Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel HLA-B18 Restricted CD8+ T Cell Epitope Is Efficiently Cross-Presented by Dendritic Cells from Soluble Tumor Antigen

NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8+ T cell epitope, NY-ESO-188–96 (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1157–165 epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-188–96 is much more efficiently cross-presented from the soluble form, than NY-ESO-1157–165. On the other hand, NY-ESO-1157–165 is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A26–35; whereas NY-ESO-188–96 was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-188–96 is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18+ melanoma patients. Surprisingly, all the detectable responses to NY-ESO-188–96 from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8+ T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed.
Probing large conformational rearrangements in wild-type and mutant spectrin using structural mass spectrometry

Significance Chemical cross-linking coupled with mass spectrometry has recently emerged as a powerful method for providing medium-resolution spatial information for proteins that are too large or too flexible for crystallography or NMR. To date, crystal structures of only small segments of the highly flexible, conformationally dynamic spectrin family of proteins have been obtained. In this study we combined cross-link–derived spatial constraints with homology modeling to produce the first experimentally verified medium-resolution structures of wild-type spectrin closed dimers and tetramers. These structures coupled with the closed dimer structure of a very common spectrin mutation associated with hereditary hemolytic anemia provide mechanistic insights into how some mutations located large distances from the spectrin tetramerization site can destabilize red cell membranes. Conformational changes of macromolecular complexes play key mechanistic roles in many biological processes, but large, highly flexible proteins and protein complexes usually cannot be analyzed by crystallography or NMR. Here, structures and conformational changes of the highly flexible, dynamic red cell spectrin and effects of a common mutation that disrupts red cell membranes were elucidated using chemical cross-linking coupled with mass spectrometry. Interconversion of spectrin between closed dimers, open dimers, and tetramers plays a key role in maintaining red cell shape and membrane integrity, and spectrins in other cell types serve these as well as more diverse functions. Using a minispectrin construct, experimentally verified structures of closed dimers and tetramers were determined by combining distance constraints from zero-length cross-links with molecular models and biophysical data. Subsequent biophysical and structural mass spectrometry characterization of a common hereditary elliptocytosis-related mutation of α-spectrin, L207P, showed that cell membranes were destabilized by a shift of the dimer–tetramer equilibrium toward closed dimers. The structure of αL207P mutant closed dimers provided previously unidentified mechanistic insight into how this mutation, which is located a large distance from the tetramerization site, destabilizes spectrin tetramers and cell membrane integrity.
Early Attachment as a Pathway to Adolescent Peer Competence.

Forty-one adolescents ages 15-16, a subset of participants from an ongoing longitudinal study, were observed and interviewed during a 2-day-long camp reunion. Early attachment information was available for all participants. Counselors rated them on several personal and interpersonal characteristics after the reunion, including social competence. The participants were also interviewed regarding their experience and their thoughts about friendships and romantic interests of themselves and other campers. The interviews were coded for the extent to which the adolescent was willing to discuss people and relationships during the interview and the degree to which the participants were aware of the patterns of interaction in the social network around them. Results show that concurrent interest in relationships is a stronger predictor of social competence for participants with anxious histories, although participants with secure histories are more socially competent overall. This may indicate that participants wit.
Neural Paraphrase Generation using Transfer Learning

Progress in statistical paraphrase generation has been hindered for a long time by the lack of large monolingual parallel corpora. In this paper, we adapt the neural machine translation approach to paraphrase generation and perform transfer learning from the closely related task of entailment generation. We evaluate the model on the Microsoft Research Paraphrase (MSRP) corpus and show that the model is able to generate sentences that capture part of the original meaning, but fails to pick up on important words or to show large lexical variation.
Structural Diversity of Small Molecule Libraries

A novel method for assessing structural diversity is presented. Maximum common subgraph identity is used as the measure of similarity between two chemical structures. A conditional probability treatment of similarity distributions for libraries of chemical structures is used to define diversity. This evaluation method together with the evaluation of traditional physicochemical properties is used to assess a large number of chemical libraries and to understand structural differences between these.
Becoming a Consumer of Care: Developing a Sociological Account of the ‘New Community Care’

