Miracle-dz/UniFAR-FTUs huggingface dataset:
Nature Genetics Advance Online Publication Extensive and Coordinated Transcription of Noncoding Rnas within Cell-cycle Promoters

Mammalian genomes are more pervasively transcribed than previously expected 1–4. In addition to protein-coding genes, many types of non-coding RNAs (ncRNAs) are transcribed. Small regulatory ncRNAs, including small interfering RNAs (siRNAs), microRNAs (miRNAs) and Piwi-associated RNAs (piRNAs), function in genome defense and post-transcriptional regulation 5–7. Near transcriptional start sites (TSS), divergent transcription by RNA polymerase can generate small ncRNAs ranging from 20 to 200 nucleotides, which have been variously named promoter-associated small RNAs (PASRs), transcription-initiation RNAs (tiRNAs) and TSS-associated RNAs (TSSa-RNAs) 8–11. However, it remains uncertain if these ncRNAs are functional or just represent byproducts of RNA polymerase infidelity 12,13. lncRNAs vary in length from several hundred bases to tens of kb; lncRNAs may be located in isolation from protein coding genes (long intergenic ncRNAs, or lincRNAs), or they may be interspersed nearby or within protein coding genes 14,15. Moreover, recent evidence suggest that active enhancer elements are also transcribed to produce ncRNAs 16,17. Although evidence for function of IncRNAs as a group is lacking, several lncRNAs have been implicated in transcriptional regulation. Two prime examples are in the genomic loci of cell-cycle genes. In the CCND1 (encoding cyclin D1) promoter, an ncRNA transcribed 2 kb upstream of CCND1 is induced by ionizing radiation and regulates transcription of CCND1 in cis by forming a ribonucleoprotein repressor complex 18. This ncRNA binds to and allosterically activates the RNA-binding protein TLS (translated in liposarcoma), which inhibits histone acetyltransferases, resulting in repression of CCND1 transcription. A second example is an antisense ncRNA gene CDKN2B-AS1 (also known as p15AS or ANRIL) that overlaps with the p15 coding sequence, and CDKN2B-AS1 expression is increased in human leukemias with an inverse correlation with p15 expression 19,20. CDKN2B-AS1 can transcriptionally silence p15 directly as well as through induction of heterochromatin formation. Many well-studied lncRNAs, such as those involved in dosage compensation and imprinting, regulate gene expression in cis 21 , but other lincRNAs, such as HOTAIR and linc-p21, can regulate the activity of distantly located genes in trans 22–24. Inspired by these examples, we hypothesized that the genomic loci of cell-cycle genes may harbor other functional ncRNAs that have yet to be discovered. Transcription of long noncoding RNAs (lncRNAs) within gene regulatory elements can modulate gene activity in response to external stimuli, but the scope and functions of such activity are not known. Here we use an ultrahigh-density array that tiles the promoters of 56 cell-cycle genes …
WHY HAVE HMMS BEEN SO SUCCESSFUL FOR AUTOMATIC SPEECH RECOGNITION AND HOW MIGHT THEY BE IMPROVED

Most of the current successful systems for automatic speech recognition are based on hidden Markov models (HMMs). HMMs are basically general-purpose statistical pattern matchers, but have so far proved more successful than approaches which have been based on specific knowledge about speech. This paper discusses the likely reasons for this success. It is argued that, in addition to providing a tractable mathematical framework with straightforward algorithms for training and recognition, HMMs have a general structure which is broadly appropriate for speech: both shortterm spectral variability and temporal variability can be modelled. This general structure can be tailored to known characteristics of the sounds being modelled, but the actual parameters are optimized based on t raining data. Another very important characteristic of HMMs is that they provide a complete model which can also be employed at higher levels (such as syntax), with only a single decision being made based on finding the best match at all levels. All these aspects combine to make HMMs a powerful approach to speech modelling. It is therefore argued that, in order to progress recognition capabilities further, the best approach is to retain all these advantages of the general framework but to overcome the limitations of the current HMM formalism by making it segment-based rather than frame-based.
Empathic tutoring software agents using real-time eye tracking

This paper describes an empathic software agent (ESA) interface using eye movement information to facilitate empathy-relevant reasoning and behavior. Eye movement tracking is used to monitor user's attention and interests, and to personalize the agent behaviors. The system reacts to user eye information in real-time, recording eye gaze and pupil dilation data during the learning process. Based on these measures, the ESA infers the focus of attention and motivational status of the learner and responds accordingly with affective (display of emotion) and instructional behaviors. In addition to describing the design and implementation of empathic software agents, this paper will report on some preliminary usability test results concerning how users respond to the empathic functions that are provided.
O-GlcNAc Signaling in the Cardiovascular System

Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of posttranslational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function. Known as the &bgr;-O-linkage of N-acetylglucosamine (ie, O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiological and pathological functions. This review introduces readers to the general concepts related to O-GlcNAc, the regulation of this modification, and its role in primary pathophysiology. Much of the existing literature regarding the role of O-GlcNAcylation in disease addresses the protracted elevations in O-GlcNAcylation observed during diabetes. In this review, we focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (eg, hypoxia, ischemia, oxidative stress), whereas limiting O-GlcNAcylation exacerbates cell damage in similar models. In addition to addressing the potential mechanisms of O-GlcNAc–mediated cardioprotection, we discuss technical issues related to studying protein O-GlcNAcylation in biological systems. The reader should gain an understanding of what protein O-GlcNAcylation is and that its roles in the acute and chronic disease settings appear distinct.
Two Faces of “Rheumatoid Arthritis”: Type A Versus Type B Disease

Is rheumatoid arthritis one disease or a “catch-all” term for inflammatory arthritis that tends to spare axial joints? We have subdivided “rheumatoid arthritis,” utilizing the criteria of periarticular osteopenia and marginally (distributed), symmetrical polyarticular erosions, in absence of axial (odontoid disease excepted) involvement as type A and presence of peripheral joint fusion and subchondral erosions as type B.Biomechanical analysis of axial joint sparing inflammatory arthritis also revealed the two distinct patterns. The low vibration/power cluster (type A) had symmetrical polyarticular marginal erosions, but no peripheral joint fusion. The high vibration/power cluster (type B) had both subchondral and marginal erosions, and/or peripheral joint fusion, indistinguishable from spondyloarthropathy (S). Erosive arthritis also was noted in two distinct patterns in pre-Columbian North American cemeteries. The type B pattern was never observed in populations with the type A pattern. The type B pattern was only observed in populations with spondyloarthropathy. Demographic analysis in a modern skeletal population revealed that spondyloarthropathy and type B were quite similar to each other, but easily distinguished from type A. Evaluation of over 500 skeletons of animals with erosive arthritis revealed only type B.As type B is indistinguishable from spondyloarthropathy, it is suggested that type B be recategorized with spondyloarthropathv and that only type A be classified as rheumatoid arthritis.
Domain specific phase by phase effort estimation in software projects

Software cost and effort estimation models mostly focus on predicting the overall project cost rather than the cost of phases separately. In addition to that, no previous research has a domain specific view on phase by phase effort estimation. In this research, domain specific data analysis is conducted to discover the difference in phase distribution profiles in different application domains. Furthermore, a regression model is built in order to see whether a domain specific approach provides improvement in effort estimation accuracy. Our experimental results showed when domain specific data and phase by phase approach is used the prediction accuracy increases up to 74%.
Gabapentin fails to alter P/Q‐type Ca2+ channel‐mediated synaptic transmission in the hippocampus in vitro

Gabapentin (Neurontin) has been successfully used in the treatment of both epilepsy and neuropathic pain. Despite its widespread clinical use, its mechanism of action is very poorly understood. Indeed, the only protein it is known to interact with is the α2δ subunit of the voltage‐gated Ca2+ channel complex. In a recent article, gabapentin was reported to inhibit synaptic transmission in the spinal cord through an inhibitory effect on presynaptic P/Q‐type Ca2+ channels in both glutamatergic primary afferents and glycinergic interneuones. To examine if such inhibition of P/Q‐channel‐mediated synaptic transmission by gabapentin generalised to other synaptic pathways, we tested the actions of gabapentin of P/Q‐type Ca2+ channel‐mediated synaptic responses in the CA1 subfield of the hippocampus. We found that gabapentin was completely inactive on such synaptic responses even at 10 times the maximally effective concentration used in the spinal cord. A small (∼10%) but consistent depression of control synaptic responses was elicited by 10 μM gabapentin. No greater response was observed at a 10 times higher concentration. From these data we conclude that gabapentin is not a generic inhibitor of presynaptic P/Q‐type channels and its actions at the spinal level must represent a feature of the P/Q‐type channel not present in the hippocampus. Given the known interactions of this compound, the best candidate for this is the presence, subtype, or state of the α2δ subunit. Synapse 55:262–269, 2005. © 2005 Wiley‐Liss, Inc.
The Melanin-Concentrating Hormone (MCH) System Modulates Behaviors Associated with Psychiatric Disorders

