Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted Chemotherapy for Head and Neck Cancer with a Chimeric Oncolytic Adenovirus Coding for Bifunctional Suicide Protein FCU1

Purpose: Transfer of prodrug activation systems into tumors by using replication-deficient viruses has been suggested to be an effective method for achieving high local and low systemic anticancer drug concentrations. However, most current suicide gene therapy strategies are still hindered by poor efficiency of in vivo gene transfer, inefficient tumor penetration, limited bystander cell killing effect, and need of large prodrug doses. We hypothesized that local amplification provided by a replication competent platform would help overcome these limitations. Experimental Design: We generated a transductionally and transcriptionally targeted oncolytic adenovirus Ad5/3-Δ24FCU1 expressing the fusion suicide gene FCU1. FCU1 encodes a bifunctional fusion protein that efficiently catalyzes the direct conversion of 5-FC, a relatively nontoxic antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine monophosphate, bypassing the natural resistance of certain human tumor cells to 5-fluorouracil. Results: We examined the efficacy of Ad5/3-Δ24FCU1 and the replication-defective control Ad5/3-FCU1 with and without 5-FC. FCU1 expression was confirmed by Western blot, whereas enzymatic conversion levels in vitro and in vivo were determined by high-performance liquid chromatography separation. Significant antitumor effect was observed in vitro and in vivo in a murine model of head and neck squamous cell carcinoma. Although we observed a decrease in viral DNA copy number in vitro and in tumors treated with Ad5/3-Δ24FCU1 and 5-FC, suggesting an effect on virus replication, the highest antitumor effect was observed for this combination. Conclusions: It seems feasible and efficacious to combine adenovirus replication to the FCU1 prodrug activation system. Clin Cancer Res; 16(9); 2540–9. ©2010 AACR.
Depression and associated physical diseases and symptoms

Depression can occur in association with virtually all the other psychiatric and physical diagnoses. Physical illness increases the risk of developing severe depressive illness. There are two broadly different mechanisms. The most obvious has a psychological or cognitive mechanism. Thus, the illness may provide the life event or chronic difficulty that triggers a depressive episode in a vulnerable Individual. Secondly more specific associations appear to exist between depression and particular physical disorders. These may turn out to be of particular etiological interest. The best examples are probably stroke and cardiovascular disease. Finally major depression, but especially minor depression, dysthymia, and depressive symptoms merge with other manifestations of human distress with which patients present to their doctors, Such somatic presentations test the conventional distinction between physical and mental disorder, and are a perennial source of controversy.
Sequential shear-wave elastography of liver and spleen rules out clinically significant portal hypertension in compensated advanced chronic liver disease

With interest we read the letter entitled ‘Ruling in and ruling out with elastography in compensated advanced chronic liver disease’ by Agustin et al 1 to our study ‘Algorithm to rule-out clinically significant portal hypertension combining Shear-wave elastography of liver and spleen: a prospective multi-centre study’. 2 Indeed, we would like to thank our colleagues for their interest in our study and deciphering the strengths and weaknesses of this study. Besides acknowledging the merits of the study, the colleagues commented on the selection of patients regarding severity and aetiology of advanced chronic liver disease (ACLD), as well as the clinical importance of ruling out or ruling in clinically significant portal hypertension (CSPH). The criticism about the selection of patients stimulated us to perform new calculations. Even though the algorithm was calculated including patients with decompensated ACLD (dACLD), it performed much better in …
Nanoreinforcement of Pectin Film to Enhance its Functional Packaging Properties by Incorporating ZnO Nanoparticles

The main objective of this study was to enhance functional packaging properties of pectin film by using zinc oxide nanoparticles (ZnO-NPs) as nanoreinforcing agent. Pectin/ZnO bio-nanocomposite films were fabricated at 4 levels of ZnO-NPs, i.e., 0.5, 1.0, 2.0 and 5.0% (w/w). The effects of ZnO-NPs incorporation on improving the mechanical properties and water resistance of the films were investigated. ZnO-NPs were successfully incorporated into pectin films by nanodispersion technique followed by casting method. The presence of ZnO-NPs inside pectin films was observed clearly by SEM. The improvement in tensile strength could be achieved with ZnO-NPs incorporation without obvious loss in elasticity. Potential antimicrobial activity of pectin-ZnO nanocomposite films was proved in the absence of mold after exposing them at 97% RH and room temperature for 14 days, whereas the growth of mold had been observed in pure pectin film after 3 days of exposure. In terms of film transparency, the significant change in film opacity was only found in the film prepared with 5% of ZnO. Results suggested that it would be favorable to prepare pectin/ZnO nanocomposite film by using ZnO-NPs at the amount of 2% (w/w) in the future work.
The receiver domain of FrzE, a CheA–CheY fusion protein, regulates the CheA histidine kinase activity and downstream signalling to the A‐ and S‐motility systems of Myxococcus xanthus

