Miracle-dz/UniFAR-FTUs huggingface dataset:
Non‐clinical safety assessment of single and repeated administration of gE/AS01 zoster vaccine in rabbits

HZ/su is an investigational recombinant subunit vaccine for the prevention of shingles, a disease resulting from the reactivation of varicella zoster virus. The vaccine is composed of recombinant varicella zoster virus glycoprotein E (gE), and liposome‐based Adjuvant System AS01. To evaluate the potential local and systemic effects of this vaccine, three studies were performed in rabbits. In the first two studies, rabbits received a single intramuscular (IM; study 1) or subcutaneous (SC; study 2) dose of gE/AS01, AS01 alone (in study 2 only) or saline, and the local tolerance was evaluated up to 3 days after administration. Under these conditions, only local inflammatory reactions at the injection sites were detected by microscopic evaluation. In the third study, gE/AS01, AS01 alone or saline, were injected SC or IM on four occasions at 2 week intervals. General health status, local tolerance, ophthalmology, haematology and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed after termination of the study. The only treatment‐related changes included a transient increase in neutrophils, C‐reactive protein and fibrinogen levels and microscopic signs of inflammation at the injection sites, which are expected observations related to the elicited inflammatory reaction. The SC and IM routes of administration produced similar systemic effects. However, microscopic findings at the injection sites differed. One month after the last injection, recovery was complete in all groups. In conclusion, the single and repeated SC and IM administration of the gE/AS01 vaccine were locally and systemically well‐tolerated in rabbits and support the clinical development of the vaccine. Copyright © 2016 John Wiley & Sons, Ltd.
A Provable Approach for Double-Sparse Coding

Sparse coding is a crucial subroutine in algorithms for various signal processing, deep learning, and other machine learning applications. The central goal is to learn an overcomplete dictionary that can sparsely represent a given dataset. However, storage, transmission, and processing of the learned dictionary can be untenably high if the data dimension is high. In this paper, we consider the double-sparsity model introduced by Rubinstein, Zibulevsky, and Elad (2010) where the dictionary itself is the product of a fixed, known basis and a data-adaptive sparse component. First, we introduce a simple algorithm for double-sparse coding that can be amenable to efficient implementation via neural architectures. Second, we theoretically analyze its performance and demonstrate asymptotic sample complexity and running time benefits over existing (provable) approaches for sparse coding. To our knowledge, our work introduces the first computationally efficient algorithm for double-sparse coding that enjoys rigorous statistical guarantees. Finally, we support our analysis via several numerical experiments on simulated data, confirming that our method can indeed be useful in problem sizes encountered in practical applications.
PKCα promotes local advancement via its dual roles in nasopharyngeal carcinoma

Abstract Conclusion: In patients with nasopharyngeal carcinoma (NPC), PKCα is linked to local advancement and plays dual roles in tumorigenesis. Moreover, positive PKCα is associated with 2-year overall survival of NPC. Objective: This study seeks to investigate the role of PKCα to identify different sub-types in NPC. Methods: PKCα expression levels were detected in a collection of NPC samples. CT and MRI scans of the corresponding patients were used to assess adjacent tissue invasion and lymph node metastasis. The correlation of tumour invasion and PKCα levels was evaluated by statistical analysis. The correlation between expression level of PKCα and 2-year overall survival was analysed by the Kaplan-Meier curves. Moreover, a multivariate Cox proportional hazard regression analysis was used to identify the independent prognostic factors for NPC. Results: PKCα is linked to the invasion of adjacent tissues, especially in the skull base. However, down-regulation of PKCα is a risk factor for regional lymph node metastasis. The 2-year overall survival of the PKCα negative group is better than that of the PKCα positive group (PKCα negative group 100%, PKCα positive group 88.5%, p = 0.034). Based on the multivariate Cox proportional hazard regression analysis, age was identified as a risk factor.
Joint Concept Correlation and Feature-Concept Relevance Learning for Multilabel Classification

In recent years, multilabel classification has attracted significant attention in multimedia annotation. However, most of the multilabel classification methods focus only on the inherent correlations existing among multiple labels and concepts and ignore the relevance between features and the target concepts. To obtain more robust multilabel classification results, we propose a new multilabel classification method aiming to capture the correlations among multiple concepts by leveraging hypergraph that is proved to be beneficial for relational learning. Moreover, we consider mining feature-concept relevance, which is often overlooked by many multilabel learning algorithms. To better show the feature-concept relevance, we impose a sparsity constraint on the proposed method. We compare the proposed method with several other multilabel classification methods and evaluate the classification performance by mean average precision on several data sets. The experimental results show that the proposed method outperforms the state-of-the-art methods.
ZpdN, a Plasmid-Encoded Sigma Factor Homolog, Induces pBS32-Dependent Cell Death in Bacillus subtilis

