Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the Pore-lining Residues of the BM2 Ion Channel Protein of Influenza B Virus*

The influenza B virus BM2 proton-selective ion channel is essential for virus uncoating, a process that occurs in the acidic environment of the endosome. The BM2 channel causes acidification of the interior of the virus particle, which results in dissociation of the viral membrane protein from the ribonucleo-protein core. The BM2 protein is similar to the A/M2 protein ion channel of influenza A virus (A/M2) in that it contains an HXXXW motif. Unlike the A/M2 protein, the BM2 protein is not inhibited by the antiviral drug amantadine. We used mutagenesis to ascertain the pore-lining residues of the BM2 ion channel. The specific activity (relative to wild type), reversal voltage, and susceptibility to modification by (2-aminoethyl)-methane thiosulfonate and N-ethylmaleimide of cysteine mutant proteins were measured in oocytes. It was found that mutation of transmembrane domain residues Ser9, Ser12, Phe13, Ser16, His19, and Trp23 to cysteine were most disruptive for ion channel function. These cysteine mutants were also most susceptible to (2-aminoethyl)-methane thiosulfonate and N-ethylmaleimide modification. Furthermore, considerable amounts of dimer were formed in the absence of oxidative reagents when cysteine was introduced at positions Ser9, Ser12, Ser16, or Trp23. Based on these experimental data, a BM2 transmembrane domain model is proposed. The presence of polar residues in the pore is a probable explanation for the amantadine insensitivity of the BM2 protein and suggests that related but more polar compounds might serve as useful inhibitors of the protein.
On causal and semicausal codes for joint information embedding and source coding

A source of random message bits is to be embedded into a covertext modeled as a discrete memoryless source (DMS), resulting in a stegotext from which the embedded bits should be recoverable. A causal code for such a scenario consists of an encoder that generates the stegotext as a causal function of the message bits and the covertext, and a decoder that reproduces the message bits as a causal function of the stegotext. A semicausal code, on the other hand, has an encoder that is causal only with respect to the covertext, and not necessarily with respect to the message, and has a possibly noncausal decoder. We analyze the possible tradeoffs among: a) the distortion between the stegotext and the covertext, b) the compressibility of the stegotext, and c) the rate at which random bits are embedded, that are achievable with causal and semicausal codes, with and without attacks on the stegotext. We also study causal and semicausal codes for the private version of the above scenario in which the decoder has access to the covertext. Connections are made with the causal rate-distortion function of Neuhoff and Gilbert, as well as the problem of channel coding with causal side information at the transmitter analyzed by Shannon.
Sensitivity and specificity in diagnostic accuracy: ROC solid or lost in translation?

I thank Bharti and Bharti for their appreciation of the article on receiver-operating characteristics curve (ROC) analysis in biomarker research.1 In the ROC article, I mentioned the diagnostic accuracy as defined by sensitivity and specificity, and how a shift in any chosen test cut-off may influence the sensitivity and specificity, illustrated in a figure.2 Indeed, and as pointed out by Bharti et al , the figure displaying the shift in cut-off threshold for a given test and the influence on sensitivity and sensitivity contains an error, in that it has mixed the terms “sensitivity” and “specificity” in the text boxes. I apologise to the readers for causing this confusion. The concept of diagnostic accuracy, including the terms sensitivity and specificity, although used on a global scale, every day in clinical decision-making, may be easily confused, and I shall easily admit …
Lifelong quercetin enrichment and cardioprotection in Mdx/Utrn+/- mice.

