Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase 2 Studies of Sunitinib and AG013736 in Patients with Cytokine-Refractory Renal Cell Carcinoma

Frequent loss of the von Hippel-Lindau (VHL) gene product in conventional-type renal cell carcinoma results in constitutive expression of proangiogenic growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). VEGF and PDGF function in a paracrine manner to stimulate tumor angiogenesis that results in a hypervascular phenotype. Dependency on this hypervascularity is underscored by the recent clinical efficacy shown by inhibition of the VEGF pathway. Most strategies that primarily target the VEGF pathway (neutralizing antibodies or receptor tyrosine kinase inhibitors) result in objective tumor responses in ≤10% of cases but show a significant delay in time to disease progression. In contrast, two multitargeted receptor tyrosine kinase inhibitors that target both VEGF and PDGF receptors (sunitinib and AG013736) have shown ≥40% objective responses with clinically important duration. Several hypotheses may explain the discrepancy of these response rates from other strategies in the class, including the synergistic effects of dual inhibition of VEGF and PDGF receptors, supported by preclinical studies. Ultimately, further clinical investigations with pharmacodynamic and correlative science end points are needed to clarify the mechanisms of action and resistance to build on the biological and clinical effects of these multitargeted agents.
Contrasting population genetic patterns and evolutionary histories among sympatric Sonoran Desert cactophilic Drosophila

We studied population genetic differentiation in the sympatric Sonoran Desert cactophilic flies Drosophila pachea, D. mettleri and D. nigrospiracula across their continental and peninsular ranges. These flies show marked differences in ecology and behaviour including dispersal distances and host cactus specialization. Examination of a fragment of the mitochondrial cytochrome oxidase subunit I gene (mtCOI) reveals that the Sea of Cortez has constituted an effective dispersal barrier for D. pachea, leading to significant genetic differentiation between the continental and peninsular ranges of this species. No genetic differentiation was detected, however, within its continental and peninsular ranges. In contrast, our mtCOI‐based results for D. mettleri and D. nigrospiracula are consistent with a previous allozyme‐based study that showed no significant genetic differentiation between continental and peninsular ranges of these two species. For D. mettleri, we also found that the insular population from Santa Catalina Island, California, is genetically differentiated with respect to continental and peninsular localities. We discuss how differences in the genetic structure patterns of D. pachea, D. mettleri and D. nigrospiracula may correspond to differences in their dispersal abilities, host preferences and behaviour.
Visual analysis of viseme dynamics

Face to face dialogue is the most natural mode of communication between humans. The combination of human visual perception of expression and perception in changes in intonation provides semantic information that communicates idea, feelings and concepts. The realistic modelling of speech movements, through automatic facial animation, and maintaining audio-visual coherence is still a challenge in both the computer graphics and film industry. A common approach to producing visual speech is to interpolate parameters that describe mouth variation in sequence, known as visemes. A viseme corresponds to a phoneme in an utterance. Most talking head systems use sets of static visemes, represented by a single mouth shape image or 3D model. However, discretising visemes in this way does not account for context-dependent dynamic information, coarticulation. This thesis presents several visual analysis and dynamic modelling techniques for visual phones. This spans several areas of work, from capture and representation through to analysis and synthesis of speech movements and coarticulation. A novel method is reported for the automatic extraction of inner-lip contour edges from sequences of mouth images in speech. The proposed detection technique is a key-frame exemplar-based method that is not dependent on any prior frame information for intitialisation allowing for reliable and accurate inner-lip localisation for large frame to frame changes in lip-shape inherent in 25Hz video of visual speech. Visual analysis of phonemes in continuous speech is performed, that involves the investigation of mouth representations as well as a comparative analysis between static and dynamic representations of visemes. The analysis shows the need to analyse and model the underlying dynamics of visemes due to coarticulation. Finally, visual analysis of lip coarticulation in Vowel-Consonant-Vowel (VCV) utterances is presented. Based on ensemble statistics a novel approach to analysis and modelling of temporal dynamics is presented. Results show that the temporal influence of coarticulation is significant both in lip shape variation and timings of lip movement during coarticulation. This work shows that the effect of temporal variation due to coarticulation is statistically significant and should be taken into account in modelling visual speech synthesis. The work in this thesis provides the foundation for further research towards achieving perceptually realistic animation of a talking head and the understanding of visual dynamics of shape and texture during speech.
Choosing the Precision of Performance Metrics

