Miracle-dz/UniFAR-FTUs huggingface dataset:
Rectal Immunization with Rotavirus Virus-Like Particles Induces Systemic and Mucosal Humoral Immune Responses and Protects Mice against Rotavirus Infection

ABSTRACT To evaluate whether the rectal route of immunization may be used to provide appropriate protection against enteric pathogens such as rotaviruses (RV), we studied the antibody response and the protection induced by rectal immunization of mice with RV virus-like particles (VLP). For this purpose, 6-week-old BALBc mice were rectally immunized twice with RV 8-2/6/7-VLP derived from the bovine RV RF81 strain either alone or combined with various adjuvants including four toxins [cholera toxin (CT) and three attenuated Escherichia coli-derived heat-labile toxins (LTs), LT(R192G), LT(R72), and LT(K63)] and two Toll-like receptor-targeting adjuvants (CpG and resiquimod). Six weeks after the second immunization, mice were challenged with murine RV strain ECw. RV VLP administered alone were not immunogenic and did not protect mice against RV challenge. By contrast, RV VLP combined with any of the toxin adjuvants were immunogenic (mice developed significant titers of anti-RV immunoglobulin A [IgA] in both serum and feces and of anti-RV IgG in serum) and either efficiently induced complete protection of the mice (no detectable fecal virus shedding) or, for LT(K63), reduced the amount of fecal virus shedding after RV challenge. When combined with RV VLP, CpG and resiquimod failed to achieve protection, although CpG efficiently induced an antibody response to RV. These results support the consideration of the rectal route for the development of new immunization strategies against RV infection. Rectal delivery of a VLP-based vaccine might allow the use of adjuvants less toxic than, but as efficient as, CT.
Mechanical Stretching Stimulates Smooth Muscle Cell Growth, Nuclear Protein Import, and Nuclear Pore Expression through Mitogen-activated Protein Kinase Activation*

Although it is known that mechanical stretching of cells can induce significant increases in cell growth and shape, the intracellular signaling pathways that induce this response at the level of the cell nucleus is unknown. The transport of molecules from the cell cytoplasm to the nucleoplasm through the nuclear pore is a key pathway through which gene expression can be controlled in some conditions. It is presently unknown if mechanical stimuli can induce changes in nuclear pore expression and/or function. The purpose of the present investigation was to determine if mechanical stretching of a cell will alter nuclear protein import and the mechanisms that may be responsible. Vascular smooth muscle cells that were mechanically stretched exhibited an increase in proliferating cell nuclear antigen expression, cell number, and cell size within 24–48 h. Cells were microinjected with marker proteins for nuclear import. Nuclear protein import was significantly stimulated in stretched cells when compared with control. This was associated with an increase in the expression of nuclear pore proteins as detected by Western blots. Inhibition of the MAPK pathway blocked the stretch-induced stimulation of both cell proliferation and nuclear protein import. We conclude that nuclear protein import and nuclear pore density can adapt to mechanical stimuli during the process of cell growth through a MAPK-mediated mechanism.
Visual Attention in Children with Perinatal Brain Injury: Asymmetric Effects of Bilateral Lesions

The neural systems underlying visual attention have been well-documented in adults through studies examining the effects of brain lesions on specific attentional operations (Posner, Cohen, & Rafal, 1982). The questions of how this attentional system develops and how it is affected by disruption during development are only beginning to be addressed. In the present study, a covert orienting task (Posner et al., 1982) was administered to 33 children with bilateral perinatal injury to anterior, posterior, or diffuse brain regions and 36 normal children to determine the effects of such injury on visual attention. Children with bilateral anterior lesions showed lateralized impairment indicating compromise of left hemisphere early attentional processes. In contrast, children with posterior lesions that typically disrupt attention in adults showed only general slowing, with no differences in right or left visual field performance or deficits in specific attentional operations. These results suggest that anterior brain regions play an important role in the development of visual attention, and that left hemisphere attentional processes are particularly affected by disruption of anterior function.
ANALYSIS OF LOSSLESS REVERSIBLE TRANSFORMATION ALGORITHMS TO ENHANCE DATA COMPRESSION

