Miracle-dz/UniFAR-FTUs huggingface dataset:
CDK4 phosphorylation status and a linked gene expression profile predict sensitivity to palbociclib

Cyclin D‐CDK4/6 are the first CDK complexes to be activated in the G1 phase in response to oncogenic pathways. The specific CDK4/6 inhibitor PD0332991 (palbociclib) was recently approved by the FDA and EMA for treatment of advanced ER‐positive breast tumors. Unfortunately, no reliable predictive tools are available for identifying potentially responsive or insensitive tumors. We had shown that the activating T172 phosphorylation of CDK4 is the central rate‐limiting event that initiates the cell cycle decision and signals the presence of active CDK4. Here, we report that the profile of post‐translational modification including T172 phosphorylation of CDK4 differs among breast tumors and associates with their subtypes and risk. A gene expression signature faithfully predicted CDK4 modification profiles in tumors and cell lines. Moreover, in breast cancer cell lines, the CDK4 T172 phosphorylation best correlated with sensitivity to PD0332991. This gene expression signature identifies tumors that are unlikely to respond to CDK4/6 inhibitors and could help to select a subset of patients with HER2‐positive and basal‐like tumors for clinical studies on this class of drugs.
Improvement of rejection performance of keyword spotting using anti-keywords derived from large vocabulary considering acoustical similarity to keywords

This paper proposes an efficient anti-keyword derivation method to improve the rejection performance of keyword spotting. In this method, each anti-keyword is derived from the large vocabulary lexicon considering acoustic similarity to keywords, making use of the confusion matrix. Experimental results show that a 3 % improvement of the rejection rate is obtained compared to conventional methods that do not have our anti-keyword models
Incremental Direct Expenditure of Treating Asthma in the United States

Objective. There is a wide range in the estimates of cost of asthma that are available in the literature. Given the growing prevalence of asthma and its associated healthcare resource use in the United States (U.S.), it is important to obtain current and precise cost estimates attributable to asthma treatment. The objectives of this study were to estimate the incremental direct expenditures associated with asthma in the U.S. Methods. Retrospective analysis was conducted using the 2004 Medical Expenditure Panel Survey (MEPS) data that are representative of the civilian non-institutionalized population of the U.S. Asthma respondents were identified as those with International Classification of Diseases-9-Clinical Modification (ICD-9-CM) diagnosis codes for asthma in 2004 or those who had a self-report of having asthma in 2004. Incremental total expenditures and expenditures for various categories of resource use including physician office visits, emergency room visits, outpatient visits, inpatient visits, medications, and other medical visits associated with asthma were estimated separately in children (age < 18 years) and in adults (age ≥ 18 years) using generalized linear regression models. The models were adjusted for covariates including age, gender, race, ethnicity, education, marital status (for age group ≥ 18 years), geographic region, insurance status, and comorbidities. Results. The prevalence of asthma among children and adults in 2004 was estimated at 8.7% (6.4 million persons) and 6.72% (14.8 million persons), respectively. The annual adjusted mean incremental total expenditure associated with asthma was $1,004.6 (SE: $326.1; p = 0.002) per person among children and was $2,077.5 (SE: $544.5; p < 0.0001) per person among adults, after adjusting for covariates. Prescription medications and physician office visits were the major drivers of total expenditures and constituted approximately 38% and 49% of the total incremental expenditures for asthma in children and adults, respectively. Inpatient visit expenditures were high in both age groups but were not significantly different from zero. Conclusion. Given the prevalence of asthma among U.S. children and adults and its associated incremental expenditures, the annual direct medical expenditure attributable to asthma treatment is estimated at approximately $37.2 billion in 2007 U.S. dollars representing a significant portion of healthcare resource use in the U.S.
Plausibility and the Processing of Unbounded Dependencies:An Eye-Tracking Study

Two eye-tracking experiments investigated processing of unbounded dependency constructions. Experiment 1 employed sentences likeThat's the garage/pistol with which the heartless killer shot the man yesterday afternoon.Readers experienced greater processing difficulty in implausible sentences than in plausible sentences immediately after encountering the verbshot.This demonstrated that they did not wait until the purported gap location aftermanbefore forming the unbounded dependency. Experiment 2 considered sentences which locally appear to have an unbounded dependency that turns out to be incorrect. Data from this experiment demonstrated that readers formed the unbounded dependency immediately, even though they had to reanalyze later. However, there was no evidence that readers formed this unbounded dependency when it was rendered ungrammatical by island-constraint information. We argue that the processor constructs unbounded dependencies in a manner that is maximally efficient from the point of view of incremental processing.
Economic comparison of selective laser melting and conventional subtractive manufacturing processes