There is a standard trade-off in compensation contracts between the provision of incentives and insurance. We hypothesize that this trade-off influences the precision with which firm performance is measured. We find that firm outcomes are measured less precisely when chance plays a large role in these outcomes. Further, this precision is determined through the choice of shares outstanding. This has several novel implications. Nominal stock prices can remain constant over time, and firms with unpredictable cash flows should have more shares and lower stock price levels, all else equal. We find evidence consistent with these implications.
GTP hydrolysis by Ran occurs at the nuclear pore complex in an early step of protein import

Mediated import of proteins into the nucleus involves multiple cytosolic factors, including the small GTPase Ran. Whether Ran functions by interacting with other cytosolic proteins or components of the nuclear pore complex has been unclear. Furthermore, the precise transport step where Ran acts has not been determined. To address these questions, we have analyzed the binding interactions of Ran using permeabilized cells and isolated nuclear envelopes. By light and electron microscope immunolocalization, we have found that Ran accumulates specifically at the cytoplasmic surface of the nuclear pore complex when nuclear import in permeabilized cells is inhibited by nonhydrolyzable analogs of GTP. Ran associates with a peripheral pore complex region that is similar to the area where transport ligands accumulate by depletion of ATP, which arrests an early step of transport. Binding studies with isolated nuclear envelopes in the absence of added cytosol indicate that Ran-GTP directly interacts with a pore complex protein. Using blot overlay techniques, we detected a single prominent polypeptide of isolated nuclear envelopes that binds Ran-GTP. This corresponds to the 358-kD protein RanBP2, a Ran binding pore complex protein recently identified by two-hybrid screening. Thus, RanBP2 is likely to constitute the Ran-GTP-binding site detected at the cytoplasmic periphery of the pore complex. These data support a model in which initial ligand binding to the nuclear pore complex occurs at or near RanBP2, and that hydrolysis of GTP by Ran at this site serves to define commitment to the nuclear import pathway.
Recombinant follicle stimulating hormone (rFSH; Puregon) in assisted reproduction: more oocytes, more pregnancies. Results from five comparative studies.

The clinical assessment of recombinant follicle stimulating hormone (rFSH; Puregon) in assisted reproduction technologies such as in-vitro fertilization (IVF) has probably been the most extensive clinical trial programme ever performed for the evaluation of a new fertility drug. It started with a pilot study to evaluate the potential of rFSH to stimulate the ovaries in the absence of luteinizing hormone (LH) using various gonadotrophin-releasing hormone (GnRH) agonists. After it became clear that FSH-induced steroidogenesis was not jeopardized even after severe pituitary suppression, comparisons between rFSH and urinary FSH or human menopausal gonadotrophins were made using different GnRH agonists or no agonists at all. In addition, the effects of the route of administration (s.c. or i.m.) were assessed. The study with the strongest statistical power to truly assess clinically relevant differences between rFSH and urinary FSH included approximately 1000 patient cycles. It indicated that after rFSH treatment, significantly more oocytes were retrieved, more embryos obtained and, as a result, more pregnancies achieved when the results of the cryoprogramme were included.
Analysis of Copper and Zinc Plasma Concentration and the Efficacy of Zinc Therapy in Individuals with Asperger’s Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Autism