In this paper we analyze and present the benefits offered in the lossless compression by applying a choice of preprocessing methods that exploits the advantage of redundancy of the source file. Textual data holds a number of properties that can be taken into account in order to improve compression. Pre-processing cope up with these properties by applying a number of transformations that make the redundancy “more visible” to the compressor. Many pre-processing algorithms come into being for text files which complement each other and are performed prior to actual compression. Here our focus is on the Length-Index Preserving Transform (LIPT), its derivatives ILPT, NIT & LIT and StarNT Transformation algorithm. The algorithms are briefly presented before calling attention to their analysis
Direct synovial gene transfer with retroviral vectors in rat adjuvant arthritis.

OBJECTIVE To evaluate the feasibility of direct in vivo gene transfer in an animal model of arthritis using a retroviral vector. METHODS The timing and dose of retroviral vector was examined using very high titer retroviral vector (> or = 10(9) CFU) in rat adjuvant arthritis. Retroviral vector expressing beta-galactosidase (beta-gal) or vehicle alone was injected into the right ankle of rats with adjuvant arthritis. Ankles were injected either on Day 7 (pre-arthritis), Day 10 (early arthritis), Day 15 (accelerating arthritis), or Day 28 (chronic arthritis) after adjuvant immunization. Joints were harvested 3 days later and extracts were assayed for beta-gal activity. RESULTS Synovial beta-gal expression was minimal in the Day 7 group and elevated in the Day 10, Day 15, and Day 28 groups. Gene transfer with retroviral vector did not exacerbate the local inflammatory response. Minimal or no beta-gal expression was observed in the contralateral uninjected paw or in the spleen, lung, liver, and kidneys. Frozen sections of retroviral vector injected joints were stained with X-gal and revealed transduced cells in the lining and superficial sublining layers. To determine the longevity of gene expression, ankle joints were injected with vector on Day 15 post-adjuvant, harvested, and assayed for beta-gal activity for up to 49 days after injection. Expression of the enzyme peaked from Day 3 to 7 and was still readily detected up to 49 days after retrovirus infection. CONCLUSION This is the first report of successful direct in vivo gene transfer in the rat adjuvant arthritis model using a retroviral vector. Appropriate timing of administration and very high titer retroviral vector preparations are key determinants of adequate gene transduction.
A decentralized game theoretic approach for team formation and task assignment by autonomous unmanned aerial vehicles

A number of autonomous unmanned aerial vehicles (UAV) are tasked to search an unknown/uncertain environment, and neutralize targets whenever they come across such threats. Due to resource constraints of the UAVs, neutralizing some threats require simultaneous effort of a certain number of UAVs in minimum. When a UAV detects multiple such targets which require team efforts, it needs to communicate with its neighbour UAVs asking for their cooperation to form colaitions to neutralize the targets. Since the involved entities are dynamic in nature, a UAV may have to terminate information exchange with its neighbours within a few iterative steps so that the decision making process can be finished before any topological change takes place. Moreover, due to sensor range and communication bandwidth limitations, a UAV cannot know about other tasks available to its neighbours in an instantaneous manner. Through communication, UAVs can learn correspondence between their own utilities and utilities of the neighbour UAVs to different joint action profiles, but not the decisions of other UAVs. We formulate the problem that a UAV faces when it detects multiple such targets and needs to decide as to which target it should try to neutralize, given the uncertainty over the decisions of its neighbour UAVs, in a game theoretic framework. We propose a correlated equilibrium concept based decentralized game theoretic solution that requires local information of the UAVs.
Clinical Impact of Vitamin K Dosing on Sorafenib Treatment for Hepatocellular Carcinoma

