Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Notch1 Antibodies That Inhibit Signaling of Both Normal and Mutated Notch1 Receptors

Background Notch receptors normally play a key role in guiding a variety of cell fate decisions during development and differentiation of metazoan organisms. On the other hand, dysregulation of Notch1 signaling is associated with many different types of cancer as well as tumor angiogenesis, making Notch1 a potential therapeutic target. Principal Findings Here we report the in vitro activities of inhibitory Notch1 monoclonal antibodies derived from cell-based and solid-phase screening of a phage display library. Two classes of antibodies were found, one directed against the EGF-repeat region that encompasses the ligand-binding domain (LBD), and the second directed against the activation switch of the receptor, the Notch negative regulatory region (NRR). The antibodies are selective for Notch1, inhibiting Jag2-dependent signaling by Notch1 but not by Notch 2 and 3 in reporter gene assays, with EC50 values as low as 5±3 nM and 0.13±0.09 nM for the LBD and NRR antibodies, respectively, and fail to recognize Notch4. While more potent, NRR antibodies are incomplete antagonists of Notch1 signaling. The antagonistic activity of LBD, but not NRR, antibodies is strongly dependent on the activating ligand. Both LBD and NRR antibodies bind to Notch1 on human tumor cell lines and inhibit the expression of sentinel Notch target genes, including HES1, HES5, and DTX1. NRR antibodies also strongly inhibit ligand-independent signaling in heterologous cells transiently expressing Notch1 receptors with diverse NRR “class I” point mutations, the most common type of mutation found in human T-cell acute lymphoblastic leukemia (T-ALL). In contrast, NRR antibodies failed to antagonize Notch1 receptors bearing rare “class II” or “class III” mutations, in which amino acid insertions generate a duplicated or constitutively sensitive metalloprotease cleavage site. Signaling in T-ALL cell lines bearing class I mutations is partially refractory to inhibitory antibodies as compared to cell-penetrating gamma-secretase inhibitors. Conclusions/Significance Antibodies that compete with Notch1 ligand binding or that bind to the negative regulatory region can act as potent inhibitors of Notch1 signaling. These antibodies may have clinical utility for conditions in which inhibition of signaling by wild-type Notch1 is desired, but are likely to be of limited value for treatment of T-ALLs associated with aberrant Notch1 activation.
Nutrient Stress Activates Inflammation and Reduces Glucose Metabolism by Suppressing AMP-Activated Protein Kinase in the Heart

OBJECTIVE Heart failure is a major cause of mortality in diabetes and may be causally associated with altered metabolism. Recent reports indicate a role of inflammation in peripheral insulin resistance, but the impact of inflammation on cardiac metabolism is unknown. We investigated the effects of diet-induced obesity on cardiac inflammation and glucose metabolism in mice. RESEARCH DESIGN AND METHODS Male C57BL/6 mice were fed a high-fat diet (HFD) for 6 weeks, and heart samples were taken to measure insulin sensitivity, glucose metabolism, and inflammation. Heart samples were also examined following acute interleukin (IL)-6 or lipid infusion in C57BL/6 mice and in IL-6 knockout mice following an HFD. RESULTS Diet-induced obesity reduced cardiac glucose metabolism, GLUT, and AMP-activated protein kinase (AMPK) levels, and this was associated with increased levels of macrophages, toll-like receptor 4, suppressor of cytokine signaling 3 (SOCS3), and cytokines in heart. Acute physiological elevation of IL-6 suppressed glucose metabolism and caused insulin resistance by increasing SOCS3 and via SOCS3-mediated inhibition of insulin receptor substrate (IRS)-1 and possibly AMPK in heart. Diet-induced inflammation and defects in glucose metabolism were attenuated in IL-6 knockout mice, implicating the role of IL-6 in obesity-associated cardiac inflammation. Acute lipid infusion caused inflammation and raised local levels of macrophages, C-C motif chemokine receptor 2, SOCS3, and cytokines in heart. Lipid-induced cardiac inflammation suppressed AMPK, suggesting the role of lipid as a nutrient stress triggering inflammation. CONCLUSIONS Our findings that nutrient stress activates cardiac inflammation and that IL-6 suppresses myocardial glucose metabolism via inhibition of AMPK and IRS-1 underscore the important role of inflammation in the pathogenesis of diabetic heart.
Dynamic Video Transcoding Using Hadoop Distributed File System