Aim To assess plasma zinc and copper concentration in individuals with Asperger's Syndrome, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) and autistic disorder, and to analyze the efficacy of zinc therapy on the normalization of zinc and copper levels and symptom severity in these disorders. Subjects and methods Plasma from 79 autistic individuals, 52 individuals with PDD-NOS, 21 individuals with Asperger's Syndrome (all meeting DSM-IV diagnostic criteria), and 18 age and gender similar neurotypical controls, were tested for plasma zinc and copper using inductively-coupled plasma-mass spectrometry. Results Autistic and PDD-NOS individuals had significantly elevated plasma levels of copper. None of the groups (autism, Asperger's or PDD-NOS) had significantly lower plasma zinc concentrations. Post zinc and B-6 therapy, individuals with autism and PDD-NOS had significantly lower levels of copper, but individuals with Asperger's did not have significantly lower copper. Individuals with autism, PDD-NOS and Asperger's all had significantly higher zinc levels. Severity of symptoms decreased in autistic individuals following zinc and B-6 therapy with respect to awareness, receptive language, focus and attention, hyperactivity, tip toeing, eye contact, sound sensitivity, tactile sensitivity and seizures. None of the measured symptoms worsened after therapy. None of the symptoms in the Asperger's patients improved after therapy. Discussion These results suggest an association between copper and zinc plasma levels and individuals with autism, PDD-NOS and Asperger's Syndrome. The data also indicates that copper levels normalize (decrease to levels of controls) in individuals with autism and PDD-NOS, but not in individuals with Asperger's. These same Asperger's patients do not improve with respect to symptoms after therapy, whereas many symptoms improved in the autism group. This may indicate an association between copper levels and symptom severity.
HST NICMOS Imaging of z ~ 2, 24 μm-selected Ultraluminous Infrared Galaxies

We present Hubble Space Telescope NICMOS H-band imaging of 33 ultraluminous infrared galaxies (ULIRGs) at z ∼ 2 that were selected from the 24 μm catalog of the Spitzer Extragalactic First Look Survey. The images reveal that at least 17 of the 33 objects are associated with interactions. Up to one-fifth of the sources in our sample could be minor mergers, whereas only two systems are merging binaries with luminosity ratio ≤ 3:1, which is characteristic of local ULIRGs. The rest-frame optical luminosities of the sources are of the order 1010-1011 L☉ and their effective radii range from 1.4 to 4.9 kpc. The most compact sources are either those with a strong active nucleus continuum or those with a heavy obscuration in the mid-infrared regime, as determined from Spitzer Infrared Spectrograph data. The luminosity of the 7.7 μm feature produced by polycyclic aromatic hydrocarbon molecules varies significantly among compact systems, whereas it is typically large for extended systems. A bulge-to-disk decomposition performed for the six brightest (mH < 20) sources in our sample indicates that they are best fit by disklike profiles with small or negligible bulges, unlike the bulge-dominated remnants of local ULIRGs. Our results provide evidence that the interactions associated with ultraluminous infrared activity at z ∼ 2 can differ from those at z ∼ 0.
Automatic Taxonomy Extraction from Query Logs with no Additional Sources of Information

Search engine logs store detailed information on Web users interactions. Thus, as more and more people use search engines on a daily basis, important trails of users common knowledge are being recorded in those files. Previous research has shown that it is possible to extract concept taxonomies from full text documents, while other scholars have proposed methods to obtain similar queries from query logs. We propose a mixture of both lines of research, that is, mining query logs not to find related queries nor query hierarchies, but actual term taxonomies that could be used to improve search engine effectiveness and efficiency. As a result, in this study we have developed a method that combines lexical heuristics with a supervised classification model to successfully extract hyponymy relations from specialization search patterns revealed from log missions, with no additional sources of information, and in a language independent way.
A Minimalistic Approach to Appearance-Based Visual SLAM

This paper presents a vision-based approach to simultaneous localization and mapping (SLAM) in indoor/outdoor environments with minimalistic sensing and computational requirements. The approach is based on a graph representation of robot poses, using a relaxation algorithm to obtain a globally consistent map. Each link corresponds to a relative measurement of the spatial relation between the two nodes it connects. The links describe the likelihood distribution of the relative pose as a Gaussian distribution. To estimate the covariance matrix for links obtained from an omnidirectional vision sensor, a novel method is introduced based on the relative similarity of neighboring images. This new method does not require the determination of distances to image features using multiple-view geometry, for example. Combined indoor and outdoor experiments demonstrate that the approach can handle different environments (without modification of the parameters), and it can cope with violations of the ldquoflat floor assumptionrdquo to some degree and scales well with increasing size of the environment, producing topologically correct and geometrically accurate maps at low computational cost. Further experiments demonstrate that the approach is also suitable for combining multiple overlapping maps, e.g., for solving the multirobot SLAM problem with unknown initial poses.
Brain development during puberty: state of the science.

