Miracle-dz/UniFAR-FTUs huggingface dataset:
A Neural Correlate of Reward-Based Behavioral Learning in Caudate Nucleus: A Functional Magnetic Resonance Imaging Study of a Stochastic Decision Task

Humans can acquire appropriate behaviors that maximize rewards on a trial-and-error basis. Recent electrophysiological and imaging studies have demonstrated that neural activity in the midbrain and ventral striatum encodes the error of reward prediction. However, it is yet to be examined whether the striatum is the main locus of reward-based behavioral learning. To address this, we conducted functional magnetic resonance imaging (fMRI) of a stochastic decision task involving monetary rewards, in which subjects had to learn behaviors involving different task difficulties that were controlled by probability. We performed a correlation analysis of fMRI data by using the explanatory variables derived from subject behaviors. We found that activity in the caudate nucleus was correlated with short-term reward and, furthermore, paralleled the magnitude of a subject's behavioral change during learning. In addition, we confirmed that this parallelism between learning and activity in the caudate nucleus is robustly maintained even when we vary task difficulty by controlling the probability. These findings suggest that the caudate nucleus is one of the main loci for reward-based behavioral learning.
Trachypithecus cristatus (Primates: Cercopithecidae)

Abstract Trachypithecus cristatus (Raffles, 1821), silvered lutung, is a colobine monkey of the Malay Peninsula and Archipelago. It has a pointed crest and outward-projecting cheek hairs, and gray skin and pelage with some grayish white hairs that are lighter distally, giving a silvered appearance. Diurnal and arboreal, it runs and jumps quadrupedally, with limited semibrachiation. Its large stomach and foregut fermentation allow it to digest a diet with a high proportion of leaves. It lives in single male–multifemale groups and smaller multimale groups in a polygynous, cooperative-breeding mating system. As with other nonhuman primates, it is threatened throughout its range by logging, hunting for meat and medicinal uses, and capture for the pet trade.
CDSchecker: checking concurrent data structures written with C/C++ atomics

Writing low-level concurrent software has traditionally required intimate knowledge of the entire toolchain and often has involved coding in assembly. New language standards have extended C and C++ with support for low-level atomic operations and a weak memory model, enabling developers to write portable and efficient multithreaded code. Developing correct low-level concurrent code is well-known to be especially difficult under a weak memory model, where code behavior can be surprising. Building reliable concurrent software using C/C++ low-level atomic operations will likely require tools that help developers discover unexpected program behaviors. In this paper we present CDSChecker, a tool for exhaustively exploring the behaviors of concurrent code under the C/C++ memory model. We develop several novel techniques for modeling the relaxed behaviors allowed by the memory model and for minimizing the number of execution behaviors that CDSChecker must explore. We have used CDSChecker to exhaustively unit test several concurrent data structure implementations on specific inputs and have discovered errors in both a recently published C11 implementation of a work-stealing queue and a single producer, single consumer queue implementation.
Dialect/Accent Classification Using Unrestricted Audio

This study addresses novel advances in English dialect/accent classification. A word-based modeling technique is proposed that is shown to outperform a large vocabulary continuous speech recognition (LVCSR)-based system with significantly less computational costs. The new algorithm, which is named Word-based Dialect Classification (WDC), converts the text-independent decision problem into a text-dependent decision problem and produces multiple combination decisions at the word level rather than making a single decision at the utterance level. The basic WDC algorithm also provides options for further modeling and decision strategy improvement. Two sets of classifiers are employed for WDC: a word classifier DW(k) and an utterance classifier D u. DW(k) is boosted via the AdaBoost algorithm directly in the probability space instead of the traditional feature space. Du is boosted via the dialect dependency information of the words. For a small training corpus, it is difficult to obtain a robust statistical model for each word and each dialect. Therefore, a context adapted training (CAT) algorithm is formulated, which adapts the universal phoneme Gaussian mixture models (GMMs) to dialect-dependent word hidden Markov models (HMMs) via linear regression. Three separate dialect corpora are used in the evaluations that include the Wall Street Journal (American and British English), NATO N4 (British, Canadian, Dutch, and German accent English), and IViE (eight British dialects). Significant improvement in dialect classification is achieved for all corpora tested
Use of Corneal Confocal Microscopy to Detect Corneal Nerve Loss and Increased Dendritic Cells in Patients With Multiple Sclerosis