When there is an ever increasing demand for videos related to several fields, it is paramount to ensure that videos are seamlessly and efficiently delivered. This needs to be done to preserve the viewing experience regardless of the device which is used for viewing. In order to provide such an experience in a computationally efficient manner that also minimizes storage requirements, it is proposed to implement a system which uses video transcoding software such as FFMPEG. This is used to transcode videos and segments them for reliable transmission as required by a client. Here, the quality of the video is determined by taking advantage of HTTP adaptive streaming and the space requirements are reduced by using a popularity index measure which limits the number of videos transcoded beforehand and are stored in the system. To further facilitate storage, the entire system is implemented using the Hadoop Distributed File System (HDFS). Keywords-Popularity Index, On-The-Fly (OTF) Chunking, HTTP Adaptive Streaming, Hadoop Distributed File System, Dynamic Video Transcoding, MapReduce framework.
Reversal of the lift force on an oblate bubble in a weakly viscous linear shear flow

We compute the flow about an oblate spheroidal bubble of prescribed shape set fixed in a viscous linear shear flow in the range of moderate to high Reynolds numbers. In contrast to predictions based on inviscid theory, the numerical results reveal that for weak enough shear rates, the lift force and torque change sign in an intermediate range of Reynolds numbers when the bubble oblateness exceeds a critical value that depends on the relative shear rate. This effect is found to be due to the vorticity generated at the bubble surface which, combined with the velocity gradient associated with the upstream shear, results in a system of two counter-rotating streamwise vortices whose sign is opposite to that induced by the classical inviscid tilting of the upstream vorticity around the bubble. We show that this lift reversal mechanism is closely related to the wake instability mechanism experienced by a spheroidal bubble rising in a stagnant liquid.
High‐Resolution genomic arrays identify CNVs that phenocopy the chromosome 22q11.2 deletion syndrome

The 22q11 Deletion Syndrome includes the overlapping phenotypes of DiGeorge/Velocardiofacial Syndromes, characterized by conotruncal heart defects, cleft palate, thymus, and parathyroid gland dysplasia. The majority (90%) of patients harbor detectable chr22q11.2 deletions, but a genetic etiology for the remainder of patients without a deletion can remain undefined despite major birth defects. We analyzed DNA from eight patients with normal 22q11 FISH studies by high‐density single nucleotide polymorphism (SNP) arrays and identified potentially pathogenic copy number variants (CNVs) in four of eight patients. Two patients showed large CNVs in regions of known genomic disorders: one a deletion of distal chr22q11.2 and the other a duplication of chr5q35. A 3‐Mb deletion of chr19p13.3 that includes a gene associated with conotruncal heart defects was found in a third patient. Two potentially pathogenic CNVs were found in a fourth patient: a large heterozygous deletion of chr6p24 and a smaller duplication of chr9p24. Our findings support a recent consensus statement advocating chromosomal microarray analysis as a first‐line diagnostic approach for patients with multiple congenital anomalies. In patients with phenotypes suggestive of the 22q11.2 syndrome spectrum and normal FISH, microarray analysis can uncover the molecular basis of other genomic disorders whose features overlap those of 22q11.2 deletions.Hum Mutat 31:1–7, 2010. © 2010 Wiley‐Liss, Inc.
ROBUST REAL-TIME MUSIC TRACKING

This paper describes our ’any-time’ real-time music tracking system which is based on an on-line version of the well-known Dynamic Time Warping (DTW) algorithm and includes some extensions to improve both the precision and the robustness of the alignment (e.g. a tempo model and the ability to reconsider past decisions). A unique feature of our system is the ability to cope with arbitrary structural deviations (e.g. jumps, re-starts) online during a live performance.
The Role of Pain in Reduced Quality of Life and Depressive Symptomology in Children With Spina Bifida

