Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical lumping and molecular splitting of LEOPARD and NF1/NF1‐Noonan syndromes

To the Editor:Noonan syndrome (NS) and LEOPARD syndrome(LS) are clinically recognizable developmentaldisorders with overlapping features. NS patientstypically display short stature, facial dysmorphisms,low-set and posteriorly rotated ears, short andwebbedneck,thoracicandotherskeletalanomalies,cryptorchidism, and congenital heart defects (CHD)[Allanson, 1987; Noonan, 1994]. LS manifests withfacial features similar to those of NS, together with ahigh prevalence of hypertrophic cardiomyopathy,arrhythmias, cafe`-au-lait spots (CLS), multiplelentigines(ML),sensorineuraldeafnessandneonatalhypotonia [Voron et al., 1976; Coppin and Temple,1997;Digilioetal. ,2006]. CLSandMLaredistinguish-ingsignsofLS,sincetheyoccuronlyinaminorityofsubjects with NS [Allanson, 1987]. NS and LS areallelic Mendelian traits resulting from distinctPTPN11 gene mutations, with distinctive functionalconsequences on protein function [Tartaglia et al.,2001, 2006; Digilio et al., 2002]. Both the disordersaregeneticallyheterogeneous[Jamiesonetal. ,1994;Kalidas et al., 2005]. While a wide spectrum ofmissense PTPN11 mutations accounts for approxi-mately 40–50% of NS cases, a few mutations of thisgene are observed in more than 85% of LS cases[Tartaglia et al., 2002; Sarkozy et al., 2003, 2004;Tartaglia and Gelb, 2005]. Recently, KRAS and SOS1mutations have been documented in approximately10% of NS patients with a distinctive phenotype[Carta et al., 2006; Schubbert et al., 2006; Robertset al., 2007; Tartaglia et al., 2007]. NSandLSdisplayphenotypicoverlapwithneuro-ﬁbromatosis-Noonan syndrome (NFNS), whichmanifestsfeaturesofbothNSandneuroﬁbromatosistype 1 (NF1), including CLS, neuroﬁbromas, centralnervous system, and skeletal anomalies [Opitz andWeaver,1985;FriedmanandBirch1997]. Inpediatricage,NSandNFNSsharedistinctivefacialdysmorph-isms, short stature and CHD [Opitz and Weaver,1985], while isolated CLS and/or lentigines posedifﬁcult differential diagnosis between LS, NF1, andNFNS [Sarkozy et al., 2004; Digilio et al., 2006]. Suchoverlappingmanifestationsinthesedisordersreﬂectperturbations in a common biochemical pathway.Indeed, NF1 and NFNS are mainly due to hetero-zygousmutationsinNF1[Xuetal. ,1990;Baralleetal. ,2003;DeLucaetal. ,2005],whichencodesaGTPaseactivating protein (GAP), neuroﬁbromin, negativelycontrolling RAS function [Cichowski and Jacks,2001]. Similarly,PTPN11 encodesSHP-2,acytoplas-mic protein tyrosine phosphatase functioning as atransducer that positively modulates RAS signaling[Neel et al., 2003]. WhilewerecentlyexcludedNF1genemutationsasa major molecular event causing NS [De Luca et al.,2005],Wuetal. [1996]documentedtheoccurrenceofa missense NF1 mutation in a single LS patient,suggestingNF1asLSdiseasecausinggene. Thelatterobservationhasnotbeenconﬁrmedbyothergroups.
A robust parser for spoken language understanding

This paper describes a robust parsing algorithm for spoken language understanding. Comparing with the other work in robust parsing, we focus on building a parser that is robust to not only ill-formed spontaneous spoken language inputs but also under-specified grammars. Preliminary experiment results show that the parsing performance deteriorates more gracefully than another parser we have used when the grammar is more underspecified.
Towards designing secure virtualized systems

Virtual machine technology is rapidly gaining acceptance as a fundamental building block in enterprise data centers. It is most known for improving efficiency and ease of management. However, it also provides a compelling approach to enhancing system security, offering new ways to rearchitect todays systems and opening the door for a wide range of future security technologies. While this technology is meant to enhance the security of computer systems, some recent attacks show that virtual machine technology has many weaknesses and becomes exposed to many security threats. In this paper we present some of these threats and show how we protect these systems through intrusion detection and security policies mechanisms.
Don't Think about Your Movements: Effects of Attentional Instructions on Rowing Performance

