Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunogenicity of a p 210 BCR-ABL Fusion Domain Candidate DNA Vaccine Targeted to Dendritic Cells by a Recombinant Adeno-associated Virus Vector in Vitro 1

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) translocation, which results in the expression of chimeric BCR-ABL fusion oncoproteins that are necessary for oncogenesis, unique to the leukemic clones, and represent enticing targets for immunotherapy. As a strategy for the immunotherapy of CML, we constructed a recombinant adeno-associated virus vector encoding the p210 b3a2 variant fusion region with flanking sequences (CWRBA) and used it to express the BCR-ABL fusion region within primary human dendritic cells (DCs), the most potent antigen-presenting cells currently known. Peripheral blood mononuclear cells from healthy donors were primed and restimulated in vitro with autologous DCs transduced with purified CWRBA, CWRAP (negative control), or pulsed with a peptide corresponding to the fusion domain (positive control). No specific responses were generated using DCs transduced with CWRAP. In contrast, CWRBA-transduced DCs primed autologous T cells in an antigen-specific, MHC-restricted fashion to levels comparable with the positive control. CWRBA-transduced DCs elicited both cytotoxic CD4 /Th1 and CD8 responses, although the former were more readily detected in this system. Cytotoxicity against a tumor cell line endogenously expressing the p210 b3a2 variant fusion region was also demonstrable. In addition, HLA-DRB5 0101 DRA (DR2a) was identified as a new restriction element capable of presenting the b3a2 BCR-ABL fusion region epitope. Thus, the construct developed herein may serve as a candidate vaccine for gene-based antigen-specific immunotherapy of CML and may serve as a paradigm for the use of DCs transduced with recombinant adeno-associated virus vectors encoding multiepitope immunogens for vaccine development.
A Peptide from Heat Shock Protein 60 Is the Dominant Peptide Bound To Qa-1 in the Absence of the MHC Class Ia Leader Sequence Peptide Qdm1

The MHC class Ib molecule Qa-1 binds specifically and predominantly to a single 9-aa peptide (AMAPRTLLL) derived from the leader sequence of many MHC class Ia proteins. This peptide is referred to as Qdm. In this study, we report the isolation and sequencing of a heat shock protein 60-derived peptide (GMKFDRGYI) from Qa-1. This peptide is the dominant peptide bound to Qa-1 in the absence of Qdm. A Qa-1-restricted CTL clone recognizes this heat shock protein 60 peptide, further verifying that it binds to Qa-1 and a peptide from the homologous Salmonella typhimurium protein GroEL (GMQFDRGYL). These observations have implications for how Qa-1 can influence NK cell and T cell effector function via the TCR and CD94/NKG2 family members, and how this effect can change under conditions that cause the peptides bound to Qa-1 to change.
Fruit Transpiration: Mechanisms and Significance for Fruit Nutrition and Growth

Water and minerals transport in plant occur through the transpiration stream as triggered mainly by the environmental conditions. The transpiration of leaves has been studied in great detail over many years and the roles played by the various leaf structures (cuticle, stomata, lenticels etc) are well understood. Similarly well understood are the influences on foliar transpiration of meteorological variables such as temperature, radiation, vapour pressure deficit and wind, also, how these variables can be differently important to foliar transpiration depending on whether one is considering an isolated leaf or an entire canopy (Jarvis, 1985). In contrast with this, the transpiration of fruits has not been studied to nearly the same extent, neither with regard to skin structures and their associated functional properties nor with regard to the transpiration response of fruit to the various meteorological variables.
Early Innate Recognition of Herpes Simplex Virus in Human Primary Macrophages Is Mediated via the MDA5/MAVS-Dependent and MDA5/MAVS/RNA Polymerase III-Independent Pathways

