Miracle-dz/UniFAR-FTUs huggingface dataset:
University of Birmingham Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors

In the adult thymus, the development of self-tolerant thymocytes requires interactions with thymic epithelial cells (TECs). Although both cortical and medullary TECs (cTECs/mTECs) are known to arise from common bipotent TEC progenitors, the phenotype of these progenitors and the timing of the emergence of these distinct lineages remain unclear. Here, we have investigated the phenotype and developmental properties of bipotent TEC progenitors during cTEC/mTEC lineage development. We show that TEC progenitors can undergo a stepwise acquisition of ﬁrst cTEC and then mTEC hallmarks, resulting in the emergence of a progenitor population simultaneously expressing the cTEC marker CD205 and the mTEC regulator Receptor Activator of NF-κ B (RANK). In vivo analysis reveals the capacity of CD205 + TECs to generate functionally competent cortical and medullary microenvironments containing both cTECs and Aire + mTECs. Thus, TEC development involves a stage in which bipotent progenitors can co-express hallmarks of the cTEC and mTEC lineages through sequential acquisition, arguing against a simple binary model in which both lineages diverge simultaneously from bipotent lineage negative TEC progenitors. Rather, our data reveal an unexpected overlap in the phenotypic properties of these bipotent TECs with their lineage-restricted counterparts.
Nucleosome positioning by genomic excluding-energy barriers

Recent genome-wide nucleosome mappings along with bioinformatics studies have confirmed that the DNA sequence plays a more important role in the collective organization of nucleosomes in vivo than previously thought. Yet in living cells, this organization also results from the action of various external factors like DNA-binding proteins and chromatin remodelers. To decipher the code for intrinsic chromatin organization, there is thus a need for in vitro experiments to bridge the gap between computational models of nucleosome sequence preferences and in vivo nucleosome occupancy data. Here we combine atomic force microscopy in liquid and theoretical modeling to demonstrate that a major sequence signaling in vivo are high-energy barriers that locally inhibit nucleosome formation rather than favorable positioning motifs. We show that these genomic excluding-energy barriers condition the collective assembly of neighboring nucleosomes consistently with equilibrium statistical ordering principles. The analysis of two gene promoter regions in Saccharomyces cerevisiae and the human genome indicates that these genomic barriers direct the intrinsic nucleosome occupancy of regulatory sites, thereby contributing to gene expression regulation.
Growing Stem Cells: The Impact of Federal Funding Policy on the US Scientific Frontier

This paper articulates a citation-based approach to science policy evaluation and employs that approach to investigate the impact of the United States’ 2001 policy regarding the federal funding of human embryonic stem cell (hESC) research. We evaluate the impact of the policy on the level of U.S. hESC research, the U.S. position at the knowledge frontier, and the strategic response of U.S. scientists. Consistent with recent research on the science of science and innovation policy, we employ a difference-in-differences approach using bibliometric data with the aim of analyzing the causal impact of the policy on cumulative research. Our estimates suggest that in the aftermath of the 2001 policy, U.S. production of hESC research lagged 35 to 40 percent behind anticipated levels. However, this relative decline was largely concentrated in the years 2001 to 2003 and ameliorated over time. The rebound in U.S. hESC research after 2003 was driven by contributions by researchers at elite U.S. institutions and U.S. researchers who collaborated with international partners. The results suggest that scientists respond strategically to research funding restrictions and that modest science policy shifts can have a significant influence on the within-country composition of research and the pattern of global research collaboration.
Satin: Simple and Efficient Java-based Grid Programming

Grid programming environments need to be both portable and efficient to exploit the computational power of dynamically available resources. In previous work, we have presented the divide-and-conquer based Satin model for parallel computing on clustered wide-area systems. In this paper, we present the Satin implementation on top of our new Ibis platform which combines Java's write once, run everywhere with efficient communication between JVMs. We evaluate Satin/Ibis on the testbed of the EU-funded GridLab project, showing that Satin's load-balancing algorithm automatically adapts both to heterogeneous processor speeds and varying network performance, resulting in efficient utilization of the computing resources. Our results show that when the wide-area links suffer from congestion, Satin's load-balancing algorithm can still achieve around 80% efficiency, while an algorithm that is not grid aware drops to 26% or less.
Computable Convergence Rates for Subgeometrically Ergodic Markov Chains

In this paper, we give quantitative bounds on the $f$-total variation distance from convergence of an Harris recurrent Markov chain on an arbitrary under drift and minorisation conditions implying ergodicity at a sub-geometric rate. These bounds are then specialized to the stochastically monotone case, covering the case where there is no minimal reachable element. The results are illustrated on two examples from queueing theory and Markov Chain Monte Carlo.
Non-verbal responses and affiliative conflict theory.

