins in saliva after TRP channel agonist mouth rinsing. Menthol and nonivamide mouth rinsing increased saliva flow rates and Cystatin S was increased in nonivamide stimulated saliva. TRPM8 and TRPV1 agonists have potential in treating chronically dry mouth. Graphical Abstract Highlights Salivary secretion was increased by mouth rinsing with TRP channel agonists. The salivary proteome varied over time and was changed by TRP channel stimulation. Immunoreactive Cystatin S was increased in saliva after TRPV1 stimulation. Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.
Physiological Importance of Pectin Modifying Genes During Rice Pollen Development

Although cell wall dynamics, particularly modification of homogalacturonan (HGA, a major component of pectin) during pollen tube growth, have been extensively studied in dicot plants, little is known about how modification of the pollen tube cell wall regulates growth in monocot plants. In this study, we assessed the role of HGA modification during elongation of the rice pollen tube by adding a pectin methylesterase (PME) enzyme or a PME-inhibiting catechin extract (Polyphenon 60) to in vitro germination medium. Both treatments led to a severe decrease in the pollen germination rate and elongation. Furthermore, using monoclonal antibodies toward methyl-esterified and de-esterified HGA epitopes, it was found that exogenous treatment of PME and Polyphenon 60 resulted in the disruption of the distribution patterns of low- and high-methylesterified pectins upon pollen germination and during pollen tube elongation. Eleven PMEs and 13 PME inhibitors (PMEIs) were identified by publicly available transcriptome datasets and their specific expression was validated by qRT-PCR. Enzyme activity assays and subcellular localization using a heterologous expression system in tobacco leaves demonstrated that some of the pollen-specific PMEs and PMEIs possessed distinct enzymatic activities and targeted either the cell wall or other compartments. Taken together, our findings are the first line of evidence showing the essentiality of HGA methyl-esterification status during the germination and elongation of pollen tubes in rice, which is primarily governed by the fine-tuning of PME and PMEI activities.
A comparison of estimation methods for fitting Weibull, Johnson's SB and beta functions to Pinus pinaster, Pinus radiata and Pinus sylvestris stands in northwest Spain.

The purpose of this study was to compare the accuracy of the Weibull, Johnson’s S B and beta distributions, fitted with some of the most usual methods and with different fixed values for the location parameters, for describing diameter distributions in even-aged stands of Pinus pinaster , Pinus radiata and Pinus sylvestris in northwest Spain. A total of 155 permanent plots in Pinus sylvestris stands throughout Galicia, 183 plots in Pinus pinaster stands throughout Galicia and Asturias and 325 plots in Pinus radiata stands in both regions were measured to describe the diameter distributions. Parameters of the Weibull function were estimated by Moments and Maximum Likelihood approaches, those of Johnson’s S B function by Conditional Maximum Likelihood and by Knoebel and Burhart’s method, and those of the beta function with the method based on the moments of the distribution. The beta and the Johnson’s S B functions were slightly superior to Weibull function for Pinus pinaster stands; the Johnson’s S B and beta functions were more accurate in the best fits for Pinus radiata stands, and the best results of the Weibull and the Johnson’s S B functions were slightly superior to beta function for Pinus sylvestris stands. However, the three functions are suitable for this stands with an appropriate value of the location parameter and estimation of parameters method.
Frugivorous birds mediate sex-biased facilitation in a dioecious nurse plant

Abstract Facilitation by dispersal occurs if the nurse plant acts as a focus which is actively selected by seed dispersers and enhances the fitness of the facilitated plant. Sex-biased facilitation may be produced if seed dispersers tend to concentrate the seeds under female, fruit-bearing plants of dioecious species more often than under conspecific males. Juniperus sabina is a dioecious shrub with a prostrate growth form from Mediterranean high mountains that modifies many microhabitat characteristics related to seedling establishment and survival. Soil water availability, maximum soil temperature in summer, organic matter and total nitrogen content, were different on open ground as compared with beneath J. sabina shrubs, irrespective of its sex. Other studied characteristics such as soil bulk density and soil compaction after rain did not differ between the microhabitats considered. Some species, such as Juniperus communis, Pinus nigra, Helleborus foetidus and Euphorbia nicaeensis, are spatially associated to J. sabina shrubs, strongly suggesting a facilitative role. The anemochorous P. nigra and myrmechorous H. foetidus and E. nicaeensis did not associate preferentially to any sex of J. sabina. Only J. communis, an endozoochorous species sharing the same bird dispersers as J. sabina, presented a female-biased spatial association with the nurse plant. Seed dispersal mediated by birds attracted by the fruit-rewarding females of J. sabinaexplains the sex-biased spatial pattern of Juniperus communis. Nomenclature: Mateo & Crespo (1998). Abbreviation: PAR = Photosynthetically active radiation.
Characteristics of the 24-h ambulatory blood pressure monitoring in patients with Parkinson's disease – the SFC BP multicentre study in China

Objectives: Cardiovascular dysautonomia can be present at early, late and even prodromal stages of Parkinson's disease. This study aimed to describe the characteristics of 24-h ambulatory blood pressure (BP) monitoring and investigate the frequency of cardiovascular dysautonomia in Parkinson's disease without an abnormal BP history. Methods: Parkinson's disease patients without history of abnormal BP were consecutively enrolled from three Chinese centres, on whom office BP measurement, neurological evaluations and 24-h ambulatory BP monitoring were performed. Results: Totally, 101 Parkinson's disease patients (42.6% women) with an average age of 66.6 ± 8.2 years were included in our cohort, and data analysis revealed that 26 (25.74%) patients suffered from orthostatic hypotension, among whom 18 (69.23%) were symptomatic. Patients with orthostatic hypotension compared with those without had significantly higher nocturnal SBP level, and more severe nonmotor symptoms, autonomic dysfunction and cognitive impairment. Further, 54 out of 101 (53.47%) individuals had a reverse dipping pattern in SBP and/or DBP. Reverse dippers had more cases of orthostatic hypotension (P < 0.001), and more severe nonmotor symptoms. SBP dipping ratio of less than −2.98% generated 76.9% of sensitivity, 69.3% of specificity, 46.5% of positive predictive value (PPV), 89.7% of negative predictive value (NPV) and 77.4% of accuracy, while diastolic dipping ratio of less than −1.80% generated 76.9% of sensitivity, 70.7% specificity, 47.6% of PPV, 89.8% of NPV and 77.8% of accuracy for suspecting orthostatic hypotension. Conclusion: Orthostatic hypotension can occur in one-fourth Parkinson's disease patients without abnormal BP history, and reverse dipping was present in more than half of patients with Parkinson's disease. Reverse dipping pattern was helpful to suspect orthostatic hypotension.