ObjectivesChildren with spina bifida report both chronic and acute pain caused by both their condition and the treatments they undergo regularly. This research provides a description of the impact of this pain on their quality of life. MethodsA sample of 68 children (56% female) between the ages of 8 and 19 completed the Varni/Thompson Pediatric Pain Questionnaire, a supplementary questionnaire on pain, the Children's Depression Inventory, the Nowicki-Strickland Locus of Control Scale for Children, and a pediatric measure of health related quality of life. ResultsHealth related quality of life was shown to be systematically low in this group as compared with a reference sample of chronically ill children. It was negatively impacted by high reported frequency of pain and high ratings of current pain. Both pain and low quality of life were strongly associated with Children's Depression Inventory scores. Locus of control scores was not associated with quality of life or reported pain. ConclusionThe unmanaged pain in children with spina bifida can have a substantial negative impact on quality of life. Better treatment and surveillance of pain and depression symptoms may significantly improve quality of life.
Protective effect of agmatine on a reperfusion model after transient cerebral ischemia: Temporal evolution on perfusion MR imaging and histopathologic findings.

BACKGROUND AND PURPOSE The goal of thrombolytic therapy in patients with acute ischemic stroke is early recanalization, but this may result in delayed reperfusion injury. The purpose of this study was to evaluate the neuroprotective effect of agmatine in a transient ischemic cat model by using MR perfusion imaging and histopathologic analyses. METHOD One-hour temporary occlusion of the left middle cerebral artery of cats was performed in the control ischemia group (n = 10), and 100 mg/kg of agmatine was intravenously injected immediately after recanalization in the agmatine-treated group (n = 15). MR imaging was performed at 1, 24, and 48 hours after recanalization, and the perfusion patterns were investigated. Terminal-deoxynucleotidyl transferase mediated nick and end-labeling (TUNEL) and hematoxylin-eosin (H&E) stainings were performed at the corresponding sections. RESULTS In the control ischemia group, the number of TUNEL-positive cells was significantly increased in the areas with reperfusion hyperemia (P < .05). In the agmatine-treated group, no significant increase in the number of TUNEL-positive cells was noted in the areas of reperfusion hyperemia. The difference in the number of TUNEL-positive cells between the control ischemia and agmatine-treated group in the areas of reperfusion hyperemia was significant (P < .05). The total number of TUNEL-positive cells and the area of severe ischemic neuronal damage on H&E stain were also significantly attenuated in the agmatine-treated cats compared with the control ischemia cats (P < .05). CONCLUSION Our results suggest that agmatine has neuroprotective effects against reperfusion injury and ischemia.
A Hermetic Wireless Subretinal Neurostimulator for Vision Prostheses

A miniaturized, hermetically encased, wirelessly operated retinal prosthesis has been developed for preclinical studies in the Yucatan minipig, and includes several design improvements over our previously reported device. The prosthesis attaches conformally to the outside of the eye and electrically drives a microfabricated thin-film polyimide array of sputtered iridium oxide film electrodes. This array is implanted into the subretinal space using a customized ab externo surgical technique. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete circuit components. Feedthroughs in the case connect the stimulator chip to secondary power and data receiving coils on the eye and to the electrode array under the retina. Long-term in vitro pulse testing of the electrodes projected a lifetime consistent with typical devices in industry. The final assembly was tested in vitro to verify wireless operation of the system in physiological saline using a custom RF transmitter and primary coils. Stimulation pulse strength, duration, and frequency were programmed wirelessly from a Peripheral Component Interconnect eXtensions for Instrumentation (PXI) computer. Operation of the retinal implant has been verified in two pigs for up to five and a half months by detecting stimulus artifacts generated by the implanted device.
Utilizing User Posts to Enrich Web Document Summarization with Matrix Co-factorization