The beneficial effect of adopting an external as opposed to an internal focus of attention during movement execution is well established for a range of motor tasks. As up-to-date findings in the field of endurance sports using physiological outcome measures are rare, the aim of this study was to examine attentional focus effects in rowing using oxygen consumption (V̇O2) as the main dependent variable. Eighteen experienced athletes rowed three times eight minutes at a submaximum intensity on a rowing ergometer. For each of the three rowing blocks they had to adopt a different focus of attention which was on leg movement (internal), on a video (external) or without instructions (control). Results revealed an increase in V̇O2 in the internal focus condition compared with the external as well as with the control condition. We conclude that it is an internal focus that led to performance decrements rather than an external focus enhancing performance. The implications of these findings for application in practice are discussed.
CHFR Promoter Methylation Indicates Poor Prognosis in Stage II Microsatellite Stable Colorectal Cancer

Purpose: Data on the prognostic significance of promoter CpG island methylation in colorectal cancer (CRC) are conflicting, possibly due to associations between methylation and other factors affecting survival such as genetic alterations and use of adjuvant therapy. Here, we examine the prognostic impact of promoter methylation in patients with CRC treated with surgery alone in the context of microsatellite instability (MSI), BRAF and KRAS mutations. Experimental Methods: One hundred and seventy-three CRCs were analyzed for promoter methylation of 19 tumor suppressor and DNA repair genes, the CpG island methylator phenotype (CIMP), MSI, the exon 15 V600E BRAF mutation and KRAS codon 12 and 13 mutations. Results: Unsupervised hierarchical clustering based on methylation status of 19 genes revealed three subgroups: cluster 1 [CL1, 57% (98/173) of CRCs], cluster 2 [CL2, 25% (43/173) of CRCs], and cluster 3 [CL3, 18% (32/173) of CRCs]. CL3 had the highest methylation index (0.25, 0.49, and 0.69, respectively, P = <0.01) and was strongly associated with CIMP (P < 0.01). Subgroup analysis for tumor stage, MSI, and BRAF status showed no statistically significant differences in survival between CL1, CL2, and CL3 nor between CIMP and non-CIMP CRCs. Analyzing genes separately revealed that CHFR promoter methylation was associated with a poor prognosis in stage II, microsatellite stability (MSS), BRAF wild-type (WT) CRCs: multivariate Cox proportional HR = 3.89 [95% confidence interval (CI), 1.58–9.60, P < 0.01; n = 66] and HR = 2.11 (95% CI, 0.95–4.69, P = 0.068, n = 136) in a second independent population-based study. Conclusions: CHFR promoter CpG island methylation, which is associated with MSI, also occurs frequently in MSS CRCs and is a promising prognostic marker in stage II, MSS, BRAF WT CRCs. Clin Cancer Res; 20(12); 3261–71. ©2014 AACR.
Trans-Planckian physics and signature change events in Bose gas hydrodynamics

We present an example of emergent spacetime as the hydrodynamic limit of a more fundamental microscopic theory. The low-energy, long-wavelength limit in our model is dominated by collective variables that generate an effective Lorentzian metric. This system naturally exhibits a microscopic mechanism allowing us to perform controlled signature change between Lorentzian and Riemannian geometries. We calculate the number of quasiparticles produced from a finite-duration Euclidean-signature event, where we take the position that to a good approximation the dynamics is dominated by the evolution of the linearized perturbations, as suggested by Calzetta and Hu [Phys. Rev. A 68, 043625 (2003)]. We adapt the ideas presented by Dray et al. [Gen. Relativ. Gravit. 23, 967 (1991)], such that the field and its canonical momentum are continuous at the signature-change event. We investigate the interplay between the underlying microscopic structure and the emergent gravitational field, focussing on its impact on quasiparticle production in the ultraviolet regime. In general, this can be thought of as the combination of trans-Planckian physics and signature-change physics. Further we investigate the possibility of using the proposed signature-change event as an amplifier for analogue ``cosmological particle production'' in condensed matter experiments.
Antiangiogenic therapy in cancer: a new era has begun.

Although the idea of utilizing antiangiogenic agents to hinder tumor growth is not new,[1] and the discovery of angiogenesis in tumors is even older,[2] this field of research is still in its infancy. Much has been learned about angiogenesis in tumor growth and development, yet the process is exceedingly complex and tightly regulated by a sophisticated interplay between pro- and antiangiogenic factors. Decades will pass before these regulatory mechanisms are well elucidated and understood.
Emocje moralne jako podstawa zmysłu moralnego. Defekty zmysłu moralnego

It is shown that, contrary to the rationalist tradition which is prevalent in philosophical ethics and to the traditional views of moral psychology, research results in the field of neuroethics suggest that the basis for moral sensitivity is constituted by certain emotions such as: blame, mercy and compassion which are classified as a special class of moral emotions. In fact, they are mainly neurophysiological processes that are launched automatically. The existence of such emotions is proved by the results of brain imagining neuropsychological experiments performed on healthy subjects as well as on lesion patients.
The format of children’s mental images: Penetrability of spatial images