Duchenne Muscular Dystrophy (DMD) is associated with progressive cardiac pathology; however, the SIRT1/PGC1-α activator quercetin may cardioprotect dystrophic hearts. We tested the extent to which long-term 0.2% dietary quercetin enrichment attenuates dystrophic cardiopathology in Mdx/Utrn+/- mice. At 2 mo, Mdx/Utrn+/- mice were fed quercetin-enriched (Mdx/Utrn+/--Q) or control diet (Mdx/Utrn+/-) for 8 mo. Control C57BL/10 (C57) animals were fed a control diet for 10 mo. Cardiac function was quantified by MRI at 2 and 10 mo. Spontaneous physical activity was quantified during the last week of treatment. At 10 mo hearts were excised for histological and biochemical analysis. Quercetin feeding improved various physiological indexes of cardiac function in diseased animals. Mdx/Utrn+/--Q also engaged in more high-intensity physical activity than controls. Histological analyses of heart tissues revealed higher expression and colocalization of utrophin and α-sarcoglycan. Lower abundance of fibronectin, cardiac damage (Hematoxylin Eosin-Y), and MMP9 were observed in quercetin-fed vs. control Mdx/Utrn+/- mice. Quercetin evoked higher protein abundance of PGC-1α, cytochrome c, ETC complexes I-V, citrate synthase, SOD2, and GPX compared with control-fed Mdx/Utrn+/- Quercetin decreased abundance of inflammatory markers including NFκB, TGF-β1, and F4/80 compared with Mdx/Utrn+/-; however, P-NFκB, P-IKBα, IKBα, CD64, and COX2 were similar between groups. Dietary quercetin enrichment improves cardiac function in aged Mdx/Utrn+/- mice and increases mitochondrial protein content and dystrophin glycoprotein complex formation. Histological analyses indicate a marked attenuation in pathological cardiac remodeling and indicate that long-term quercetin consumption benefits the dystrophic heart. NEW & NOTEWORTHY The current investigation provides first-time evidence that quercetin provides physiological cardioprotection against dystrophic pathology and is associated with improved spontaneous physical activity. Secondary findings suggest that quercetin-dependent outcomes are in part due to PGC-1α pathway activation.
PL-ILT: A web tool for creation of pronunciation lexicon in Indian languages

This paper present the efforts involved in designing a mass development tool to create comprehensive machine readable pronunciation lexicon for Indian languages. The lexicon file contains the orthography, corresponding pronunciations, parts-of-speech, morphosyntactic description, idiolectic variation of word pronunciation and meaning of lexical entries in a format based on requirements defined by the W3C Voice Browser Activity Pronunciation Lexicon Specification (PLS) 1.0. The current version of the Pronunciation Lexicon for Indian Languages Toolkit (PL-ILT) PLS contains approximately 2 million lexical entries for Bengali. Although in this paper we only describe language specific issues related to Bengali, PL-ILT has the ability to adapt different languages.
Hepatocytes induce Foxp3+ regulatory T cells by Notch signaling

The liver plays a pivotal role in maintaining immunological tolerance, although the exact molecular mechanism is still largely unknown. The induction of systemic tolerance by liver resident APCs has been attributed to peripheral deletion and to the induction of Tregs. HCs, the parenchymal cells in the liver, could function as nonprofessional APCs and interact and establish cell–cell contact with T lymphocytes. We hypothesized that HCs from healthy or regenerated livers may contribute to induction of functional Tregs. Here, we show that murine HCs induced Foxp3+ Tregs within CD4+ T cells in vitro, which increased in the presence of TGF‐β. Interestingly, a further Foxp3+ Treg expansion was observed if HCs were isolated from regenerated livers. Additionally, the induction of Foxp3+ Tregs was associated with the Notch signaling pathway, as the ability of HCs to enhance Foxp3 was abolished by γ‐secretase inhibition. Furthermore, HC‐iTregs showed ability to suppress the proliferative response of CD4+ T cells to anti‐CD3 stimulation in vitro. Thus, HCs may play a pivotal role in the induction of tolerance via Notch‐mediated conversion of CD4+ T cells into Foxp3+ Tregs upon TCR stimulation.
Wing morphometry as a tool for correct identification of primary and secondary New World screwworm fly

Abstract Cochliomyia hominivorax and Cochliomyia macellaria are endemic Neotropical Calliphoridae species. The former causes severe myiasis in hosts while the latter is Sarcosaprophagous, but commonly found as a second invader in wounds. Due to the morphological similarity between them and the potential losses that C. hominivorax represents for cattle breeders, the rapid and correct identification of these two species is very important. In addition to a correct identification of these species, a good knowledge of C. hominivorax biology can be helpful for designing control programs. We applied geometric morphometric methods to assess wing differences between C. hominivorax and C. macellaria and conduct a preliminary analysis of wing morphological variation in C. hominivorax populations. Canonical variate analysis, using wing shape data, correctly classified 100% of the individuals analyzed according to sex and species. This result demonstrates that wing morphometry is a simple and reliable method for identifying C. hominivorax and C. macellaria samples and can be used to monitor C. hominivorax. Both species show sexual dimorphism, but in C. hominivorax it is magnified. We suggest that this may reflect different histories of selection pressures operating on males and females. Significant differences in wing size and shape were obtained among C. hominivorax populations, with little correlation with latitude. This result suggests that wing variation is also a good morphological marker for studying population variation in C. hominivorax.
Utility of the diagnostic interview schedule for children for assessing Tourette syndrome in children.

OBJECTIVE The Diagnostic Interview Schedule for Children IV (DISC) has been used extensively in research and screening. Despite wide use, little information exists on the validity of the DISC for diagnosing tic disorders. METHODS Participants were 181 youth with expert clinician-diagnosed Tourette syndrome (TS). RESULTS Using expert clinician-diagnosed TS as the gold standard, the sensitivity of the DISC-Y (youth, 0.27) and DISC-P (parent, 0.44) was poor. The DISC-Y identified 29.7% of youth with diagnosed TS whereas the DISC-P identified 47.4% of cases. Only 54% of cases of TS were detected by either the DISC-Y or -P. Diagnostic agreement between the DISC and expert clinician diagnosis was poor. The DISC-Y/P results did not differ as a function of tic severity. CONCLUSIONS Despite utility for assessing child psychiatric disorders, the sensitivity of the DISC for detecting TS appears poor. This study suggests that DISC has low agreement with expert clinician diagnosis of TS. Findings highlight the need for modification of the DISC and/or the identification and development of more sensitive measures for TS screening.
Modeling the Influences of Cyclic Top-Down and Bottom-Up Processes for Reinforcement Learning in Eye Movements

Understanding and reproducing complex human oculomotor behaviors using computational models is a challenging task. In this paper, two studies are presented, which focus on the development and evaluation of a computational model to show the influences of cyclic top-down and bottom-up processes on eye movements. To explain these processes, reinforcement learning was used to control eye movements. The first study showed that, in a picture-viewing task, different policies obtained from different picture-viewing conditions produced different types of eye movement patterns. In another visual search task, the second study illustrated that feedback information from each saccadic eye movement could be used to update the model's eye movement policy, generating different patterns in the following saccade. These two studies demonstrate the value of an integrated reinforcement learning model in explaining both top-down and bottom-up processes of eye movements within one computational model.
Titanium Casting Molds via Selective Laser Sintering

A mold material system has been developed that can be SLS processed and used to cast titanium alloys. Stabilized zirconia, chosen forits low reactivity with molten titanium, has been sintered into mold shapes. The molds have been infiltrated with a colloidal solution ofunstabilized zirconia and fired to create a partially stabilized structure. ·SEM analysis shows that the unstabilized zirconia forms bridges between the larger stabilized zirconia particles that provide strength to the mold. Introduction Titanium has interested designers for years because of its light weight, high strength, corrosion resistance and its abundance as a natural resource. Difficulties in roomtemperature machining and forming have prevented wider spread use of titanium. Nearnet-shape fabrication processes such as casting are the most commonly used methods to produce titanium parts since they require minimal post machining. Investment casting is a conventional way to produce titanium parts. Because molten titanium reacts with most solids, liquids and gases, specific mold materials and casting environments are used to minimize contamination of the final part. Rammed graphite molds are widely used because of the low cost and availability of graphite. However, the carbon reacts with titanium and forms a hardened titanium shell on the cast part that must be machined off. When casting parts in small quantities, a less reactive, more expensive mold material can be cost efficient by reducing the post-machining costs. Several studies show that zirconia is one of the least reactive materials with molten titanium [1,2]. However, zirconia undergoes a destructive phase transformation at 11 OO°C that can crack the mold during casting. It converts from a monoclinic to a tetragonal atomic structure, resulting in a 7 percent volume shrinkage. The addition of a small amount of yttria stabilizes the zirconia in a cubic structure that does not change phase at 11OO°C [3]. If a cubic phase zirconia mold is fabricated and infiltrated with unstabilized monoclinic zirconia, a "partially stabilized" structure is created. The partially stabilized zirconia structure has better thermal shock resistance than either the unstabilized Or fully stabilized structures [4].
Myoanatomy and anterior muscle regeneration of the fireworm Eurythoe cf. complanata (Annelida: Amphinomidae)