In the context of social media, users tend to post relevant information corresponding to an event mentioned in a Web document. This paper presents a model to capture the nature of the relationships between sentences and user posts such as relevant comments in sharing hidden topics for enriching summarization. Unlike the previous methods which usually base on hand-crafted features, our approach ranks sentences and comments based on their importance affecting the topics. The sentence-comment relation is formulated in a share topic matrix, which presents their mutual reinforcement support. Our newly proposed matrix co-factorization algorithm computes the score of each sentence and comment and extracts top m ranked sentences and m comments as the summarization. Experimental results on two datasets in English and Vietnamese of the social context summarization task and DUC 2004 confirm the efficiency of our model in summarizing Web documents.
Exact Solutions for a Generalized Variable Coefficient Gardner Equation

In this paper, a generalized variable coefficient Gardner equation is investigated. Exp-function method combined with F-expansion method are used to determine six families of exact solutions of exp-function type for this equation. Under different parametric conditions, every family of solution can be reduced to some solitary wave solutions and periodic wave solutions. The results presented in this paper improve the previous results. Mathematics Subject Classification: 35Q51; 35Q58;
Quantitative DY‐maleimide‐based proteomic 2‐DE‐labeling strategies using human skin proteins

Sensitive differential proteomic analysis is challenging and often limited by distinct labeling or tagging strategies. In this study, we have examined the sensitivity, linearity, and photophysical properties of novel protein labeling DY‐maleimide dyes (DY‐505‐MAL, DY‐555‐MAL and DY‐635‐MAL). All MS compatible DY‐maleimide dyes exhibited excellent emission spectra, high sensitivity, and high linearity, when applied to standard 1‐DE protein analysis. Correspondingly, 2‐DE analysis of DY‐635‐MAL or DY‐505‐MAL maximal‐labeled human keratinocyte proteins displayed remarkably high sensitivity. Compared with a standard fluorescent protein stain, DY‐635‐MAL or DY‐505‐MAL 2‐DE analysis demonstrated equally high spot quality with an overall increase in the number of spots detectable (up to threefold higher;>1000 spots/gel). However, as determined with a FLA‐5100 imaging system, comparative MultiGauge, and Delta2D analysis, not all DY‐maleimide dyes possessed DIGE compatible fluorescent emission properties. However, DY‐505‐MAL and DY‐635‐MAL were found to be suitable for more complex, time and gel intensive, focused multiplexing analyses. Notably – as demonstrated with allergen‐stimulated human skin proteins – defined, singular DY‐maleimide dye protein labeling (SDPL) allows high quality, time saving, simple, and reliable differential proteomic examination.
Reorganization and Stability for Motor and Language Areas Using Cortical Stimulation: Case Example and Review of the Literature

The cerebral organization of language in epilepsy patients has been studied with invasive procedures such as Wada testing and electrical cortical stimulation mapping and more recently with noninvasive neuroimaging techniques, such as functional MRI. In the setting of a chronic seizure disorder, clinical variables have been shown to contribute to cerebral language reorganization underscoring the need for language lateralization and localization procedures. We present a 14-year-old pediatric patient with a refractory epilepsy disorder who underwent two neurosurgical resections of a left frontal epileptic focus separated by a year. He was mapped extraoperatively through a subdural grid using cortical stimulation to preserve motor and language functions. The clinical history and extensive workup prior to surgery is discussed as well as the opportunity to compare the cortical maps for language, motor, and sensory function before each resection. Reorganization in cortical tongue sensory areas was seen concomitant with a new zone of ictal and interictal activity in the previous tongue sensory area. Detailed neuropsychological data is presented before and after any surgical intervention to hypothesize about the extent of reorganization between epochs. We conclude that intrahemispheric cortical plasticity does occur following frontal lobe resective surgery in a teenager with medically refractory seizures.
ON A MULTILEVEL KRYLOV METHOD FOR THE HELMHOLTZ EQUATION PRECONDITIONED BY SHIFTED LAPLACIAN