ABSTRACT The ancestral Bacillus subtilis strain 3610 contains an 84-kb plasmid called pBS32 that was lost during domestication of commonly used laboratory derivatives. Here we demonstrate that pBS32, normally present at 1 or 2 copies per cell, increases in copy number nearly 100-fold when cells are treated with the DNA-damaging agent mitomycin C. Mitomycin C treatment also caused cell lysis dependent on pBS32-borne prophage genes. ZpdN, a sigma factor homolog encoded by pBS32, was required for the plasmid response to DNA damage, and artificial expression of ZpdN was sufficient to induce pBS32 hyperreplication and cell death. Plasmid DNA released by cell death was protected by the capsid protein ZpbH, suggesting that the plasmid was packaged into a phagelike particle. The putative particles were further indicated by CsCl sedimentation but were not observed by electron microscopy and were incapable of killing B. subtilis cells extracellularly. We hypothesize that pBS32-mediated cell death releases a phagelike particle that is defective and unstable. IMPORTANCE Prophages are phage genomes stably integrated into the host bacterium's chromosome and less frequently are maintained as extrachromosomal plasmids. Here we report that the extrachromosomal plasmid pBS32 of Bacillus subtilis encodes a prophage that, when activated, kills the host. pBS32 also encodes both the sigma factor homolog ZpdN that is necessary and sufficient for prophage induction and the protein ComI, which is a potent inhibitor of DNA uptake by natural transformation. We provide evidence that the entire pBS32 sequence may be part of the prophage and thus that competence inhibition may be linked to lysogeny.
Self-reported Concussion History and Sensorimotor Tests Predict Head/Neck Injuries

Purpose Sport-related concussion (SRC) is a risk for players involved in high-impact, collision sports. A history of SRC is a risk factor for future concussions, but the mechanisms underlying this are unknown. Despite evidence that most visible signs and symptoms associated with sports concussion resolve within 7–10 d, it has been proposed that subclinical loss of neuromuscular control and impaired motor functioning may persist and be associated with further injury. Alternatively, indicators of poor sensorimotor performance could be independent risk factors. This study investigated if a history of SRC and/or preseason sensorimotor performance predicted season head/neck injuries. Methods A total of 190 male rugby league, rugby union, and Australian Football League players participated. Preseason assessments included self-report of SRC within the previous 12 months and a suite of measures of sensorimotor function (balance, vestibular function, cervical proprioception, and trunk muscle function). Head/neck injury data were collected in the playing season. Results Forty-seven players (25%) reported a history of SRC. A history of concussion was related to changes in size and contraction of trunk muscles. Twenty-two (11.6%) players sustained a head/neck injury during the playing season, of which, 14 (63.6%) players had a history of SRC. Predictors of in-season head/neck injuries included history of SRC, trunk muscle function, and cervical proprioceptive errors. Five risk factors were identified, and players with three or more of these had 14 times greater risk of sustaining a season neck/head injury (sensitivity of 75% and specificity of 82.5%) than did players with two or fewer risk factors. Conclusions The modifiable risk factors identified could be used to screen football players in the preseason and guide the development of exercise programs aimed at injury reduction.
Combustion synthesis and luminescence characteristic of rare earth activated LiCaBO_3

Lithium calcium borate (LiCaBO3) polycrystalline thermoluminescence (TL) phosphor doped with rare earth (Tb3+ and Dy3+) elements was synthesized by novel solution combustion synthesis. The reaction produced very stable crystalline LiCaBO3:D(D=Tb3+ and Dy3+) phosphors. These rare earth doped phosphors material showed maximum TL sensitivity with favorable glow curve shape. TL glow curve of X-ray irradiated that LiCaBO3:Tb3+ and LiCaBO3:Dy3+ samples showed two major well-separated glow peaks. The TL sensitivity of these phosphors to X-ray radiation was comparable with that of TLD-100(Harshaw). Photoluminescence spectra of LiCaBO3:Tb3+ and LiCaBO3:Dy3+ showed the characteristic Tb3+ and Dy3+ peaks respectively. TL response to X-ray radiation dose was linear up to 25 Gy.
Fundamentals of Polymer-Clay Nanocomposites

Written for graduate students, researchers, and practitioners, Fundamentals of Polymer–Clay Nanocomposites provides a complete introduction to the science, engineering, and commercial applications of this new class of material. Starting with a discussion of general concepts, the authors define in detail the specific terms used in the field, providing newcomers with a strong foundation in the area. Then, the physical and mechanical properties of polymer–clay nanocomposites are described, with chapters on thermodynamics and kinetics, engineering properties, barrier properties, and flame retardancy. Mechanisms underpinning observed effects, such as UV resistance, solvent resistance, and hardness, are also explained. Throughout each chapter, experimental results are combined with theory, ensuring that the reader gains a full appreciation of the subject matter. In-depth discussions of clay and clay surface treatment, fabrication, and characterization of nanocomposites are provided, and particular emphasis is placed on the proper use and interpretation of analytical techniques, helping the reader to avoid artifacts in their own work. With commercial applications discussed throughout, this is an ideal reference for those working in polymer science.
The effect of intra-articular hyaluronate and tramadol injection on patients with adhesive capsulitis of the shoulder