The chapter evaluates the reformed arrangements for the management and delivery of social care following the NHS and Community Care Act 1990 using a framework drawn from economic sociology. Research findings describing how a group of newly disabled older people fared as consumers of the services are summarized. An explanatory account is given drawing upon concepts and theory to be found in the growing literature on the sociology of economic life, particularly studies of consumption. The central conclusion is that it is difficult to account for the effects of the recent reforms on community care consumers without situating them within a context of existing social relations and institutions. If the reforms are to succeed they must change not just the practical mechanics of service funding and delivery but deeply embedded values and behavioural norms.
Mixture Discriminant Monitoring: A Hybrid Method for Statistical Process Monitoring and Fault Diagnosis/Isolation

To better utilize historical process data from faulty operations, supervised learning methods, such as Fisher discriminant analysis (FDA), have been adopted in process monitoring. However, such methods can only separate known faults from normal operations, and they have no means to deal with unknown faults. In addition, most of these methods are not designed for handling non-Gaussian distributed data; however, non-Gaussianity is frequently observed in industrial processes. In this paper, a hybrid multivariate approach named mixture discriminant monitoring (MDM) was proposed, in which supervised learning and statistical process control (SPC) charting techniques are integrated. MDM is capable of solving both of the above problems simultaneously during online process monitoring. Then, for known faults, a root-cause diagnosis can be automatically achieved, while for unknown faults, abnormal variables can be isolated through missing variable analysis. MDM was used on the benchmark Tennessee Eastman (TE) process, and the results showed the capability of the proposed approach.
A Novel Time-Varying Sparse Channel Estimation Based on Block-Type Pilot and SAMP

Using OMP algorithm for time-delay detecting and apply BEM based on comb-type pilot for channel estimation is the most commonly used method for sparse time-frequency doubly-selective channels, but the channel estimation performance will decrease sharply when the number of channel paths is large, and this method need to obtain the channel sparsity as prior information in advance. In this paper, a novel sparse channel estimation method based on block-type pilot and SAMP has been proposed, whereby using SAMP for time-delay detecting, using the BEM coefficients of pilot symbols and interpolation algorithm to obtain the BEM coefficients of the data symbols. The simulation verifies the proposed algorithm can achieve a good performance in the case of the channel paths is large and the channel sparsity is unknown.
Co-clustering as multilinear decomposition with sparse latent factors

The K-means clustering problem seeks to partition the columns of a data matrix in subsets, such that columns in the same subset are ‘close’ to each other. The co-clustering problem seeks to simultaneously partition the rows and columns of a matrix to produce ‘coherent’ groups called co-clusters. Co-clustering has recently found numerous applications in diverse areas. The concept readily generalizes to higher-way data sets (e.g., adding a temporal dimension). Starting from K-means, we show how co-clustering can be formulated as constrained multilinear decomposition with sparse latent factors. In the case of three- and higher-way data, this corresponds to a PARAFAC decomposition with sparse latent factors. This is important, for PARAFAC is unique under mild conditions - and sparsity further improves identifiability. This allows us to uniquely unravel a large number of possibly overlapping co-clusters that are hidden in the data. Interestingly, the imposition of latent sparsity pays a collateral dividend: as one increases the number of fitted co-clusters, new co-clusters are added without affecting those previously extracted. An important corollary is that co-clusters can be extracted incrementally; this implies that the algorithm scales well for large datasets. We demonstrate the validity of our approach using the ENRON corpus, as well as synthetic data.
Multi-OMICs and Genome Editing Perspectives on Liver Cancer Signaling Networks

The advent of the human genome sequence and the resulting ~20,000 genes provide a crucial framework for a transition from traditional biology to an integrative “OMICs” arena (Lander et al., 2001; Venter et al., 2001; Kitano, 2002). This brings in a revolution for cancer research, which now enters a big data era. In the past decade, with the facilitation by next-generation sequencing, there have been a huge number of large-scale sequencing efforts, such as The Cancer Genome Atlas (TCGA), the HapMap, and the 1000 genomes project. As a result, a deluge of genomic information becomes available from patients stricken by a variety of cancer types. The list of cancer-associated genes is ever expanding. New discoveries are made on how frequent and highly penetrant mutations, such as those in the telomerase reverse transcriptase (TERT) and TP53, function in cancer initiation, progression, and metastasis. Most genes with relatively frequent but weakly penetrant cancer mutations still remain to be characterized. In addition, genes that harbor rare but highly penetrant cancer-associated mutations continue to emerge. Here, we review recent advances related to cancer genomics, proteomics, and systems biology and suggest new perspectives in targeted therapy and precision medicine.
Adolescent Depression Prevention Programs-A Review