In Erlangga and Nabben [SIAM J. Sci. Comput. , 30 (2008), pp. 15 72–1595], a multilevel Krylov method is proposed to solve linear systems with symmetric and non symmetric matrices of coefficients. This multilevel method is based on an operator which shifts some small ei genvalues to the largest eigenvalue, leading to a spectrum which is favorable for convergence acceleration of a Krylov subspace method. This shift technique involves a subspace or coarse-grid solve. The multilevel Krylo v method is obtained via a recursive application of the shift operator on the coarse-grid system. This method has b een applied successfully to 2D convection-diffusion problems for which a standard multigrid method fails to converg e. In this paper, we extend this multilevel Krylov method to indefi nite linear systems arising from a discretization of the Helmholtz equation, preconditioned by shifted Laplacia n as introduced by Erlangga, Oosterlee and Vuik [SIAM J. Sci. Comput. 27 (2006), pp. 1471–1492]. Within the Krylov i teration and the multilevel steps, for each coarse-grid solve a multigrid iteration is used to approximately invert th e shifted Laplacian preconditioner. Hence, a multilevel Krylov-multigrid (MKMG) method results. Numerical results are given for high wavenumbers and show the e ffectiveness of the method for solving Helmholtz problems. Not only can the convergence be made almost inde pe nt of grid sizeh, but also linearly dependent on the wavenumber k, with a smaller proportional constant than for the multigrid p reconditioned version, presented in the aforementioned paper.
Diode laser welding of polypropylene: investigations of the microstructures in the welded seam

Laser welding of thermoplastic polymers is a non-contact process especially efficient for joining thermoplastic polymers. This innovative technology is already used for industrial series production in different sectors (automobile, packaging,.). The majority of the basic research concerns the weld strength depending on polymer nature, optical properties, butt design and process parameters. Nevertheless, a lack of knowledge concerning the influence of thermal history of the weld seam on morphology of semicrystalline polymer still exists, when this parameter strongly influences the strength of the weld. Actual results of diode laser transmission welding (LTW) experiments on polypropylene, a semicrystalline polymer widely used in industry, could contribute to a better understanding of the process itself and to success in practical applications.
Accuracy Enhancement Techniques in Low-Voltage High-Speed Pipelined ADC Design

encouragement and insightful guidance throughout my Ph.D. studies. I am also grateful to Professors Gábor C. Temes, Karti Mayaram and Terri Fiez for their helps in both research and academic matters. I would also like to acknowledge all members of my committee, for taking the time to serve on my defense. All my colleagues in the Analog Group have not hesitated to offer their help to me. First, I would like to thank Jose Silva. He has offered great help to me from the beginning of my research in school to the end of my study. I would also like to thank discussions. Last, I would like to thank all my friends for their understanding, support and sharing happiness with me.
Construction of a Basque Dependency Treebank

This paper presents the process followed to build the Basque Dependency Treebank. We think that it is a necessary resource for the linguistic research in general and for the development of real applications in the area of NLP. This work is part of a general project which objective is to build annotated corpora with linguistic annotation at syntactic, semantic and pragmatic levels. We annotate syntactically the Eus3LB corpus following the dependencybased formalism as explained in Aduriz et al, (2002). This formalism is also used in the Prague Dependency Treebank for Czech (Hajic, 1998) and in Oflazer et al.,(1999) and, is the one that could best deal with the free word order (Skut et al. 1997) displayed by Basque syntax. Eus3LB is a corpus of standard written Basque that contains 25.000 word-forms from EPEC (Aduriz et al., 2003) and 25.000 words coming from newspapers that can be considered equivalent to the corpora in the other languages in the project. In order to define the syntactic tagging system, we adopted the framework presented in Carroll et al. (1998, 1999). However, there are certain differences: in our system, arguments that are not lexicalised may appear in grammatical relations (for example, the phonetically empty pro argument which appears in the so-called pro-drop languages). Figure 1 shows the coding-system based on hierarchies of grammatical relations. The tag set employed describes the most important grammatical structures such as relative clauses, causative sentences, coordination, discontinuous elements, elliptic elements and so on. The hierarchy distinguishes between several general levels, which are further specified in subsequent levels. Thus, for instance, in the general level we find structurally case-marked complements, modifiers, negation, linkingwords, auxiliaries, others and semantic relations. Some of them, for example