The Frz chemosensory system is a two‐component signal transduction pathway that controls cell reversals and directional movements for the two motility systems in Myxococcus xanthus. To trigger cell reversals, FrzE, a hybrid CheA–CheY fusion protein, autophosphorylates the kinase domain at His‐49, and phosphoryl groups are transferred to aspartate residues (Asp‐52 and Asp‐220) in the two receiver domains of FrzZ, a dual CheY‐like protein that serves as the pathway output. The role of the receiver domain of FrzE was unknown. In this paper, we characterize the FrzE protein in vitro and show that the receiver domain of FrzE negatively regulates the autophosphorylation activity of the kinase domain of FrzE. Unexpectedly, it does not appear to play a direct role in phospho‐relay as in most other histidine kinase receiver domain hybrid systems. The regulatory role of the FrzE receiver domain suggests that it may interact with or be phosphorylated by an unknown protein. We also show the dynamics of motility system‐specific marker proteins in FrzE mutants as cells move forward and reverse. Our studies indicate that the two motility systems are functionally co‐ordinated and that any system‐specific branching of the pathway most likely occurs downstream of FrzE.
Hyaluronan Breakdown Contributes to Immune Defense against Group A Streptococcus*

Background: The role of hyaluronan catabolism in group A Streptococcus (GAS) infection has not been studied. Results: Hyaluronan size differentially influenced GAS infection in vitro and in mice. Conclusion: Digestion of hyaluronan derived from either the bacterium or host enhances host immune defense. Significance: Digestion of hyaluronan during GAS infection may be a previously unrecognized mechanism for host defense. Group A Streptococcus (GAS) commonly infects human skin and occasionally causes severe and life-threatening invasive diseases. The hyaluronan (HA) capsule of GAS has been proposed to protect GAS from host defense by mimicking endogenous HA, a large and abundant glycosaminoglycan in the skin. However, HA is degraded during tissue injury, and the functions of short-chain HA that is generated during infection have not been studied. To examine the impact of the molecular mass of HA on GAS infection, we established infection models in vitro and in vivo in which the size of HA was defined by enzymatic digestion or custom synthesis. We discovered that conversion of high molecular mass HA to low molecular mass HA facilitated GAS phagocytosis by macrophages and limited the severity of infection in mice. In contrast, native high molecular mass HA significantly impaired internalization by macrophages and increased GAS survival in murine blood. Thus, our data demonstrate that GAS virulence can be influenced by the size of HA derived from both the bacterium and host and suggest that high molecular mass HA facilitates GAS deep tissue infections, whereas the generation of short-chain HA can be protective.
The characterization of classification problems by classifier disagreements

In this paper we try to characterize a set of classification problems. For this, we use the disagreement between a set of standard classifiers. The disagreement patterns do not only point towards different types of classification problems, but also indicate the novelty and the usefulness of a classifier with respect to a set of classification problems and classifiers. Some experiments show when known classification problems become unknown after changing their feature size or their training set size.
Underlying mechanisms of tinnitus: review and clinical implications.

BACKGROUND The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus. PURPOSE The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus. RESULTS It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems. CONCLUSIONS Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions.
Dimerization and thiol sensitivity of the salicylic acid binding thimet oligopeptidases TOP1 and TOP2 define their functions in redox-sensitive cellular pathways

A long-term goal in plant research is to understand how plants integrate signals from multiple environmental stressors. The importance of salicylic acid (SA) in plant response to biotic and abiotic stress is known, yet the molecular details of the SA-mediated pathways are insufficiently understood. Our recent work identified the peptidases TOP1 and TOP2 as critical components in plant response to pathogens and programmed cell death (PCD). In this study, we investigated the characteristics of TOPs related to the regulation of their enzymatic activity and function in oxidative stress response. We determined that TOP1 and TOP2 interact with themselves and each other and their ability to associate in dimers is influenced by SA and the thiol-based reductant DTT. Biochemical characterization of TOP1 and TOP2 indicated distinct sensitivities to DTT and similarly robust activity under a range of pH values. Treatments of top mutants with Methyl Viologen (MV) revealed TOP1 and TOP2 as a modulators of the plant tolerance to MV, and that exogenous SA alleviates the toxicity of MV in top background. Finally, we generated a TOP-centered computational model of a plant cell whose simulation outputs replicate experimental findings and predict novel functions of TOP1 and TOP2. Altogether, our work indicates that TOP1 and TOP2 mediate plant responses to oxidative stress through spatially separated pathways and positions proteolysis in a network for plant response to diverse stressors.
Envelope Protein Glycosylation Status Influences Mouse Neuroinvasion Phenotype of Genetic Lineage 1 West Nile Virus Strains