Importance Multiple sclerosis (MS) is characterized by demyelination, axonal degeneration, and inflammation. Corneal confocal microscopy has been used to identify axonal degeneration in several peripheral neuropathies. Objective To assess corneal subbasal nerve plexus morphologic features, corneal dendritic cell (DC) density, and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with MS. Design, Setting, and Participants This single-center, cross-sectional comparative study was conducted at a tertiary referral university hospital between May 27, 2016, and January 30, 2017. Fifty-seven consecutive patients with relapsing-remitting MS and 30 healthy, age-matched control participants were enrolled in the study. Corneal subbasal nerve plexus measures and DC density were quantified in images acquired with the laser scanning in vivo corneal confocal microscope, and peripapillary RNFL thickness was measured with spectral-domain optical coherence tomography. Main Outcomes and Measures Corneal nerve fiber density, nerve branch density, nerve fiber length, DC density, peripapillary RNFL thickness, and association with the severity of neurologic disability as assessed by the Kurtzke Expanded Disability Status Scale (score range, 0-10; higher scores indicate greater disability) and Multiple Sclerosis Severity Score (score range, 0.01-9.99; higher scores indicate greater severity). Results Of the 57 participants with MS, 42 (74%) were female and the mean (SD) age was 35.4 (8.9) years; of the 30 healthy controls, 19 (63%) were female and the mean (SD) age was 34.8 (10.2) years. Corneal nerve fiber density (mean [SE] difference, −6.78 [2.14] fibers/mm2; 95% CI, −11.04 to −2.52; P = .002), nerve branch density (mean [SE] difference, −17.94 [5.45] branches/mm2; 95% CI, −28.77 to −7.10; P = .001), nerve fiber length (mean [SE] difference, −3.03 [0.89] mm/mm2; 95% CI, −4.81 to −1.25; P = .001), and the mean peripapillary RNFL thickness (mean [SE] difference, −17.06 [3.14] &mgr;m; 95% CI, −23.29 to −10.82; P < .001) were reduced in patients with MS compared with healthy controls. The DC density was increased (median [interquartile range], 27.7 [12.4-66.8] vs 17.3 [0-28.2] cells/mm2; P = .03), independent of a patient’s history of optic neuritis. Nerve fiber density and RNFL thickness showed inverse associations with the Expanded Disability Status Scale (&rgr; = −0.295; P = .03 for nerve fiber density and &rgr; = −0.374; P = .004 for RNFL thickness) and the Multiple Sclerosis Severity Score (R = −0.354; P = .007 for nerve fiber density and R = −0.283; P = .03 for RNFL thickness), whereas other study measures did not. Conclusions and Relevance These data suggest that corneal confocal microscopy demonstrates axonal loss and increased DC density in patients with MS. Additional longitudinal studies are needed to confirm the use of corneal confocal microscopy as an imaging biomarker in patients with MS.
Does the Minimum Legal Drinking Age Save Lives?

The minimum legal drinking age (MLDA) is widely believed to save lives by reducing traffic fatalities among underage drivers. Further, the Federal Uniform Drinking Age Act, which pressured all states to adopt an MLDA of 21, is regarded as having contributed enormously to this life-saving effect. This article challenges both claims. State-level panel data for the past 30 yr show that any nationwide impact of the MLDA is driven by states that increased their MLDA prior to any inducement from the federal government. Even in early-adopting states, the impact of the MLDA did not persist much past the year of adoption. The MLDA appears to have only a minor impact on teen drinking. (JEL H11, K42)
Filgrastim (r-metHuG-CSF): the first 10 years.

T HAS BEEN KNOWN for at least three decades that very specific factors control hematopoiesis, acting on early cells in the hematopoietic system to produce mature, functional cells. The isolation, purification, and cloning of these factors has lead to a new class of therapeutic agents, including the colony-stimulating factors and interleukins. This review is devoted to granulocyte colony-stimulating factor (G-CSF), specifically Filgrastim (r-metHuG-CSF), the bacterially synthesized recombinant protein form of GCSF, that acts on neutrophils, the body's major defense against infections. The purification and molecular cloning of Filgrastim were performed between 1984 and 1986,L-3 and the clinical development of Filgrastim commenced in 1986, with approval for clinical use in cancer patients treated with chemotherapy4" obtained in the United States in February 1991. In the 5 years since its approval, 1.2 million patients have been treated with Filgrastim (Amgen [Thousand Oaks, CA], data on file). Filgrastim was initially used as an adjunct to chemotherapy for ameliorating neutropenia, one of the major side effects of cancer chemotherapy. Its use has led to reduced infections and hospital admissions for patients with cancer. Besides chemotherapy-induced neutropenia, Filgrastim has been approved in more than 70 countries for the treatment of myelosuppression after bone marrow transplantation, severe chronic neutropenia (SCN), acute leukemia, aplastic anemia (AA), myelodysplastic syndromes (MDS), and mobilization of peripheral blood progenitor cells (PBPCs) for transplantation. The use of Filgrastim has made possible delivery of full-dose chemotherapy and high-dose chemotherapy and has benefited patients who are immunocompromised. A second form of rHuG-CSF (lenograstim) received approval in Europe in 1993. The biologic properties of Filgrastim and lenograstim are similar and are given in Table 1. This review focuses on Filgrastim and reviews the first 10 years of clinical development and the first 5 years of postapproval use as well as additional potential clinical applications. PHARMACOLOGY OF FlLGRASTlM The pharmacodynamics and pharmacokinetics of Filgrastim were studied in rodents',' and primates". " and then in normal volunteers and in patients with malignant disease. The results of these studies indicated that Filgrastim had a consistent and predictable pharmacologic profile when ad
Study of Hypersaline Deposits and Analysis of Their Signature in Airborne and Spaceborne SAR Data: Example of Death Valley, California