In previous research cited in support of the affiliative conflict theory of Argyle & Dean (1965) only eye contact was measured, and no effort was made to measure the amount of smiling, a behaviour also relevant to the theory. In the research reported here, interpersonal distance and topic intimacy were manipulated and both eye contact and smiling were measured. In addition, two classes of variables relevant to the interaction process–gestures and paraverbal variables–were measured. Consistent with earlier findings, looking while talking was greatest at low levels of topic intimacy and looking while listening was greatest at the far interaction distance. Contrary to previous findings and predictions made by affiliative conflict theory, the amount of smiling increased as the distance between interactants decreased. This latter finding, along with the data on gestures and paraverbal variables, is discussed as a possible indicator of anxiety, or interpersonal discomfort.
Convergence rate analysis of an asynchronous space decomposition method for convex Minimization

We analyze the convergence rate of an asynchronous space decomposition method for constrained convex minimization in a reflexive Banach space. This method includes as special cases parallel domain decomposition methods and multigrid methods for solving elliptic partial differential equations. In particular, the method generalizes the additive Schwarz domain decomposition methods to allow for asynchronous updates. It also generalizes the BPX multigrid method to allow for use as solvers instead of as preconditioners, possibly with asynchronous updates, and is applicable to nonlinear problems. Applications to an overlapping domain decomposition for obstacle problems are also studied. The method of this work is also closely related to relaxation methods for nonlinear network flow. Accordingly, we specialize our convergence rate results to the above methods. The asynchronous method is implementable in a multiprocessor system, allowing for communication and computation delays among the processors.
Latitude, Birth Date, and Allergy

Background The space and time distribution of risk factors for allergic diseases may provide insights into disease mechanisms. Allergy is believed to vary by month of birth, but multinational studies taking into account latitude have not been conducted. Methods and Findings A questionnaire was distributed in 54 centres to a representative sample of 20- to 44-y-old men and women mainly in Europe but also including regions in North Africa, India, North America, Australia, and New Zealand. Data from 200,682 participants were analyzed. The median prevalence of allergic rhinitis was 22%, with a substantial variation across centres. Overall, allergic rhinitis decreased with geographical latitude, but there were many exceptions. No increase in prevalence during certain winters could be observed. Also, no altered risk by birth month was found, except borderline reduced risks in September and October. Effect estimates obtained by a multivariate analysis of total and specific IgE values in 18,085 individuals also excluded major birth month effects and confirmed the independent effect of language grouping. Conclusion Neither time point of first exposure to certain allergens nor early infections during winter months seems to be a major factor for adult allergy. Although there might be effects of climate or environmental UV exposure by latitude, influences within language groups seem to be more important, reflecting so far unknown genetic or cultural risk factors.
Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice

We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C∶P∶F = 63∶15∶22), a low carbohydrate (LC, C∶P∶F = 38∶25∶37) diet and a severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies.
Ventilatory response of the newborn infant to mild hypoxia

The transition from an immature (biphasic) to a mature (sustained hyperpneic) response to a brief period of sustained hypoxia is believed to be well advanced by postnatal day 10 for newborn infants. However, a review of the supporting evidence convinced us that this issue warranted further, more systematic investigation. Seven healthy term infants aged 2 days to 8 weeks were studied. The ventilatory response (VR) elicited by 5 min breathing of 15% O2 was measured during quiet sleep. Arterial SaO2 (pulse oximeter) and minute ventilation (expressed as a change from control, ΔV′i) were measured continuously. Infants were wrapped in their usual bedding and slept in open cots at room temperature (23°–25°).
PageTailor: reusable end-user customization for the mobile web

