Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma Glutamine is a Minor Precursor for the Synthesis of Citrulline: a Multispecies Study

Glutamine is considered the main precursor for citrulline synthesis in many species, including humans. The transfer of 15N from 2‐[15N] glutamine to citrulline has been used as evidence for this precursor‐product relationship. Research in mice, however, has shown that nitrogen and carbon tracers follow different moieties of glutamine and that glutamine contribution to the synthesis of citrulline is minor. It is unclear if this small contribution of glutamine is also true in other species, including humans. For this reason the current research was designed to determine the contribution of glutamine to citrulline production using nitrogen and carbon skeleton tracers in multiple species. Humans (n=4), pigs (n=5), rats (n=6), and mice (n=5), were infused with L‐2‐[15N] and L‐[2H5] glutamine, and L‐5,5‐[2H2] citrulline for 4 h. The contribution of glutamine to citrulline synthesis was calculated using different precursor‐product pairs: ‘glutamine M+1 to citrulline M+1’, ‘2‐[15N] glutamine to 2‐[15N] citrulline’ and ‘[2H5] glutamine to [2H5] citrulline’. Species specific differences in glutamine and citrulline fluxes were found (P < 0.001), with rats having the largest fluxes, followed by mice, pigs and humans (glutamine: 3789±162, 3228±89, 882±39, 423±25 μmol•kg−1•h−1 and citrulline: 198±11, 81±5, 47±3, 11±2 μmol•kg−1•h−1, respectively). The contribution of glutamine to citrulline estimated using ‘glutamine M+1 to citrulline M+1’ ranged from 88±8% in humans to 46±3% in pigs (rats= 57±3%; mice= 60± 4%). However, using 2‐[15N] glutamine and 2‐[15N] citrulline as precursor and product yielded values of 48±5% in humans and 28±2% in pigs (rats=35±3%; mice= 29± 4%). Furthermore, the use of ‘[2H5] glutamine to [2H5] citrulline’ yielded lower values (P < 0.001), resulting in a contribution of glutamine to the synthesis of citrulline of 10±1% in humans and 3±0.4% in pigs (rats=17±1%; mice= 14± 1%). In conclusion, the use of [15N] glutamine to determine the contribution of glutamine to the synthesis of citrulline yields higher values than the use of the deuterated tracer. This is due to the recycling of the 15N label and the non‐specific incorporation into any of the three nitrogen groups of citrulline. In contrast, the deuterated tracer follows the carbon skeleton of glutamine and for this reason provides a truthful estimate of the contribution of glutamine to the synthesis of citrulline. This work shows that glutamine is a minor precursor for the synthesis of citrulline in humans, pigs, rats and mice.
Connectivity pattern differences bilaterally in the cerebellum posterior lobe in healthy subjects after normal sleep and sleep deprivation: a resting-state functional MRI study

Objective The aim of this study was to use functional magnetic resonance imaging (fMRI) technique to explore the resting-state functional connectivity (rsFC) differences of the bilaterial cerebellum posterior lobe (CPL) after normal sleep (NS) and after sleep deprivation (SD). Methods A total of 16 healthy subjects (eight males, eight females) underwent an fMRI scan twice at random: once following NS and the other following 24 hours’ SD, with an interval of 1 month between the two scans. The fMRI scanning included resting state and acupuncture stimulation. The special activated regions located during the acupuncture stimulation were selected as regions of interest for rsFC analysis. Results Bilateral CPLs were positively activated by acupuncture stimulation. In the NS group, the left CPL showed rsFC with the bilateral CPL, bilateral frontal lobe (BFL), left precuneus and right inferior parietal lobule, while the right CPL showed rsFC with the bilateral temporal lobe, right cerebellum anterior lobe, right CPL, left frontal lobe, left anterior cingulate, right posterior cingulate, and bilateral inferior parietal lobule. In the SD group, the left CPL showed rsFC with the left posterior cingulate gyrus bilateral CPL, left precuneus, left precentral gyrus, BFL, and the left parietal lobe, while the right CPL showed rsFC with bilateral cerebellum anterior lobe, bilateral CPL, left frontal lobe and left temporal lobe. Compared with the NS group, the left CPL had increased rsFC in the SD group with the right inferior frontal gyrus, right fusiform gyrus, right cingulate gyrus, right thalamus, and bilateral precuneus, and decreased rsFC with the BFL, while the right CPL had increased rsFC with the left superior frontal gyrus and decreased rsFC with the left precentral gyrus, right superior temporal gyrus, and the BFL. Conclusion Bilateral CPL are possibly involved in acupuncture stimulation in different manners, and the right CPL showed more rsFC impairment.
A feasibility study using TomoDirect for craniospinal irradiation

