Miracle-dz/UniFAR-FTUs huggingface dataset:
Racial variation in medical outcomes among living kidney donors.

BACKGROUND Data regarding health outcomes among living kidney donors are lacking, especially among nonwhite persons. METHODS We linked identifiers from the Organ Procurement and Transplantation Network (OPTN) with administrative data of a private U.S. health insurer and performed a retrospective study of 4650 persons who had been living kidney donors from October 1987 through July 2007 and who had post-donation nephrectomy benefits with this insurer at some point from 2000 through 2007. We ascertained post-nephrectomy medical diagnoses and conditions requiring medical treatment from billing claims. Cox regression analyses with left and right censoring to account for observed periods of insurance benefits were used to estimate absolute prevalence and prevalence ratios for diagnoses after nephrectomy. We then compared prevalence patterns with those in the 2005-2006 National Health and Nutrition Examination Survey (NHANES) for the general population. RESULTS Among the donors, 76.3% were white, 13.1% black, 8.2% Hispanic, and 2.4% another race or ethnic group. The median time from donation to the end of insurance benefits was 7.7 years. After kidney donation, black donors, as compared with white donors, had an increased risk of hypertension (adjusted hazard ratio, 1.52; 95% confidence interval [CI], 1.23 to 1.88), diabetes mellitus requiring drug therapy (adjusted hazard ratio, 2.31; 95% CI, 1.33 to 3.98), and chronic kidney disease (adjusted hazard ratio, 2.32; 95% CI, 1.48 to 3.62); findings were similar for Hispanic donors. The absolute prevalence of diabetes among all donors did not exceed that in the general population, but the prevalence of hypertension exceeded NHANES estimates in some subgroups. End-stage renal disease was identified in less than 1% of donors but was more common among black donors than among white donors. CONCLUSIONS As in the general U.S. population, racial disparities in medical conditions occur among living kidney donors. Increased attention to health outcomes among demographically diverse kidney donors is needed. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)
Astrocytic swelling in the ipsilateral substantia nigra after occlusion of the middle cerebral artery in rats.

BACKGROUND AND PURPOSE Focal cerebral ischemia results in neuronal changes in remote areas that have fiber connections with the ischemic area. We reported previously that a high-signal-intensity lesion was observed in the substantia nigra after striatal infarction on T2-weighted MR images in both clinical and experimental cases. However, the origin of these changes in signal intensity remains unclear. The aim of this study was to investigate the nigral changes by examining the correlation between the apparent diffusion coefficient (ADC) and the tissue structure. METHODS Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Four days after the occlusion, when T2-weighted images revealed the presence of an area of high signal intensity in the ipsilateral substantia nigra, diffusion-weighted imaging was performed using a 4.7-T superconductive MR unit, and the ADCs were calculated and imaged. Histopathologic examination by both light and electron microscopy was performed on day 4 after surgery. RESULTS Diffusion-weighted images showed an area of high signal intensity in the ipsilateral substantia nigra, and the ADC map revealed uniform reduction of the ADC in this area. Swelling of astrocytic end-feet was observed, especially in the pars reticulata. CONCLUSION These findings suggest that MR changes in the ipsilateral substantia nigra after striatal injury consist mainly of swelling in the astrocytic end-feet.
Meiotic Crossover Control by Concerted Action of Rad51-Dmc1 in Homolog Template Bias and Robust Homeostatic Regulation

During meiosis, repair of programmed DNA double-strand breaks (DSBs) by recombination promotes pairing of homologous chromosomes and their connection by crossovers. Two DNA strand-exchange proteins, Rad51 and Dmc1, are required for meiotic recombination in many organisms. Studies in budding yeast imply that Rad51 acts to regulate Dmc1's strand exchange activity, while its own exchange activity is inhibited. However, in a dmc1 mutant, elimination of inhibitory factor, Hed1, activates Rad51's strand exchange activity and results in high levels of recombination without participation of Dmc1. Here we show that Rad51-mediated meiotic recombination is not subject to regulatory processes associated with high-fidelity chromosome segregation. These include homolog bias, a process that directs strand exchange between homologs rather than sister chromatids. Furthermore, activation of Rad51 does not effectively substitute for Dmc1's chromosome pairing activity, nor does it ensure formation of the obligate crossovers required for accurate homolog segregation. We further show that Dmc1's dominance in promoting strand exchange between homologs involves repression of Rad51's strand-exchange activity. This function of Dmc1 is independent of Hed1, but requires the meiotic kinase, Mek1. Hed1 makes a relatively minor contribution to homolog bias, but nonetheless this is important for normal morphogenesis of synaptonemal complexes and efficient crossing-over especially when DSB numbers are decreased. Super-resolution microscopy shows that Dmc1 also acts to organize discrete complexes of a Mek1 partner protein, Red1, into clusters along lateral elements of synaptonemal complexes; this activity may also contribute to homolog bias. Finally, we show that when interhomolog bias is defective, recombination is buffered by two feedback processes, one that increases the fraction of events that yields crossovers, and a second that we propose involves additional DSB formation in response to defective homolog interactions. Thus, robust crossover homeostasis is conferred by integrated regulation at initiation, strand-exchange and maturation steps of meiotic recombination.
Permanent or reversible conjugation of 2′-O- or 5′-O-aminooxymethylated nucleosides with functional groups as a convenient and efficient approach to the modification of RNA and DNA sequences

2′-O-Aminooxymethyl ribonucleosides are prepared from their 3′,5′-disilylated 2′-O-phthalimidooxymethyl derivatives by treatment with NH4F in MeOH. The reaction of these novel ribonucleosides with 1-pyrenecarboxaldehyde results in the efficient formation of stable and yet reversible ribonucleoside 2′-conjugates in yields of 69–82%. Indeed, exposure of these conjugates to 0.5 M tetra-n-butylammonium fluoride (TBAF) in THF results in the cleavage of their iminoether functions to give the native ribonucleosides along with the innocuous nitrile side product. Conversely, the reaction of 5-cholesten-3-one or dansyl chloride with 2′-O-aminooxymethyl uridine provides permanent uridine 2′-conjugates, which are left essentially intact upon treatment with TBAF. Alternatively, 5′-O-aminooxymethyl thymidine is prepared by hydrazinolysis of its 3′-O-levulinyl-5′-O-phthalimidooxymethyl precursor. Pyrenylation of 5′-O-aminooxymethyl thymidine and the sensitivity of the 5′-conjugate to TBAF further exemplify the usefulness of this nucleoside for modifying DNA sequences either permanently or reversibly. Although the versatility and uniqueness of 2′-O-aminooxymethyl ribonucleosides in the preparation of modified RNA sequences is demonstrated by the single or double incorporation of a reversible pyrenylated uridine 2′-conjugate into an RNA sequence, the conjugation of 2′-O-aminooxymethyl ribonucleosides with aldehydes, including those generated from their acetals, provides reversible 2′-O-protected ribonucleosides for potential applications in the solid-phase synthesis of native RNA sequences. The synthesis of a chimeric polyuridylic acid is presented as an exemplary model.
Multi-lingual Semantic Matching with OrdPath in Relational Systems

The volume of information in natural languages in electronic format is increasing exponentially. The demographics of users of information management systems are becoming increasingly multilingual. Together these trends create a requirement for information management systems to support processing of information in multiple natural languages seamlessly. Database systems, the backbones of information management, should support this requirement effectively and efﬁciently. Earlier research in this area had proposed multilingual operators [7, 8] for relational database systems, and discussed their implementation using existing database features. In this paper, we speciﬁcally focus on the SemEQUAL operator [8], implementing a multilingual semantic matching predicate using WordNet [12]. We explore the implementation of SemEQUAL using OrdPath [10], a positional representation for nodes of a hierarchy that is used successfully for supporting XML documents in relational systems. We propose the use of OrdPath to represent position within the Wordnet hierarchy, leveraging its ability to compute transitive closures efﬁciently. We show theoretically that an implementation using OrdPath will outperform those implementations proposed previously. Our initial experimental results conﬁrm this analysis, and show that the OrdPath implementation performs signiﬁcantly better. Further, since our technique is not speciﬁcally rooted to linguistic hierarchies, the same approach may beneﬁt other applications that utilize alternative hierarchical ontologies.
The construction of an edifice: the story of a First Great Debate

Over the last decade, critical historiographers have established that the story of a First Debate, which tells of a struggle between idealism/utopianism and realism between the 1920s and 1940s, is a misleading characterisation of the history of academic international thought. This article adds to this critical literature by exploring how the story of a First Debate became a part of disciplinary orthodoxy between the 1950s and 1990s. Our analysis reveals that scholars produced the myth of a First Debate by detaching the concept of a struggle between idealism and realism from the unique historical milieu in which it was conceived, and employing this dichotomy for a new set of rhetorical purposes. We use these findings to suggest refinements for the historiographical methods employed to understand past international thought, and to illuminate the historical contingency of contemporary notions of scholarly purpose in international relations.
Graph Wavelets for Multiscale Community Mining