ABSTRACT The introduction of West Nile virus (WNV) into North America has been associated with relatively high rates of neurological disease and death in humans, birds, horses, and some other animals. Previous studies identified strains in both genetic lineage 1 and genetic lineage 2, including North American isolates of lineage 1, that were highly virulent in a mouse neuroinvasion model, while other strains were avirulent or significantly attenuated (D. W. C. Beasley, L. Li, M. T. Suderman, and A. D. T. Barrett, Virology 296:17-23, 2002). To begin to elucidate the basis for these differences, we compared a highly virulent New York 1999 (NY99) isolate with a related Old World lineage 1 strain, An4766 (ETH76a), which is attenuated for mouse neuroinvasion. Genomic sequencing of ETH76a revealed a relatively small number of nucleotide (5.1%) and amino acid (0.6%) differences compared with NY99. These differences were located throughout the genome and included five amino acid differences in the envelope protein gene. Substitution of premembrane and envelope genes of ETH76a into a NY99 infectious clone backbone yielded a virus with altered in vitro growth characteristics and a mouse virulence phenotype comparable to ETH76a. Further site-specific mutagenesis studies revealed that the altered phenotype was primarily mediated via loss of envelope protein glycosylation and that this was associated with altered stability of the virion at mildly acidic pH. Therefore, the enhanced virulence of North American WNV strains compared with other Old World lineage 1 strains is at least partly mediated by envelope protein glycosylation.
Feature-Based Registration of Retinal Images

Registration of retinal images taken at different times frequently is required to measure changes caused by disease or to document retinal location of visual stimuli. Cross-correlation has been used previously for such registration, but it is computationally intensive. We have modified a faster algorithm, sequential similarity detection (SSD), to use only the portion of the template that contains retinal vessels. When compared to standard SSD and cross-correlation, this modification improves the reliability of detection for a variety of retinal imaging modalities. The improved reliability enables implementation of a two-stage registration strategy that further decreases the amount of computation and increases the speed of registration.
Enterohemorrhagic Escherichia coli O157: epidemiology and ecology in bovine production environments

Abstract Enterohemorrhagic Escherichia coli, particularly the O157(:H7) serogroup, has become a worldwide public health concern. Since cattle feces are often implicated as the source of E. coli O157 in human infections, considerable resources have been devoted to defining the epidemiology and ecology of E. coli O157 in cattle environments so that control might begin at the farm level. Diagnostic limitations and the complexity of often interrelated microbial, animal, herd, environmental and production factors have hindered the determination of the epidemiology, ecology and subsequent farm-level control of E. coli O157. The widespread distribution of E. coli O157, the transitory nature of fecal shedding, multiple potential environmental sources, lack of species specificity, and age-, feed- and time-related differences in cattle prevalence are documented. However, the significance and/or role of these factors in the epidemiology and ecology of E. coli O157 is still unclear. Cattle are a major source of E. coli O157, but it may be simplistic to believe that most herds are relatively closed systems with small percentages of cattle serving as true reservoirs. Practical on-farm control may require explicit definitions of the seemingly complex system(s) and the microbial, animal, herd, environmental and production factors involved in the multiplication, maintenance and transmission of E. coli O157.
Sipuleucel-T immunotherapy for castration-resistant prostate cancer. A systematic review and meta-analysis

Introduction Sipuleucel-T is a novel active cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC). It is assumed to be associated with less adverse events than conventional docetaxel-based chemotherapy. Material and methods A systematic review of literature published between January, 1 1966 and February, 6 2012 was performed to assess the efficacy and safety of sipuleucel-T in patients with mCRPC. Databases were searched: Medline, EMBASE, Cochrane, CancerLit as well as ASCO and ESCO websites. Results Three randomized clinical trials with a total of 737 participants fulfilled established criteria. The overall survival of patients who received sipuleucel-T in comparison to the control group was significantly longer with a hazard ratio (HR) of 0.73 (95% CI: 0.61-0.88; p = 0.001). Time to disease progression was not prolonged using sipuleucel-T compared to placebo, HR = 0.89 (95% CI: 0.75-1.05; p = 0.18). Relative benefit (RB) of serum PSA level reduction of at least 50% for sipuleucel-T compared to placebo did not meet statistical significance, RB = 1.97 (95% CI: 0.48-8.14; p = 0.38). The safety population consisted of 729 patients with mCRPC. Compared to the control group, the pooled relative risks (RR) of all adverse events – RR = 1.03 (95% CI: 1.00-1.05; p = 0.06), grade 3 to 5 adverse events – RR = 0.98 (95% CI: 0.79-1.22; p = 0.86) and cerebrovascular events – RR = 1.93 (95% CI: 0.73-5.09; p = 0.18) were not significantly higher for men treated with sipuleucel-T. Conclusions The use of sipuleucel-T prolonged the overall survival among men with mCRPC. No effect on time to disease progression was observed and the safety profile was acceptable.
Trapping set enumerators for specific LDPC codes