Background: Some researchers have suggested that vitamin K enhances the antitumor effect of sorafenib for hepatocellular carcinoma (HCC) in vitro and in vivo. In this study, we examined the clinical impact of vitamin K dosing for sorafenib treatment. Methods: Twenty-nine out of 65 patients treated with sorafenib for HCC were simultaneously dosed with vitamin K. We retrospectively investigated progression-free survival (PFS) and overall survival (OS) in the vitamin K-dosed group and sorafenib alone group. We also examined the changes in serum des-γ-carboxy prothrombin (DCP) levels, which vitamin K is involved with. Results: The median PFS was prolonged in the sorafenib + vitamin K group compared with the sorafenib alone group (6.0 months and 2.0 months, respectively; P<0.001, hazard ratio〔HR〕: 0.25). The median OS was also significantly extended (12.5 months vs. 10.0 months; P=0.009, HR: 0.47). Despite suppressed tumor growth, serum DCP levels had increased in cases of disease-controlled patients in the sorafenib alone group 8 weeks after the beginning of treatment, (2.28±0.91 to 2.64±1.03, P= 0.048). In contrast, the serum DCP levels of the sorafenib + vitamin K group had declined both in patients with controlled disease and in patients with progressive disease (1.97±0.57 to 1.29±0.28, P=0.002 and 2.90±1.32 to 1.78±0.53, P=0.034, respectively). Conclusions: To the best of our knowledge, this is the first clinical report showing enhanced antitumor action of sorafenib by vitamin K. Our clinical findings suggest that vitamin K may have the synergistic effect by suppressing production of DCP, a tumor growth and angiogenesis factor.
Animal models as a tool in hepatocellular carcinoma research: A Review

Cancer is the first cause of death in developed countries and the second in developing countries. Concerning the most frequent worldwide-diagnosed cancer, primary liver cancer represents approximately 4% of all new cancer cases diagnosed globally. However, among primary liver cancer, hepatocellular carcinoma is by far the most common histological subtype. Notwithstanding the health promotion and disease prevention campaigns, more than half a million new hepatocellular carcinoma cases are reported yearly, being estimated to growth continuously until 2020. Taking this scenario under consideration and the fact that some aspects concerning hepatocellular carcinoma evolution and metastasize process are still unknown, animal models assume a crucial role to understand this disease. The animal models have also provided the opportunity to screen new therapeutic strategies. The present review was supported on research and review papers aiming the complexity and often neglected chemically induced animal models in hepatocarcinogenesis research. Despite the ongoing debate, chemically induced animal models, namely, mice and rat, can provide unique valuable information on the biotransformation mechanisms against xenobiotics and apprehend the deleterious effects on DNA and cell proteins leading to carcinogenic development. In addition, taking under consideration that no model achieves all hepatocellular carcinoma research purposes, criteria to define the “ideal” animal model, depending on the researchers’ approach, are also discussed in this review.
NMR-based structure of anticancer drug mitoxantrone stacked with terminal base pair of DNA hexamer sequence d-(ATCGAT)2

Mitoxantrone is a promising antitumor drug having considerably reduced cardiotoxicity as compared to anthracyclines. Its binding to deoxyhexanucleotides sequence d-(ATCGAT)2 has been studied by proton and phosphorous-31 nuclear magnetic resonance spectroscopy. The stoichiometry reveals that 1:1 and 2:1 mitoxantrone-d(ATCGAT)2 complexes are formed in solution. Significant upfield shifts in 6H/7H, 2H/3H, 11NH, and 12NH protons (∼.5 ppm) of mitoxantrone and T6NH imino protons (∼.3 ppm) are observed. The phosphorous resonances do not shift significantly indicating that the base pairs do not open at any nucleotide step along the sequence of hexamer. Several inter-molecular Nuclear Overhauser Enhancement connectivities between mitoxantrone and hexanucleotide protons indicate that mitoxantrone chromophore stacks with terminal A1-T6 base pair and side chains involving 12CH2, 12NH, and 14OH protons are in close proximity of A1, T2, A5, and T6 bases. Absorption and emission spectra show red shift in wavelength maxima, which is characteristic of stacking interaction. At higher mitoxantrone to nucleic acid ratios, electrostatic interactions are dominant. The 2:1 drug/DNA stoichiometric structure obtained by restrained Molecular Dynamics simulations shows considerable distortions in backbone torsional angles and helicoidal parameters although structural fluctuations in 25 ps analysis of trajectory are found to be negligible. Mitoxantrone binds as a monomer at either or both ends of hexamer externally with side chains interacting specifically with DNA. The findings are relevant to the understanding of pharmacological action of drug.
Continuous limit of the Nagel-Schreckenberg model.