Field measurements of dielectric properties of hypersaline deposits were realized over an arid site located in Death Valley, CA. The dielectric constant of salt and water mixtures is usually high but can show large variations, depending on the considered salt. We confirmed values observed on the field with laboratory measurements and used these results to model both the amplitude and phase behaviors of the synthetic aperture radar (SAR) signal at C- and L-bands. Our analytical simulations allow reproducing specific copolar signatures observed in both Airborne SAR (AIRSAR) and Spaceborne Imaging Radar (SIR-C) data, corresponding to the saltpan of the Cottonball Basin. More precisely, the main objective of the present paper is to understand the influence of soil salinity as a function of soil moisture on the dielectric constant of soils and then on the backscattering coefficients recorded by airborne and spaceborne SAR systems. We also propose the copolarized backscattering ratio and phase difference as indicators of moistened and salt-affected soils. More precisely, we show that these copolar indicators should allow monitoring of the seasonal variations of the dielectric properties of saline deposits at both C- and L-bands. Because of the frequency dependence of the ionic conductivity, we also show that L-band SAR systems should be efficient tools for detecting both soil moisture and salinity, while C-band SAR systems are more suitable for the monitoring of soil moisture only. Through the study of terrestrial evaporitic environments by means of spaceborne SAR systems, our results could also be of great interest for defining future planetary missions, particularly for the exploration of Mars.
Consistent Robust Regression

We present the first efficient and provably consistent estimator for the robust regression problem. The area of robust learning and optimization has generated a significant amount of interest in the learning and statistics communities in recent years owing to its applicability in scenarios with corrupted data, as well as in handling model mis-specifications. In particular, special interest has been devoted to the fundamental problem of robust linear regression where estimators that can tolerate corruption in up to a constant fraction of the response variables are widely studied. Surprisingly however, to this date, we are not aware of a polynomial time estimator that offers a consistent estimate in the presence of dense, unbounded corruptions. In this work we present such an estimator, called CRR. This solves an open problem put forward in the work of (Bhatia et al, 2015). Our consistency analysis requires a novel two-stage proof technique involving a careful analysis of the stability of ordered lists which may be of independent interest. We show that CRR not only offers consistent estimates, but is empirically far superior to several other recently proposed algorithms for the robust regression problem, including extended Lasso and the TORRENT algorithm. In comparison, CRR offers comparable or better model recovery but with runtimes that are faster by an order of magnitude.
Differences in voriconazole trough plasma concentrations per oral dosages between children younger and older than 3 years of age

The relationship between trough plasma concentrations and daily doses of voriconazole was retrospectively analyzed in ≤18‐year‐old children because optimal oral voriconazole dosages for children, especially <2 years of age, is unknown. We demonstrated that the relationship changed around the age of 3 years, and that children <3 years of age required higher optimal daily doses with greater variations compared with those for older children, resulting in complicated optimal dose adjustments. Therefore, plasma concentration monitoring and individual dose adjustments are recommended for optimal and less toxic voriconazole treatments, especially for <3‐year‐old children, although additional studies are needed to validate this approach. Pediatr Blood Cancer 2010;54:1050–1052 © 2010 Wiley‐Liss, Inc.
Usa1p Is Required for Optimal Function and Regulation of the Hrd1p Endoplasmic Reticulum-associated Degradation Ubiquitin Ligase*

Usa1p is a recently discovered member of the HRD ubiquitin ligase complex. The HRD pathway is a conserved route of ubiquitin-dependent, endoplasmic reticulum (ER)-associated degradation (ERAD) of numerous lumenal (ERAD-L) and membrane-anchored (ERAD-M) substrates. We have investigated Usa1p to understand its importance in HRD complex action. Usa1p was required for the optimal function of the Hrd1p E3 ubiquitin ligase; its loss caused deficient degradation of both membrane-associated and lumenal proteins. Furthermore, Usa1p functioned in regulation of Hrd1p by two mechanisms. First, Hrd1p self-degradation, which serves to limit the levels of uncomplexed E3, is absolutely dependent on Usa1p and the ubiquitin-like (Ubl) domain of Usa1p. We found that Usa1p allows Hrd1p degradation by promoting trans interactions between Hrd1p molecules. The Ubl domain of Usa1p was required specifically for Hrd1p self-ubiquitination but not for degradation of either ERAD-L or ERAD-M substrates. In addition, Usa1p was able to attenuate the activity-dependent toxicity of Hrd1p without compromising substrate degradation, indicating a separate role in ligase regulation that operates in parallel to stability control. Many of the described actions of Usa1p are distinct from those of Der1p, which is recruited to the HRD complex by Usa1p. Thus, this novel, conserved factor is broadly involved in the function and regulation of the HRD pathway of ERAD.
Generic oracles and oracle classes

