Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Plasmodium chabaudi Infection Generates CD4 Memory T Cells with Increased T Cell Receptor Sensitivity but Poor Secondary Expansion and Increased Apoptosis

ABSTRACT Exposure to blood-stage malaria infection is often persistent, leading to generation of CD4 effector and effector memory T cells that contribute to protection. We showed previously that chronic exposure to blood-stage Plasmodium chabaudi offers the best protection from parasitemia and pathology in reinfection cases, correlating with an increase in Th1 cells. Although much is known about the features of resting or exhausted memory T cells (Tmem), little is known about the functional capacities of chronically stimulated but protective T cells. To determine the functional capacity of CD4 T cells generated by chronic infection upon reexposure to parasite, we compared their responses to known features of classical Tmem. The numbers of cytokine-producing T cells increased following infection in the polyclonal populations, suggesting an increase in pathogen-specific T cells. Malaria antigen-specific B5 T cell receptor (TCR) transgenic (Tg) T cells from chronic infection proliferated on reinfection and were highly sensitive to TCR stimulation without costimulation, as shown for Tmem in acute stimulations. However, B5 Tmem did not accumulate more than naive B5 T cells in vivo or in vitro and became apoptotic. Failure to accumulate was partly the result of chronic stimulation, since eliminating persistent parasites before reinfection slightly increased the accumulation of B5 Tg T cells upon reinfection. The levels of specific gamma interferon-positive, interleukin-10-positive T cells, which protect animals from pathology, increased after malaria infection. These data demonstrate that although chronic infection generates a protective T cell population with increased TCR sensitivity and cytokine production, they do not reexpand upon reexposure due to increased apoptosis.
Loss of Lon1 in Arabidopsis Changes the Mitochondrial Proteome Leading to Altered Metabolite Profiles and Growth Retardation without an Accumulation of Oxidative Damage1[W][OA]

Lon1 is an ATP-dependent protease and chaperone located in the mitochondrial matrix in plants. Knockout in Arabidopsis (Arabidopsis thaliana) leads to a significant growth rate deficit in both roots and shoots and lowered activity of specific mitochondrial enzymes associated with respiratory metabolism. Analysis of the mitochondrial proteomes of two lon1 mutant alleles (lon1-1 and lon1-2) with different severities of phenotypes shows a common accumulation of several stress marker chaperones and lowered abundance of Complexes I, IV, and V of OXPHOS. Certain enzymes of the tricarboxylic acid (TCA) cycle are modified or accumulated, and TCA cycle bypasses were repressed rather than induced. While whole tissue respiratory rates were unaltered in roots and shoots, TCA cycle intermediate organic acids were depleted in leaf extracts in the day in lon1-1 and in both lon mutants at night. No significant evidence of broad steady-state oxidative damage to isolated mitochondrial samples could be found, but peptides from several specific proteins were more oxidized and selected functions were more debilitated in lon1-1. Collectively, the evidence suggests that loss of Lon1 significantly modifies respiratory function and plant performance by small but broad alterations in the mitochondrial proteome gained by subtly changing steady-state protein assembly, stability, and damage of a range of components that debilitate an anaplerotic role for mitochondria in cellular carbon metabolism.
A systematic review of the role of community pharmacies in improving the transition from secondary to primary care Authors and affiliations:

Publisher's copyright statement: This is the accepted version of the following article: Nazar, H. , Nazar, Z. , Portlock, J., Todd, A. and Slight, S.P. (2015) 'A systematic review of the role of community pharmacies in improving the transition from secondary to primary care. ', British journal of clinical pharmacology, 80(5): 936-948, which has been published in nal form at http://dx.doi. org/10.1111/bcp.12718. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Multi-level multi-channel air cache designs for broadcasting in a mobile environment

Investigates efficient ways of broadcasting data to mobile users over multiple physical channels, which cannot be coalesced into a lesser number of high-bandwidth channels. We propose the use of an MLMC (multi-level multi-channel) air cache, which can provide mobile users with data based on their popularity factor. We provide a wide range of design considerations for the server which broadcasts over the MLMC cache. We also investigate some novel techniques for a mobile user to access data from the MLMC cache and show the advantages of designing the broadcasting strategy in tandem with the access behavior of the mobile users. Finally, we provide experimental results to compare the techniques we introduce.
Deploying artificial landmarks to foster data association in simultaneous localization and mapping

