Miracle-dz/UniFAR-FTUs huggingface dataset:
YY1 associates with the macrosatellite DXZ4 on the inactive X chromosome and binds with CTCF to a hypomethylated form in some male carcinomas

DXZ4 is an X-linked macrosatellite composed of 12–100 tandemly arranged 3-kb repeat units. In females, it adopts opposite chromatin arrangements at the two alleles in response to X-chromosome inactivation. In males and on the active X chromosome, it is packaged into heterochromatin, but on the inactive X chromosome (Xi), it adopts a euchromatic conformation bound by CTCF. Here we report that the ubiquitous transcription factor YY1 associates with the euchromatic form of DXZ4 on the Xi. The binding of YY1 close to CTCF is reminiscent of that at other epigenetically regulated sequences, including sites of genomic imprinting, and at the X-inactivation centre, suggesting a common mode of action in this arrangement. As with CTCF, binding of YY1 to DXZ4 in vitro is not blocked by CpG methylation, yet in vivo both proteins are restricted to the hypomethylated form. In several male carcinoma cell lines, DXZ4 can adopt a Xi-like conformation in response to cellular transformation, characterized by CpG hypomethylation and binding of YY1 and CTCF. Analysis of a male melanoma cell line and normal skin cells from the same individual confirmed that a transition in chromatin state occurred in response to transformation.
Spatiotemporal Integration in Somatosensory Perception: Effects of Sensory Saltation on Pointing at Perceived Positions on the Body Surface

In the past, sensory saltation phenomena (Geldard and Sherrick, 1972) have been used repeatedly to analyze the spatiotemporal integration capacity of somatosensory and other sensory mechanisms by means of their psychophysical characteristic. The core phenomenon consists in a systematic mislocalization of one tactile stimulus (the attractee) toward another successive tactile stimulus (the attractant) presented at another location, increasing with shorter intervals. In a series of four experiments, sensory saltation characteristics were studied at the forearm and the abdomen. Participants reported the perceived positions of attractees, attractants, and reference stimuli by pointing. In general, saltation characteristics compared well to those reported in previous studies, but we were able to gain several new insights regarding this phenomenon: (a) the attractee–attractant interval did not exclusively affect the perceived attractee position, but also the perceived attractant position; (b) saltation characteristics were very similar at different body sites and orientations, but did show differences suggesting anisotropy (direction-dependency) in the underlying integration processes; (c) sensory saltation could be elicited with stimulation patterns crossing the body midline on the abdomen. In addition to the saltation-specific results, our experiments demonstrate that pointing reports of perceived positions on the body surface generally show pronounced systematic biases compared to veridical positions, moderate intraindividual consistency, and a high degree of inter-individual variability. Finally, we address methodological and terminological controversies concerning the sensory saltation paradigm and discuss its possible neurophysiological basis.
An empirical analysis of user uncertainty in problem-solving child-machine interactions

the widespread use of technologies directed towards children, child-machine interactions have become a topic of great interest. Computers must interpret relevant contextual user cues in order to provide a more natural interactive environment. Our focus in this paper is analyzing audio-visual user uncertainty cues using spontaneous conversations between a child and computer in a problem-solving setting. We hypothesize that we can predict when a child is uncertain in a given turn using a combination of acoustic, lexical, and visual gestural cues. First, we carefully annotated the audio-visual uncertainty cues. Next, we trained decision trees using leave-one-speaker-out cross-validation to find the more universal uncertainty cues across different children, attaining 0.494 kappa agreement with ground-truth uncertainty labels. Lastly, we trained decision trees using leave-one-turn-out cross-validation for each child to determine which cues had more intra-child predictive power and attained 0.555 kappa agreement. Both of these results were significantly higher than a voting baseline method but worse than average human kappa agreement of 0.744. We explain which annotated features produced the best results, so that future research can concentrate on automatically recognizing these uncertainty cues from the audio/video signal.
ToBI or not toBI?

In the decade that has passed since the introduction of the ToBI system for the transcription of prosody, speech technology has moved out of the laboratory and into commercial applications on several fronts. However, virtually none of the commercial products have made large-scale use of prosody. Nevertheless, researchers in both recognition and synthesis continue to agree that better utilization of prosody is essential to improving the performance and acceptability of commercial systems. In this paper, we review the current state of prosody in commercial systems, and examine how the ongoing discussions related to what and how to transcribe with respect to prosody have simultaneously advanced and inhibited the field. In particular, we argue that, in hindsight, the ToBI system contains several flaws that have limited its acceptance and application.
Flux Growth and Crystal Structure Refinement of Calcite Type Borate GaBO3

