Miracle-dz/UniFAR-FTUs huggingface dataset:
Batch means and spectral variance estimators in Markov chain Monte Carlo

Calculating a Monte Carlo standard error (MCSE) is an important step in the statistical analysis of the simulation output obtained from a Markov chain Monte Carlo experiment. An MCSE is usually based on an estimate of the variance of the asymptotic normal distribution. We consider spectral and batch means methods for estimating this variance. In particular, we establish conditions which guarantee that these estimators are strongly consistent as the simulation effort increases. In addition, for the batch means and overlapping batch means methods we establish conditions ensuring consistency in the mean-square sense which in turn allows us to calculate the optimal batch size up to a constant of proportionality. Finally, we examine the empirical finite-sample properties of spectral variance and batch means estimators and provide recommendations for practitioners.
Phosphorylation of Ser24 in the Pleckstrin Homology Domain of Insulin Receptor Substrate-1 by Mouse Pelle-like Kinase/Interleukin-1 Receptor-associated Kinase

Inflammation contributes to insulin resistance in diabetes and obesity. Mouse Pelle-like kinase (mPLK, homolog of human IL-1 receptor-associated kinase (IRAK)) participates in inflammatory signaling. We evaluated IRS-1 as a novel substrate for mPLK that may contribute to linking inflammation with insulin resistance. Wild-type mPLK, but not a kinase-inactive mutant (mPLK-KD), directly phosphorylated full-length IRS-1 in vitro. This in vitro phosphorylation was increased when mPLK was immunoprecipitated from tumor necrosis factor (TNF)-α-treated cells. In NIH-3T3IR cells, wild-type mPLK (but not mPLK-KD) co-immunoprecipitated with IRS-1. This association was increased by treatment of cells with TNF-α. Using mass spectrometry, we identified Ser24 in the pleckstrin homology (PH) domain of IRS-1 as a specific phosphorylation site for mPLK. IRS-1 mutants S24D or S24E (mimicking phosphorylation at Ser24) had impaired ability to associate with insulin receptors resulting in diminished tyrosine phosphorylation of IRS-1 and impaired ability of IRS-1 to bind and activate PI-3 kinase in response to insulin. IRS-1-S24D also had an impaired ability to mediate insulin-stimulated translocation of GLUT4 in rat adipose cells. Importantly, endogenous mPLK/IRAK was activated in response to TNF-α or interleukin 1 treatment of primary adipose cells. In addition, using a phospho-specific antibody against IRS-1 phosphorylated at Ser24, we found that interleukin-1 or TNF-α treatment of Fao cells stimulated increased phosphorylation of endogenous IRS-1 at Ser24. We conclude that IRS-1 is a novel physiological substrate for mPLK. TNF-α-regulated phosphorylation at Ser24 in the pleckstrin homology domain of IRS-1 by mPLK/IRAK represents an additional mechanism for cross-talk between inflammatory signaling and insulin signaling that may contribute to metabolic insulin resistance.
Eggshell Porosity Provides Insight on Evolution of Nesting in Dinosaurs

Knowledge about the types of nests built by dinosaurs can provide insight into the evolution of nesting and reproductive behaviors among archosaurs. However, the low preservation potential of their nesting materials and nesting structures means that most information can only be gleaned indirectly through comparison with extant archosaurs. Two general nest types are recognized among living archosaurs: 1) covered nests, in which eggs are incubated while fully covered by nesting material (as in crocodylians and megapodes), and 2) open nests, in which eggs are exposed in the nest and brooded (as in most birds). Previously, dinosaur nest types had been inferred by estimating the water vapor conductance (i.e., diffusive capacity) of their eggs, based on the premise that high conductance corresponds to covered nests and low conductance to open nests. However, a lack of statistical rigor and inconsistencies in this method render its application problematic and its validity questionable. As an alternative we propose a statistically rigorous approach to infer nest type based on large datasets of eggshell porosity and egg mass compiled for over 120 extant archosaur species and 29 archosaur extinct taxa/ootaxa. The presence of a strong correlation between eggshell porosity and nest type among extant archosaurs indicates that eggshell porosity can be used as a proxy for nest type, and thus discriminant analyses can help predict nest type in extinct taxa. Our results suggest that: 1) covered nests are likely the primitive condition for dinosaurs (and probably archosaurs), and 2) open nests first evolved among non-avian theropods more derived than Lourinhanosaurus and were likely widespread in non-avian maniraptorans, well before the appearance of birds. Although taphonomic evidence suggests that basal open nesters (i.e., oviraptorosaurs and troodontids) were potentially the first dinosaurs to brood their clutches, they still partially buried their eggs in sediment. Open nests with fully exposed eggs only became widespread among Euornithes. A potential co-evolution of open nests and brooding behavior among maniraptorans may have freed theropods from the ground-based restrictions inherent to covered nests and allowed the exploitation of alternate nesting locations. These changes in nesting styles and behaviors thus may have played a role in the evolutionary success of maniraptorans (including birds).
Temperature dependence of microhardness of tetragonal hen-egg-white lysozyme single crystals