Data association is an essential problem in simultaneous localization and mapping. It is hard to solve correctly, especially in ambiguous environments. We consider a scenario where the robot can ease the data association problem by deploying a limited number of uniquely identifiable artificial landmarks along its path and use them afterwards as fixed anchors. Obviously, the choice of the positions where the robot should drop these markers is crucial as poor choices might prevent the robot from establishing accurate data associations. In this paper, we present a novel approach for learning when to drop the landmarks so as to optimize the data association performance. We use Monte Carlo reinforcement learning for computing an optimal policy and apply a statistical convergence test to decide if the policy is converged and the learning process can be stopped. Extensive experiments also carried out with a real robot demonstrate that the data association performance using landmarks deployed according to our learned policies is significantly higher compared to other strategies.
Molecular dynamics studies on HIV‐1 protease: Drug resistance and folding pathways

Drug resistance to HIV‐1 protease involves the accumulation of multiple mutations in the protein. We investigate the role of these mutations by using molecular dynamics simulations that exploit the influence of the native‐state topology in the folding process. Our calculations show that sites contributing to phenotypic resistance of FDA‐approved drugs are among the most sensitive positions for the stability of partially folded states and should play a relevant role in the folding process. Furthermore, associations between amino acid sites mutating under drug treatment are shown to be statistically correlated. The striking correlation between clinical data and our calculations suggest a novel approach to the design of drugs tailored to bind regions crucial not only for protein function, but for folding as well. Proteins 2001;43:365–372. © 2001 Wiley‐Liss, Inc.
Clinical comparison of microporous biocompatible composite of PMMA, PHEMA and calcium hydroxide grafts and expanded polytetrafluoroethylene barrier membranes in human mandibular molar Class II furcations. A case series.

BACKGROUND Class II furcations present difficult treatment problems. Several treatment approaches to obtain furcation fill have been used with varying success. METHODS The response of mandibular Class II furcations to treatment with either a microporous biocompatible composite of PMMA (poly-methyl-methacrylate), PHEMA (poly-hydroxyl-ethyl methacrylate) and calcium hydroxide graft synthetic bone (HTR) replacement graft material; ePTFE barrier membrane; or a combination of the two was evaluated in trios of mandibular molars with Class II furcations in 8 patients with moderate to advanced periodontitis. Following initial preparation, full-thickness flaps were raised in the areas being treated, the bone and furcation defects debrided of granulomatous tissue, and the involved root surfaces mechanically prepared and chemically conditioned. By random allocation, HTR, ePTFE, or a combination of both was placed into and/or fitted over the furcations, packed and/or secured in place, and the host flap replaced or coronally positioned with sutures. Postsurgical deplaquing was performed every 10 days leading up to ePTFE removal at approximately 6 weeks. Continuing periodontal maintenance therapy was provided until surgical reentry at 6 months for documentation and any further necessary treatment. RESULTS Direct clinical measurements demonstrated essentially similar clinical results with all 3 treatments for bone and soft tissue changes. There were no statistically or clinically significant differences except for better horizontal amount and percent defect fill with HTR alone. Four of 8 furcations became Class I clinically with HTR alone, 5 of 8 became Class I with ePTFE alone, and 5 of 8 with combination treatment. The only complete furcation closure occurred with HTR. CONCLUSION The findings of this study suggest essentially equal clinical results with HTR bone replacement graft material alone, ePTFE barrier alone, and a combination of the two in mandibular molar Class II furcations. However, a real difference may not have been detected based on the small number of subjects in the study.
Environmental Cardiology: Getting to the Heart of the Matter

This review is a short update on the diversity of swine biomedical models and the importance of genomics in their continued development. The swine has been used as a major mammalian model for human studies because of the similarity in size and physiology, and in organ development and disease progression. The pig model allows for deliberately timed studies, imaging of internal vessels and organs using standard human technologies, and collection of repeated peripheral samples and, at kill, detailed mucosal tissues. The ability to use pigs from the same litter, or cloned or transgenic pigs, facilitates comparative analyses and genetic mapping. The availability of numerous well defined cell lines, representing a broad range of tissues, further facilitates testing of gene expression, drug susceptibility, etc. Thus the pig is an excellent biomedical model for humans. For genomic applications it is an asset that the pig genome has high sequence and chromosome structure homology with humans. With the swine genome sequence now well advanced there are improving genetic and proteomic tools for these comparative analyses. The review will discuss some of the genomic approaches used to probe these models. The review will highlight genomic studies of melanoma and of infectious disease resistance, discussing issues to consider in designing such studies. It will end with a short discussion of the potential for genomic approaches to develop new alternatives for control of the most economically important disease of pigs, porcine reproductive and respiratory syndrome (PRRS), and the potential for applying knowledge gained with this virus for human viral infectious disease studies.
A comparison between Lynch syndrome and sporadic colorectal cancer survivors’ satisfaction with their healthcare providers