In this paper, a method is presented for enumerating the trapping sets of a specific LDPC code given its Tanner graph. The technique involves augmenting the original Tanner graph with additional variable nodes, and then applying a weight-enumeration algorithm to the augmented Tanner graph. The proposed method is used to find trapping set enumerators for several LDPC codes in communication standards. The complexity of the proposed algorithm is discussed.
First-principles study of ring to cage structural crossover in small ZnO Clusters

Density functional, full-potential computations are performed to study the origin and consequences of the ring to cage structural crossover in (ZnO)n (n = 2–16) clusters. The origin of this structural crossover, which is found to occur at n = 10, is studied by investigating the behavior of the Zn–O–Zn bond angle, the Zn–O bond strength, and the number of bonds in the systems. It is argued that 12 is the lowest magic number of ZnO clusters in the ground state, while finite temperature vibrational excitations enhance the relative stability of the (ZnO)9 cluster to make it a magic system at temperatures above about 170 K. The obtained electronic structure of the clusters before and after applying the many-body GW corrections evidence a size-induced redshift originating from the ring to cage structural crossover in the system. The behavior of the electron density bond points of the clusters along with the extrapolated cluster binding energy at very large sizes may indicate the existence of a metastable structure for large ZnO nanostructures, different from the bulk ZnO structure.
Primary health care assessment by users with and without disabilities

Accepted: November 09, 2017 Study conducted at the Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional, Faculdade de Medicina, Universidade de São Paulo – USP São Paulo (SP), Brazil. 1 Universidade de São Paulo – USP São Paulo (SP) Brazil. Financial support: Edital PPSUS 2013 FAPESP 2014/50012-8 and Programa de Educação pelo Trabalho na Saúde-Redes de Atenção (PET/Redes 2013-2015). Conflict of interests: nothing to declare. ABSTRACT
The complete chloroplast genome sequence of the relict woody plant Metasequoia glyptostroboides Hu et Cheng

Metasequoia glyptostroboides Hu et Cheng is the only species in the genus Metasequoia Miki ex Hu et Cheng, which belongs to the Cupressaceae family. There were around 10 species in the Metasequoia genus, which were widely spread across the Northern Hemisphere during the Cretaceous of the Mesozoic and in the Cenozoic. M. glyptostroboides is the only remaining representative of this genus. Here, we report the complete chloroplast (cp) genome sequence and the cp genomic features of M. glyptostroboides. The M. glyptostroboides cp genome is 131,887 bp in length, with a total of 117 genes comprised of 82 protein-coding genes, 31 tRNA genes and four rRNA genes. In this genome, 11 forward repeats, nine palindromic repeats, and 15 tandem repeats were detected. A total of 188 perfect microsatellites were detected through simple sequence repeat (SSR) analysis and these were distributed unevenly within the cp genome. Comparison of the cp genome structure and gene order to those of several other land plants indicated that a copy of the inverted repeat (IR) region, which was found to be IR region A (IRA), was lost in the M. glyptostroboides cp genome. The five most divergent and five most conserved genes were determined and further phylogenetic analysis was performed among plant species, especially for related species in conifers. Finally, phylogenetic analysis demonstrated that M. glyptostroboides is a sister species to Cryptomeria japonica (L. F.) D. Don and to Taiwania cryptomerioides Hayata. The complete cp genome sequence information of M. glyptostroboides will be great helpful for further investigations of this endemic relict woody plant and for in-depth understanding of the evolutionary history of the coniferous cp genomes, especially for the position of M. glyptostroboides in plant systematics and evolution.
Reoptimizing Data Parallel Computing

Performant execution of data-parallel jobs needs good execution plans. Certain properties of the code, the data, and the interaction between them are crucial to generate these plans. Yet, these properties are difficult to estimate due to the highly distributed nature of these frameworks, the freedom that allows users to specify arbitrary code as operations on the data, and since jobs in modern clusters have evolved beyond single map and reduce phases to logical graphs of operations. Using fixed apriori estimates of these properties to choose execution plans, as modern systems do, leads to poor performance in several instances. We present RoPE, a first step towards re-optimizing data-parallel jobs. RoPE collects certain code and data properties by piggybacking on job execution. It adapts execution plans by feeding these properties to a query optimizer. We show how this improves the future invocations of the same (and similar) jobs and characterize the scenarios of benefit. Experiments on Bing's production clusters show up to 2× improvement across response time for production jobs at the 75th percentile while using 1.5× fewer resources.