As one of the leading techniques in additive manufacturing processes, selective laser melting (SLM) has shown great potential for commercialization and scale-up in various applications in industry. The ability to build near net shape end-usable products shows advantages in some cases, with more freedom in product design and processing; greater part complexity; and increased ability to structurally optimize parts that are manufactured directly from powder metal materials. In this study, cost analyses of selective laser melting process is compared with conventional subtractive manufacturing (SM) processes. A generic cost models for SLM and SM processing were developed, and several case studies are used to illustrate the conditions and drivers that demonstrate cost advantages for SLM processing. Factors such as production volume and raw material price are analyzed to investigate the influence on fabrication cost. A part manufacturing complexity factor is also defined to provide insights regarding economic decision making for process selection.
Improvement of lightness modification method based on Craik-O'Brien effect for dichromats

Dichromats is difficult to distinguish some color pairs. There is lightness modification method which considers the Craik-O'Brien effect. Although the method can obtain good results in many cases, there is a room for improvement. In this paper, a new lightness modification method which considers the Craik-O'Brien effect is proposed. In the proposed method, the lightness modification is mainly performed at parts which are difficult to distinguish for dichromats. The validity of the proposed method is shown by experiments using some images.
Secondary nucleation of monomers on fibril surface dominates α-synuclein aggregation and provides autocatalytic amyloid amplification

Abstract Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation. Here, we aim to distinguish between these mechanisms. The nature of the secondary processes was investigated using differential sedimentation analysis, trap and seed experiments, quartz crystal microbalance experiments and super-resolution microscopy. The results identify secondary nucleation of monomers on the fibril surface as the dominant secondary process leading to rapid generation of new aggregates, while no significant contribution from fragmentation was found. The newly generated oligomeric species quickly elongate to further serve as templates for secondary nucleation and this may have important implications in the spreading of PD.
Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis

The role of epitope spreading in the pathology of relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) was examined. Using peripherally induced immunologic tolerance as a probe to analyze the neuropathologic T cell repertoire, we show that the majority of the immunopathologic reactivity during the acute phase of R-EAE in SJL/J mice induced by active immunization with the intact proteolipid (PLP) molecule is directed at the PLP139-151 epitope and that responses to secondary encephalitogenic PLP epitopes may contribute to the later relapsing phases of disease. Intermolecular epitope spreading was demonstrated by showing the development of T cell responses to PLP139- 151 after acute disease in mice in which R-EAE was initiated by the transfer of T cells specific for the non-cross-reactive MBP84-104 determinant. Intramolecular epitope spreading was demonstrated by showing that endogenous host T cells specific for a secondary encephalitogenic PLP epitope (PLP178-191) are demonstrable by both splenic T cell proliferative and in vivo delayed-type hypersensitivity responses in mice in which acute central nervous system damage was initiated by T cells reactive with the immunodominant, non-cross- reactive PLP139-151 sequence. The PLP178-191-specific responses are activated as a result of and correlate with the degree of acute tissue damage, since they do not develop in mice tolerized to the initiating epitope before expression of acute disease. Most importantly, we show that the PLP178-191-specific responses are capable of mediating R-EAE upon adoptive secondary transfer to naive recipient mice. Furthermore, induction of tolerance to intact PLP (which inhibits responses to both the initiating PLP139-151 epitope and to the PLP178-191 epitope) after the acute disease episode is sufficient to prevent relapsing disease. These results strongly support a contributory role of T cell responses to epitopes released as a result of acute tissue damage to the immunopathogenesis of relapsing clinical episodes and have important implications for the design of antigen-specific immunotherapies for the treatment of chronic autoimmune disorders in humans.
Charge-exchange nuclear reactions at NSCL using radioactive beams : Development of the LENDA low energy neutron detector array