Most pages on the Web are designed for the desktop environment and render poorly on the small screens available on handheld devices. We introduce Reusable End-User Customization (REUC), a technique that lets end users adapt the layout of Web pages by removing, resizing and moving page elements. REUC records the user's customizations and automatically reapplies them on subsequent visits to the same page or to other, similar pages, on the same Web site. We present PageTailor, a REUC prototype based on the Minimo Web browser that runs on Windows Mobile PDAs. We show that users can utilize PageTailor to adapt sophisticated Web sites, such as Amazon, BBC and MSN, for browsing on a PDA. Moreover, the customizations remain effective for up to a year, even as the content of pages is updated, and can be reused across similar pages, limiting the customization effort required to browse a site.
Integrated Radio Resource Allocation for Multihop Cellular Networks With Fixed Relay Stations

Recently, the notion that a logical next step towards future mobile radio networks is to introduce multihop relaying into cellular networks, has gained wide acceptance. Nevertheless, due to the inherent drawbacks of multihop relaying, e.g., the requirement for extra radio resources for relaying hops, and the sensitivity to the quality of relaying routes, multihop cellular networks (MCNs) require a well-designed radio resource allocation strategy in order to secure performance gains. In this paper, the optimal radio resource allocation problem in MCNs, with the objective of throughput maximization, is formulated mathematically and proven to be NP-hard. Considering the prohibitive complexity of finding the optimal solution for such an NP-hard problem, we propose an efficient heuristic algorithm, named integrated radio resource allocation (IRRA), to find suboptimal solutions. The IRRA is featured as a low-complexity algorithm that involves not only base station (BS) resource scheduling, but also routing and relay station (RS) load balancing. Specifically, a load-based scheme is developed for routing. A mode-aware BS resource-scheduling scheme is proposed for handling links in different transmission modes, i.e., direct or multihop. Moreover, a priority-based RS load balancing approach is presented for the prevention of the overloading of RSs. Within the framework of the IRRA, the above three functions operate periodically with coordinated interactions. To prove the effectiveness of the proposed IRRA algorithm, a case study was carried out based on enhanced uplink UMTS terrestrial radio access/frequency-division duplex with fixed RSs. The IRRA is evaluated through system level simulations, and compared with two other cases: 1) nonrelaying and 2) relaying with a benchmark approach. The results show that the proposed algorithm can ensure significant gains in terms of cell throughput
Transactivation specificity is conserved among p53 family proteins and depends on a response element sequence code

Structural and biochemical studies have demonstrated that p73, p63 and p53 recognize DNA with identical amino acids and similar binding affinity. Here, measuring transactivation activity for a large number of response elements (REs) in yeast and human cell lines, we show that p53 family proteins also have overlapping transactivation profiles. We identified mutations at conserved amino acids of loops L1 and L3 in the DNA-binding domain that tune the transactivation potential nearly equally in p73, p63 and p53. For example, the mutant S139F in p73 has higher transactivation potential towards selected REs, enhanced DNA-binding cooperativity in vitro and a flexible loop L1 as seen in the crystal structure of the protein–DNA complex. By studying, how variations in the RE sequence affect transactivation specificity, we discovered a RE-transactivation code that predicts enhanced transactivation; this correlation is stronger for promoters of genes associated with apoptosis.
Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance*

Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies, and patients have a dismal prognosis, with a <10% five-year survival rate. The identification of markers that can predict the potential for metastases will have a great effect in improving patient outcomes. In this study, we used differential proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to identify proteins that are differentially expressed in metastatic and primary RCC. We identified 1256 non-redundant proteins, and 456 of these were quantified. Further analysis identified 29 proteins that were differentially expressed (12 overexpressed and 17 underexpressed) in metastatic and primary RCC. Dysregulated protein expressions of profilin-1 (Pfn1), 14–3-3 zeta/delta (14–3-3ζ), and galectin-1 (Gal-1) were verified on two independent sets of tissues by means of Western blot and immunohistochemical analysis. Hierarchical clustering analysis showed that the protein expression profile specific for metastatic RCC can distinguish between aggressive and non-aggressive RCC. Pathway analysis showed that dysregulated proteins are involved in cellular processes related to tumor progression and metastasis. Furthermore, preliminary analysis using a small set of tumors showed that increased expression of Pfn1 is associated with poor outcome and is a potential prognostic marker in RCC. In addition, 14–3-3ζ and Gal-1 also showed higher expression in tumors with poor prognosis than in those with good prognosis. Dysregulated proteins in metastatic RCC represent potential prognostic markers for kidney cancer patients, and a greater understanding of their involved biological pathways can serve as the foundation of the development of novel targeted therapies for metastatic RCC.
Rediversion after urinary diversion: A single-centre experience