A single crystal of gallium borate, GaBO3, 4 × 4 × 0.2 mm3 in size has been grown by spontaneous crystallization with a molten flux based on a Bi2O3-3B2O3 solvent. From single crystal X-ray diffraction measurement, GaBO3 was found to crystallize in the trigonal calcite type, space group R-3c, with cell dimensions a = 4.56590(10) and c = 14.1764(4) A, Z = 6. Layers of distorted [GaO6] octahedra are interleaved by layers of triangular planar [BO3] unites. The transmission spectrum on a single crystal indicated that the band gap of GaBO3 is 3.62 eV.
Selectivity of Chemoresistive Sensors Made of Chemically Functionalized Carbon Nanotube Random Networks for Volatile Organic Compounds (VOC)

Different grades of chemically functionalized carbon nanotubes (CNT) have been processed by spraying layer-by-layer (sLbL) to obtain an array of chemoresistive transducers for volatile organic compound (VOC) detection. The sLbL process led to random networks of CNT less conductive, but more sensitive to vapors than filtration under vacuum (bucky papers). Shorter CNT were also found to be more sensitive due to the less entangled and more easily disconnectable conducting networks they are making. Chemical functionalization of the CNT’ surface is changing their selectivity towards VOC, which makes it possible to easily discriminate methanol, chloroform and tetrahydrofuran (THF) from toluene vapors after the assembly of CNT transducers into an array to make an e-nose. Interestingly, the amplitude of the CNT transducers’ responses can be enhanced by a factor of five (methanol) to 100 (chloroform) by dispersing them into a polymer matrix, such as poly(styrene) (PS), poly(carbonate) (PC) or poly(methyl methacrylate) (PMMA). COOH functionalization of CNT was found to penalize their dispersion in polymers and to decrease the sensors’ sensitivity. The resulting conductive polymer nanocomposites (CPCs) not only allow for a more easy tuning of the sensors’ selectivity by changing the chemical nature of the matrix, but they also allow them to adjust their sensitivity by changing the average gap between CNT (acting on quantum tunneling in the CNT network). Quantum resistive sensors (QRSs) appear promising for environmental monitoring and anticipated disease diagnostics that are both based on VOC analysis.
Simultaneous and Exact Interval Estimates for the Contrast of Two Groups Based on an Extremely High Dimensional Response Variable: Application to Mass Spec Data Analysis

Motivation: Analysis of high-throughput proteomic/genomic data, in particular, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) data and microarray data, has led to a multitude of techniques aimed at identifying potential biomarkers. For SELDI-TOF MS data, most of these techniques rely on arbitrary, user-defined rules for identifying peaks and do not control for global error, potentially leading to false positives. Results: We have devised a simultaneous confidence bands method capable of detecting potential biomarkers, while controlling for overall Type I error, in high-dimensional genomic/proteomic datasets that discriminate two treatment groups using a permutation scheme. For example, for the SELDI-TOF MS data, we treat the entire spectrum as a stochastic process and construct confidence bands for the mean differences between groups. Furthermore, peaks were identified based on the maximal differences between the groups as determined by the confidence bands. The analysis method herein described gives both qualitative (significance in terms of p-value) and quantitative data (magnitude of difference). The Clinical Proteomics Programs Databank’s ovarian cancer dataset and data from in-house samples containing known spiked-in proteins were analyzed. We were able to identify potential biomarkers similar to those described in previous analysis of the ovarian cancer data, however, while these markers are highly significant between cancer and normal groups, our analysis indicated the absolute difference between the two groups was minimal. In addition, we found additional markers than those previously described with greater differences in average intensities. The proposed confidence bands method successfully detected the spiked-in peaks, as well as, secondary peaks generated by adducts and double-charged species. We also illustrate our method utilizing paired gene expression data from a prostate cancer microarray experiment by constructing confidence bands for the fold changes between cancer and normal samples. Availability: The R and C codes are available from the authors. Contact: park@jimmy.harvard. edu to whom correspondence should be addressed These authors contributed equally to this work
Cardiac involvement in adult and juvenile idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIM) include the main subgroups polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and juvenile DM (JDM). The mentioned subgroups are characterised by inflammation of skeletal muscles leading to muscle weakness and other organs can also be affected as well. Even though clinically significant heart involvement is uncommon, heart disease is one of the major causes of death in IIM. Recent studies show an increased prevalence of traditional cardiovascular risk factors in JDM and DM/PM, which need attention. The risk of developing atherosclerotic coronary artery disease is increased twofold to fourfold in DM/PM. New and improved diagnostic methods have in recent studies in PM/DM and JDM demonstrated a high prevalence of subclinical cardiac involvement, especially diastolic dysfunction. Interactions between proinflammatory cytokines and traditional risk factors might contribute to the pathogenesis of cardiac dysfunction. Heart involvement could also be related to myocarditis and/or myocardial fibrosis, leading to arrhythmias and congestive heart failure, demonstrated both in adult and juvenile IIM. Also, reduced heart rate variability (a known risk factor for cardiac morbidity and mortality) has been shown in long-standing JDM. Until more information is available, patients with IIM should follow the same recommendations for cardiovascular risk stratification and prevention as for the corresponding general population, but be aware that statins might worsen muscle symptoms mimicking myositis relapse. On the basis of recent studies, we recommend a low threshold for cardiac workup and follow-up in patients with IIM.
Harmonic and Percussive Separation Based on NMF and Tonality Mask