Charge-exchange reactions on stable nuclei have been used frequently to study the spin-isospin response on nuclei, which is, for example, crucial for estimating weak-transition rates in late stellar evolution. Because a large fraction of the relevant nuclei in such scenarios are unstable, there is a strong need to expand charge-exchange studies to unstable nuclei, which requires that experiments must be carried out in inverse kinematics. A promising probe for experiments in the ∆Tz=-1 direction is the (p,n) reaction. The “Low Energy Neutron Detector Array” (LENDA) is currently under development at the NSCL (National Superconducting Cyclotron Laboratory). The array will consist of 24 plastic scintillator bars with dimensions of 300× 45× 25 mm. The neutron energy is measured using the time-of-flight technique. Position sensitivity along the bar is achieved by combining the timing and pulse height signals. In this work results of measurements using prototype modules and results of simulations are presented. 10th Symposium on Nuclei in the Cosmos Mackinac Island, Michigan, USA 27 July – 1 August, 200 * Speaker t This work was supported by the US NSF, grants PHY-0216783 (JINA) and PHY-0606007
Manipulating the Mechanical Microenvironment: Microdevices for High-throughput Studies in Cellular Mechanobiology

Determining how biological cells respond to external factors in the environment can aid in understanding disease progression, lead to rational design strategies for tissue engineering, and contribute to understanding fundamental mechanisms of cellular function. Dynamic mechanical forces exist in vivo and are known to alter cellular response to other stimuli. However, identifying the roles multiple external factors play in regulating cell fate and function is currently impractical, as experimental techniques to mechanically stimulate cells in culture are severely limited in throughput. Hence, determining cell response to combinations of mechanical and biological factors is technically limited. In this thesis, microfabricated systems were designed, implemented and characterized to screen for the effects of mechanical stimulation in a highthroughput manner. Realizing these systems required the development of a fabrication process for precisely-aligned multilayer microstructures, and the development of a method to integrate non-traditional and clinically-relevant biomaterials into the microfabrication process. Three microfabricated platforms were developed for this application. First, an array was designed for experiments with high mechanical throughput, in which cells cultured on a surface experience a range of cyclic, uniform, equibiaxial strains. Using this array, a novel timeand strain-dependent mechanism regulating nuclear β-catenin accumulation in valve interstitial cells was identified.
The Systemic Correlation Between Mental Models and Sustainable Design: Implications for Engineering Educators

Many studies have illuminated our understanding of the kinds of competencies and behaviors exhibited by effective designers. Againstthe backdrop of global challenges made more urgent by unintentional negative impacts of engineered products and systems, however, weare left to deduce that our ways of educating engineering designers is fundamentally flawed. We assert that one can trace the cause ofour collective, unintended negative consequences to the mental models of reality that we consciously or unconsciously carry. In thispaper, we present the case for developing awareness and facility with mental models. We also suggest an alternate mental model as thefoundation for sustainable design. This model depicts reality as embedded systems of economies inside society and inside theenvironment. We also discuss how the engineering educator can use the model to build a foundation for holistically viewing design forsustainability. Student responses to a course based on the proposed ideas are also presented as evidence that students’ can value mentalmodels and that working with them effectively changes their world conception.
The Continuous Node Degree: a New Measure for Complex Networks

A key measure that has been used extensively in analyzing complex networks is the degree of a node (the number of the node's neighbors). Because of its discrete nature, when the degree measure was used in analyzing weighted networks, weights were either ignored or thresholded in order to retain or disregard an edge. Therefore, despite its popularity, the degree measure fails to capture the disparity of interaction between a node and its neighbors. We introduce in this paper a generalization of the degree measure that addresses this limitation: the continuous node degree (C-degree). The C-degree of a node reflects how many neighbors are effectively being used, taking interaction disparity into account. More importantly, if a node interacts uniformly with its neighbors (no interaction disparity), we prove that the C-degree of the node becomes identical to the node's (discrete) degree. We analyze four real-world weighted networks using the new measure and show that the C-degree distribution follows the power-law, similar to the traditional degree distribution, but with steeper decline. We also show that the ratio between the C-degree and the (discrete) degree follows a pattern that is common in the four studied networks.
EBUS-TBNA: A Decade of Progress

