Miracle-dz/UniFAR-FTUs huggingface dataset:
Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome

Purpose: Antitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). Experimental Design: Serum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels. Results: In patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P < 0.01), but not control. IgG responses (≥2-fold elevation posttreatment) occurred in ≥25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T–treated patients from IMPACT (P ≤ 0.05). Conclusions: Sipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. Clin Cancer Res; 21(16); 3619–30. ©2015 AACR. See related commentary by Hellstrom and Hellstrom, p. 3581
An Iterative and Incremental Data Quality Improvement Procedure for Reducing the Risk of Big Data Project

Big data applications can enhance the market competitive advantages of enterprises and organizations and can improve people's quality of life. However, by the impact of many factors, failure rate of big data project is higher than the IT project. In order to reduce the risk of failure, big data projects must overcome a serial of challenges. Ambiguous requirements, poor data quality, and lacking changeability and extensity will directly affect the results of big data analytics. And even cause the wrong decision, inaccurate prediction and improper planning to make the big data projects with potential high risk. For this, this paper migrates iterative and incremental development (IID) features to the data preprocessing, and draws up the iterative and incremental data quality improvement (IIDQI) procedure. IIDQI procedure applies data preprocessing task frame to repeatedly detect and identify the defects of data quality, and incrementally strengthen big data quality and control the factors of failure risk. Iterative inspection activities can effectively enhance data quality, intercommunication efficiency, and precision requirement and objective to reduce the risk of big data project failure.
Dynamics of abducens nucleus neurons in the awake rabbit.

1. We recorded abducens neurons, identified by electrical stimulation as internuclear neurons or motoneurons, in awake rabbits. The relationship of firing rate to eye movement was determined from responses during stable fixations, sinusoidal rotation in the light (0.05-0.8 Hz), and triangular optokinetic stimulation at 0.1 Hz. 2. All abducens neurons were excited during temporal movement of the ipsilateral eye. Temporal and nasal saccades were associated with bursts or pauses, respectively, in the firing rate. 3. Motoneurons and internuclear neurons are qualitatively indistinguishable. There was no significant quantitative difference between the phase and sensitivity of the two groups for 0.2-Hz sinusoidal rotation in the light. 4. On the basis of the response to stable eye positions, we determined static eye position sensitivity of the abducens neuron pool to be 8.2 +/- 2.5 (SD) spikes.s-1/0, with a static hysteresis of 8.9 spikes/s (1.14 +/- 0.37 degrees). 5. We determined apparent eye position sensitivity (k) and apparent eye velocity sensitivity (r) from the responses to sinusoidal rotation in the light. k increases and r decreases with stimulus frequency, which indicates that the simplest transfer function mediating conversion of abducens nucleus (VI) firing rate to eye position (E) has two poles and one zero. 6. The VI-->E relationship has an "amplitude nonlinearity," manifest as a tendency for k, r, and firing rate phase lead to decrease as eye movement amplitude increases at a fixed frequency. On a percentage basis, phase is less affected than are the sensitivities. The nonlinearity becomes less pronounced for stimulus amplitudes > 2.5 degrees, and consequently a linear model of the VI-->E transformation remains useful, provided that consideration is restricted to the appropriate range of stimulus/response amplitudes. 7. We determined time constants of the linear two-pole, one-zero transfer function from the variation of r/k versus stimulus frequency. The pole time constants were T1 = 3.4 s and T2 = 0.28 s, and the zero time constant (Tz) = 1.6 s. The magnitude of Tz was corroborated by measuring the time constant of the exponential decay in firing rate after step changes in eye position. This transient method yielded a Tz of 1.1 s. 8. The time constants of the VI-->E transfer function are roughly 10 times larger than those reported for the rhesus macaque. The difference is attributable to the reported 10-fold lower stiffness of the rabbit oculomotor plant, which may in turn relate to rabbits postulated lower degree of activation of extraocular muscles at any given position. (ABSTRACT TRUNCATED AT 400 WORDS)
Hyperopia and Emergent Literacy of Young Children: Pilot Study