ABSTRACT Innate recognition of viruses is mediated by pattern recognition receptors (PRRs) triggering expression of antiviral interferons (IFNs) and proinflammatory cytokines. In mice, Toll-like receptor 2 (TLR2) and TLR9 as well as intracellular nucleotide-sensing pathways have been shown to recognize herpes simplex virus (HSV). Here, we describe how human primary macrophages recognize early HSV infection via intracellular pathways. A number of inflammatory cytokines, IFNs, and IFN-stimulated genes were upregulated after HSV infection. We show that early recognition of HSV and induction of IFNs and inflammatory cytokines are independent of TLR2 and TLR9, since inhibition of TLR2 using TLR2 neutralizing antibodies did not affect virus-induced responses and the macrophages were unresponsive to TLR9 stimulation. Instead, HSV recognition involves intracellular recognition systems, since induction of tumor necrosis factor alpha (TNF-α) and IFNs was dependent on virus entry and replication. Importantly, expression of IFNs was strongly inhibited by small interfering RNA (siRNA) knockdown of MAVS, but this MAVS-dependent IFN induction occurred independently of the recently discovered polymerase III (Pol III)/RIG-I DNA sensing system. In contrast, induction of TNF-α was largely independent of MAVS, suggesting that induction of inflammatory cytokines during HSV infection proceeds via a novel pathway. Transfection with ODN2006, a broad inhibitor of intracellular nucleotide recognition, revealed that nucleotide-sensing systems are employed to induce both IFNs and TNF-α. Finally, using siRNA knockdown, we found that MDA5, but not RIG-I, was the primary mediator of HSV recognition. Thus, innate recognition of HSV by human primary macrophages occurs via two distinct intracellular nucleotide-sensing pathways responsible for induction of IFNs and inflammatory cytokine expression, respectively.
An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine

This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.
Experimental Study and Modelling of an Adhesive-Bonded Polycarbonate Assembly for Application in Consumer Electronics

In this work, adhesive bond strength and fracture energy were characterized using a standard Arcan fixture to provide data for product design simulation. Tests were performed on polycarbonate-adhesive-polycarbonate specimens to extract adhesive properties for numerical modelling. The bond strengths and fracture energy of the adhesive between polycarbonate substrates were determined at different loading rates and loading directions. Effects of adhesive aging were also investigated. Data from pure tensile (Mode I) and pure shear (Mode II) loadings were transformed into a cohesive law in a finite element model. Failure criteria were defined using damage theory. Simulations at different loading angles were compared with experimental results to evaluate the appropriateness of such a model. Simulation results were in good agreement with experiment in most cases. This study highlights the feasibility and challenges related to adhesive characterization using a standard Arcan test for modelling with a cohesive law.
Polymorphisms in the GAD2 gene‐region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders

Glutamate decarboxylase (GAD) is the rate limiting enzyme for conversion of glutamic acid to gamma‐aminobutyric acid (GABA). The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short‐term demands for GABA. We analyzed 18 single nucleotide polymorphisms (SNPs) in the GAD2‐gene region for associations with psychiatric diagnosis and behavioral inhibition (BI) derived from the personality traits neuroticism and extraversion as defined by the Eysenck Personality Questionaire (EPQ). A total of 268 patients with anxiety disorder (AD), 541 with unipolar depression (MD), and 541 healthy controls were included. We observe associations for five tag‐SNPs with BI in the AD‐ and control samples as well as two additional case–control associations in the MD‐sample. The associated SNPs lie within a 16KB linkage disequilibrium‐block, including putative 5′ GAD2‐promoter‐elements as well as the 3′ end of the gene MYO3A. Using open access mRNA‐expression data, we could show that BI‐associated SNPs appear to be associated with differences in MYO3A‐ but not GAD2 lymphoblastoid‐mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. However, data from expression studies imply that these polymorphisms could tag functional effects on the neighboring gene MYO3A, which is also expressed in the brain, including the cingulate cortex and the amygdala. © 2009 Wiley‐Liss, Inc.
A Meta-Analysis

Background: Numerous empirical studies from various populations and settings link patient treatment adherence to physician-patient communication. Meta-analysis allows estimates of the overall effects both in correlational research and in experimental interventions involving the training of physicians’ communication skills. Objectives: Calculation and analysis of “r effect sizes” and moderators of the relationship between physician’s communication and patient adherence, and the effects of communication training on adherence to treatment regimens for varying medical conditions. Methods: Thorough search of published literature (1949–August 2008) producing separate effects from 106 correlational studies and 21 experimental interventions. Determination of random effects model statistics and the detailed examination of study variability using moderator analyses. Results: Physician communication is significantly positively correlated with patient adherence; there is a 19% higher risk of nonadherence among patients whose physician communicates poorly than among patients whose physician communicates well. Training physicians in communication skills results in substantial and significant improvements in patient adherence such that with physician communication training, the odds of patient adherence are 1.62 times higher than when a physician receives no training. Conclusion: Communication in medical care is highly correlated with better patient adherence, and training physicians to communicate better enhances their patients’ adherence. Findings can contribute to medical education and to interventions to improve adherence, supporting arguments that communication is important and resources devoted to improving it are worth investing in. Communication is thus an important factor over which physicians have some control in helping their patients to adhere.
California Center for Population Research On-line Working Paper Series Weather Regime Prediction Using Statistical Learning Weather Regime Prediction Using Statistical Learning