© 2006 The Authors children during a nonspatial working memory task with functional MRI. Neuroimage , 2 (3), 221–229. Casey, B.J., Thomas, K.M. , Davidson, M.C. , Kunz, K. , & Franzen, P.L. (2002). Dissociating striatal and hippocampal function developmentally with a stimulus–response compatibility task. Journal of Neuroscience , 22 (19), 8647–8652. Casey, B.J., Trainor, R.J., Orendi, J.L. , Schubert, A.B. , Nystrom, L.E. , Giedd, J.N. , Castellanos, F.X. , Haxby, J.V. , Noll, D.C., Cohen, J.D. , Forman, S.D. , Dahl, R.E. , & Rapoport, J.L. (1997). A developmental functional MRI study of prefrontal activation during performance of a go-no-go task. Journal of Cognitive Neuroscience , 9 (6), 835– 847. Cohen, M.S., & DuBois, R.M. (1999). Stability, repeatability, and the expression of signal magnitude in functional magnetic resonance imaging. Journal of Magnetic Resonance Imaging , 10 (1), 33–40. Durston, S. , Davidson, M.C. , Tottenham, N. , Galvan, A. , Spicer, J., Fossella, J.A. , & Casey, B.J. (2006). A shift from diffuse to focal cortical activity with development. Developmental Science , 9 (1), 1–8. Gaillard, W.D. , Hertz-Pannier, L. , Mott, S.H. , Barnett, A.S. , LeBihan, D. , & Theodore, W.H. (2000). Functional anatomy of cognitive development: fMRI of verbal fluency in children and adults. Neurology , 54 , 180–185. Hertz-Pannier, L. , Gaillard, W. , Mott, S.H. , Cuenod, D.A. , Bookheimer, S.Y. , Weinstein, D. , Conry, J., Papero, P.H. , Schiff, S.J., Le Bihan, D. , & Theodore, W.H. (1997). Noninvasive assessment of language dominance in children and adolescents with functional MRI: a preliminary study. Neurology , 48 , 1003–1012. Holland, S.K. , Plante, E. , Weber Byars, A. , Strawsburg, R.H. , Schmithorst, V.J., & Ball, W.S. Jr. (2001). Normal fMRI brain activation patterns in children performing a verb generation task. Neuroimage , 14 (4), 837–843. Johnson, M.H. (2000). Functional brain development in infants: elements of an interactive specialization framework. Child Development , 71 (1), 75–81. Murphy, K. , & Garavan, H. (2004). Artifactual fMRI group and condition differences driven by performance confounds. Neuroimage , 21 (1), 219–228. O’Leary, D.D. , & Nakagawa, Y. (2002). Patterning centers, regulatory genes and extrinsic mechanisms controlling arealization of the neocortex. Current Opinion in Neurobiology , 12 (1), 14–25. Passarotti, Alessandra M. , Paul, Brianna M. , Bussiere, Joseph R. , Buxton, Richard B. , Wong, Eric C. , & Stiles, Joan (2003). The development of face and location processing: an fMRI study. Developmental Science , 6 (1), 100–117. Schlaggar, B.L. , Brown, T.T. , Lugar, H.M. , Visscher, K.M. , Miezin, F.M. , & Petersen, S.E. (2002). Functional neuroanatomical differences between adults and school-age children in the processing of single words. Science , 296 , 1476–1479. Stiles, J., Moses, P., Passarotti, A. , Dick, F.K. , & Buxton, R. (2003). Exploring developmental change in the neural bases of higher cognitive functions: the promise of functional magnetic resonance imaging. Developmental Neuropsychology , 24 (2–3), 641–668.
Motor cortical activity during drawing movements: population representation during sinusoid tracing.