In this paper, we examine various complexity issues relative to an oracle for a generic set in order to determine which are the more "natural" conjectures for these issues. Generic oracle results should be viewed as parallels to random oracle results, as in [BG]; the two are in many ways related, but, as we shall exhibit, not equivalent. Looking at computation relative to a generic oracle is in some ways a better reflection of computation without an oracle; for example, whereas adding a random oracle allows a deterministic polynomial-time machine to solve any problem in BPP, adding a generic oracle will not help solve any recursive problem faster than it could be solved without an oracle. Generic sets were first introduced by Cohen as a tool for proving independence results in set theory [Co]. Their recursion theoretic properties have also been explored in depth; for example, see [J] and [Ku2]. Some related work using forcing and/or generic sets as tools in oracle constructions can be found in [Ku3], [Do], [P], and [A-SFH]. However, this is to our knowledge the first knowledge the first thorough examination of complexity relative to a generic Oracle.
HDAC2 blockade by nitric oxide and histone deacetylase inhibitors reveals a common target in Duchenne muscular dystrophy treatment

The overlapping histological and biochemical features underlying the beneficial effect of deacetylase inhibitors and NO donors in dystrophic muscles suggest an unanticipated molecular link among dystrophin, NO signaling, and the histone deacetylases (HDACs). Higher global deacetylase activity and selective increased expression of the class I histone deacetylase HDAC2 were detected in muscles of dystrophin-deficient MDX mice. In vitro and in vivo siRNA-mediated down-regulation of HDAC2 in dystrophic muscles was sufficient to replicate the morphological and functional benefits observed with deacetylase inhibitors and NO donors. We found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation. These data reveal a special contribution of HDAC2 in the pathogenesis of Duchenne muscular dystrophy and indicate that HDAC2 inhibition by NO-dependent S-nitrosylation is important for the therapeutic response to NO donors in MDX mice. They also define a common target for independent pharmacological interventions in the treatment of Duchenne muscular dystrophy.
Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells

A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.
Vemurafenib Resistance Signature by Proteome Analysis Offers New Strategies and Rational Therapeutic Concepts

The FDA-approved BRAF inhibitor vemurafenib achieves outstanding clinical response rates in patients with melanoma, but early resistance is common. Understanding the pathologic mechanisms of drug resistance and identification of effective therapeutic alternatives are key scientific challenges in the melanoma setting. Using proteomic techniques, including shotgun analysis and 2D-gel electrophoresis, we identified a comprehensive signature of the vemurafenib-resistant M24met in comparison with the vemurafenib-sensitive A375 melanoma cell line. The resistant cells were characterized by loss of differentiation, induction of transformation, enhanced expression of the lysosomal compartment, increased potential for metastasis, migration, adherence and Ca2+ ion binding, enhanced expression of the MAPK pathway and extracellular matrix proteins, and epithelial–mesenchymal transformation. The main features were verified by shotgun analysis with QEXACTIVE orbitrap MS, electron microscopy, lysosomal staining, Western blotting, and adherence assay in a VM-1 melanoma cell line with acquired vemurafenib resistance. On the basis of the resistance profile, we were able to successfully predict that a novel resveratrol-derived COX-2 inhibitor, M8, would be active against the vemurafenib-resistant but not the vemurafenib-sensitive melanoma cells. Using high-throughput methods for cell line and drug characterization may thus offer a new way to identify key features of vemurafenib resistance, facilitating the design of effective rational therapeutic alternatives. Mol Cancer Ther; 14(3); 757–68. ©2015 AACR.
Efficient planar graph cuts with applications in Computer Vision

We present a fast graph cut algorithm for planar graphs. It is based on the graph theoretical work and leads to an efficient method that we apply on shape matching and image segmentation. In contrast to currently used methods in computer vision, the presented approach provides an upper bound for its runtime behavior that is almost linear. In particular, we are able to match two different planar shapes of N points in O(N2 log N) and segment a given image of N pixels in O(N log N). We present two experimental benchmark studies which demonstrate that the presented method is also in practice faster than previously proposed graph cut methods: On planar shape matching and image segmentation we observe a speed-up of an order of magnitude, depending on resolution.