Abstract To investigate the format of mental images and the penetrability of mental imagery performance to top-down influences in the form of gravity information, children (4-, 6-, 8- and 10-year-olds) and adults (N = 112) performed mental rotation tasks. A linear increase in response time with rotation angle emerged at 6-years, suggesting that spatial properties are represented in children’s mental images. Moreover, 6-, 8-, and 10-year-olds, but not 4-year-olds or adults, took longer to respond to rotated stimuli pairs when gravity information was incongruent with the direction of rotation rather than congruent. Overall, findings suggest that in contrast to adults’, 6- to 10-year-olds’ mental rotation performance was penetrated by top-down information. This research (a) provides insight into the format of young children’s mental images and (b) shows that children’s mental rotation performance is penetrable by top-down influences.
Application de l'analyse réseau à la modélisation de la visite d'un site web

L'objectif de notre recherche est de présenter une nouvelle méthode d'analyse du trafic sur un site web et de valider un nouveau modèle de la répartition du trafic entre les pages du site. Cette modélisation est fondée sur l'analyse réseau et les chaînes de Markov. La première partie présente les différentes approches disponibles pour mesurer l'audience et le trafic sur un site web. Après avoir exposé la méthodologie mise en œuvre, nous appliquons la modélisation envisagée au site Intranet de la SNCF et évaluons sa qualité en tant qu'outil de simulation. Enfin, nous développons les implications théoriques et managériales de notre recherche et exposons les voies de recherche futures.
Conformal metrics on $\R^{2m}$ with constant Q-curvature

We study the conformal metrics on $\R^{2m}$ with constant Q-curvature $Q$ having finite volume, particularly in the case $Q\leq 0$. We show that when $Q 1$. Moreover we study their asymptotic behavior at infinity, in analogy with the case $Q>0$, which we treated in a recent paper. When Q=0, we show that such metrics have the form $e^{2p}g_{\R^{2m}}$, where $p$ is a polynomial such that $2\leq \deg p\leq 2m-2$ and $\sup_{\R^{2m}}p<+\infty$. In dimension 4, such metrics are exactly the polynomials $p$ of degree 2 with $\lim_{|x|\to+\infty}p(x)=-\infty$.
See also Eight Survival Strategies in Traumatic Stress

Post-traumatic stress disorder (PTSD) in its fourth criterion relies on the consequences of fight and flight survival responses. However, this limits understanding of a much wider variety of stress responses from other survival strategies. Information from a variety of disciplines suggests eight survival strategies including fight and flight. The anatomy, physiology, cognitions, emotions and social expressions of these strategies are described in animals, and human infants and adults. A wider variety of survival strategies enriches conceptualization of PTSD and apparent comorbid phenomena.
Human Activity Helps Prey Win the Predator-Prey Space Race

Predator-prey interactions, including between large mammalian wildlife species, can be represented as a “space race”, where prey try to minimize and predators maximize spatial overlap. Human activity can also influence the distribution of wildlife species. In particular, high-human disturbance can displace large carnivore predators, a trait-mediated direct effect. Predator displacement by humans could then indirectly benefit prey species by reducing predation risk, a trait-mediated indirect effect of humans that spatially decouples predators from prey. The purpose of this research was to test the hypothesis that high-human activity was displacing predators and thus indirectly creating spatial refuge for prey species, helping prey win the “space race”. We measured the occurrence of eleven large mammal species (including humans and cattle) at 43 camera traps deployed on roads and trails in southwest Alberta, Canada. We tested species co-occurrence at camera sites using hierarchical cluster and nonmetric multidimensional scaling (NMS) analyses; and tested whether human activity, food and/or habitat influenced predator and prey species counts at camera sites using regression tree analysis. Cluster and NMS analysis indicated that at camera sites humans co-occurred with prey species more than predator species and predator species had relatively low co-occurrence with prey species. Regression tree analysis indicated that prey species were three times more abundant on roads and trails with >32 humans/day. However, predators were less abundant on roads and trails that exceeded 18 humans/day. Our results support the hypothesis that high-human activity displaced predators but not prey species, creating spatial refuge from predation. High-human activity on roads and trails (i.e., >18 humans/day) has the potential to interfere with predator-prey interactions via trait-mediated direct and indirect effects. We urge scientist and managers to carefully consider and quantify the trait-mediated indirect effects of humans, in addition to direct effects, when assessing human impacts on wildlife and ecosystems.
Canadian ophthalmology residency training: an evaluation of resident satisfaction and comparison with international standards.