Amphinomidae or so‐called “fireworms” are known for their inflammatory substances and their regeneration ability. Recent transcriptome‐based molecular analyses revealed that these remarkable annelids are a basal branching taxon outside the annelid main radiation (Pleistoannelida). Although several studies dealing with analyses of the morphology of these annelids have been published, detailed investigations of the anterior muscle regeneration and the musculature in general are largely lacking for amphinomids. Using histology, phalloidin labeling together with subsequent confocal laser scanning microscopy (cLSM), and further light microscopic image acquisition of different regeneration stages, we here present the first morphological study describing the myoanatomy and muscular regeneration. During anterior muscular regeneration, longitudinal muscle bundles develop prior to transverse muscle fibers and segment boundaries. Additionally, Eurythoe cf. complanata develops an independent muscular ring surrounding the mouth opening in an early stage of regeneration. Detailed investigation of adult body wall musculature and the parapodial muscle complex in amphinomids show that E. cf. complanata bears well‐developed dorsal and ventral longitudinal muscle bundles as well as outer transverse muscles comparable to the pattern described for several Pleistoannelida. Furthermore, the biramous parapodia possess a complex meshwork of distinct muscle fibers allowing detailed comparisons with other annelid families. J. Morphol. 277:306–315, 2016. © 2015 Wiley Periodicals, Inc.
Assessment of effective dose to an individual carrying materials useful for radiation dosimetry by optically stimulated luminescence

Optically stimulated luminescence (OSL) from ordinary household salt has proven high potential for very low dose retrospective dosimetry. In the present paper other common place materials are considered and their dosimetric OSL-properties compared with household salt. The potential for assessment of the effective dose to an individual carrying such materials is investigated.
Bayesian estimation methods for n-gram language model adaptation

Stochastic n-gram language models have been successfully applied in continuous speech recognition for several years. Such language models provide many computational advantages but also require huge text corpora for parameter estimation. Moreover, the texts must exactly reflect, in a statistical sense, the user's language. Estimating a language model on a sample that is not representative severely affects speech recognition performance. A solution to this problem is provided by the Bayesian learning framework. Beyond the classical estimates, a Bayes derived interpolation model is proposed. Empirical comparisons have been carried out on a 10,000-word radiological reporting domain. Results are provided in terms of perplexity and recognition accuracy.
A prototype arm signature identification system

The S-Model identification algorithm described in [6,7] is a technique which can be used to accurately identify the actual kinematic parameters of serial link robotic manipulators. The actual kinematic parameters of a manipulator differ from the design parameters due to the presence of random manufacturing errors. The set of identified kinematic parameters is called the arm signature. Accurate arm signatures are needed to control and improve the end-effector positioning accuracy of robotic manipulators for a variety of important tasks. This paper describes the hardware and software implementation of a prototype arm signature identification system. This system uses an external ultrasonic range sensor to measure the Cartesian position of target points placed on the links of the robot. Algorithms to compensate the primary range measurements for spatial variations in air temperature and humidity are also incorporated. The relative Cartesian positioning accuracy of the sensor system is ± . 02cm. The general characteristics of our sensor design and the overall system design which exploits averaging over many sensor readings offer numerous advantages for arm signature identification. The prototype system has been applied in [6] to improve the kinematic performance of seven Puma 560 robots. For these robots relative positioning accuracy was improved by a factor of 10 on straight'line positioning tasks. Analysis and simulation of systematic errors confirms that the resolution of our sensor system should provide kinematic performance close to the limitations of the joint encoders. Our experimental studies show that sensor bias ultimately limits kinematic performance using this arm signature system. Experience with this prototype system has demonstrated that the S-Model identification algorithm is a practical and viable method for improving the kinematic performance of robotic manipulators.
A fully associative software-managed cache design