BACKGROUND: Local administration of opioids causes effective analgesia without adverse effects related to the central nervous system. After the beneficial demonstration of peripheral opioid receptors in joint synovia, intra-articular opioid injections were used for pain treatment. Clinical studies have reported the safety and efficacy of hyaluronate injection in the shoulder joint of patients with osteoarthritis, periarthritis, rotator cuff tears, and adhesive capsulitis. OBJECTIVES: To estimate the efficacy of intra-articular hyaluronate and tramadol injection for adhesive capsulitis of the shoulder compared with that of intra-articular hyaluronate injection alone. METHODS: Thirty patients with adhesive capsulitis of the shoulder were randomized to the hyaluronate group (n= 16) or the tramadol group (n= 14). Hyaluronate group members were administered five weekly intra-articular hyaluronate injections; tramadol group members were administered three weekly intra-articular hyaluronate and tramadol injections and then two weekly intra-articular injections of hyaluronate. Visual Analog Scale (VAS), passive range of motion (PROM) of the shoulder joint, and Shoulder Pain and Disability Index (SPADI) scores were assessed at baseline and weeks 1, 2, 3, 4, and 6 after the initial injection. RESULTS: A significant improvement was observed in VAS, PROM, and SPADI scores between time points in both groups. In comparison in both groups at weeks 1 and 2 after the initial injection the VAS scores of the tramadol group were significantly lower than those of the hyaluronate group. CONCLUSIONS: Intra-articular hyaluronate with tramadol showed more rapid and strong analgesic effects than intra-articular hyaluronate alone and did not induce any adverse effects.
Entry of Bluetongue Virus Capsid Requires the Late Endosome-specific Lipid Lysobisphosphatidic Acid*

The entry of viruses into host cells is one of the key processes of infection. The mechanisms of cellular entry for enveloped virus have been well studied. The fusion proteins as well as the facilitating cellular lipid factors involved in the viral fusion entry process have been well characterized. The process of non-enveloped virus cell entry, in comparison, remains poorly defined, particularly for large complex capsid viruses of the family Reoviridae, which comprises a range of mammalian pathogens. These viruses enter cells without the aid of a limiting membrane and thus cannot fuse with host cell membranes to enter cells. Instead, these viruses are believed to penetrate membranes of the host cell during endocytosis. However, the molecular mechanism of this process is largely undefined. Here we show, utilizing an in vitro liposome penetration assay and cell biology, that bluetongue virus (BTV), an archetypal member of the Reoviridae, utilizes the late endosome-specific lipid lysobisphosphatidic acid for productive membrane penetration and viral entry. Further, we provide preliminary evidence that lipid lysobisphosphatidic acid facilitates pore expansion during membrane penetration, suggesting a mechanism for lipid factor requirement of BTV. This finding indicates that despite the lack of a membrane envelope, the entry process of BTV is similar in specific lipid requirements to enveloped viruses that enter cells through the late endosome. These results are the first, to our knowledge, to demonstrate that a large non-enveloped virus of the Reoviridae has specific lipid requirements for membrane penetration and host cell entry.
Approximating Fair Queueing on Reconfigurable Switches

Congestion control today is predominantly achieved via end-to-end mechanisms with little support from the network. As a result, end-hosts must cooperate to achieve optimal throughput and fairness, leading to inefficiencies and poor performance isolation. While router mechanisms such as Fair Queuing guarantee fair bandwidth allocation to all participants and have proven to be optimal in some respects, they require complex flow classification, buffer allocation, and scheduling on a per-packet basis. These factors make them expensive to implement in high-speed switches. In this paper, we use emerging reconfigurable switches to develop an approximate form of Fair Queueing that operates at line-rate. We leverage configurable perpacket processing and the ability to maintain mutable state inside switches to achieve fair bandwidth allocation across all traversing flows. Further, present our design for a new dequeuing scheduler, called Rotating Strict Priority scheduler that lets us transmit packets from multiple queues in approximate sorted order. Our hardware emulation and software simulations on a large leafspine topology show that our scheme closely approximates ideal Fair Queueing, improving the average flow completion times for short flows by 2-4x and 99th tail latency by 4-8x relative to TCP and DCTCP.
Designability, thermodynamic stability, and dynamics in protein folding: A lattice model study