Purpose. To compare emergent literacy skills in uncorrected hyperopic and emmetropic children. Methods. “Hyperopes” (≥2.00 D sphere along the most hyperopic meridian; n = 13; aged 67 ± 13 mo) and “emmetropes” (≤1.50 D sphere along the most hyperopic meridian; n = 19; aged 58 ± 12 mo) were tested for visual acuity (VA) and assessed for their emergent literacy skills [three standard tests (letter/word reading skills, receptive vocabulary and phonological awareness) and an experimental test of emergent orthography]. Parents completed a survey of family demographics, health/developmental concerns and home literacy experiences. Visual motor and visual perceptual skills tests were used to assess any visual cognitive differences. Results. There were no differences in single letter VA for hyperopes and emmetropes and crowded letters for the right eye. Crowding effects were significantly greater in the left eye for hyperopes (t (30) = −2.74, p = 0.01), with two of the hyperopes showing abnormal crowding. Hyperopes lagged behind emmetropes in letter and word recognition ability (Mann-Whitney U = 72, p = 0.049), receptive vocabulary (F(1,30) = 9.64, p = 0.004), and emergent orthography (F(1,29) = 5.43, p = 0.03). The groups did not differ in phonological awareness skills (F(1,29) = 0.39, p = 0.54). No statistically significant differences between the two groups were found for visual motor or visual perceptual skills, age, and some family variables known to contribute to emergent literacy skills. Conclusions. In this pilot study, uncorrected hyperopic children, ages 4 to 7 years, show reduced performance on tests of letter and word recognition, receptive vocabulary, and emergent orthography and crowded VA, despite no difference in phonological awareness skills, visual cognitive skills, and other family variables known to affect the acquisition of literacy skills. The relationship between hyperopia and the poorer progress in emergent literacy is complex, and it is not clear if the relationship is causal, and whether the hyperopes will catch up to the emmetropes with time.
FUNCTIONAL PEARL On merging and selection

Given two ascending lists xs and ys of combined length greater than n, consider the computation of formula here The standard function merge merges two ascending sequences and (! ) denotes list indexing. With a lazy evaluator the computation takes O(n) steps; with an eager one it takes O(p+q) steps, where p=length xs and q=length ys. Now in functional programming it is more efficient to index a tree than a list, so the question arises: can we find a faster solution if xs and ys are each represented by a tree? Somewhat surprisingly the answer is yes: if xs and ys are each represented by balanced binary search trees, then the computation can be reduced to O(log p+log q) steps. This is despite the fact that there is no known method for merging two binary search trees in better than linear time. The details, presented below, depend on a subtle relationship between merging and indexing.
HIV Quasispecies and Resampling

Letters from: [ Shan-Lu Liu, et al . ][1] [ Barton F. Haynes, et al . ][1] Human immunodeficiency virus (HIV) behaves as an evolving quasispecies in infected individuals. When the populations of genetic variants that make up this quasispecies are characterized, it is common practice to obtain
Defining 'current drinkers' in national surveys: results of the 2000 National Alcohol Survey.

AIMS The purpose of this study is to determine which respondents of national surveys who report low 'usual' past year drinking frequency, are unsure of their drinking frequency or refuse to answer, are misclassified either as 'current drinkers' or as 'ex-drinkers. ' DESIGN AND SETTING The data are from the 2000 National Alcohol Survey, a national household telephone probability sample of adults in all 50 US States and Washington, DC (n = 7612). PARTICIPANTS A subsample of 1734 respondents who reported drinking 'less than once a month but at least once a year', 'less than once a year', 'refused' and 'don't knows' were also asked if they had consumed a whole drink of any alcoholic beverage in the 12 months using dates to anchor the question. MEASUREMENTS Five alcohol measures were used to compare groups who changed or did not change their drinking status based on the followup question: volume, mean number of days 5 +, social consequences, dependence symptoms and DSM-IV. FINDINGS The results indicate that only 4.6% of respondents (n = 349) changed their drinking status, and the percentages were equal in both directions. Women were more likely to change their drinking status and specifically become ex-drinkers based on the follow-up question. Respondents who became current drinkers drank significantly at a lower average volume than those who remained current drinkers. The prevalence rates based on the five alcohol measures were not affected by how 'current drinker' is defined. CONCLUSIONS Adding the follow-up question is recommended for new alcohol surveys so that fewer respondents are misclassified.
Effects of Salicylic Acid on Alternative Pathway Respiration and Alternative Oxidase Expression in Tobacco Calli

The alternative pathway (AP) respiration of plants is a cyanide-resistant and non-phosphorylating electron transport pathway in mitochondria. Alternative oxidase (AOX) is the terminal oxidase of the AP and exists in plant mitochondria as two states: the reduced, noncovalently linked state or the oxidized, covalently cross-linked state. In the present study, the effects of 20 μm exogenous salicylic acid (SA) on both AP activity and AOX expression in mitochondria of tobacco (Nicotiana rustica L. cv. yellow flower) calli were investigated. The results showed that SA treatment enhanced the AP activity. During the process of SA treatment, the AP activity increased dramatically and achieved the peak value after 8 h of treatment. Then it declined until 16 h, and maintained a steady level between 16 and 24 h. Changes in both the total AOX protein level and the reduced state were in accordance with the AP activity, but the oxidized state changed differently. The aox1 gene transcript level also showed a similar change as the AP activity and AOX protein level. The induction of AOX expression by low concentrations of SA was inferred through a reactive oxygen species (ROS)-independent pathway. These results indicate that the enhancement of AP activity in response to SA is correlated to the expression of AOX, and the reduced, non-covalently linked state of AOX plays an important role during this process.
Distinct Nrf2 Signaling Mechanisms of Fumaric Acid Esters and Their Role in Neuroprotection against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Experimental Parkinson's-Like Disease

A promising approach to neurotherapeutics involves activating the nuclear-factor-E2-related factor 2 (Nrf2)/antioxidant response element signaling, which regulates expression of antioxidant, anti-inflammatory, and cytoprotective genes. Tecfidera, a putative Nrf2 activator, is an oral formulation of dimethylfumarate (DMF) used to treat multiple sclerosis. We compared the effects of DMF and its bioactive metabolite monomethylfumarate (MMF) on Nrf2 signaling and their ability to block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinson's disease (PD). We show that in vitro DMF and MMF activate the Nrf2 pathway via S-alkylation of the Nrf2 inhibitor Keap1 and by causing nuclear exit of the Nrf2 repressor Bach1. Nrf2 activation by DMF but not MMF was associated with depletion of glutathione, decreased cell viability, and inhibition of mitochondrial oxygen consumption and glycolysis rates in a dose-dependent manner, whereas MMF increased these activities in vitro. However, both DMF and MMF upregulated mitochondrial biogenesis in vitro in an Nrf2-dependent manner. Despite the in vitro differences, both DMF and MMF exerted similar neuroprotective effects and blocked MPTP neurotoxicity in wild-type but not in Nrf2 null mice. Our data suggest that DMF and MMF exhibit neuroprotective effects against MPTP neurotoxicity because of their distinct Nrf2-mediated antioxidant, anti-inflammatory, and mitochondrial functional/biogenetic effects, but MMF does so without depleting glutathione and inhibiting mitochondrial and glycolytic functions. Given that oxidative damage, neuroinflammation, and mitochondrial dysfunction are all implicated in PD pathogenesis, our results provide preclinical evidence for the development of MMF rather than DMF as a novel PD therapeutic. SIGNIFICANCE STATEMENT Almost two centuries since its first description by James Parkinson, Parkinson's disease (PD) remains an incurable disease with limited symptomatic treatment. The current study provides preclinical evidence that a Food and Drug Administration-approved drug, dimethylfumarate (DMF), and its metabolite monomethylfumarate (MMF) can block nigrostriatal dopaminergic neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of PD. We elucidated mechanisms by which DMF and its active metabolite MMF activates the redox-sensitive transcription factor nuclear-factor-E2-related factor 2 (Nrf2) to upregulate antioxidant, anti-inflammatory, mitochondrial biosynthetic and cytoprotective genes to render neuroprotection via distinct S-alkylating properties and depletion of glutathione. Our data suggest that targeting Nrf2-mediated gene transcription using MMF rather than DMF is a promising approach to block oxidative stress, neuroinflammation, and mitochondrial dysfunction for therapeutic intervention in PD while minimizing side effects.
A new Telecom Architecture for the Convergence of TDM with IP and usage in Internet of Things

Historically, Telecom Networks were a Mixture of TDM/Circuit Switched and Packet/Datagram based and used techniques such as TDMoIP and IPoTDM for internetwork communication. Voice and Data Networks were separate. NGN was envisioned as a pathway towards a converged ALL-IP network capable to cater to Voice, Video and Data services. Around 2005, newer services such as SAN’s, NAS’s, CDN’s, WSNs, Location Aware Services, BYOD, Data Centers, Cloud-Based Services, Big Data, XaaS, Internet of Things, Over-the-Top Content etc. were developed that required a more Flexible and Scalable network infrastructure. These services are Application Focused and require the network to be more Service-Centric than InfrastructureCentric. This gave rise to the Concept of Software Defined Networks (SDNs) and Network Function Virtualization (NFV). However, these concepts saw strong opposition from Telecom Equipment Manufacturers and it was not until late 2010 that Telecom OEMs started adopting SDN and NFV. This research tries to develop a Simple and Modular Router/Protocol that implements Telecom Functions as opposed to the more complicated and complex concurrent telecom networks.
Soft-Decision Decoding in Noncoherent Massive MIMO Systems

Noncoherent multi-user detection schemes are attractive in massive MIMO uplink systems. In particular, sorted decision-feedback differential detection (DFDD) in combination with noncoherent decision-feedback equalization (nDFE) over the users has been shown to perform well, avoiding the need for channel estimation. So far, integrating channel coding in massive MIMO systems requires knowledge of the channel, where reliability information for the bits is calculated after combining a large number of symbol observations at the receiver. In this paper, we address one method to calculate reliability information by augmenting the sorted decision-feedback differential detection process. To this end, an equivalent trellis-encoder representation of bit-to-symbol mapping and differential encoding is established. Based on this, log-likelihood ratios for the differential symbols can be calculated. The performance of soft-decision decoding in noncoherent massive MIMO systems is assessed by means of numerical simulations and compared to that of a coherent scheme using channel estimation.
Accidental Decannulation OF TRACHEOSTOMY TUBES - Case Series.