In this letter, we present a new algorithm for the harmonic and percussive separation of jazz music. Using a short‐time Fourier transform and nonnegative matrix factorization, the signal is decomposed into rank components. Each component is then split into harmonic and percussive parts using masks calculated based on their tonalities. Finally, the harmonic and percussive parts are separated after applying the masks and a summation. We evaluate the algorithm based on real audio examples using both objective and subjective assessments. The proposed algorithm performs well for the separation of harmonic and percussive parts of jazz excerpts.
Layering a Public Key Distribution Service Over Secure DNS: "Everybody Comes to RIKS"

We present the Internet Key Service (IKS), a distributed architecture for authenticated distribution of public keys, layered on Secure DNS (DNSSEC). Clients wishing to manage or retrieve public keys use DNSSEC to securely discover the identities of the relevant IKS key registration and distribution servers, and send their key lookup / management requests directly to these servers using a special-purpose protocol. Clients can validate and authenticate keys retrieved from IKS servers using key commitments published in DNSSEC. Applications can use the public keys obtained from IKS to authenticate each other and establish secure end-to-end communications. A feature of our approach is that IKS derives its authentication authority from the authority DNS domains have over names. The IKS architecture is loosely coupled with DNS to minimize the overhead on DNS servers. We also present the Riverside Internet Key Server (RIKS), a prototype IKS implementation.
A remark concerning m -divisibility and the discrete logarithm in the divisor class group of curves

The aim of this paper is to show that the computation of the discrete logarithm in the m-torsion part of the divisor class group of a curve X over a finite field ko (with char(ko) prime to m), or over a local field k with residue field ko, can be reduced to the computation of the discrete logarithm in k0(4m)* . For this purpose we use a variant of the (tame) Tate pairing for Abelian varieties over local fields. In the same way the problem to determine all linear combinations of a finite set of elements in the divisor class group of a curve over k or ko which are divisible by m is reduced to the computation of the discrete logarithm in ko(Cm)* -
T4/N2 classification nasopharyngeal carcinoma benefit from concurrent chemotherapy in the era of intensity-modulated radiotherapy

Although the benefits of concurrent chemotherapy (CC) in the treatment of locally advanced nasopharyngeal carcinoma (NPC) had been proven in the era of two-dimensional radiotherapy, long-term efficacy and safety of using CC combined with intensity-modulated radiotherapy (IMRT) remain unclear. A retrospective analysis of 1,182 patients who underwent IMRT for clinical II-Iva NPC was performed. Propensity score matching algorithm was used to identify two matched cohorts with or without CC (264 patients per cohort). Median follow-up time was 45.6 and 43.6 months for the two cohorts. The estimated 5-year overall survival rate was 81.8% (95% CI 76.6-87.4) in patients treated with CC and 73.7% (95% CI 67.8-80.0) in those treated without CC, respectively (hazard ratio 0.64, 95% CI 0.44–0.93; p = 0.018). The benefit of CC was mainly observed in those patients with good performance status, male, age > 48 years, T4 and N2 classification. Grade 3/4 acute toxicities were more common in those patients administrated with CC. The grade and incidence of late salivary glands damage were also increased by CC (p = 0.003). These findings indicated that the addition of CC significantly improved treatment outcomes of NPC patients treated with IMRT, but accompanied increased toxicities. Tailored CC and optimizing schedule of IMRT and systemic therapy were needed, provided that distant metastasis was the predominant pattern of failure in patients treated with IMRT.
Ecto-5′-Nucleotidase (CD73) Inhibits Nociception by Hydrolyzing AMP to Adenosine in Nociceptive Circuits