The mechanical properties of high-quality single crystals of tetragonal hen-egg-white lysozyme from hen egg white were investigated by the indentation method. The indentation marks were clearly observed on the crystal surface and elastic recovery did not occur. The micro-Vickers hardness of the crystals in the wet condition was observed to be 20 MPa at room temperature. To investigate deformation, the temperature dependence of the hardness was investigated from 278 to 308 K. The hardness strongly depended on the temperature above 290 K. From these results the deformation of lysozyme single crystals was explained in terms of dislocation mechanisms.
SAT sweeping with local observability don't-cares

SAT sweeping is a method for simplifying an AND/inverter graph (AIG) by systematically merging graph vertices from the inputs towards the outputs using a combination of structural hashing, simulation, and SAT queries. Due to its robustness and efficiency, SAT sweeping provides a solid algorithm for Boolean reasoning in functional verification and logic synthesis. In previous work, SAT sweeping merges two vertices only if they are functionally equivalent. In this paper we present a significant extension of the SAT-sweeping algorithm that exploits local observability don't-cares (ODCs) to increase the number of vertices merged. We use a novel technique to bound the use of ODCs and thus the computational effort to find them, while still finding a large fraction of them. Our reported results based on a set of industrial benchmark circuits demonstrate that ODC-based SAT sweeping results in significantly more graph simplification with great benefit for Boolean reasoning with a moderate increase in computational effort
Genetic Identification of a High-Affinity Ni Transporter and the Transcriptional Response to Ni Deprivation in Synechococcus sp. Strain WH8102

ABSTRACT One biological need for Ni in marine cyanobacteria stems from the utilization of the Ni metalloenzyme urease for the assimilation of urea as a nitrogen source. In many of the same cyanobacteria, including Synechococcus sp. strain WH8102, an additional and obligate nutrient requirement for Ni results from usage of a Ni superoxide dismutase (Ni-SOD), which is encoded by sodN. To better understand the effects of Ni deprivation on WH8102, parallel microarray-based analysis of gene expression and gene knockout experiments were conducted. The global transcriptional response to Ni deprivation depends upon the nitrogen source provided for growth; fewer than 1% of differentially expressed genes for Ni deprivation on ammonium or urea were concordantly expressed. Surprisingly, genes for putative Ni transporters, including one colocalized on the genome with sodN, sodT, were not induced despite an increase in Ni transport. Knockouts of the putative Ni transporter gene sodT appeared to be lethal in WH8102, so the genes for sodT and sodN in WH8102 were interrupted with the gene for Fe-SOD, sodB, and its promoter from Synechococcus sp. strain WH7803. The sodT::sodB exconjugants were unable to grow at low Ni concentrations, confirming that SodT is a Ni transporter. The sodN::sodB exconjugants displayed higher growth rates at low Ni concentrations than did the wild type, presumably due to a relaxed competition between urease and Ni-SOD for Ni. Both sodT::sodB and sodN::sodB lines exhibited an impaired ability to grow at low Fe concentrations. We propose a posttranslational allosteric SodT regulation involving the binding of Ni to a histidine-rich intracellular protein loop.
Aetiology of childhood leukemia