Deficits in sensorimotor gating measured by prepulse inhibition (PPI) of the startle have been known as characteristics of patients with schizophrenia and related neuropsychiatric disorders. PPI disruption is thought to rely on the activity of the mesocorticolimbic dopaminergic system and is inhibited by most antipsychotic drugs. These drugs however act also at the nigrostriatal dopaminergic pathway and exert adverse locomotor responses. Finding a way to inhibit the mesocorticolimbic- without affecting the nigrostriatal-dopaminergic pathway may thus be beneficial to antipsychotic therapies. The melanin-concentrating hormone (MCH) system has been shown to modulate dopamine-related responses. Its receptor (MCH1R) is expressed at high levels in the mesocorticolimbic and not in the nigrostriatal dopaminergic pathways. Interestingly a genomic linkage study revealed significant associations between schizophrenia and markers located in the MCH1R gene locus. We hypothesize that the MCH system can selectively modulate the behavior associated with the mesocorticolimbic dopamine pathway. Using mice, we found that central administration of MCH potentiates apomorphine-induced PPI deficits. Using congenic rat lines that differ in their responses to PPI, we found that the rats that are susceptible to apomorphine (APO-SUS rats) and exhibit PPI deficits display higher MCH mRNA expression in the lateral hypothalamic region and that blocking the MCH system reverses their PPI deficits. On the other hand, in mice and rats, activation or inactivation of the MCH system does not affect stereotyped behaviors, dopamine-related responses that depend on the activity of the nigrostriatal pathway. Furthermore MCH does not affect dizocilpine-induced PPI deficit, a glutamate related response. Thus, our data present the MCH system as a regulator of sensorimotor gating, and provide a new rationale to understand the etiologies of schizophrenia and related psychiatric disorders.
Integrating rule and template-based approaches for emotional Malay speech synthesis

The manipulation of prosody, including pitch, duration and intensity, is one of the leading approaches in synthesizing emotion. This paper reports work on the development of a Malay Emotional synthesizer capable of expressing four basic emotions, namely happiness, anger, sadness and fear for any form of text input with various intonation patterns using the prosody manipulation principle. The synthesizer makes use of prosody templates and prosody parametric manipulation for different types of sentence structure.
Super-connected: How Techno Tourism Redesigns Our Lives Through Meaningful Travel

The techno-tourism life brings together insights about innovative tourism and examines how travel life is influenced when social network structure like “Facebook” enters the picture. The end result is a landmark analysis of digital socialization and the knock of the internet and digital media across travel institutions. This research circumscribes the ‘tourists-marketers facebook pages’ of Nepal. Using archived online narratives from facebook page of travel-marketers (TMs), after the event of Nepal earthquake 2015, this study seeks to examine how techno-tourism redesigns lives through meaningful travel plus the coverage toward which event enthusiasts participate in chats of interactional causes. This study first of all dissects the intrinsic features of the facebook just like facebook pages exploitation by travel marketers during Nepal’s earthquake disaster at district, zonal and state level. The study then offers some interesting insights for tourism marketers. It involves the statistical and mathematical model to observational and experimental datasets of their facebook posts and fans participation. This research drafts the importance of network science of super-connected digital voyagers, studying their sways, their point of views, their approaches of travel and their intensions for inspiring this style of travel feasible in requisites of work and money. As relationships are the foundation for social media sites; facebook is primarily used to raise awareness and create story telling. Hence this investigative study also has meaningful implications for public policy as well as super-connection as global impact. By adducing human race into one another’s care, letting them to fathom commonalities, likewise endowing the resources by which they can super-connect one another, the digital media and World Wide Web chip-in greatly to the “techno-social life”. This research is a great choice for general readers interested in this topic as well.
The Cascade Decision-Tree Improvement Algorithm Based on Unbalanced Data Set

In the past research, the data mining that using single classifier can not obtain satisfactory results. This paper proposed an improved decision-tree classification algorithm MAdaBoost for solving the customers’ chruning problem. The idea of this algorithm is that using cascaded structure to construct more decision tree classifier based on AdaBoost. This tree have a better classification results according to the experimental results.
Comprehending Technical Texts: Predicting and Defining Unfamiliar Terms

We investigate how to improve access to medical literature for health consumers. Our focus is on medical terminology. We present a method to predict automatically in a given text which medical terms are unlikely to be understood by a lay reader. Our method, which is linguistically motivated and fully unsupervised, relies on how common a specific term is in texts that we already know are familiar to a lay reader. Once a term is identified as unfamiliar, an appropriate definition is mined from the Web to be provided to the reader. Our experiments show that the prediction and the addition of definitions significantly improve lay readers' comprehension of sentences containing technical medical terms.
Extracting and Visualizing Semantic Relationships from Chinese Biomedical Text