A generalized version of the Nagel-Schreckenberg model of traffic flow is presented that allows for continuous values of the velocities and spatial coordinates. It is shown that this generalization reveals structures of the dynamics that are masked by the discreteness of the original model and thus helps to clarify the physical interpretation of the dynamics considerably. It is shown numerically that the transition leading from the free flow regime to the congested flow regime bears strong similarities with a first-order phase transition in equilibrium thermodynamics. A similar behavior is observed in more complicated microscopic models and in hydrodynamical descriptions of traffic flow, putting the model within a broader context of other models of traffic flow. An additional advantage of this continuous model is that it is much easier to calibrate with empirical data, only slightly decreasing numerical efficiency. \textcopyright{} 1996 The American Physical Society.
Defining left ventricular hypertrophy in children on peritoneal dialysis.

BACKGROUND AND OBJECTIVES Left ventricular hypertrophy (LVH) is an important end point of dialysis-associated cardiovascular disease. The objective of this study was to evaluate the effect of different pediatric reference systems on the estimated prevalence of LVH in children on chronic peritoneal dialysis (CPD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Echocardiographic studies in 507 pediatric CPD patients from neonatal age to 19 years were collected in 55 pediatric dialysis units around the globe. We compared the prevalence of LVH on the basis of the traditional cutoff of left ventricular mass (LVM) index (>38.5 g/m(2.7)) with three novel definitions of LVH that were recently established in healthy pediatric cohorts. RESULTS Application of the new reference systems eliminated the apparently increased prevalence of LVH in young children obtained by the traditional fixed LVM index cutoff currently still recommended by consensus guidelines. However, substantial differences of LVM distribution between the new reference charts resulted in a marked discrepancy in estimated LVH prevalence ranging between 27.4% and 51.7%. CONCLUSIONS Although our understanding of the anthropometric determinants of heart size during childhood is improving, more consistent normative echocardiographic data from large populations of healthy children are required for cardiovascular diagnostics and research.
Impact of clarification strategy on chromatographic separations: Pre‐processing of cell homogenates

This research focused on how the extent and type of primary solid–liquid separation can affect the performance of guard filtration and chromatography, in this instance hydrophobic interaction chromatography. The system used in the study was yeast (Saccharomyces cerevisiae) with the target molecule being an intracellular protein; alcohol dehydrogenase (ADH). As expected, loading more poorly clarified suspensions (both centrates and primary filtrates) required proportionally larger guard filtration areas. In addition for feed suspensions prepared by centrifugation, increased clarification led to greater column capacity. However, where filtration was used to achieve similar clarification considerably lower column capacity was achieved. These results were attributed to centrifugation leading to the aggregation of lipids and their subsequent removal in this form before application to the column. Clarification by filtration leaves such lipids in their original “soluble” state and hence they are not removed. The importance of the need to examine such interactive effects in bioprocess studies is discussed. This observation was confirmed with further analytical work into the nature of the aggregated material formed in the supernatant under centrifugation conditions. This material was only soluble in an organic solvent, and identified as phophatidylcholine and ergosterol as among the components removed by centrifugation and guard filtration as opposed to filtration and guard filtration. Biotechnol. Bioeng. 2008;100: 941–949. © 2008 Wiley Periodicals, Inc.
Diagnostic Efficiency of an Ability-Focused Battery

An ability-focused battery (AFB) is a selected group of well-validated neuropsychological measures that assess the conventional range of cognitive domains. This study examined the diagnostic efficiency of an AFB for use in clinical decision making with a mixed sample composed of individuals with neurological brain dysfunction and individuals referred for cognitive assessment without evidence of neurological disorders. Using logistic regression analyses and ROC curve analysis, a five-domain model composed of attention, processing speed, visual-spatial reasoning, language/verbal reasoning, and memory domain scores was fitted that had an AUC of.89 (95% CI =.84–.95). A more parsimonious two-domain model using processing speed and memory was also fitted that had an AUC of.90 (95% confidence interval =.84–.95). A model composed of a global ability score calculated from the mean of the individual domain scores was also fitted with an AUC of.88 (95% CI =.82–.94).
Uncertainty of Social Network Members in the Case of Communication-Debilitating Illness or Injury

Uncertainty is a consequential aspect of chronic illness for patients as well as their family and friends, yet little research has focused on how non-ill individuals experience uncertainty about the condition of someone in their social network. Thirty-one individuals with loved ones who had a communication-debilitating illness or injury (CDI) participated in one-on-one interviews about their experiences. We analyzed transcripts for participants' sources of uncertainty and for ways that they managed the uncertainty. Participants' experiences with uncertainty included questions about the condition itself and involved the impaired communication resulting from the CDI. Participants described managing uncertainty through information seeking, changing the ways they communicated with the person with the CDI, and creating schemata to help reduce uncertainty. We discuss the findings in terms of predominant conceptualizations of uncertainty in illness and address the prevalence of communication as both a significant source of uncertainty and an important means of managing uncertainty.
Introns 1 and 22 inversions and factor VIII inhibitors in patients with severe haemophilia A in southern Brazil

Summary. A total of 107 unrelated severe haemophilia A patients living in the southern Brazilian state of Rio Grande do Sul were studied in relation to the prevalence of inversions present in introns 22 and 1 and a subsample of them (95) tested for the presence of Factor VIII inhibitors. These data were then incorporated with those from 15 other countries and 3871 patients. The frequencies of these two inversions show a remarkable homogeneity in series collected in different continents, from people with diverse ethnic extraction. The prevalence of inhibitors among patients with inversion 22, on the other hand, varies widely (5–51%; seven countries, 1482 patients), the value observed by us being the highest. The importance of obtaining data from patients throughout the world to clarify the aetiology of this important complicating factor in the therapeutics of the disease is emphasized.
Pharmacological characterization of the interaction between tiotropium and olodaterol administered at 5:5 concentration-ratio in equine bronchi

ABSTRACT Equine airways represent a suitable ex vivo model to study the functional impact of pharmacological treatments on human chronic obstructive pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD). We aimed to characterize the pharmacological interaction between the long-acting muscarinic antagonist (LAMA) tiotropium and the long-acting β2-agonist (LABA) olodaterol in equine airways. The effect of tiotropium and olodaterol, administered alone and in combination at the ratio of concentrations reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combination (FDC) (5:5), was investigated on the cholinergic contractile tone induced by the parasympathetic activation of equine isolated airways. The drug interaction was analysed by using the Bliss Independence and Unified Theory models. Both tiotropium and olodaterol induced a sub-maximal concentration-dependent inhibition of bronchial contractility (Emax: tiotropium 83.6 ± 14.8%, olodaterol 76.9 ± 17.9%; pEC50: tiotropium 8.2 ± 0.5; olodaterol 8.3 ± 0.6). When administered at 5:5 concentration-ratio, tiotropium plus olodaterol completely inhibited the bronchial contractility (Emax 102.7 ± 8.4%; pEC50 9.0 ± 0.7). Strong synergistic interaction was detected for tiotropium/olodaterol combination (combination index 0.011). When administered at low concentrations, the drug mixture elicited up to 94.6 ± 9.5% effect that was 36.0 ± 8.1% greater than the expected additive effect. The results of this study demonstrate that the co-administration of tiotropium plus olodaterol at 5:5 concentration-ratio leads to synergistic inhibition of equine bronchial contractility when compared with either drug administered alone. These findings suggest that the currently available LABA/LABA FDC may be effective in delivering tiotropium/olodaterol combination at equipotency concentrations of each monocomponent into the lung and, thus, inducing synergistic effect in the airways.