We develop a signal processing approach to the multiscale detection of communities in networks, that is of groups of nodes well connected together. The method relies on carefully engineered wavelets on graphs to introduce the notion of scale and to obtain a local view of the graph from each node. Computing the correlations between wavelets centered at different nodes, one has access to a notion of similarity between nodes, thereby enabling a clustering procedure that groups nodes according to their community at the scale of analysis. By using a collection of random vectors to estimate the correlation between the nodes, we show that the method is suitable for the analysis of large graphs. Furthermore, we introduce a notion of partition stability and a statistical test allowing us to assess which scales of analysis of the network are relevant. The effectiveness of the method is discussed first on multiscale graph benchmarks, then on real data of social networks and on models for signal processing on graphs.
Inflammatory Pathways in Knee Osteoarthritis: Potential Targets for Treatment

Osteoarthritis (OA) of the knee is a wide-spread, debilitating disease that is prominent in Western countries. It is associated with old age, obesity, and mechanical stress on the knee joint. By examining the recent literature on the effect of the anti-inflammatory prostaglandins 15d-PGJ2 and Δ12-PGJ2, we propose that new therapeutic agents for this disease could facilitate the transition from the COX-2-dependent pro-inflammatory synthesis of the prostaglandin PGE2 (catalyzed by mPGES-1), to the equally COX-2-dependent synthesis of the aforementioned anti-inflammatory prostaglandins. This transition could be instrumental in halting the breakdown of cartilage via matrix metalloproteinases (MMPs) and aggrecanases, as well as promoting the matrix regeneration and synthesis of cartilage by chondrocytes. Another desirable property of new OA therapeutics could involve the recruitment of mesenchymal stem cells to the damaged cartilage and bone, possibly resulting in the generation of chondrocytes, synoviocytes, and, in the case of bone, osteoblasts. Moreover, we propose that research promoting this transition from pro-inflammatory to anti-inflammatory prostaglandins could aid in the identification of new OA therapeutics.
Multi-domain text-to-speech synthesis by automatic text classification

This paper describes a multi-domain text-to-speech (MD-TTS) synthesis strategy for generating speech among different domains and so increasing the flexibility of high quality TTS systems. To that effect, the MD-TTS introduces a flexible TTS architecture that includes an automatic domain classification module, which allows MD-TTS systems to be implemented by different synthesis strategies and speech corpus typologies. In this work, the performance of a corpus-based MD-TTS system is subjectively validated by means of several perceptual tests.
NMSSM Higgs Discovery at the LHC

We demonstrate that Higgs discovery at the LHC is possible in the context of the NMSSM even for those scenarios such that the only strongly produced Higgs boson is a very SM-like CP-even scalar which decays almost entirely to a pair of relatvely light CP-odd states. In combination with other search channels, we are on the verge of demonstrating that detection of at least one of the NMSSM Higgs bosons is guaranteed at the LHC for accumulated luminosity of 300 fb −1 .
A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD.

BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder (ADHD), but no longer-term (i.e., >4 months) investigations have compared these 2 treatments or their combination. METHODS A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent-to-treat random-effects regression procedures. RESULTS All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacher-rated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period. CONCLUSIONS For ADHD symptoms, our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes.
A new view of avian life-history evolution tested on an incubation paradox

Viewing life–history evolution in birds based on an age–specific mortality framework can explain broad life–history patterns, including the long incubation periods in southern latitudes documented here. I show that incubation periods of species that are matched phylogenetically and ecologically between Argentina and Arizona are longer in Argentina. Long incubation periods have mystified scientists because they increase the accumulated risk of time–dependent mortality to young without providing a clear benefit. I hypothesize that parents of species with low adult mortality accept increased risk of mortality to their young from longer incubation if this allows reduced risk of mortality to themselves. During incubation, songbird parents can reduce risk of mortality to themselves by reducing nest attentiveness (percentage of time on the nest). Here I show that parents of species with lower adult mortality exhibit reduced nest attentiveness and that lower attentiveness is associated with longer incubation periods. However, the incubation period is also modified by juvenile mortality. Clutch size variation is also strongly correlated with age–specific mortality. Ultimately, adult and juvenile mortality explain variation in incubation and other life–history traits better than the historical paradigm.
The Continuity of Consciousness