This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case–case‐matched CRC survivors with (n = 75) or without (n = 75) LS (mean age of 55; range: 27–93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P < 0.05), interpersonal treatment (78.58 vs. 85.30; P < 0.05), and knowledge of the patient (60.34 vs. 69.86; P < 0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center (CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs.
ING4 Inhibits Proliferation and Induces Apoptosis in Human Melanoma A375 Cells via the Fas/Caspase-8 Apoptosis Pathway

Background: Inhibitor of growth 4 (ING4) plays a role in regulating the cell cycle, apoptosis, cell invasion and migration, but the mechanisms involved remain to be elucidated. Objective: To explore how ING4 affects human malignant melanoma A375 cells. Methods: Recombinant lentiviral vectors (A375/pLenO-GTP-ING4) were constructed and transfected into A375 cells (experimental group). The impact of ING4 on the proliferation and apoptosis of A375 cells was investigated in in vitro and in vivo experiments in mice using the MTT assay and flow cytometry. Results: In the experimental group, optical density was lower and apoptotic cells were more frequent from days 2-5 (p = 0.000 and p < 0.01); there were smaller xenografts and more apoptotic cells in mice (all p < 0.05); moreover, increased levels of Fas, cleaved caspase-8 and caspase-3, and decreased levels of FasL and procyclic acidic repetitive protein were observed in vitro and in vivo. Conclusion: ING4 might suppress proliferation and enhance apoptosis in human malignant melanoma cells by activating Fas-induced apoptosis in a caspase-8-dependent pathway.
CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design

We have developed a new primer design strategy for PCR amplification of distantly related gene sequences based on consensus-degenerate hybrid oligonucleotide primers (CODEHOPs). An interactive program has been written to design CODEHOP PCR primers from conserved blocks of amino acids within multiply-aligned protein sequences. Each CODEHOP consists of a pool of related primers containing all possible nucleotide sequences encoding 3-4 highly conserved amino acids within a 3' degenerate core. A longer 5' non-degenerate clamp region contains the most probable nucleotide predicted for each flanking codon. CODEHOPs are used in PCR amplification to isolate distantly related sequences encoding the conserved amino acid sequence. The primer design software and the CODEHOP PCR strategy have been utilized for the identification and characterization of new gene orthologs and paralogs in different plant, animal and bacterial species. In addition, this approach has been successful in identifying new pathogen species. The CODEHOP designer (http://blocks.fhcrc.org/codehop.html) is linked to BlockMaker and the Multiple Alignment Processor within the Blocks Database World Wide Web (http://blocks.fhcrc.org).
Risk factors involved in orofacial cleft predisposition – review

Abstract Clefts that occur in children are a special topic. Avoiding risk factors, and also an early diagnosis of cleft possibility can result in minimizing or avoiding them. If on the other hand when clefts occur they require a long-term, multistage specialized treatment. Etiology of clefts seems to be related to many factors. Factors such as genetic, environmental, geographic and even race factors are important. Identification of risk factors can lead to prevention and prophylactic behaviors in order to minimize its occurrence. Exposure to environmental factors at home and work that lead to cleft predisposition should not be disregarded. It seems that before planning a family it would be wise to consult with doctors of different specializations, especially in high-risk families with cleft history in order to analyze previous lifestyle. Clefts are very common in hereditary facial malformations and are causing a lot of other irregularities in the head and neck region. In this paper after a brief papers review authors present socio-geographic, environmental and also work place related factors that are influencing pregnant women condition and should be taken under serious consideration.
Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes

Background Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear. Methods MSI status was assessed in 414 cases of gastric cancer using polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed. Results Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (≥2/high power field, p<0.001), expanding growth patterns (p=0.038), gastric predominant mucin phenotypes (p=0.028), and MUC6 expression (p=0.016). Tumor necrosis (≥10% of mass, p=0.031), tumor-infiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p=0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197). Conclusions Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.
The isolated neutron star X-ray pulsars RX J0420.0-5022 and RX J0806.4-4123: New X-ray and optical observations

We report on the analysis of new X-ray data obtained with XMM-Newton and Chandra from two ROSAT-discovered X-ray dim isolated neutron stars (XDINs). RX J0806.4−4123 was observed with XMM-Newton in April 2003, 2.5 years after the first observation. The EPIC-pn data confirm that this object is an X-ray pulsar with 11.371 s neutron star spin period. The X-ray spectrum is consistent with absorbed black-body emission with a temperature kT = 96 eV and N H = 4 × 10 19 cm −2 without significant changes between the two observations. Four XMM-Newton observations of RX J0420.0−5022 between December 2002 and July 2003 did not confirm the 22.7 s pulsations originally indicated in ROSAT data, but clearly reveal a 3.453 s period. A fit to the X-ray spectrum using an absorbed black-body model yields kT = 45 eV, the lowest value found from the small group of XDINs and N H = 1.0 × 10 20 cm −2. Including a broad absorption line improves the quality of the spectral fits considerably for both objects and may indicate the presence of absorption features similar to those reported from RBS1223, RX J1605.3+3249 and RX J0720.4−3125. For both targets we derive accurate X-ray positions from the Chandra data and present an optical counterpart candidate for RX J0420.0−5022 with B = 26.6 ± 0.3 mag from VLT imaging.
Levels and Values of Circulating Hematopoietic and Endothelial Progenitor Cells in Patients with Hepatocellular Carcinoma

Objective: Development of HCC is associated with the process of angiogenesis and leads to the increment of the number of stem cells in the peripheral blood circulation. This study evaluated whether the level of hematopoietic stem cells and endothelial progenitor cells (HSCs & EPCs) could indicate the unfavorable tumour biology and the progress of disease in HCC. Methods: The study covered 146 HCC patients; 53 selected for liver resection, 49 for liver transplantation, 44 for palliation. Control consisted of 42 patients with liver cirrhosis and 43 healthy individuals. The cells were enumerated with CD45, CD34, CD133, CD309 markers. The cell rates were measured by phenotypic analysis of 2 ml fresh blood in a flow cytometer. The data were evaluated statistically. Results: There were significant differences in the levels of HSCs and EPCs between patients with HCC, with liver cirrhosis and healthy volunteers (Chisq = 45.92, p<0.001, Chisq = 16.22, p<0.001), as well as between the groups of patients with HCC selected for liver resection, liver transplantation and palliation (Chisq=40.86, p<0.001, Chisq=18.81, p<0.001), respectively. The multivariate analysis of regression indicated the rates of hematopoietic stem cells and the endothelial progenitor cells as the factor predicting poor tumour differentiation (W=3.95, p<0.04 and W=7.11, p<0.008). Conclusions: Liver cirrhosis and the development of hepatocellular carcinoma cause significant changes in the levels of circulating hematopoietic and endothelial progenitor cells. The cell levels correlate with the advances of liver pathology and allow anticipating the unfavorable biology of the tumour.
Realistic haptic rendering of interacting deformable objects in virtual environments

A new computer haptics algorithm to be used in general interactive manipulations of deformable virtual objects is presented. In multimodal interactive simulations, haptic feedback computation often comes from contact forces. Subsequently, the fidelity of haptic rendering depends significantly on contact space modeling. Contact and friction laws between deformable models are often simplified in up to date methods. They do not allow a "realistic" rendering of the subtleties of contact space physical phenomena (such as slip and stick effects due to friction or mechanical coupling between contacts). In this paper, we use Signorini's contact law and Coulomb's friction law as a computer haptics basis. Real-time performance is made possible thanks to a linearization of the behavior in the contact space, formulated as the so-called Delassus operator, and iteratively solved by a Gauss-Seidel type algorithm. Dynamic deformation uses corotational global formulation to obtain the Delassus operator in which the mass and stiffness ratio are dissociated from the simulation time step. This last point is crucial to keep stable haptic feedback. This global approach has been packaged, implemented, and tested. Stable and realistic 6D haptic feedback is demonstrated through a clipping task experiment.