Roberto F Casal1*, Donald R Lazarus2, Georgie A Eapen1 and Kazuhiro Yasufuku3 1Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2Section of Pulmonary and Critical Care Medicine, Michael E DeBakey VA Medical Center, Baylor College of Medicine, Houston, Texas, USA 3Division of Thoracic Surgery, Toronto General Hospital, Toronto, Canada *Corresponding author: Roberto F Casal, Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, Tel: +1-713-794-1753; E-mail: rfcasal@mdanderson.org
On the Support Properties of Scaling VectorsPeter

In Chui and Wang 3], support properties are derived for a scaling function generating a function space V 0 L 2 (IR). Motivated by this work, we consider support properties for scaling vectors. In 9], Goodman and Lee derive necessary and suucient conditions for the scaling vector f 1 ; : : :; r g, r 1, to form a Riesz basis for V 0 and develop a general theory for spline wavelets of multiplicity r > 1. We consider conditions under which linear combinations of scaling functions generate V 0. These conditions also characterize all other scaling vectors that generate the same V 0. In addition we describe the scaling vectors of minimal support for V 0. Next, we give suucient conditions on the two-scale symbol for scaling vectors under which a given matrix reenement equation can be solved. A spline-wavelet example illustrates these results. For the single scaling function , the support of is characterized by the degree of the two-scale symbol. The situation is more complicated in the scaling vector case. We prove a result that gives the support of the scaling vector under certain conditions on the coeecient matrices. This result is illustrated by an example of fractal wavelets derived in Geronimo, Hardin, and Massopust 8].
The Role of Multimedia Content in Determining the Virality of Social Media Information

The paper provides empirical evidence supporting the assumption that content plays a critical role in determining the virality, i.e., the influence, of social media information. The analysis focuses on multimedia content on Twitter and explores the idea that links to multimedia information increase the virality of posts. In particular, we put forward the following three main hypotheses: (1) posts with a link to multimedia content (photo or video) are more retweeted than posts without a link; (2) posts linking a photo are more retweeted than posts linking a video, and (3) posts linking a video raise more sentiment than posts linking a photo. Hypotheses are tested on a sample of roughly two million tweets posted in July 2011 including comments on Berlin, London, Madrid, and Milan relevant from a tourism perspective. Findings support our hypotheses and indicate that multimedia content plays an important role in determining not only the volumes of retweeting, but also the dynamics of the virality of posts measured as speed of retweeting.
Application of a Probability-Based Algorithm to Extraction of Product Features from Online Reviews

Prior research has demonstrated the viability of automatically extracting product features from online reviews. In this paper, I present a probability-based algorithm and compare it to an existing support-based approach. Specifically, I used each algorithm to extract features from 7 Amazon.com product categories and then asked end users to rate the features in terms of helpfulness for choosing products. The end users preferred the features identified by the probability-based algorithm. This probability-based algorithm can identify features that comprise a single noun or two successive nouns (which end users rated as more helpful than features comprising only one noun), yet even for collections of tens of thousands of reviews, it still executes fast enough (at around 1ms per review) for practical use.
Localization of pain‐related brain activation: A meta‐analysis of neuroimaging data

A meta‐analysis of 140 neuroimaging studies was performed using the activation‐likelihood‐estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. The third analysis assessed the implications of using either a warm stimulus or a resting baseline as the control condition to reveal activation attributed to noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values that were restricted to cortical regions with known nociceptive input. The fourth analysis tested for a hemispheric dominance in pain processing and showed the importance of the right hemisphere, with the strongest ALE peaks and clusters found in the right insula and ACC. The fifth analysis compared noxious muscle with cutaneous stimuli and the former type was more likely to evoke activation in the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal cortex, and cerebellum. In general, results indicate that some brain regions such as the thalamus, insula and ACC have a significant likelihood of activation regardless of the type of noxious stimuli, while other brain regions show a stimulus‐specific likelihood of being activated. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Query answering in resource-based answer set semantics*

Abstract In recent work we defined resource-based answer set semantics, which is an extension to answer set semantics stemming from the study of its relationship with linear logic. In fact, the name of the new semantics comes from the fact that in the linear-logic formulation every literal (including negative ones) were considered as a resource. In this paper, we propose a query-answering procedure reminiscent of Prolog for answer set programs under this extended semantics as an extension of XSB-resolution for logic programs with negation. 1 We prove formal properties of the proposed procedure. Under consideration for acceptance in TPLP.