Abstract Objective. This study aimed to reveal the late results of rediversion after urinary diversion. Material and methods. From 1985 to 2009, 28 patients underwent rediversion at the Department of Urology, Lund University Hospital, Sweden. Median follow-up after rediversion was 147 months (range 7–300 months, interquartile range 63–214). The following rediversions were performed: ileal conduit, cutaneous ureterostomy, ureterosigmoidostomy and rectal bladder to continent cutaneous diversion (group I, n = 17); cutaneous ureterostomy to neobladder (group II, n = 1); ileal conduit and cutaneous ureterostomy to gastric conduit (group III, n = 2); and continent cutaneous diversion and neobladder to ileal conduit (group IV, n = 8). Results. In group I, reoperations were necessary after rediversion in nine of the 17 patients. Excellent functional results were obtained in 14 patients. Two patients, both with Kock pouches, underwent multiple operations and finally required rediversion to an ileal conduit. The sole patient in group II had a ureteric reimplantation owing to ureterointestinal stricture and is now continent but performs clean intermittent catheterization. Both patients in group III underwent reoperations owing to ureteric strictures and renal stones. In group IV, one patient had ureteric stenosis, and one died owing to complications related to later surgery for small bowel obstruction. Conclusions. Complications are common after urinary rediversion, and several of the present patients required reoperations for a variety of reasons. Modern techniques for continent cutaneous diversion can provide excellent functional results. Patients with difficulties in accepting a urostomy bag pose special problems and need extensive information and counselling.
Evaluating the Validity of Simplified Chinese Version of LIWC in Detecting Psychological Expressions in Short Texts on Social Network Services

The increasing need of automated analyzing web texts especially the short texts on Social Network Services (SNS) brings new demands of computerized text analysis instruments. The psychometric properties are the basis of the extensive use of these instruments such as the Linguistic Inquiry and Word Count (LIWC). For this study, Sina Weibo statuses were analyzed via rater coding and Simplified Chinese version of LIWC (SCLIWC), in order to evaluate the validity of SCLIWC in detecting psychological expressions in Weibo statuses (n = 60) and in identifying the psychological meaning of a single Weibo status (n = 11). Significant correlations between human ratings and SCLIWC scores and the high sensitivities of capturing single statuses with certain expressions identified by raters, proved the validity of SCLIWC in detecting psychological expressions. The results also suggested that, the efficiency of SCLIWC in detecting psychological expressions of SNS short texts could be higher if using status count scoring method, rather than the word count method as the common usage of LIWC. However, SCLIWC may not perform well in identifying the psychological meaning of a single piece of SNS short text because of its over-identification of target expressions. This study provided primary evidence of validity of SCLIWC, as well as the proper way of using it efficiently on SNS short texts.
Anticonvulsant mechanisms of piperine, a piperidine alkaloid

Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms. Furthermore the latency for development of convulsions and mortality rate was recorded in different experimental mouse models of epilepsy (pentylenetetrazole, maximal electroshock, NMDA, picrotoxin, bicuculline, BAYK-8644, strychnine-induced convulsions) after administration of various doses of piperine (5, 10 and 20 mg/kg, i.p.). Finally, the effect of piperine on Na+ and Ca2+ channels were evaluated using the whole cell patch clamp techniqueOur results revealed that piperine decreased mortality in the MES-induced seizure model. Moreover, piperine (10 mg/kg) delayed the onset of tonic clonic convulsions in the pentylenetetrazole test and reduced associated mortality. Furthermore, an anticonvulsant dose of piperine also delayed the onset of tonic clonic seizures in strychnine, picrotoxin and BAY K-8644. Complete protection against mortality was observed in BAYK-8644 induced convulsions. Finally, whole cell patch clamp analysis suggested an inhibitory effect of piperine on Na+ channels. Together, our data suggest Na+ channel antagonist activity as a contributor to the complex anticonvulsant mechanisms of piperine.