OBJECTIVE To evaluate the adequacy of Canadian ophthalmology residency programs in achieving the competencies outlined by the International Council of Ophthalmology (ICO) and to assess residents' satisfaction with their training programs. PARTICIPANTS Canadian residents enrolled in the final 2 years of English and French ophthalmology programs, as well as recent graduates from 2005 to 2008. METHODS Graduates and eligible residents were invited to participate in the 43-item survey during the autumn of 2008. Data were categorized by demographic variables, and basic statistics were done. RESULTS Of the 99 individuals surveyed, 40 (40%) responded, representing 26 current residents and 14 graduates. The vast majority (85%) of respondents were satisfied with their residency program. Clinic-based training was generally rated satisfactorily; however, respondents reported insufficient exposure to low-vision rehabilitation (77.5%), refraction and glasses prescription (65%), and neuro-ophthalmology (45%). Respondents were similarly satisfied with their surgical experiences, most of them (>60%) rating case volume, complexity, and variety as satisfactory or better. However, many stated that they had insufficient exposure to extracapsular cataract extraction (72.5%), refractive surgery (72.5%), and orbital surgery (57.5%). Of the graduates surveyed, all passed their Royal College licensing examinations on the first attempt and felt that residency adequately prepared them for the examinations. They reported insufficient training in certain nonclinical areas, such as practice management, and staffing and administration skills. CONCLUSIONS Canadian ophthalmology residents express high levels of satisfaction with their residency training programs. Although most programs appear to adequately address most ICO core objectives, certain curriculum modifications are required.
3-D prestack migration of common-azimuth data

In principle, downward continuation of 3-D prestack data should be carried out in the 5-D space of full 3-D prestack geometry (recording time, source surface location, and receiver surface location), even when the data sets to be migrated have fewer dimensions, as in the case of common‐azimuth data sets that are only four dimensional. This increase in dimensionality of the computational space causes a severe increase in the amount of computations required for migrating the data. Unless this computational efficiency issue is solved, 3-D prestack migration methods based on downward continuation cannot compete with Kirchhoff methods. We address this problem by presenting a method for downward continuing common‐azimuth data in the original 4-D space of the common‐azimuth data geometry. The method is based on a new common‐azimuth downward‐continuation operator derived by a stationary‐phase approximation of the full 3-D prestack downward‐continuation operator expressed in the frequency‐wavenumber domain. Althou.
Childrenâ€™s social and spatial exclusion in the city:

This paper deals with the social and spatial exclusion of children in the city from an alternative point of view. There is a significant literature about the objective factors that lead to children’s exclusion in the city, including all the disadvantages of technocratic and child-unfriendly urban planning and the social and economic consequences of the urban crisis. Th e research presents the creation of an internal image of oppression that make s children reproduce the conditions of their exclusion in the city. The research took place in a primary school Athens of 9 to 12 years old.
The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia.

The discovery of an early Upper Paleolithic human burial at the Abrigo do Lagar Velho, Portugal, has provided evidence of early modern humans from southern Iberia. The remains, the largely complete skeleton of a approximately 4-year-old child buried with pierced shell and red ochre, is dated to ca. 24,500 years B.P. The cranium, mandible, dentition, and postcrania present a mosaic of European early modern human and Neandertal features. The temporal bone has an intermediate-sized juxtamastoid eminence. The mandibular mentum osseum and the dental size and proportions, supported by mandibular ramal features, radial tuberosity orientation, and diaphyseal curvature, as well as the pubic proportions align the skeleton with early modern humans. Body proportions, reflected in femorotibial lengths and diaphyseal robusticity plus tibial condylar displacement, as well as mandibular symphyseal retreat and thoracohumeral muscle insertions, align the skeleton with the Neandertals. This morphological mosaic indicates admixture between regional Neandertals and early modern humans dispersing into southern Iberia. It establishes the complexities of the Late Pleistocene emergence of modern humans and refutes strict replacement models of modern human origins.
ATINER's Conference Paper Series EDU2012-0043

While virtual technology for training in the simulation field has had a long history in medicine and the military, the application of emerging and innovative technologies in teacher preparation and education has been limited. TeachMETM (Teaching in a Mixed Reality Environment) is an innovative mixed-reality environment (the blending of real and synthetic content) where prospective teachers can interact with a group of virtual students. The purpose of the virtual teaching environment of TeachMETM is to positively impact teacher recruitment, preparation, and retention in education by allowing teachers to improve their skills with virtual students, providing a more ethical approach to learning the art of teaching. This paper introduces the project, the mixed-reality environment, and the results of its effectiveness on pre-service teachers. Contact Information of Corresponding author: ATINER CONFERENCE PAPER SERIES No: EDU2012-0043
Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of beo mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish shocked (sho) mutants have a defect in slc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch-once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch-once’ mutants, including beo and sho, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs.