Miracle-dz/UniFAR-FTUs huggingface dataset:
A Human Type 1 Diabetes Susceptibility Locus Maps to Chromosome 21q22.3

OBJECTIVE— The Type 1 Diabetes Genetics Consortium (T1DGC) has assembled and genotyped a large collection of multiplex families for the purpose of mapping genomic regions linked to type 1 diabetes. In the current study, we tested for evidence of loci associated with type 1 diabetes utilizing genome-wide linkage scan data and family-based association methods. RESEARCH DESIGN AND METHODS— A total of 2,496 multiplex families with type 1 diabetes were genotyped with a panel of 6,090 single nucleotide polymorphisms (SNPs). Evidence of association to disease was evaluated by the pedigree disequilibrium test. Significant results were followed up by genotyping and analyses in two independent sets of samples: 2,214 parent-affected child trio families and a panel of 7,721 case and 9,679 control subjects. RESULTS— Three of the SNPs most strongly associated with type 1 diabetes localized to previously identified type 1 diabetes risk loci: INS, IFIH1, and KIAA0350. A fourth strongly associated SNP, rs876498 (P = 1.0 × 10−4), occurred in the sixth intron of the UBASH3A locus at chromosome 21q22.3. Support for this disease association was obtained in two additional independent sample sets: families with type 1 diabetes (odds ratio [OR] 1.06 [95% CI 1.00–1.11]; P = 0.023) and case and control subjects (1.14 [1.09–1.19]; P = 7.5 × 10−8). CONCLUSIONS— The T1DGC 6K SNP scan and follow-up studies reported here confirm previously reported type 1 diabetes associations at INS, IFIH1, and KIAA0350 and identify an additional disease association on chromosome 21q22.3 in the UBASH3A locus (OR 1.10 [95% CI 1.07–1.13]; P = 4.4 × 10−12). This gene and its flanking regions are now validated targets for further resequencing, genotyping, and functional studies in type 1 diabetes.
Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathwayss⃞ Published, JLR Papers in Press, December 5, 2006.

Endocytosis of LDL and modified LDL represents regulated and unregulated cholesterol delivery to macrophages. To elucidate the mechanisms of cellular cholesterol transport and egress under both conditions, various primary macrophages were labeled and loaded with cholesterol or cholesteryl ester from LDL or acetylated low density lipoprotein (AcLDL), and the cellular cholesterol traffic pathways were examined. Confocal microscopy using fluorescently labeled 3,3′-dioctyldecyloxacarbocyanine perchlorate-labeled LDL and 1,1′-dioctyldecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate-labeled AcLDL demonstrated their discrete traffic pathways and accumulation in distinct endosomes. ABCA1-mediated cholesterol efflux to apolipoprotein A-I (apoA-I) was much greater for AcLDL-loaded macrophages compared with LDL. Treatment with the liver X receptor ligand 22-OH increased efflux to apoA-I in AcLDL-loaded but not LDL-loaded cells. In contrast, at a level equivalent to AcLDL, LDL-derived cholesterol was preferentially effluxed to HDL, in keeping with increased ABCG1. In vivo studies of reverse cholesterol transport (RCT) from cholesterol-labeled macrophages injected intraperitoneally demonstrated that LDL-derived cholesterol was more efficiently transported to the liver and secreted into bile than AcLDL-derived cholesterol. This indicates a greater efficiency of HDL than lipid-poor apoA-I in interstitial fluid in controlling in vivo RCT. These assays, taken together, emphasize the importance of mediators of diffusional cholesterol efflux in RCT.
Isolation and characterization of microsatellite loci for the large-seeded tree Protorhus deflexa (Anacardiaceae)1

Premise of the study: Protorhus deflexa is an endemic large-seeded tree in Madagascar that depends heavily on insects for cross-pollination and on large-bodied frugivores for seed dispersal. Because such mutualistic relationships are vulnerable to human disturbance, the development of microsatellite markers will enhance analyses of gene flow in this tree species in degraded forests. Methods and Results: Nineteen microsatellite markers were developed for P. deflexa using 454 pyrosequencing. The number of alleles ranged from two to nine, and the ranges of observed and expected heterozygosities were 0.200–0.800 and 0.303–0.821, respectively. The parentage exclusion probability by the 19 loci reached 0.98583 for the first parent and 0.99971 for the second parent. Conclusions: These markers will be useful for studying gene flow via pollination and seed dispersal by animals and the genetic structure of P. deflexa in protected and degraded forests in Madagascar.
Inhibition of Rho‐kinase by Fasudil protects dopamine neurons and attenuates inflammatory response in an intranasal lipopolysaccharide‐mediated Parkinson's model

Microglia activation and inflammatory factors in brain microenvironment are associated with degeneration of neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients and various PD models. There is increasing evidence that the Rho/ROCK (Rho kinase) signalling pathway may play a critical role in the inflammatory response, and ROCK inhibitor has been reported to have neuroprotective effects. In this study, we examined the neuroprotective potential and possible mechanism of ROCK inhibitor Fasudil in an intranasal lipopolysaccharide (LPS)‐induced PD model. ROCK was activated with LPS stimulation and inhibited by Fasudil treatment in this PD model. Behavioural tests demonstrated a clear improvement in motor performance after Fasudil treatment. Furthermore, Fasudil resulted in a significant attenuation of dopamine cell loss, α‐synuclein accumulation and inflammatory response with the reversion of inflammatory M1 to anti‐inflammatory M2 microglia, decreased NF‐кB activation, and IL‐12 and TNF‐α generation in the SN and olfactory bulb in this model. This study establishes a role for Fasudil in protecting against LPS‐mediated dopamine degeneration and provides a therapeutic strategy for the treatment of PD.
Power exploration for dynamic data types through virtual memory management refinement

In this paper we present our novel power exploration methodology for applications with dynamic data types. Our methodology is crucial to obtain effective solutions in an embedded (HW or SW) processor context. The contributions are twofold. First we define the complete search space for virtual memory management (VMM) mechanisms in a structured way with orthogonal decision trees. Secondly we present our systematic methodology for exploration of the maximal power that takes into account characteristics of the application to heavily prune the search space guiding the choices of a VMM mechanism. Finally we demonstrate for two industrial examples that power can vary considerably depending on the VMM chosen. Moreover these experiments show the effectiveness of our exploration methodology.
Regulation of the endocycle/gene amplification switch by Notch and ecdysone signaling

The developmental signals that regulate the switch from genome-wide DNA replication to site-specific amplification remain largely unknown. Drosophila melanogaster epithelial follicle cells, which begin synchronized chorion gene amplification after three rounds of endocycle, provide an excellent model for study of the endocycle/gene amplification (E/A) switch. Here, we report that down-regulation of Notch signaling and activation of ecdysone receptor (EcR) are required for the E/A switch in these cells. Extended Notch activity suppresses EcR activation and prevents exit from the endocycle. Tramtrack (Ttk), a zinc-finger protein essential for the switch, is regulated negatively by Notch and positively by EcR. Ttk overexpression stops endoreplication prematurely and alleviates the endocycle exit defect caused by extended Notch activity or removal of EcR function. Our results reveal a developmental pathway that includes down-regulation of Notch, activation of the EcR, up-regulation of Ttk to execute the E/A switch, and, for the first time, the genetic interaction between Notch and ecdysone signaling in regulation of cell cycle programs and differentiation.
A pattern matching algorithm for codon optimization and CpG motif-engineering in DNA expression vectors

Codon optimization enhances the efficiency of DNA expression vectors used in DNA vaccination and gene therapy by increasing protein expression. Additionally, certain nucleotide motifs have experimentally been shown to be immuno-stimulatory while certain others immuno-suppressive. In this paper, we present algorithms to locate a given set of immuno-modulatory motifs in the DNA expression vectors corresponding to a given amino acid sequence and maximize or minimize the number and the context of the immuno-modulatory motifs in the DNA expression vectors. The main contribution is to use multiple pattern matching algorithms to synthesize a DNA sequence for a given amino acid sequence and a graph theoretic approach for finding the longest weighted path in a directed graph that will maximize or minimize certain motifs. This is achieved using O(n/sup 2/) time, where n is the length of the amino acid sequence. Based on this, we develop a software tool.
Performance Analysis of a P2P-Based VoIP Software