In recent years, there has been an increasing focus on prevention of depression among adolescents. This review delineates and evaluates major depression prevention programs for adolescents developed and tested world-wide, according to the three major types, viz. universal, selective, and indicated. Overall, targeted prevention with selective and indicated programs seem to give better results with higher effect sizes than a universal approach. School-based cognitive-behavioural approach interventions have been found to significantly reduce depressive symptoms among adolescents, with some evidence that the intervention provides long-lasting effects. However, further research to ameliorate the understanding of the development and maintenance of depression is essential in order also to improve the effects of prevention and intervention
Effect of Experience on Cognition, Affect and Satisfaction: The Case of Japanese Visitors to Macau

The aim of the paper was to test the effect of experience on two key antecedents of destination satisfaction, cognition and affect. The analysis utilized the Macau Visitor Experience Survey (2005). The results indicate that both cognition and affect are pre-determinants of satisfaction and that cognition positively influences affective reactions to a destination. While the effect of cognition on destination satisfaction judgments increases as an individual's experience accumulates and the effect of affect decreases with experience, in both cases the influence of experience is limited. Prior experience was not found to have statistically significant moderating effect on cognition and affect's relationship with satisfaction. The results bear important implications for destination visitor experience management and planning.
Infrastructure Mobility: A What-if Analysis

Mobile computing has traditionally implied mobile clients connected to a static infrastructure. This paper breaks away from this point of view and envisions the possibility of injecting mobility into infrastructure. We envision a WiFi access point on wheels, that moves to optimize desired performance metrics. Movements need not necessarily be all around the floor of a home or office, neither do they have to operate on batteries, or connect wirelessly to the Internet. At homes, they could remain tethered to power and Ethernet outlets while moving in small areas (perhaps under the study table). In offices of the future, perhaps APs could move on tracks installed on top of false ceilings. This paper explores the viability of this vision and presents early measurements from various home/office environments. We find that complex multipath characteristics of indoor environments cause large fluctuations in link quality even when the antenna moves in the scale of few centimeters. Mobile APs can leverage this spatial variation by relocating to a location that is strong for its own clients and yet weak from its interferers. Experiment results show that such micro-mobility itself can offer up to 2x throughput gains. Additional opportunities may emerge, such as in energy savings, security, QoS, and even in applications such as indoor localization. While this paper explores a small fraction of the landscape of opportunities, the results have been far more promising than what we had anticipated originally.
A geometric characterization of optimal designs for regression models with correlated observations

Summary. We consider the problem of optimal design of experiments for random‐effects models, especially population models, where a small number of correlated observations can be taken on each individual, whereas the observations corresponding to different individuals are assumed to be uncorrelated. We focus on c‐optimal design problems and show that the classical equivalence theorem and the famous geometric characterization of Elfving from the case of uncorrelated data can be adapted to the problem of selecting optimal sets of observations for the n individual patients. The theory is demonstrated by finding optimal designs for a linear model with correlated observations and a non‐linear random‐effects population model, which is commonly used in pharmaco‐kinetics.
Wyner–Ziv Video Compression and Fountain Codes for Receiver-Driven Layered Multicast

The increasing popularity of video streaming applications that distribute data to a large number of clients motivates the design of reliable multimedia delivery systems capable of adapting to diverse transmission conditions. Receiver-driven layered multicast (RLM) efficiently addresses the issue of heterogeneity in clients' available bandwidths and packet loss rates by shifting rate control to the receiver side. We propose a system for RLM over the Internet and 3G wireless networks based on layered Wyner-Ziv video coding and digital fountain codes. Layered Wyner-Ziv video coding improves robustness to packet loss compared to current scalable video coders, such as MPEG-4 FGS coder, while generating a scalable output bit stream. Digital fountain codes are near-capacity erasure protection codes that are ideally suited for multicast applications due to their rateless property. By combining an error-resilient Wyner-Ziv video coder and rateless fountain codes, our system allows reliable video multicast to an arbitrary number of heterogeneous receivers without the requirement of feedback channels. Simulation results show performance improvements over a previous scheme that exploits multiple description and layered coding.
New Adaptive Routing Proposal for DTN