Tracheostomy tube (TT) is usually removed in a planned manner once the patient ceases to have the condition that necessitated the procedure. Accidental decannulation or extubation refers to inadvertent removal of tracheostomy tube out of the stoma. It could prove fatal in an otherwise stable patient. We review a variety of unexpected and often-overlooked causes of accidental decannulation with suggestions on preventive measures. We therefore present three cases of accidental decannulation of tracheostomy tubes in order to report our experiences in the management of the condition. CONCLUSION Accidental decannulation occurs both in hospitalized and patient on home care of their tracheostomy tubes. Reduction in neck circumference due to weight loss predisposes to accidental decannulation, which could be prevented by suturing the flange to the skin.
Alterations in the T-lymphocyte subpopulation in patients with rhinoscleroma

T-lymphocyte subpopulations were studied in a group of patients with rhinoscleroma due to Klebsiella rhinoscleromatis. The data demonstrated that these patients had a significantly greater number of T-suppressor/cytotoxic lymphocytes than did clinically healthy individuals. This finding correlated with a diminished response to the T-cell mitogen concanavalin A. The evidence indicated that the T-cell response of these patients was decreased and may reflect the host's response to the bacterial invader, thus explaining the chronicity of the disease.
Do extremely low frequency magnetic fields enhance the effects of environmental carcinogens? A meta-analysis of experimental studies

Purpose: This paper is a meta-analysis of data from in vitro studies and short-term animal studies that have combined extremely low frequency magnetic fields with known carcinogens or other toxic physical or chemical agents. Materials and methods: The data was analyzed by systematic comparison of study characteristics between positive and negative studies to reveal possible consistent patterns. Results: The majority of the studies reviewed were positive, suggesting that magnetic fields do interact with other chemical and physical exposures. Publication bias is unlikely to explain the findings. Interestingly, a nonlinear ‘dose-response’ was found, showing a minimum percentage of positive studies at fields between 1 and 3 mT. The radical pair mechanism (magnetic field effects on recombination of radical pairs) is a good candidate mechanism for explaining the biphasic dose-response seen in the present analysis. Conclusions: Most of the studies reviewed used magnetic fields of 100 μT or higher, so the findings are not directly relevant for explaining the epidemiological findings suggesting increased risk of childhood leukemia above 0.4 μT. However, confirmed adverse effects even at 100 μT would have implications for risk assessment and management, including the need to reconsider the exposure limits for magnetic fields. There is an obvious need for further studies on combined effects with magnetic fields.
Comparison of shear velocity dispersion in viscoelastic phantoms measured by ultrasound-based shear wave elastography and magnetic resonance elastography

Pathological processes in soft tissues cause changes in mechanical properties. Elastography methods have emerged to make quantitative measurements of the shear modulus or shear wave speed (SWS) as a noninvasive way to provide diagnostic information. In an effort to standardize ultrasound-based measurements of SWS, the Radiological Society of North America Quantitative Imaging Biomarkers Alliance (RSNA QIBA) has established working groups to develop profiles for different biomarkers including the use of SWS for staging of patients with liver fibrosis. To understand how ultrasound-based measurements vary with tissue viscoelasticity, measurements were made in viscoelastic phantoms with ultrasound-based shear wave elastography (US-SWE) and magnetic resonance elastography (MRE) over a wide frequency range.
BiCMOS Switched-Capacitor Linear-Phase Bandpass Filter for RDS applications

The design of an 8th order switched-capacitor bandpass filter centered at 57kHz with 3kHz bandwidth and linear phase characteristics in the passband is reported. Four biquads are cascaded and operated at 4.332 MHz with double-sampling technique. The group delay performance have been analyzed via Monte Carlo simulations: there results an expected mean value of 230 ¿s with 2.9 ¿s standard deviation, using a unit capacitor statistic with 0.15% relative standard deviation. The filter is a basic circuit for an RDS integrated decoder and is realized in high performance BiCMOS technology.
Determination of Force Fields for Ode-based and Skeleton Driven Character Animation

In the existing work, character modelling and animation are two separate tasks. After a character model is built, a lot of time and efforts are still required to animate the character model. Ordinary differential equation-based surface modelling and animation using physically based deformable curves to define and deform skin surfaces of 3D character models. With such a technique, character modelling and animation can be integrated into a unified framework by introducing time-dependent varying force fields into ordinary differential equations. This paper addresses the issue of determination of the force fields and proposes three models, i. e. linear transformation model, interpolation model and extrapolation model, to obtain timedependent varying force fields. Some application examples are presented which demonstrates the force fields obtained from the three models create believable skin deformations of character models.