Leukemia is the most common cancer to affect children, accounting for approximately a third of all childhood cancers. The major morphological subtypes of leukemia, acute lymphoblastic leukemia (ALL), and acute myeloblastic leukemia (AML), are characterized by chromosomal translocations involving over 200 genes including mixed lineage leukemia (MLL), TEL, and AML1. Chromosomal translocations involving the MLL gene at 11q23 are a common feature of infant acute leukemia, found in up to 80% of all cases, and there is strong evidence that rearrangements involving the MLL gene or the TEL‐AML1 gene fusion can originate in utero. As with most other cancers, the mechanism by which leukemia arises is likely to involve gene‐environment interactions. Accordingly, it is important to identify exposures that cause DNA damage and induce chromosome breaks which are inadequately repaired, ultimately leading to the initiation and disease progression. Exposures acting before birth and early in life has long been thought to be important determinants of leukemia, and the list of suspected chemical, physical, and biological agents continues to increase. Unfortunately, the evidence regarding the majority of suggested exposures is limited and often contradictory, and there are areas, which clearly warrant further investigation in order to further our understanding of the aetiology of childhood leukemia. Bioelectromagnetics Supplement 7:S5–S11, 2005. © 2005 Wiley‐Liss, Inc.
Liquid crystallinity in polymers : principles and fundamental properties

The focus of this book is on the molecular basis for liquid crystallinity in polymers, including lyotropic, thermotropic, mainchain, sidechain systems and mixtures. An entire section is devoted to conformational aspects of polymeric mesogens which is followed by a section describing current molecular theories. Another section on experimental behaviour analyzes the performance of these theories, pointing out areas where further investigation is needed. A final section deals with elastic and viscous properties, with defects and textures and with rheology of LCP. "Liquid crystallinity in polymers" is written by recognized specialists whose various chapters together reach a consensus on the current status of our understanding of LCP behaviour. Specialists, chemists, physicists and biochemists entering the field will find it useful as will material researchers closer to application.
Lung Ventilation and Perfusion in Prone and Supine Postures with Reference to Anesthetized and Mechanically Ventilated Healthy Volunteers

Background:The literature on ventilation (V) and lung perfusion (Q) distributions during general anesthesia and controlled mechanical ventilation in supine and prone position is contradictory. The authors aimed to investigate whether V, Q, and ventilation to perfusion ratio (V/Q ratio) matching in anesthetized and mechanically ventilated volunteers are gravity dependent irrespective of posture. Methods:Seven healthy volunteers were studied at two different occasions during general anesthesia and controlled mechanical ventilation. One occasion studied ventral to dorsal V and Q distributions in the supine posture and the other in the prone posture. Imaging was performed in supine posture at both occasions. A dual radiotracer technique and single photon emission computed tomography were used. V and Q were simultaneously tagged with 99mTc-Technegas (Tetley Manufacturing Ltd., Sydney, Australia) and 113mIn-labeled macroaggregates of human albumin (TechneScan LyoMAA, Mallinckrodt Medica, Petten, The Netherlands), respectively. Results:No differences in V between postures were observed. Q differed between postures, being more uniform over different lung regions in prone posture and dependent in supine posture. The contribution of the vertical direction to the total V/Q ratio heterogeneity was larger in supine (31.4%) than in prone (16.4%) (P = 0.0639, two-tailed, paired t test) posture. Conclusions:During mechanical ventilation, prone posture favors a more evenly distributed Q between lung regions. V distribution is independent of posture. This results in a tendency toward lower V/Q gradients in the ventral to dorsal direction in prone compared with supine posture.
PGC-1α encoded by the PPARGC1A gene regulates oxidative energy metabolism in equine skeletal muscle during exercise.

Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) has emerged as a critical control factor in skeletal muscle adaptation to exercise, acting via transcriptional control of genes responsible for angiogenesis, fatty acid oxidation, oxidative phosphorylation, mitochondrial biogenesis and muscle fibre type composition. In a previous study, we demonstrated a significant increase in mRNA expression for the gene encoding PGC-1α (PPARGC1A) in Thoroughbred horse skeletal muscle following a single bout of endurance exercise. In this study, we investigated mRNA expression changes in genes encoding transcriptional coactivators of PGC-1α and genes that function upstream and downstream of PGC-1α in known canonical pathways. We used linear regression to determine the associations between PPARGC1A mRNA expression and expression of the selected panel of genes. Biopsy samples were obtained from the gluteus medius pre-exercise (T(0) ), immediately post-exercise (T(1) ) and 4 h post-exercise (T(2) ). Significant (P < 0.05) expression fold change differences relative to T(0) were detected for genes functioning in angiogenesis (ANGP2 and VEGFA); Ca(2+) -dependent signalling pathway (PPP3CA); carbohydrate/glucose metabolism (PDK4); fatty acid metabolism/mitochondrial biogenesis (PPPARGC1B); haem biosynthetic process (ALAS1); insulin signalling (FOXO1, PPPARGC1A and SLC2A4); mitogen-activated protein kinase signalling (MAPK14 and MEF2A); and myogenesis (HDAC9). Gene expression associations were identified between PPARGC1A and genes involved in angiogenesis, mitochondrial respiration, glucose transport, insulin signalling and transcriptional regulation. These results suggest that PGC-1α and genes regulated by PGC-1α play significant roles in the skeletal muscle response to exercise and therefore may contribute to performance potential in Thoroughbred horses.
Parasitism by Dermocystidium ranae in a population of Rana esculenta complex in Central Italy and description of Amphibiocystidium n. gen.

We report the enigmatic parasite Dermocystidium ranae in a green frog population (Solomeo, Umbria, Italy) of the Rana esculenta complex, consisting of the parental species R. lessonae (L) and hybrid form R. esculenta (E). In this population a rapid 50% decline of the parental form L was observed. Large dermal U-shaped cysts of D. ranae were found primarily on the ventral aspect of infected individuals, with a significantly higher incidence of infection in the parental species compared to the clonal hybrid. In each form, however, there was little pathological change associated with infection, and the cause of the recent declines of R. lessonae at this site remains unknown. In this paper we present the first ultrastructural description of an amphibian Dermocystidium sp. and we review the taxonomy of Dermocystidium, Dermosporidium and Dermomycoides spp. from amphibians. We conclude that Dermosporidium multigranulare Broz & Kulda, 1954 is synonymous with Dermocystidium ranae Guyénot & Naville, 1922 and, due to lack of sufficient differences between genera and significant dissimilarities with fish Dermocystidium spp. , the 3 amphibian genera are synonymous. We propose that they should be designated to a new genus, Amphibiocystidium n. gen., and Dermocystidium retained for those species parasitic in fish.
Exploring the Role of Online Social Network Dependency in Habit Formation

Online social networking is perhaps the biggest phenomenon of the Internet. Recently, there has been a rising concern over technology dependency. Recognizing that little theoretical and empirical attention has been given to examine technology dependency in the IS discipline, this study aims to examine the role of technology dependency in habit formation in the context of online social networking sites (SNSs). The findings of an empirical study of 406 Facebook users indicate that online social network dependency (OSN dependency) is a significant antecedent of habit. The OSN dependency also plays a role in augmenting SNS users’ perceptions, which indirectly influences habit. Our theoretical model of habit formation explains 47% of the variance. Implications of the findings are discussed.
CVSSearch: searching through source code using CVS comments

CVSSearch is a tool that searches for fragments of source code by using CVS comments. CVS is a version control system that is widely used in the open source community. Our search tool takes advantage of the fact that a CVS comment typically describes the lines of code involved in the commit and this description will typically hold for many future versions. In other words, CVSSearch allows one to better search the most recent version of the code by looking at previous versions to better understand the current version. In this paper we describe our algorithm for mapping CVS comments to the corresponding source code, present a search tool based on this technique, and discuss preliminary feedback.
Metronomic Activity of CD44-Targeted Hyaluronic Acid-Paclitaxel in Ovarian Carcinoma