Disruption Tolerant Networks, packet forwarding scheme has a major drawback in terms of network congestion. In order to solve this problem, a New Adaptive Routing Proposal (NARP) has been proposed NARP uses the message forwarding probability scheme in order to increase the delivery ratio and bandwidth utilization. Also, NARP arranges the dropping sequence based on their assigned priority. The priority is determined by the average hop count and average latency. Meanwhile NARP has an ACK list exchange mechanism that is used to purge the redundant messages. Simulation of NARP was carried out and its performance was compared to well known DTN routing protocols: Epidemic Routing, and Spray and Wait Routing. Simulation results show that NARP outperforms them in terms of packet delivery ratio, average latency, and overhead ratio.
Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium

Significance Harnessing the inherent capability of stem cells to maintain and regenerate injured tissues is a prerequisite for their use in mending damage to the nervous system. In the olfactory epithelium stem cells accomplish neurogenesis and epithelial repair throughout life to an extent not seen elsewhere in the nervous system. Here we show that the transcription factor protein 63 (p63) is a master regulator of the transition from the reserve to the active stem cell pool in the epithelium. Loss of p63 expression in reserve basal cells is necessary and sufficient for activation, without compromising stem cell status. Identification of this central mechanism provides a target for stem cell activation in this uniquely accessible source of patient-specific, neurogenic stem cells. Adult tissue stem cells can serve two broad functions: to participate actively in the maintenance and regeneration of a tissue or to wait in reserve and participate only when activated from a dormant state. The adult olfactory epithelium, a site for ongoing, life-long, robust neurogenesis, contains both of these functional stem cell types. Globose basal cells (GBCs) act as the active stem cell population and can give rise to all the differentiated cells found in the normal tissue. Horizontal basal cells (HBCs) act as reserve stem cells and remain dormant unless activated by tissue injury. Here we show that HBC activation following injury by the olfactotoxic gas methyl bromide is coincident with the down-regulation of protein 63 (p63) but anticipates HBC proliferation. Gain- and loss-of-function studies show that this down-regulation of p63 is necessary and sufficient for HBC activation. Moreover, activated HBCs give rise to GBCs that persist for months and continue to act as bona fide stem cells by participating in tissue maintenance and regeneration over the long term. Our analysis provides mechanistic insight into the dynamics between tissue stem cell subtypes and demonstrates that p63 regulates the reserve state but not the stem cell status of HBCs.
Characterization of Spotted Fever Group Rickettsiae in Flea and Tick Specimens from Northern Peru

ABSTRACT Evidence of spotted fever group (SFG) rickettsiae was obtained from flea pools and individual ticks collected at three sites in northwestern Peru within the focus of an outbreak of febrile disease in humans attributed, in part, to SFG rickettsia infections. Molecular identification of the etiologic agents from these samples was determined after partial sequencing of the 17-kDa common antigen gene (htrA) as well as pairwise nucleotide sequence homology with one or more of the following genes: gltA, ompA, and ompB. Amplification and sequencing of portions of the htrA and ompA genes in pooled samples (2 of 59) taken from fleas identified the pathogen Rickettsia felis. Four tick samples yielded molecular evidence of SFG rickettsiae. Fragments of the ompA (540-bp) and ompB (2,484-bp) genes were amplified from a single Amblyomma maculatum tick (tick 124) and an Ixodes boliviensis tick (tick 163). The phylogenetic relationships between the rickettsiae in these samples and other rickettsiae were determined after comparison of their ompB sequences by the neighbor-joining method. The dendrograms generated showed that the isolates exhibited close homology (97%) to R. aeschlimannii and R. rhipicephali. Significant bootstrap values supported clustering adjacent to this nodule of the SFG rickettsiae. While the agents identified in the flea and tick samples have not been linked to human cases in the area, these results demonstrate for the first time that at least two SFG rickettsia agents were circulating in northern Peru at the time of the outbreak. Furthermore, molecular analysis of sequences derived from the two separate species of hard ticks identified a possibly novel member of the SFG rickettsiae.
Measuring Quality of Life in HIV and AIDS: A Review of the Recent Literature

This review addresses some of the recent issues surrounding the measurement of quality of life of people living with HIV and AIDS and discusses the properties of suitable instruments. More than 300 articles on quality of life in HIV and AIDS published since 1995 have been appraised. The structure and properties of two broad types of measure are considered: economic indicators or scales and subjective measures. While several good scales have been created for the assessment of people living with HIV infection, few were found to be conceptually comprehensive in terms of the dimensions offered for evaluation. Almost all these instruments were developed in the USA. Simple translation methods provide language versions that lack cross-cultural equivalence. A new cross-cultural methodology has recently been achieved in the development of the WHOQOL-HIV instrument as a measure for international research and its development is described.