The feasibility of delivering craniospinal irradiation (CSI) with TomoDirect is investigated. A method is proposed to generate TomoDirect plans using standard three‐dimensional (3D) beam arrangements on Tomotherapy with junctioning of these fields to minimize hot or cold spots at the cranial/spinal junction. These plans are evaluated and compared to a helical Tomotherapy and a three‐dimensional conformal therapy (3D CRT) plan delivered on a conventional linear accelerator (linac) for CSI. The comparison shows that a TomoDirect plan with an overlap between the cranial and spinal fields might be preferable over Tomotherapy plans because of decreased low dose to large volumes of normal tissues outside of the planning target volume (PTV). Although the TomoDirect plans were not dosimetrically superior to a 3D CRT linac plan, the patient can be easily treated in the supine position, which is often more comfortable and efficient from an anesthesia standpoint. TomoDirect plans also have only one setup position which obviates the need for matching of fields and feathering of junctions, two issues encountered with conventional 3D CRT plans. TomoDirect plans can be delivered with comparable treatment times to conventional 3D plans and in shorter times than a Tomotherapy plan. In this paper, a method is proposed for creating TomoDirect craniospinal plans, and the dosimetric consequences for choosing different planning parameters are discussed. PACS number: 87.55. D‐
Multi-mode circuit quantum electrodynamics

Submitted for the MAR11 Meeting of The American Physical Society Multi-mode circuit quantum electrodynamics JEROME BOURASSA, Universite de Sherbrooke, JAY M. GAMBETTA, IQC and University of Waterloo, ALEXANDRE BLAIS, Universite de Sherbrooke — In circuit QED experiments with low anharmonicity superconducting qubits, like the transmon, it has been shown how the many-level structure of the qubits can give rise to non-trivial effects. Examples are the straddling regime [1] and high-power qubit readout induced by qubit nonlinearities [2]. In the same spirit, there are also clear experimental evidences to the effect that higher resonator modes play an important role in setting the size of the qubit-qubit flip-flop interaction mediated by virtual resonator photons [3] and the qubit decay rate due to the Purcell effect [4]. In this talk we explore how these higher modes can be taken into account in a theoretical description of the system, and how they affect the flip-flop and Purcell decay rates. [1] Houck et al., Phys Rev. A 76, 042319 (2007); Srinivasan et al, V26.00006, 2010 March Meeting. [2] Reed et al, Phys. Rev. Lett. 105, 173601 (2010), Bishop et al, Phys. Rev. Lett. 105, 100505 (2010), Boissonneault et al, Phys. Rev. Lett. 105, 100504 (2010). [3] Filipp et al, arXiv:1011.3732v1 [4] Houck et al, PRL 101, 080502 (2008) Jerome Bourassa Universite de Sherbrooke Date submitted: 27 Dec 2010 Electronic form version 1.4
Identification of the Additional Mitochondrial Liabilities of 2-Hydroxyflutamide When Compared With its Parent Compound, Flutamide in HepG2 Cells

