Miracle-dz/UniFAR-FTUs huggingface dataset:
Nipah Virus V and W Proteins Have a Common STAT1-Binding Domain yet Inhibit STAT1 Activation from the Cytoplasmic and Nuclear Compartments, Respectively

ABSTRACT In previous reports it was demonstrated that the Nipah virus V and W proteins have interferon (IFN) antagonist activity due to their ability to block signaling from the IFN-α/β receptor (J. J. Rodriguez, J. P. Parisien, and C. M. Horvath, J. Virol. 76:11476-11483, 2002; M. S. Park et al., J. Virol. 77:1501-1511, 2003). The V, W, and P proteins are all encoded by the same viral gene and share an identical 407-amino-acid N-terminal region but have distinct C-terminal sequences. We now show that the P protein also has anti-IFN function, confirming that the common N-terminal domain is responsible for the antagonist activity. Truncation of this N-terminal domain revealed that amino acids 50 to 150 retain the ability to block IFN and to bind STAT1, a key component of the IFN signaling pathway. Subcellular localization studies demonstrate that the V and P proteins are predominantly cytoplasmic whereas the W protein is localized to the nucleus. In all cases, STAT1 colocalizes with the corresponding Nipah virus protein. These interactions are sufficient to inhibit STAT1 activation, as demonstrated by the lack of STAT1 phosphorylation on tyrosine 701 in IFN-stimulated cells expressing P, V, or W. Therefore, despite their common STAT1-binding domain, the Nipah virus V and P proteins act by retaining STAT1 in the cytoplasm while the W protein sequesters STAT1 in the nucleus, creating both a cytoplasmic and a nuclear block for STAT1. We also show that the IFN antagonist activity of the P protein is not as strong as that of V or W, perhaps explaining why Nipah virus has evolved to express these two edited products.
Acquisition and analysis of cardiovascular signals on smartphones: potential, pitfalls and perspectives

Smartphones, mobile applications (‘apps’), social media, analytics, and the cloud are profoundly changing the practice of medicine and the way health decisions are made. With the constant progress of technology, the measurement of vital signals becomes easier, cheaper, and practically a standard approach in clinical practice. The interest in measuring vital signals goes beyond medical professionals to the general public, patients, informal caregivers, and healthy individuals, who frequently lack any formal medical training. On smartphone platforms such as iOS and Android, a proliferation of health or medical ‘apps’ acquire and analyse a variety of vital signs through embedded sensors, interconnected devices or peripherals utilising on occasion analytics and social media. Smartphone vendors compete with traditional medical device manufacturers in the grey area between health care, wellness, and fitness, as US and EU regulatory bodies are setting and revising rules for these new technologies. On the other hand, in the absence of robust validation results, clinicians are hesitant to trust measurements by apps or recommend specific apps to their patients, partly also due to lack of a cost reimbursement policy. This review focuses on the acquisition and analysis on smartphones of three important vital signs in the cardiovascular and respiratory field as well as in rehabilitation i.e. heart or pulse rate, blood pressure, and blood oxygenation. The potential, pitfalls, and perspectives on mobile devices and smartphone apps for health management by patients and healthy individuals are discussed.
Home-based cardiac rehabilitation: Development and evaluation of a novel intervention with telemonitoring guidance and wearable sensors

In this thesis we have developed and evaluated the effectiveness of a home-based training intervention for cardiac rehabilitation patients that accommodates the preferences and constraints of patients while retaining the effectiveness of conventional, centre-based cardiac rehabilitation. In the first part of this thesis, we showed that the effectiveness of centre-based exercise programmes for coronary artery patients and chronic heart failure patients is mainly determined by their total energy expenditure. This means that adjustments to programme characteristics (training intensity, session duration and frequency, programme length) can be made freely, without impairing effects on exercise capacity, provided that energy expenditure as a whole is preserved. Therefore, training programmes can be tailored towards patients’ preferences and translated to the home environment. In the second part of this thesis, we showed that wearable sensors can accurately assess physical activity levels of beta-blocker-medicated cardiac patients in the home-environment. In addition, we described a randomised controlled trial studying the clinical and cost-effectiveness of home-based cardiac rehabilitation with telemonitoring guidance compared to centre-based cardiac rehabilitation. Home-based training resulted in similar improvements in physical fitness and health-related quality life as centre-based training, with a trend towards lower costs. We concluded that home-based cardiac rehabilitation with telemonitoring guidance is a useful alternative to centrebased cardiac rehabilitation for young and motivated patients with low-to-moderate cardiac risks.
Pylorus-Preserving Total Pancreatectomy