In this paper, we study how to automatically extract and visualize food (or nutrition) and disease relationships from Chinese publications of Nutritional Genomics. Different from previous approaches that mostly apply handcrafted rules or co-occurrence patterns, we propose an approach using probabilistic models and domain knowledge. In particular, we first utilize encyclopedia to construct a domain knowledge base, and then develop a sentence simplification model to simplify complicated sentences we meet. Afterwards, we treat relation extraction issue as a sequence labeling task and adopt Conditional Random Fields (CRFs) models to extract food and disease relationships. Finally, these relationships are visualized. Experimental results on real-world datasets show that the proposed approach is effective.
[Sphincterotomy followed by papillary large balloon in the management of cholecolithiasis. Therapeutic success and safety in a Lima-Peru hospital].

OBJECTIVE We present a descriptive analysis of our cases of sphincterotomy followed by papillary large balloon dilation in a single session (ES-LBD) in the management of difficult to extract calculi, with the objective of assessing rates of therapeutic success and complications in local experience. MATERIAL AND METHODS ERCP procedures with ES-LBD performed for choledocholithiasis between January 2009 and December 2014 in patients older than 18 years and without preexistent sphincterotomy were selected from records of the Gastroenterology Service at Cayetano Heredia National Hospital. A descriptive analysis of therapeutic success and complications was performed. RESULTS 73 procedures in 73 patients were included (65.8% female, 34.2% male). Patient's average age was 59.4±19.8 years. Average diameter of calculi was 14.6±3.3mm. Average diameter of dilations was 14.6±2.27 mm. In 8 cases mechanical lithotripsy was performed. Complete calculi extraction was achieved in 56 procedures (76.7%). Complications occurred in 4 cases (5.5%). There were no deaths. CONCLUSION Our figures of therapeutic success and complications with ES-LBD for difficult to extract calculi are similar to those reported in literature. ES-LBD is an effective and safe technique for management of choledocholithiasis.
Rectal Hyposensitivity: A Disorder of the Rectal Wall or the Afferent Pathway? An Assessment Using the Barostat

OBJECTIVE:Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. Diagnosis on the basis of abnormal threshold volumes on balloon distension alone may be inaccurate due to the influence of differing rectal wall properties. The aim of this study was to investigate whether RH was actually due to impaired afferent nerve function or whether it could be secondary to abnormalities of the rectal wall.METHODS:A total of 50 patients were referred consecutively to a tertiary referral unit for physiologic assessment of constipation (Rome II criteria), 25 of whom had associated fecal incontinence. Thirty patients had RH (elevated threshold volumes on latex balloon distension), and 20 patients had normal rectal sensation (NS). Results were compared with those obtained in 20 healthy volunteers (HV). All subjects underwent standard anorectal physiologic investigation, and assessment of rectal compliance, adaptive response to isobaric distension at urge threshold, and postprandial rectal response, using an electromechanical barostat.RESULTS:Mean rectal compliance was significantly elevated in patients with RH compared to NS and HV (p < 0.001). However, 16 patients with RH (53%) had normal compliance. Intensity of the urge to defecate during random phasic isobaric distensions was significantly reduced in patients with RH compared to NS and HV (p < 0.001). The adaptive response at urge threshold was reduced in patients with RH compared to NS and HV (p < 0.001), although spontaneous adaptation at operating pressure was similar in all three groups studied (p= 0.3). Postprandially, responses were similar between groups.CONCLUSION:In patients found to have RH on simple balloon distension, impaired perception of rectal distension may be partly explained in one subgroup by abnormal rectal compliance. However, a second subgroup exists with normal rectal wall properties, suggestive of a true impairment of the afferent pathway. The barostat has an important role in the identification of these subgroups of patients.
Presynaptic calcium dynamics of learning neurons

We present a new model for the dynamics of the presynaptic intracellular calcium concentration in neurons evoked by various stimulation protocols. The aim of the model is twofold: We want to discuss the calcium transients during and after specific stimulation protocols as they are used to induce long-term-depression and long-term-potentiation. In addition we would like to provide a general tool which allows the comparison of different calcium experiments. This may help to draw conclusions on a wider base in future.
Intra-articular co-infection by Borrelia burgdorferi and Chlamydia trachomatis

OBJECTIVE Chlamydia trachomatis and Borrelia burgdorferiinfections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis. METHODS Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA fromC trachomatis and B burgdorferi using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies toC trachomatis and B burgdorferi were determined. RESULTS Six patients (8%) had DNA from both C trachomatis andB burgdorferi in the same synovial fluid specimen (mean leucocyte count 11.925/mm3, 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for Chlamydiaonly. CONCLUSIONS DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.