The androgen receptor antagonist, flutamide, is strongly associated with idiosyncratic drug-induced liver injury (DILI). Following administration, flutamide undergoes extensive first-pass metabolism to its primary metabolite, 2-hydroxyflutamide. Flutamide is a known mitochondrial toxicant; however there has been limited investigation into the potential mitochondrial toxicity of 2-hydroxyflutamide and its contribution to flutamide-induced liver injury. In this study we have used the acute glucose or galactose-conditioning of HepG2 cells to compare the mitochondrial toxicity of flutamide, 2-hydroxyflutamide and the structurally-related, non-hepatotoxic androgen receptor antagonist, bicalutamide. Compound-induced changes in mitochondrial oxygen consumption rate were assessed using Seahorse technology. Permeabilization of cells and delivery of specific substrates and inhibitors of the various respiratory complexes provided more detailed information on the origin of mitochondrial perturbations. These analyses were supported by assessment of downstream impacts including changes in cellular NAD+/NADH ratio. Bicalutamide was not found to be a mitochondrial toxicant, yet flutamide and 2-hydroxyflutamide significantly reduced basal and maximal respiration. Both flutamide and 2-hydroxyflutamide significantly reduced respiratory complex I-linked respiration, though 2-hydroxyflutamide also significantly decreased complex II and V-linked respiration; liabilities not demonstrated by the parent compound. This study has identified for the first time, the additional mitochondrial liabilities of the major metabolite, 2-hydroxyflutamide compared with its parent drug, flutamide. Given the rapid production of this metabolite upon administration of flutamide, but not bicalutamide, we propose that the additional mitochondrial toxicity of 2-hydroxyflutamide may fundamentally contribute to the idiosyncratic DILI seen in flutamide-treated, but not bicalutamide-treated patients.
Effect of Sucrose on the Physicochemical Properties , Organoleptic Qualities and Shelf-Life Stability of Aonla ( Emblica Officinalis ) Candy

This study was conducted with a view to find out the most suitable concentration of sugar for the preparation of aonla candy. In this research, six sets of aonla candy samples were made with varying syrup concentration (80 %, 70 %, 60 %, 50 % and 40 %) using sucrose and fresh aonla candy was used as control. The shelf-life stability of aonla candy was studied for 0 to 120 days at ambient temperature. The results obtained from the study revealed that moisture and total fiber content of aonla candy decreased with storage time while protein, fat, ash, total carbohydrate were increased. Ascorbic acid and total phenol content was found to decrease with increasing storage period. However, sufficient amount of ascorbic acid was retained in all samples. Titrable acidity was also increased with progressive increase of storage. Reducing sugar and total sugar was found to increase while non-reducing sugar decreased with the advancement of storage time. Almost all samples had good sensory in terms of colour, flavour, texture, taste and overall acceptability. On the basis of the results obtained in the present investigation, it can be drawn that application of various concentration of sugar syrup significantly affected the quality parameters of aonla candy.
When to recommend a second autograft in patients with relapsed myeloma?

Abstract In the current evolving landscape of myeloma therapies, no recommended salvage strategy exists for patients with relapsed multiple myeloma (MM) after initial successful autologous stem cell transplantation (ASCT) and therapeutic options extend from conventional chemotherapy and novel agents to second autologous and allogeneic transplants. In this article, we summarize the documented evidence about the utilization of second ASCT in patients with relapsed MM after a primary auto-graft and discuss the correct timing for such a salvage approach, the individual characteristics of patients who will benefit more, as well as the therapeutic role of second ASCT in the modern era of forthcoming anti-myeloma treatments.
SEXUAL BEHAVIOR IN MALE ADOLESCENTS WITH AUTISM AND ITS RELATION TO SOCIAL-SEXUAL SKILLS IN THE KINGDOM OF SAUDIARABIA MohamedA

The present study aimed to identify common sexual behavior among adolescents with autism, where parents and teachers of sixty-one male adolescents from twelve to twenty-one years of age were recruited from three cities in the Kingdom of Saudi Arabia. They were asked to respond to a sexual behavior questionnaire, and a social-sexual skills questionnaire. Only teachers were asked to respond to a screening questionnaire for Asperger syndrome and other high functioning autism spectrum disorders to determine the functional level of the adolescents with autism in the sample. This resulted in thirty-two adolescents selected from the main sample; fifteen of them with high functioning autism, and seventeen with low functioning autism. Overall, both parents and teachers reported inappropriate sexual behavior expressed by the adolescents with autism. The results also showed significant correlations between both the social-sexual skills and reported sexual behaviors in all subtests and total scores. The high functioning adolescents with autism displayed significantly less inappropriate sexual behavior and significantly more social-sexual skills when compared to adolescents with low functioning autism.
Reconciling the Firm Size and Innovation Puzzle