Background/Aims: Preservation of the pylorus is an accepted alternative procedure to the classical Whipple operation for pancreatic head resection but data describing its value for total pancreatectomy are sparse. Methods: A prospective analysis of 22 total pancreatectomies performed in a consecutive series of 436 pancreatic resections from 1.11. 93 to 1.5. 99. Results: 11 patients underwent total pancreatectomy with preservation of the pylorus. Histopathological examination revealed pancreatic adenocarcinoma in 16 cases and duodenal adenocarcinoma in 1 patient, 5 patients had other types of pancreatic neoplasm. In-hospital mortality was 4.5% (n = 1), cumulative morbidity was 59% and reoperations were performed in 9.1% of cases (n = 2). Median follow-up was 37 months (range 5–66). 62% of patients (n = 13) developed tumor recurrence and 13 patients died during the follow-up period with 10 deaths being cancer related. There was no difference concerning postoperative and follow-up morbidity of survival between patients undergoing pylorus-preserving total pancreatectomy or pancreatectomy with gastrectomy. However, postoperative body weight was increased 3, 6, 9 and 12 months following preservation of the pylorus. Conclusion: Total pancreatectomy with preservation of the pylorus is a feasible type of resection for all types of pancreatic or ampullary tumors, which shows a similar morbidity and long-term survival but improved nutritional recovery compared with standard total pancreatectomy.
Video event detection using a subclass recoding error-correcting output codes framework

In this paper, complex video events are learned and detected using a novel subclass recoding error-correcting outputs (SRECOC) design. In particular, a set of pre-trained concept detectors along different low-level visual feature types are used to provide a model vector representation of video signals. Subsequently, a subclass partitioning algorithm is used to divide only the target event class to several subclasses and learn one subclass detector for each event subclass. The pool of the subclass detectors is then combined under a SRECOC framework to provide a single event detector. This is achieved by first exploiting the properties of the linear loss-weighted decoding measure in order to derive a probability estimate along the different event subclass detectors, and then utilizing the sum probability rule along event subclasses to retrieve a single degree of confidence for the presence of the target event in a particular test video. Experimental results on the large-scale video collections of the TRECVID Multimedia Event Detection (MED) task verify the effectiveness of the proposed method. Moreover, the effect of weak or strong concept detectors on the accuracy of the resulting event detectors is examined.
Action recognition using Feature Position Constrained Linear Coding

Recently space-time interest points (STIPs) using bag-of-feature (BOF) in action recognition has been highly successful. Despite its popularity, The quantization error and the lost of semantic meaning among STIPs are the main weaknesses that severely limit the effectiveness of this method. To overcome these limitations, this paper incorporated the feature position information into coding procedure and proposed a novel Feature Position Constrained Linear Coding (FPLC) method by extending the Locality Constrained Linear Coding (LLC) approach. It first project the features into the human ROI, then codes the features locally using FPLC with the consideration of feature position. Owning to that the local area of human ROI often aggregate features extracted from the same part of human body and those features should exhibit similar values, this local coding strategy helps to alleviate the quantization error and enhance correlation between features at the same time, which helps to improve the recognition accuracy. Compared with the state-of-the-art action recognition method, experiment results demonstrated the effectiveness of the proposed method.
Protein Landscape at Drosophila melanogaster Telomere-Associated Sequence Repeats

ABSTRACT The specific set of proteins bound at each genomic locus contributes decisively to regulatory processes and to the identity of a cell. Understanding of the function of a particular locus requires the knowledge of what factors interact with that locus and how the protein composition changes in different cell types or during the response to internal and external signals. Proteomic analysis of isolated chromatin segments (PICh) was developed as a tool to target, purify, and identify proteins associated with a defined locus and was shown to allow the purification of human telomeric chromatin. Here we have developed this method to identify proteins that interact with the Drosophila telomere-associated sequence (TAS) repeats. Several of the purified factors were validated as novel TAS-bound proteins by chromatin immunoprecipitation, and the Brahma complex was confirmed as a dominant modifier of telomeric position effect through the use of a genetic test. These results offer information on the efficacy of applying the PICh protocol to loci with sequence more complex than that found at human telomeres and identify proteins that bind to the TAS repeats, which might contribute to TAS biology and chromatin silencing.
Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells

ABSTRACT The nuclear receptor hepatocyte nuclear factor 4α (HNF4α) is tumor suppressive in the liver but amplified in colon cancer, suggesting that it also might be oncogenic. To investigate whether this discrepancy is due to different HNF4α isoforms derived from its two promoters (P1 and P2), we generated Tet-On-inducible human colon cancer (HCT116) cell lines that express either the P1-driven (HNF4α2) or P2-driven (HNF4α8) isoform and analyzed them for tumor growth and global changes in gene expression (transcriptome sequencing [RNA-seq] and chromatin immunoprecipitation sequencing [ChIP-seq]). The results show that while HNF4α2 acts as a tumor suppressor in the HCT116 tumor xenograft model, HNF4α8 does not. Each isoform regulates the expression of distinct sets of genes and recruits, colocalizes, and competes in a distinct fashion with the Wnt/β-catenin mediator T-cell factor 4 (TCF4) at CTTTG motifs as well as at AP-1 motifs (TGAXTCA). Protein binding microarrays (PBMs) show that HNF4α and TCF4 share some but not all binding motifs and that single nucleotide polymorphisms (SNPs) in sites bound by both HNF4α and TCF4 can alter binding affinity in vitro, suggesting that they could play a role in cancer susceptibility in vivo. Thus, the HNF4α isoforms play distinct roles in colon cancer, which could be due to differential interactions with the Wnt/β-catenin/TCF4 and AP-1 pathways.
On space-time code design

It is shown that the separation between space-time code matrices can be described in terms of a metric of Euclidean type, which is defined via the singular values of difference code matrices, and arises naturally from a minimization of the pairwise error probability. Essentially, the distance between complex space-time code matrices is the Euclidean distance between the respective - demultiplexed and concatenated - transmit antenna streams, expressed in terms of the structure inherent to the multiple antenna arrangement. It is further shown that the determinant criterion can be strengthened, in a manner that not only suggests an optimum space-time code matrix structure, but also outlines the central role played by the Euclidean distance in quasi-static fading. Theorem 5 - which claims that in order to optimize the product distance one must optimize the Euclidean distance -establishes a close interdependence between product and Euclidean distances; it thereby links the performance determining factors in quasi-static and independent fading, and rigorously establishes the relevance of combining space-time coding and modulation in fading environments. A multidimensional space-time constellation for two transmit antennas, and its coset partitioning-based on traces of differences between constellation matrices-are described. Example codes constitute the first reporting of a space-time coded modulation scheme for fading channels, whereby a space-time constellation is partitioned in cosets.
Tsc2 Is a Molecular Checkpoint Controlling Osteoblast Development and Glucose Homeostasis

ABSTRACT Insulin signaling in osteoblasts regulates global energy balance by stimulating the production of osteocalcin, a bone-derived protein that promotes insulin production and action. To identify the signaling pathways in osteoblasts that mediate insulin's effects on bone and energy metabolism, we examined the function of the tuberous sclerosis 2 (Tsc2) protein, a key target important in coordinating nutrient signaling. Here, we show that loss of Tsc2 in osteoblasts constitutively activates mTOR and destabilizes Irs1, causing osteoblasts to differentiate poorly and become resistant to insulin. Young Tsc2 mutant mice demonstrate hypoglycemia with increased levels of insulin and undercarboxylated osteocalcin. However, with age, Tsc2 mutants develop metabolic features similar to mice lacking the insulin receptor in the osteoblast, including peripheral adiposity, hyperglycemia, and decreased pancreatic β cell mass. These metabolic abnormalities appear to result from chronic elevations in undercarboxylated osteocalcin that lead to downregulation of the osteocalcin receptor and desensitization of the β cell to this hormone. Removal of a single mTOR allele from the Tsc2 mutant mice largely normalizes the bone and metabolic abnormalities. Together, these findings suggest that Tsc2 serves as a key checkpoint in the osteoblast that is required for proper insulin signaling and acts to ensure normal bone acquisition and energy homeostasis.
Quantum sized gold nanoclusters with atomic precision.