In the framework of a lattice-model study of protein folding, we investigate the interplay between designability, thermodynamic stability, and kinetics. To be “protein-like,” heteropolymers must be thermodynamically stable, stable against mutating the amino-acid sequence, and must be fast folders. We find two criteria which, together, guarantee that a sequence will be “protein like:” (i) the ground state is a highly designable structure, i.e., the native structure is the ground state of a large number of sequences, and (ii) the sequence has a large Δ/Γ ratio, Δ being the average energy separation between the ground state and the excited compact conformations, and Γ the dispersion in energy of excited compact conformations. These two criteria are not incompatible since, on average, sequences whose ground states are highly designable structures have large Δ/Γ values. These two criteria require knowledge only of the compact-state spectrum. These claims are substantiated by the study of 45 sequences, with various values of Δ/Γ and various degrees of designability, by means of a Borst–Kalos–Lebowitz algorithm, and the Ferrenberg–Swendsen histogram optimization method. Finally, we report on the reasons for slow folding. A comparison between a very slow folding sequence, an average folding one, and a fast folding one, suggests that slow folding originates from a proliferation of nearly compact low-energy conformations, not present for fast folders.
Phosphatase PP2A and microtubule-mediated pulling forces disassemble centrosomes during mitotic exit

ABSTRACT Centrosomes are microtubule-nucleating organelles that facilitate chromosome segregation and cell division in metazoans. Centrosomes comprise centrioles that organize a micron-scale mass of protein called pericentriolar material (PCM) from which microtubules nucleate. During each cell cycle, PCM accumulates around centrioles through phosphorylation-mediated assembly of PCM scaffold proteins. During mitotic exit, PCM swiftly disassembles by an unknown mechanism. Here, we used Caenorhabditis elegans embryos to determine the mechanism and importance of PCM disassembly in dividing cells. We found that the phosphatase PP2A and its regulatory subunit SUR-6 (PP2ASUR-6), together with cortically directed microtubule pulling forces, actively disassemble PCM. In embryos depleted of these activities, ∼25% of PCM persisted from one cell cycle into the next. Purified PP2ASUR-6 could dephosphorylate the major PCM scaffold protein SPD-5 in vitro. Our data suggest that PCM disassembly occurs through a combination of dephosphorylation of PCM components and force-driven fragmentation of the PCM scaffold. Summary: Centrosomes acquire and lose pericentriolar material during each cell cycle. We show that dephosphorylation and cortically directed forces disassemble pericentriolar material at the end of mitosis.
Efficient Synchronization of State-Based CRDTs

To ensure high availability in large scale distributed systems, Conflict-free Replicated Data Types (CRDTs) relax consistency by allowing immediate query and update operations at the local replica, with no need for remote synchronization. State-based CRDTs synchronize replicas by periodically sending their full state to other replicas, which can become extremely costly as the CRDT state grows. Delta-based CRDTs address this problem by producing small incremental states (deltas) to be used in synchronization instead of the full state. However, current synchronization algorithms for delta-based CRDTs induce redundant wasteful delta propagation, performing worse than expected, and surprisingly, no better than state-based. In this paper we: 1) identify two sources of inefficiency in current synchronization algorithms for delta-based CRDTs; 2) bring the concept of join decomposition to state-based CRDTs; 3) exploit join decompositions to obtain optimal deltas and 4) improve the efficiency of synchronization algorithms; and finally, 5) experimentally evaluate the improved algorithms.
Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations

Epidemiological studies and experimental models show that maternal nutritional constraint during pregnancy alters the metabolic phenotype of the offspring and that this can be passed to subsequent generations. In the rat, induction of an altered metabolic phenotype in the liver of the F1 generation by feeding a protein-restricted diet (PRD) during pregnancy involves the altered methylation of specific gene promoters. We therefore investigated whether the altered methylation of PPARα and glucocorticoid receptor (GR) promoters was passed to the F2 generation. Females rats (F0) were fed a reference diet (180 g/kg protein) or PRD (90 g/kg protein) throughout gestation, and AIN-76A during lactation. The F1 offspring were weaned onto AIN-76A. F1 females were mated and fed AIN-76A throughout pregnancy and lactation. F1 and F2 males were killed on postnatal day 80. Hepatic PPARα and GR promoter methylation was significantly (P < 0·05) lower in the PRD group in the F1 (PPARα 8 %, GR 10 %) and F2 (PPARα 11 %, GR 8 %) generations. There were trends (P < 0·1) towards a higher expression of PPARα, GR, acyl-CoA oxidase and phosphoenolpyruvate carboxykinase (PEPCK) in the F1 and F2 males, although this was significant only for PEPCK. These data show for the first time that the altered methylation of gene promoters induced in the F1 generation by maternal protein restriction during pregnancy is transmitted to the F2 generation. This may represent a mechanism for the transmission of induced phenotypes between generations.
CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed Multiple Myeloma

C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival. ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive. CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.