Purpose: Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid. Metronomic dosing, the frequent administration of chemotherapeutics at substantially lower than maximum tolerated doses (MTD), has been shown to result in reduced normal tissue toxicity and to minimize “off-treatment” exposure resulting in an improved therapeutic ratio. Experimental Design: We tested the hypothesis that hyaluronic acid (HA) conjugates of paclitaxel (TXL; HA-TXL) would exert strong antitumor effects with metronomic (MET) dosing and induce antiangiogenic effects superior to those achieved with MTD administration or with free TXL. Female nude mice bearing SKOV3ip1 or HeyA8 ovarian cancer cells were treated intraperitoneally (i.p.) with MET HA-TXL regimens (or MTD administration) to determine therapeutic and biologic effects. Results: All MET HA-TXL–treated mice and the MTD group revealed significantly reduced tumor weights and nodules compared with controls (all P values < 0.05) in the chemotherapy-sensitive models. However, the MTD HA-TXL–treated mice showed significant weight loss compared with control mice, whereas body weights were not affected in the metronomic groups in HeyA8-MDR model, reflecting reduced toxicity. In the taxane-resistant HeyA8-MDR model, significant reduction in tumor weight and nodule counts was noted in the metronomic groups whereas the response of the MTD group did not achieve significance. While both MTD and metronomic regimens reduced proliferation (Ki-67) and increased apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling), only metronomic treatment resulted in significant reductions in angiogenesis (CD31, microvessel density). Moreover, metronomic treatment resulted in substantial increases in thrombospondin-1 (Tsp-1), an inhibitor of angiogenesis. Conclusions: This study showed that MET HA-TXL regimens have substantial antitumor activity in ovarian carcinoma, likely via a predominant antiangiogenic mechanism. Clin Cancer Res; 18(15); 4114–21. ©2012 AACR.
Monocarboxylate transporters in the central nervous system: distribution, regulation and function

Monocarboxylate transporters (MCTs) are proton‐linked membrane carriers involved in the transport of monocarboxylates such as lactate, pyruvate, as well as ketone bodies. They belong to a larger family of transporters composed of 14 members in mammals based on sequence homologies. MCTs are found in various tissues including the brain where three isoforms, MCT1, MCT2 and MCT4, have been described. Each of these isoforms exhibits a distinct regional and cellular distribution in rodent brain. At the cellular level, MCT1 is expressed by endothelial cells of microvessels, by ependymocytes as well as by astrocytes. MCT4 expression appears to be specific for astrocytes. By contrast, the predominant neuronal monocarboxylate transporter is MCT2. Interestingly, part of MCT2 immunoreactivity is located at postsynaptic sites, suggesting a particular role of monocarboxylates and their transporters in synaptic transmission. In addition to variation in expression during development and upon nutritional modifications, new data indicate that MCT expression is regulated at the translational level by neurotransmitters. Understanding how transport of monocarboxylates is regulated could be of particular importance not only for neuroenergetics but also for areas such as functional brain imaging, regulation of food intake and glucose homeostasis, or for central nervous system disorders such as ischaemia and neurodegenerative diseases.
Meta-analysis of the relationship between risk perception and health behavior: the example of vaccination.

BACKGROUND Risk perceptions are central to many health behavior theories. However, the relationship between risk perceptions and behavior, muddied by instances of inappropriate assessment and analysis, often looks weak. METHOD A meta-analysis of eligible studies assessing the bivariate association between adult vaccination and perceived likelihood, susceptibility, or severity was conducted. RESULTS Thirty-four studies met inclusion criteria (N = 15,988). Risk likelihood (pooled r = .26), susceptibility (pooled r = .24), and severity (pooled r = .16) significantly predicted vaccination behavior. The risk perception-behavior relationship was larger for studies that were prospective, had higher quality risk measures, or had unskewed risk or behavior measures. CONCLUSIONS The consistent relationships between risk perceptions and behavior, larger than suggested by prior meta-analyses, suggest that risk perceptions are rightly placed as core concepts in theories of health behavior.