Gold nanoparticles typically have a metallic core, and the electronic conduction band consists of quasicontinuous energy levels (i.e. spacing δ ≪ k(B)T, where k(B)T is the thermal energy at temperature T (typically room temperature) and k(B) is the Boltzmann constant). Electrons in the conduction band roam throughout the metal core, and light can collectively excite these electrons to give rise to plasmonic responses. This plasmon resonance accounts for the beautiful ruby-red color of colloidal gold first observed by Faraday back in 1857. On the other hand, when gold nanoparticles become extremely small (<2 nm in diameter), significant quantization occurs to the conduction band. These quantum-sized nanoparticles constitute a new class of nanomaterial and have received much attention in recent years. To differentiate quantum-sized nanoparticles from conventional plasmonic gold nanoparticles, researchers often refer to the ultrasmall nanoparticles as nanoclusters. In this Account, we chose several typical sizes of gold nanoclusters, including Au(25)(SR)(18), Au(38)(SR)(24), Au(102)(SR)(44), and Au(144)(SR)(60), to illustrate the novel properties of metal nanoclusters imparted by quantum size effects. In the nanocluster size regime, many of the physical and chemical properties of gold nanoparticles are fundamentally altered. Gold nanoclusters have discrete electronic energy levels as opposed to the continuous band in plasmonic nanoparticles. Quantum-sized nanoparticles also show multiple optical absorption peaks in the optical spectrum versus a single surface plasmon resonance (SPR) peak at 520 nm for spherical gold nanocrystals. Although larger nanocrystals show an fcc structure, nanoclusters often have non-fcc atomic packing structures. Nanoclusters also have unique fluorescent, chiral, and magnetic properties. Due to the strong quantum confinement effect, adding or removing one gold atom significantly changes the structure and the electronic and optical properties of the nanocluster. Therefore, precise atomic control of nanoclusters is critically important: the nanometer precision typical of conventional nanoparticles is not sufficient. Atomically precise nanoclusters are represented by molecular formulas (e.g. Au(n)(SR)(m) for thiolate-protected ones, where n and m denote the respective number of gold atoms and ligands). Recently, major advances in the synthesis and structural characterization of molecular purity gold nanoclusters have made in-depth investigations of the size evolution of metal nanoclusters possible. Metal nanoclusters lie in the intermediate regime between localized atomic states and delocalized band structure in terms of electronic properties. We anticipate that future research on quantum-sized nanoclusters will stimulate broad scientific and technological interests in this special type of metal nanomaterial.
Cost–utility analysis of cardiac rehabilitation after conventional heart valve surgery versus usual care

Background While cardiac rehabilitation in patients with ischaemic heart disease and heart failure is considered cost-effective, this evidence may not be transferable to heart valve surgery patients. The aim of this study was to investigate the cost-effectiveness of cardiac rehabilitation following heart valve surgery. Design We conducted a cost–utility analysis based on a randomised controlled trial of 147 patients who had undergone heart valve surgery and were followed for 6 months. Methods Patients were randomised to cardiac rehabilitation consisting of 12 weeks of physical exercise training and monthly psycho-educational consultations or to usual care. Costs were measured from a societal perspective and quality-adjusted life years were based on the EuroQol five-dimensional questionnaire (EQ-5D). Estimates were presented as means and 95% confidence intervals (CIs) based on bootstrapping. Costs and effect differences were presented in a cost-effectiveness plane and were transformed into net benefit and presented in cost-effectiveness acceptability curves. Results No statistically significant differences were found in total societal costs (–1609 Euros; 95% CI: –6162 to 2942 Euros) or in quality-adjusted life years (–0.000; 95% CI –0.021 to 0.020) between groups. However, approximately 70% of the cost and effect differences were located below the x-axis in the cost-effectiveness plane, and the cost-effectiveness acceptability curves showed that the probability for cost- effectiveness of cardiac rehabilitation compared to usual care is at minimum 75%, driven by a tendency towards costs savings. Conclusions Cardiac rehabilitation after heart valve surgery may not have improved health-related quality of life in this study, but is likely to be cost-effective for society, outweighing the extra costs of cardiac rehabilitation.
The Hippo Pathway Effector YAP Regulates Motility, Invasion, and Castration-Resistant Growth of Prostate Cancer Cells

ABSTRACT Yes-associated protein (YAP) is an effector of the Hippo tumor suppressor pathway. The functional significance of YAP in prostate cancer has remained elusive. In this study, we first show that enhanced expression of YAP is able to transform immortalized prostate epithelial cells and promote migration and invasion in both immortalized and cancerous prostate cells. We found that YAP mRNA was upregulated in androgen-insensitive prostate cancer cells (LNCaP-C81 and LNCaP-C4-2 cells) compared to the level in androgen-sensitive LNCaP cells. Importantly, ectopic expression of YAP activated androgen receptor signaling and was sufficient to promote LNCaP cells from an androgen-sensitive state to an androgen-insensitive state in vitro, and YAP conferred castration resistance in vivo. Accordingly, YAP knockdown greatly reduced the rates of migration and invasion of LNCaP-C4-2 cells and under androgen deprivation conditions largely blocked cell division in LNCaP-C4-2 cells. Mechanistically, we found that extracellular signal-regulated kinase–ribosomal s6 kinase signaling was downstream of YAP for cell survival, migration, and invasion in androgen-insensitive cells. Finally, immunohistochemistry showed significant upregulation and hyperactivation of YAP in castration-resistant prostate tumors compared to their levels in hormone-responsive prostate tumors. Together, our results identify YAP to be a novel regulator in prostate cancer cell motility, invasion, and castration-resistant growth and as a potential therapeutic target for metastatic castration-resistant prostate cancer (CRPC).