With the development of network, multimedia will be the main application in next generation network. Voice is one of the most important applications. Recently a kind of P2P-based VoIP software, Skype, has been receiving more and more attention both in academia and industry. Skype claims that it's better than other VoIP software, because of its high call completion rate and superior sound quality. This paper will reveal Skype's technique and have a performance comparison between Skype and MSN Messenger, which uses traditional VoIP protocol. The result indicates that the voice quality of Skype is no better than traditional VoIP software and the great benefit of P2P involved with VoIP is that it can solve NAT and firewall problems.
Maximum Likelihood Set for Estimating a Probability Mass Function

We propose a new method for estimating the probability mass function (pmf) of a discrete and finite random variable from a small sample. We focus on the observed countsthe number of times each value appears in the sampleand define the maximum likelihood set (MLS) as the set of pmfs that put more mass on the observed counts than on any other set of counts possible for the same sample size. We characterize the MLS in detail in this article. We show that the MLS is a diamond-shaped subset of the probability simplex [0, 1]k bounded by at most k (k 1) hyper-planes, where k is the number of possible values of the random variable. The MLS always contains the empirical distribution, as well as a family of Bayesian estimators based on a Dirichlet prior, particularly the well-known Laplace estimator. We propose to select from the MLS the pmf that is closest to a fixed pmf that encodes prior knowledge. When using Kullback-Leibler distance for this selection, the optimization problem comprises finding the minimum of a convex function over a domain defined by linear inequalities, for which standard numerical procedures are available. We apply this estimate to language modeling using Zipf's law to encode prior knowledge and show that this method permits obtaining state-of-the-art results while being conceptually simpler than most competing methods.
Object-Oriented Design Patterns in Fortran 90/95

This paper discusses the concept, application, and usefulness of software design patterns for scientic programming in Fortran 90/95. An example from the discipline of object-oriented design patterns, that of a game based on navigation through a maze, is used to describe how some important patterns can be implemented in Fortran 90/95 and how the progressive introduction of design patterns can usefully restructure Fortran software as it evolves. This example is complemented by a discussion of how design patterns have been used in a real-life simulation of Particle-in-Cell plasma physics. The following patterns are mentioned in this paper: Factory, Strategy, Template, Abstract Factory and Facade.
Dynamic furniture modeling through assembly instructions

We present a technique for parsing widely used furniture assembly instructions, and reconstructing the 3D models of furniture components and their dynamic assembly process. Our technique takes as input a multi-step assembly instruction in a vector graphic format and starts to group the vector graphic primitives into semantic elements representing individual furniture parts, mechanical connectors (e.g., screws, bolts and hinges), arrows, visual highlights, and numbers. To reconstruct the dynamic assembly process depicted over multiple steps, our system identifies previously built 3D furniture components when parsing a new step, and uses them to address the challenge of occlusions while generating new 3D components incrementally. With a wide range of examples covering a variety of furniture types, we demonstrate the use of our system to animate the 3D furniture assembly process and, beyond that, the semantic-aware furniture editing as well as the fabrication of personalized furnitures.
Characteristics, Occurrence, and Decay Rates of Remnant Belts Associated With Three‐Belt Events in the Earth's Radiation Belts

Shortly after the launch of the Van Allen Probes, a new three‐belt configuration of the electron radiation belts was reported. Using data between September 2012 and November 2017, we have identified 30 three‐belt events and found that about 18% of geomagnetic storms result in such configuration. Based on the identified events, we evaluated some characteristics of the remnant (intermediate) belt. We determined the energy range of occurrence and found it peaks at E = 5.2 MeV. We also determined that the magnetopause location and SYM‐H value may play an important role in the outer belt losses that lead to formation and location of the remnant belt. Finally, we calculated the decay rates of the remnant belt for all events and found that their lifetime gets longer as energy increases, ranging from days at E = 1.8 MeV up to months at E = 6.3 MeV suggesting that remnant belts are extremely persistent.
An experimental evaluation of multivariate graphical point representations