Since Schumpeter, there has been a lively debate regarding the optimal firm size for innovation. Empirical results have settled into a puzzle: R&D spending increasing with scale, while R&D productivity decreases with scale. Thus large firms appear irrational. We propose and test two alternative resolutions of the puzzle: 1) that it arises from measurement problems, and 2) that firm size endogenously drives R&D strategy, and that the returns to R&D strategies depend on scale. To test both propositions we use recently available NSF BRDIS survey data of firms R&D practices (strategies) as well as a broader measure of R&D productivity. Using the broader measure, we find that both R&D spending and R&D productivity increase with scale—thus offering one resolution to the puzzle. We further find that while large firms and small firms differ in the types of R&D they conduct, there is no type whose returns decrease in scale—there are merely types for which the small firm penalty is less severe. Thus Schumpeter appears to be correct--large firms are the major engine of growth, they both spend more in aggregate than small firms, and are more productive with that spending.
E3 ubiquitin ligase Bre1 couples sister chromatid cohesion establishment to DNA replication in Saccharomyces cerevisiae

Bre1, a conserved E3 ubiquitin ligase in Saccharomyces cerevisiae, together with its interacting partner Lge1, are responsible for histone H2B monoubiquitination, which regulates transcription, DNA replication, and DNA damage response and repair, ensuring the structural integrity of the genome. Deletion of BRE1 or LGE1 also results in whole chromosome instability. We discovered a novel role for Bre1, Lge1 and H2Bub1 in chromosome segregation and sister chromatid cohesion. Bre1’s function in G1 and S phases contributes to cohesion establishment, but it is not required for cohesion maintenance in G2 phase. Bre1 is dispensable for the loading of cohesin complex to chromatin in G1, but regulates the localization of replication factor Mcm10 and cohesion establishment factors Ctf4, Ctf18 and Eco1 to early replication origins in G1 and S phases, and promotes cohesin subunit Smc3 acetylation for cohesion stabilization. H2Bub1 epigenetically marks the origins, potentially signaling the coupling of DNA replication and cohesion establishment.
Dried Blood Spots - Preparing and Processing for Use in Immunoassays and in Molecular Techniques

The idea of collecting blood on a paper card and subsequently using the dried blood spots (DBS) for diagnostic purposes originated a century ago. Since then, DBS testing for decades has remained predominantly focused on the diagnosis of infectious diseases especially in resource-limited settings or the systematic screening of newborns for inherited metabolic disorders and only recently have a variety of new and innovative DBS applications begun to emerge. For many years, pre-analytical variables were only inappropriately considered in the field of DBS testing and even today, with the exception of newborn screening, the entire pre-analytical phase, which comprises the preparation and processing of DBS for their final analysis has not been standardized. Given this background, a comprehensive step-by-step protocol, which covers al the essential phases, is proposed, i.e., collection of blood; preparation of blood spots; drying of blood spots; storage and transportation of DBS; elution of DBS, and finally analyses of DBS eluates. The effectiveness of this protocol was first evaluated with 1,762 coupled serum/DBS pairs for detecting markers of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections on an automated analytical platform. In a second step, the protocol was utilized during a pilot study, which was conducted on active drug users in the German cities of Berlin and Essen.
Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS Dietary modification has been recommended for treatment of nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent its development. We performed a prospective study to examine the association between diet quality change and change in liver fat. We also examined the association between genetic risk score and liver fat change in individuals with different levels of diet quality change. METHODS Our study included 1521 participants who attended the seventh and eighth examinations (1998-2001 and 2005-2008) of the second-generation cohort or attended the first and second examinations (2002-2005 and 2008-2011) of the third-generation cohort in the Framingham Heart Study. The self-administered semiquantitative 126-item Harvard food frequency questionnaire was used to determine dietary intake in the year leading up to an examination. We assessed levels of liver fat using liver-phantom ratio (LPR) on computed tomography images from 2002 through 2005 and again from 2008 through 2011. LPR values are inversely related to liver fat: increased LPR indicates decreased liver fat. We examined associations of changes in 2 diet scores, the Mediterranean-style diet score (MDS) and Alternative Healthy Eating Index (AHEI), with changes in liver fat and new-onset fatty liver. We evaluated interactions between diet score change and a weighted genetic risk score for NAFLD, determined based on multiple single-nucleotide polymorphisms identified in genome-wide association studies of NAFLD. The primary outcome was change in LPR between baseline and follow-up measurement. RESULTS For each 1 standard deviation increase in MDS, the LPR increased (meaning liver fat decreased) by 0.57 (95% confidence interval [CI] 0.27-0.86; P < .001) and the odds for incident fatty liver decreased by 26% (95% CI 10%-39%; P = .002). For each 1 standard deviation increase in AHEI, LPR increased by 0.56 (95% CI 0.29-0.84; P < .001) and the odds for incident fatty liver decreased by 21% (95% CI 5%-35%; P = .02). Increased diet scores were also associated with reduced odds of developing more-advanced fatty liver. Higher genetic risk scores were associated with increased liver fat accumulation in participants who had decreased MDS (P < .001) or AHEI scores (P = .001), but not in those with stable or improved diet scores (P for gene-diet interaction <.001). CONCLUSIONS In an analysis of participants in the Framingham Heart Study, increasing diet quality, determined based on MDS and AHEI scores, is associated with less liver fat accumulation and reduced risk for new-onset fatty liver. An improved diet is particularly important for individuals with a high genetic risk for NAFLD.
The role of derivative suffix productivity in the visual word recognition of complex words