As DRAM access latencies approach a thousand instruction-execution times and on-chip caches grow to multiple megabytes, it is not clear that conventional cache structures continue to be appropriate. Two key features-full associativity and software management-have been used successfully in the virtual-memory domain to cope with disk access latencies. Future systems will need to employ similar techniques to deal with DRAM latencies. This paper presents a practical, fully associative, software-managed secondary cache system that provides performance competitive with or superior to traditional caches without OS or application involvement. We see this structure as the first step toward OS- and application-aware management of large on-chip caches. This paper has two primary contributions a practical design for a fully associative memory structure, the indirect index cache (IIC), and a novel replacement algorithm, generational replacement, that is specifically designed to work with the IIC. We analyze the behavior of an IIC with generational replacement as a drop-in, transparent substitute for a conventional secondary cache. We achieve miss rate reductions from 8% to 85% relative to a 4-way associative LRU organization, matching or beating a (practically infeasible) fully associative true LRU cache. Incorporating these miss rates into a rudimentary timing model indicates that the IIC/generational replacement cache could be competitive with a conventional cache at today's DRAM latencies, and will outperform a conventional cache as these CPU-relative latencies grow.
Building Customer Models from Business Data: an Automatic Approach Based on Fuzzy Clustering and Machine Learning

Data mining (DM) is a new emerging discipline that aims to extract knowledge from data using several techniques. DM turned out to be useful in business where the data describing the customers and their transactions is in the order of terabytes. In this paper, we propose an approach for building customer models (said also profiles in the literature) from business data. Our approach is three-step. In the first step, we use fuzzy clustering to categorize customers, i.e., determine groups of customers. A key feature is that the number of groups (or clusters) is computed automatically from data using the partition entropy as a validity criteria. In the second step, we proceed to a dimensionality reduction which aims at keeping for each group of customers only the most informative attributes. For this, we define the information loss to quantify the information degree of an attribute. Hence, and as a result to this second step, we obtain groups of customers each described by a distinct set of attributes. In the third and final step, we use backpropagation neural networks to extract useful knowledge from these groups. Experimental results on real-world data sets reveal a good performance of our approach and should simulate future research.
EMDC: A Semi-supervised Approach for Word Alignment

This paper proposes a novel semi-supervised word alignment technique called EMDC that integrates discriminative and generative methods. A discriminative aligner is used to find high precision partial alignments that serve as constraints for a generative aligner which implements a constrained version of the EM algorithm. Experiments on small-size Chinese and Arabic tasks show consistent improvements on AER. We also experimented with moderate-size Chinese machine translation tasks and got an average of 0.5 point improvement on BLEU scores across five standard NIST test sets and four other test sets.
Middleboxes No Longer Considered Harmful

Intermediate network elements, such as network address translators (NATs), firewalls, and transparent caches are now commonplace. The usual reaction in the network architecture community to these so-called middleboxes is a combination of scorn (because they violate important architectural principles) and dismay (because these violations make the Internet less flexible). While we acknowledge these concerns, we also recognize that middleboxes have become an Internet fact of life for important reasons. To retain their functions while eliminating their dangerous side-effects, we propose an extension to the Internet architecture, called the Delegation-Oriented Architecture (DOA), that not only allows, but also facilitates, the deployment of middleboxes. DOA involves two relatively modest changes to the current architecture: (a) a set of references that are carried in packets and serve as persistent host identifiers and (b) a way to resolve these references to delegates chosen by the referenced host.