In a generally optimistic assessment of progress in the psychology of human-computer interaction, Moran [30] reported that the field “needs to work more at bringing existing areas of cognitive psychology and traditional human factors to bear on user behavior. ” This caveat applies especially to the area of computer graphics because of the dearth of experiments and theory on the effectiveness of various types of graphical displays. Broad applications of psychological theory to graphic design have been presented in [6], [19], [28], [32] and [33]. These articles have drawn heavily on Gestalt theory, memory models, and the theory of cognitive schemas in human judgment. They present little experimental evidence relevant to complex visual displays, however.
Towards a Digitized Protocol based on Handwriting for the Assessment of Neurodegenerative Disorders

Kinematic features of the handwriting process are promising for discriminating patients probably affected by neurodegenerative disorders from healthy controls and potentially for identifying the stage of the illness. Many tasks have been proposed and tested, however the scientific community still lacks a complete protocol able to collect different traits useful to the research community and at the same time to be of real use for doctors in their daily activities. This paper collects all the different tasks already applied and proposes a protocol for handwritten traits acquisition to be integrated into standardized cognitive and functional tests already accepted, tested and used by the medical community working on the assessment of neurodegenerative diseases.
Systematic Review of Methods for Assessing Leptomeningeal Collateral Flow

BACKGROUND AND PURPOSE: The importance of LMF in the outcome after acute ischemic stroke is increasingly recognized, but imaging presents a wide range of options for identification of collaterals and there is no single system for grading collateral flow. The aim of this study was to systematically review the literature on the available methods for measuring LMF adequacy. MATERIALS AND METHODS: We performed a systematic review of Ovid, MEDLINE, and Embase databases for studies in which flow in the leptomeningeal collateral vessels was evaluated. Imaging technique, grading scale, and reliability assessment for collateral flow measurement were recorded. RESULTS: We found 81 publications describing 63 methods for grading collateral flow on the basis of conventional angiography (n = 41), CT (n = 7), MR imaging (n = 9), and transcranial Doppler (n = 6). Inter- and/or intraobserver agreement was assessed in only 8 publications. CONCLUSIONS: There is inconsistency in how LMF is graded, with a variety of grading scales and imaging modalities being used. Consistency in evaluating collateral flow at baseline is required for the impact of collateral flow to be fully appreciated.
The role of 'naturalness' and seral stage in the assessment and management of coastal sites

Conservation and restoration of Mediterranean coastal habitats often requires rapid assessment of the ‘state of health’ of the environment. A potential solution to this issue may be represented by the implementation of a method for rapid assessment of the ‘naturalness’ of coastal areas. The degree of naturalness of a site is diagnosed by sampling and analysing the anthropogenicity of the ecosystem in the area, and, from its inverse interpretation, the naturalness grade that characterises the habitat may be deduced. We are suggesting that the principal criterion for defining values of naturalness in the upper part of the scale should be the position of a terrestrial plant community along a sere. Using species richness as a criterion for naturalness would probably not be suitable, as this value is fundamentally a statistic and does not give any information regarding the ‘state of health’ of the ecosystem. As such, the identity of the species, rather than their number would be a better indicator of naturalness. A natural habitat, one that has been undisturbed by human actions, would be characterized by a primary climax community. Disturbances (man-made and otherwise) would act to erode the integrity of the climax community and would introduce other species (usually opportunistic species) which would occupy disturbed patches and coexist with the climax vegetation. A disturbance of very large magnitude would revert the succession to early seral stages which would subsequently proceed (if undisturbed) through a secondary succession, reaching a secondary climax. When actively managed sites were compared to unmanaged coastal areas in the Maltese islands, it was found that the former were statistically more likely to show a higher position in the seral stage of the vegetation community. This emphasizes the fact that some kinds of human disturbances do not reduce the naturalness value of a site. In fact, active management and conservation practices that entail a proper strategic plan should be considered. This allows managers to spatially and temporally determine the position of a plant community along a sere and would provide them with a rapid indication of how different types and intensities of negative human disturbance affect coastal vegetation.
A Self-Organizing Crash-Resilient Topology Management System for Content-Based Publish/Subscribe