In this article we present two lexical decision experiments that examine the role of base frequency and of derivative suffix productivity in visual recognition of Spanish words. In the first experiment we find that complex words with productive derivative suffixes result in lower response times than those with unproductive derivative suffixes. There is no significant effect for base frequency, however. In experiment two, the same procedure was undertaken with pseudowords, showing that when they are composed by productive derivative suffixes they take longer to be rejected than when they are composed by unproductive derivative suffixes. Again, the role of base frequency fails to reach significance. These results endorse the view that derivative suffixes have a relevant role in visual recognition of complex words. According to our results, derivative suffixes create the conditions for taking a lexical candidate as a legal lexical entry and therefore they contribute decisively to the lexical decision.
PiCANet: Learning Pixel-Wise Contextual Attention for Saliency Detection

Contexts play an important role in the saliency detection task. However, given a context region, not all contextual information is helpful for the final task. In this paper, we propose a novel pixel-wise contextual attention network, i.e., the PiCANet, to learn to selectively attend to informative context locations for each pixel. Specifically, for each pixel, it can generate an attention map in which each attention weight corresponds to the contextual relevance at each context location. An attended contextual feature can then be constructed by selectively aggregating the contextual information. We formulate the proposed PiCANet in both global and local forms to attend to global and local contexts, respectively. Both models are fully differentiable and can be embedded into CNNs for joint training. We also incorporate the proposed models with the U-Net architecture to detect salient objects. Extensive experiments show that the proposed PiCANets can consistently improve saliency detection performance. The global and local PiCANets facilitate learning global contrast and homogeneousness, respectively. As a result, our saliency model can detect salient objects more accurately and uniformly, thus performing favorably against the state-of-the-art methods.
Gas Dynamics and Kinetics in the Cometary Coma: Theory and Observations

Our ability to describe the physical state of the expanding coma affects fundamental areas of cometary study both directly and indirectly. In order to convert measured abundances of gas species in the coma to gas production rates, models for the distribution and kinematics of gas species in the coma are required. Conversely, many different types of observations, together with laboratory data and theory, are still required to determine coma model attributes and parameters. Accurate relative and absolute gas production rates and their variations with time and from comet to comet are crucial to our basic understanding of the composition and structure of cometary nuclei and their place in the solar system. We review the gas dynamics and kinetics of cometary comae from both theoretical and observational perspectives, which are important for understanding the wide variety of physical conditions that are encountered.