Ecto-5′-nucleotidase (NT5E, CD73) is a membrane-anchored protein that hydrolyzes extracellular adenosine 5′-monophosphate (AMP) to adenosine in diverse tissues but has not been directly studied in nociceptive neurons. We found that NT5E was located on peptidergic and nonpeptidergic nociceptive neurons in dorsal root ganglia (DRG) and on axon terminals in lamina II (the substantia gelatinosa) of spinal cord. NT5E was also located on epidermal keratinocytes, cells of the dermis, and on nociceptive axon terminals in the epidermis. Following nerve injury, NT5E protein and AMP histochemical staining were coordinately reduced in lamina II. In addition, AMP hydrolytic activity was reduced in DRG neurons and spinal cord of Nt5e−/− mice. The antinociceptive effects of AMP, when combined with the adenosine kinase inhibitor 5-iodotubericidin, were reduced by ∼50% in Nt5e−/− mice and were eliminated in Adenosine A1 receptor (A1R, Adora1) knock-out mice. Additionally, Nt5e−/− mice displayed enhanced sensitivity in the tail immersion assay, in the complete Freund's adjuvant model of inflammatory pain and in the spared nerve injury model of neuropathic pain. Collectively, our data indicate that the ectonucleotidase NT5E regulates nociception by hydrolyzing AMP to adenosine in nociceptive circuits and represents a new molecular target for the treatment of chronic pain. Moreover, our data suggest NT5E is well localized to regulate nucleotide signaling between skin cells and sensory axons.
A new paradigm: innate immune sensing of viruses via the unfolded protein response

The immune system depends upon combinations of signals to mount appropriate responses: pathogen specific signals in the context of co-stimulatory “danger” signals drive immune strength and accuracy. Viral infections trigger anti-viral type I interferon (IFN) responses by stimulating endosomal and cytosolic pattern recognition receptors (PRRs). However, viruses have also evolved many strategies to counteract IFN responses. Are there intracellular danger signals that enhance immune responses to viruses? During infection, viruses place a heavy demand on the protein folding machinery of the host endoplasmic reticulum (ER). To survive ER stress, host cells mount an unfolded protein response (UPR) to decrease ER protein load and enhance protein-folding capacity. Viruses also directly elicit the UPR to enhance their replication. Increasing evidence supports an intersection between the host UPR and inflammation, in particular the production of pro-inflammatory cytokines and type I IFN. The UPR directly activates pro-inflammatory cytokine transcription factors and dramatically enhances cytokine production in response to viral PRR engagement. Additionally, viral PRR engagement may stimulate specific pathways within the UPR to enhance cytokine production. Through these mechanisms, viral detection via the UPR and inflammatory cytokine production are intertwined. Consequently, the UPR response is perfectly poised to act as an infection-triggered “danger” signal. The UPR may serve as an internal “co-stimulatory” signal that (1) provides specificity and (2) critically augments responses to overcome viral subterfuge. Further work is needed to test this hypothesis during viral infections.
Boiling Point Models of Alkanes

We developed single variable models to calculate the boiling points of special families of alkanes and multivariable boiling point models for all alkane isomers up to and including 12 carbon atoms. Our models are based on the molecular weight, the number of carbon atoms, the Hosoya index, the Wiener number, the Wiener Path numbers P , P, . , P , and the methyl and ethyl indices. We introduce the methyl and ethyl indices. We used nonlinear regression techniques using web based submission NEOS solvers to determine the coefficients and exponents of the indices in our models. A standard deviation of 2.7 ◦C was obtained from our best model which includes 187 of the alkane isomers from 6 to 12 carbon atoms for which experimental boiling point data was available. This model was used to predict the boiling points for a set of test data from 13 to 22 carbon atoms.
Phosphoinositide-mediated oligomerization of a defensin induces cell lysis

Cationic antimicrobial peptides (CAPs) such as defensins are ubiquitously found innate immune molecules that often exhibit broad activity against microbial pathogens and mammalian tumor cells. Many CAPs act at the plasma membrane of cells leading to membrane destabilization and permeabilization. In this study, we describe a novel cell lysis mechanism for fungal and tumor cells by the plant defensin NaD1 that acts via direct binding to the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2). We determined the crystal structure of a NaD1:PIP2 complex, revealing a striking oligomeric arrangement comprising seven dimers of NaD1 that cooperatively bind the anionic headgroups of 14 PIP2 molecules through a unique ‘cationic grip’ configuration. Site-directed mutagenesis of NaD1 confirms that PIP2-mediated oligomerization is important for fungal and tumor cell permeabilization. These observations identify an innate recognition system by NaD1 for direct binding of PIP2 that permeabilizes cells via a novel membrane disrupting mechanism. DOI: http://dx.doi. org/10.7554/eLife.01808. 001
Modelling trust, honour and reliability in business relationships

Successful negotiators prepare by determining their position along five dimensions: Legitimacy, Options, Goals, Independence, and Commitment. We model business relationships in terms of these dimensions and two primitive concepts: intimacy (degree of closeness) and balance (degree of fairness). The intimacy is a pair of matrices that evaluate both an agent's contribution to the relationship and its opponent's contribution each from an information view and from a utilitarian view across the five dimensions. The balance is the difference between these matrices. A relationship strategy maintains a target intimacy for each relationship that an agent would like the relationship to move towards in future. The negotiation strategy maintains a set of Options that are in-line with the current intimacy level, and then tactics wrap the Options in argumentation with the aim of attaining a successful deal and manipulating the successive negotiation balances towards the target intimacy.