Content-based routing realized through static networks of brokers usually exhibit nice performance when subscribers with similar interest are physically close to each other (e.g. in the same LAN, domain or in the same geographical area) and connected to a broker which is also nearby. If these subscribers are dispersed on the Internet, benefits of such routing strategy significantly decrease. In this paper we present a Topology Management System (TMS) which is a component of a content-based pub/sub system. The aim of a TMS is to mask dynamic changes of the brokers’ topology to the content-based routing. TMS relies on a self-organizing algorithm whose goal is to place close (in terms of TCP hops) brokers that manage subscribers with similar interests keeping acyclic the topology and without compromising network-level performance. TMS is also resilient to broker failures and allows joining of new brokers.
Measurement of wireless power transfer to multiple loads by a vector network analyser

A new scheme to use a constant current RF source (CCS) is proposed for the coupled-resonator wireless power transfer system. Considering it is hard to obtain a general-use CCS, an alternative use of common 50Ω signal source followed by Scattering to Impedance parameter transform is recommended with the theory of the transform, verification of the theory and some practical examples.
Pre‐operative variables including fitness associated with complications after oesophagectomy

Oesophagectomy is a technically‐demanding operation associated with a high level of morbidity. We analysed the association of pre‐operative variables, including those from cardiopulmonary exercise testing, with complications (logistic regression) and survival and length of stay (Cox regression) after scheduled transthoracic oesophagectomy in 273 adults, in isolation and on multivariate testing (maximum Akaike information criterion). On multivariate analysis, any postoperative complication was associated with ventilatory equivalents for carbon dioxide, odds ratio (95%CI) 1.088 (1.02–1.17), p = 0.018. Cardiorespiratory complications were associated with FEV1 and pre‐operative background survival (in an analogous group without cancer), odds ratios (95%CI) 0.55 (0.37–0.80), p = 0.002 and 0.89 (0.82–0.96), p = 0.004, respectively. Survival was associated with the ratio of expected‐to‐observed ventilatory equivalents for carbon dioxide and predicted postoperative survival, hazard ratios (95%CI) 0.17 (0.03–0.91), p = 0.039 and 0.96 (0.90–1.01), p = 0.076. Length of hospital stay was associated with FVC, hazard ratio (95%CI) 1.38 (1.17–1.63), p < 0.0001.
Transcriptional activation of RagD GTPase controls mTORC1 and promotes cancer growth

A transcriptional regulatory mechanism enables cellular adaptation to nutrient availability and supports cancer metabolism. Preparing for the feast during the fast A protein kinase complex known as mTORC1 plays a key role in cellular metabolism and nutrient sensing. Di Malta et al. elucidated a mechanism that regulates the metabolic changes that are necessary during the fast-to-feed transition. During starvation, a pair of transcription factors promotes the expression of a pair of guanosine triphosphatases that are required for mTORC1 activity and for its recruitment to the lysosome. However, mTORC1 activity also requires amino acids, which are lacking during starvation. Nevertheless, the cell becomes “primed” by this process so that on refeeding, it efficiently reactivates mTORC1, which is recruited to the lysosomal surface. This mechanism is particularly important in cancer cells. Science, this issue p. 1188 The mechanistic target of rapamycin complex 1 (mTORC1) is recruited to the lysosome by Rag guanosine triphosphatases (GTPases) and regulates anabolic pathways in response to nutrients. We found that MiT/TFE transcription factors—master regulators of lysosomal and melanosomal biogenesis and autophagy—control mTORC1 lysosomal recruitment and activity by directly regulating the expression of RagD. In mice, this mechanism mediated adaptation to food availability after starvation and physical exercise and played an important role in cancer growth. Up-regulation of MiT/TFE genes in cells and tissues from patients and murine models of renal cell carcinoma, pancreatic ductal adenocarcinoma, and melanoma triggered RagD-mediated mTORC1 induction, resulting in cell hyperproliferation and cancer growth. Thus, this transcriptional regulatory mechanism enables cellular adaptation to nutrient availability and supports the energy-demanding metabolism of cancer cells.