1. Monkeys were trained to trace sinusoids with their index fingers on a planar surface. During this task, both the direction and speed of movement varied continuously. Activity of individual units in the precentral gyrus contralateral to the moving arm was recorded as the task was performed. These cells responded to passive movement of the shoulder and/or elbow. The relation between discharge rate and movement direction for these individual cells could be described with a cosine tuning function. 2. Data recorded as the sinusoid was traced were divided into 100 bins as each cell was studied during the experiment. In each bin, the activity of a particular cell was represented by a vector. The vector ("cell vector") pointed in the direction of finger movement that corresponded to the highest rate of neuronal discharge. This direction, referred to as the preferred direction, corresponded to the peak of the cosine tuning function. The direction of the vector was constant between bins, but the magnitude of this cell's vector was a function of the instantaneous discharge rate. 3. This cell vector is a hypothetical contribution of a single cell to the population response comprised of 554 similarly derived vectors from different cells. The population response was represented as the vector that resulted from forming the sum of the vector contributions from the individual cells. A separate calculation was made for each bin, resulting in 100 population vectors for each sinusoid. 4. Within a given time series of population vectors, their lengths and directions varied in a consistent relation to the tangential velocity of the drawing movement. (ABSTRACT TRUNCATED AT 250 WORDS)
Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection.

BACKGROUND Primary pyogenic liver abscess (PLA) with septic complication by Klebsiella pneumoniae is an emerging infectious disease. METHODS AND RESULTS Using DNA microarray hybridization, we identified a 20-kb chromosomal region that contained 15 open-reading frames (ORFs), including an iron-uptake system (kfu), a phosphoenolpyruvate sugar phosphotransferase system (PTS), and 6 unknown ORFs. The region was more prevalent among tissue-invasive strains (35/46) than among noninvasive strains (19/98) (P<.0001, chi2 test). To test the role played by this region in pathogenesis, 3 different deletion mutants (NTUH-K2044 [Delta kfu], K2044 [Delta ORF7-9], and K2044 [Delta PTS]) were constructed. Only the Delta kfuABC mutants showed decreased virulence in mice, compared with the wild-type strain. An in vitro assay confirmed the involvement of kfu in iron acquisition. There was a high correlation rate (85%) between the kfu/PTS region and 2 tissue invasion-associated chromosomal regions (allS and magA). Moreover, all 3 regions were present in strains that caused PLA plus endophthalmitis or meningitis. CONCLUSION Our results suggest that chromosomal heterogeneity is present in tissue-invasive K. pneumoniae strains. A genotype containing all 3 regions is strongly associated with PLA and metastatic infection. These regions may serve as convenient markers for the rapid diagnosis of emergent tissue-invasive strains.
Accuracy Evaluation Between GPS Virtual Reference Station (VRS) and GPS Real Time Kinematic (RTK) Techniques

There are some limitations when using the GPS RTK technique such as: the limited distance for the radio transmitter; the need for base receiver; and the dependence on only one-base point to calculate the corrections. On the other hand, Virtual Reference Station VRS is an imaginary, unoccupied reference station which is only a few meters from the RTK user. The principle is to interpolate the data of several Continuous Operating Reference Station CORS in order to obtain the correction data for the rovers, which reduces the systematic influences of the RTK measurement decisively; and allowing distance between the reference station and the rover to be increased; in addition to the reliability of the system is heightened. This paper aims to comparing the X, Y and Z coordinates resulted from VRS network with the resulted coordinates for the same points resulted from RTK technique. The results supported with statistical analysis showed that horizontal positional discrepancy P between the two techniques has a mean value of 52 mm with 18 mm standard 2d deviation, while the spatial positional discrepancy P has a mean value of 67 mm with standard deviation 3d 23 mm. These findings are considered to be insignificant in the daily work of cadastral and topographic survey work, but should be taken into account for the precise surveying such as monitoring of structure deformation when combining the two techniques in the measurements.