In this paper I discuss two puzzles that concern the sense in which consciousness can be described as ‘continuous’. The first puzzle arises out of recent work by Dainton and Tye, both of whom appear to oscillate between ascribing the property of ‘continuity’ to the stream of experience, and ascribing it to the objects of experience. The second puzzle concerns the notion that the stream of consciousness could be in some sense unreal or illusory—a puzzle stemming from the thought that some of the brain processes underlying consciousness do not exhibit continuity. I argue that these problems can be solved by distinguishing between three possible bearers of the property of ‘continuity’—(1) the State of Consciousness, (2) the Stream of Experience, and (3) what is represented by experience—and two different senses of ‘continuity’—‘strict’ and ‘extreme’ continuity. I conclude by providing a positive account of the continuity of consciousness, according to which the State of Consciousness exhibits ‘strict’ continuity, and the Stream of Experience exhibits ‘extreme’ continuity.
Inorganic phosphate blocks binding of pre‐miRNA to Dicer‐2 via its PAZ domain

In Drosophila, Dicer‐1 produces microRNAs (miRNAs) from pre‐miRNAs, whereas Dicer‐2 generates small interfering RNAs from long double‐stranded RNA (dsRNA), a process that requires ATP hydrolysis. We previously showed that inorganic phosphate inhibits Dicer‐2 cleavage of pre‐miRNAs, but not long dsRNAs. Here, we report that phosphate‐dependent substrate discrimination by Dicer‐2 reflects dsRNA substrate length. Efficient processing by Dicer‐2 of short dsRNA requires a 5′ terminal phosphate and a two‐nucleotide, 3′ overhang, but does not require ATP. Phosphate inhibits cleavage of such short substrates. In contrast, cleavage of longer dsRNA requires ATP but no specific end structure: phosphate does not inhibit cleavage of these substrates. Mutation of a pair of conserved arginine residues in the Dicer‐2 PAZ domain blocked cleavage of short, but not long, dsRNA. We propose that inorganic phosphate occupies a PAZ domain pocket required to bind the 5′ terminal phosphate of short substrates, blocking their use and restricting pre‐miRNA processing in flies to Dicer‐1. Our study helps explain how a small molecule can alter the substrate specificity of a nucleic acid processing enzyme.
S-Nitrosylation at Cysteine 498 of c-Src Tyrosine Kinase Regulates Nitric Oxide-mediated Cell Invasion*

Nitric oxide (NO) plays a pivotal role in tumorigenesis, particularly with relation to cancer cell invasion and metastasis. NO can reversibly couple to cysteine thiols to form an S-nitrosothiol, which regulates the enzymatic activities of target proteins. c-Src is a tyrosine kinase that promotes cancer cell invasion and metastasis. Interestingly, c-Src can be activated by NO stimulation. However, mechanisms by which NO stimulates Src kinase activity have not been elucidated. We report here that NO causes S-nitrosylation of c-Src at cysteine 498 (Cys498) to stimulate its kinase activity. Cys498 is conserved among Src family kinases, and Cys506 of c-Yes, which corresponds to Cys498 of c-Src, was also important for the NO-mediated activation of c-Yes. Estrogens may work synergistically with NO to induce the proliferation and migration of many kinds of breast cancer cells. For example, β-estradiol induces the expression of endothelial nitric synthase and production of NO in MCF7 cells. We found that activation of c-Src in MCF7 cells by β-estradiol stimulation was mediated by the S-nitrosylation of Cys498. In addition, we report that disruption of E-cadherin junctions and enhancement of cell invasion by β-estradiol stimulation was mediated by NO-dependent activation of c-Src. These results identify a novel signaling pathway that links NO and Src family kinases to cancer cell invasion and metastasis.
A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group.

BACKGROUND The efficacy and safety of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis is still a matter of debate. METHODS Using a two-by-two factorial design, we randomly assigned 400 patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients). The rates of recurrent venous thromboembolism, death, and major bleeding were analyzed at day 12 and at two years. RESULTS At day 12, two patients assigned to receive filters (1.1 percent), as compared with nine patients assigned to receive no filters (4.8 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.22; 95 percent confidence interval, 0.05 to 0.90). At two years, 37 patients assigned to the filter group (20.8 percent), as compared with 21 patients assigned to the no-filter group (11.6 percent), had had recurrent deep-vein thrombosis (odds ratio, 1.87; 95 percent confidence interval, 1.10 to 3.20). There were no significant differences in mortality or the other outcomes. At day 12, three patients assigned to low-molecular-weight heparin (1.6 percent), as compared with eight patients assigned to unfractionated heparin (4.2 percent), had had symptomatic or asymptomatic pulmonary embolism (odds ratio, 0.38; 95 percent confidence interval, 0.10 to 1.38). CONCLUSIONS In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.