Two novel statistical methods are applied to the prediction of transitions between weather regimes. The methods are tested using a long, 6 000-day simulation of a three-layer, quasi-geostrophic (QG3) model on the sphere at T21 resolution. The two methods are the k nearest-neighbor classifier and the random-forest method. Both methods are widely used in statistical classification and machine learning; they are applied here to forecast the break of a regime and subsequent onset of another one. The QG3 model has been previously shown to possess realistic weather regimes in its Northern Hemisphere and preferred transitions between these have been determined. The two methods are applied to the three more robust transitions; they both demonstrate a skill of 35–40% better than random and are thus encouraging for use on real data. Moreover, the random-forest method allows, while keeping the overall skill unchanged, to efficiently adjust the ratio of correctly predicted transitions to false alarms. A long-standing conjecture has associated regime breaks and preferred transitions with distinct directions in the reduced model phase space spanned by a few leading empirical orthogonal functions of its variability. Sensitivity studies for several predic-tors confirm the crucial influence of the exit angle on a preferred transition path. The present results thus support the paradigm of multiple weather regimes and of their association with unstable fixed points of atmospheric dynamics.
Cyclic rickettsemia during persistent Anaplasma marginale infection of cattle

Submicroscopic levels of Anaplasma marginale rickettsemia in persistently infected cattle were determined by using nucleic acid hybridization. Within individuals, the rickettsemia levels steadily increased from less than 10(4) infected erythrocytes per ml to a peak of more than 10(6) infected erythrocytes per ml and then rapidly declined. This logarithmic variation parallels the variation of the rickettsemia level seen in acute infection and suggests that cyclic emergence of antigenic variants is a mechanism of rickettsial persistence.
Peripheral Inflammation Increases the Damage in Animal Models of Nigrostriatal Dopaminergic Neurodegeneration: Possible Implication in Parkinson's Disease Incidence

Inflammatory processes described in Parkinson's disease (PD) and its animal models appear to be important in the progression of the pathogenesis, or even a triggering factor. Here we review that peripheral inflammation enhances the degeneration of the nigrostriatal dopaminergic system induced by different insults; different peripheral inflammations have been used, such as IL-1β and the ulcerative colitis model, as well as insults to the dopaminergic system such as 6-hydroxydopamine or lipopolysaccharide. In all cases, an increased loss of dopaminergic neurons was described; inflammation in the substantia nigra increased, displaying a great activation of microglia along with an increase in the production of cytokines such as IL-1β and TNF-α. Increased permeability or disruption of the BBB, with overexpression of the ICAM-1 adhesion molecule and infiltration of circulating monocytes into the substantia nigra, is also involved, since the depletion of circulating monocytes prevents the effects of peripheral inflammation. Data are reviewed in relation to epidemiological studies of PD.
Developmental changes in intrinsic excitability of principal neurons in the rat medial nucleus of the trapezoid body

The calyx of Held synapse is a giant axosomatic synapse that has a fast relay function within the sound localization circuit of the brainstem. In the adult, each principal neuron of the medial nucleus of the trapezoid body (MNTB) is contacted by a single calyx terminal. In rodents, the calyx of Held synapse forms around the third postnatal day (P3). Here, we studied the developmental changes in the intrinsic excitability of the principal neurons during the first postnatal week by making whole‐cell recordings from brainstem slices. In slices from P0–1 rats, about 20% of the principal neurons were spontaneously active, whereas after P3, no spontaneously active cells were observed. Already at P0, principal neurons received both glutamatergic and GABAergic/glycinergic inputs. The occurrence of spontaneous action potentials depended upon the presence of spontaneous glutamatergic inputs; summation of only a few quanta was enough to reach action potential threshold. The main cause for this high excitability was a high resting membrane resistance, which decreased at least four‐fold during the first postnatal week. A relatively slow decay of synaptic currents and a relatively depolarized membrane potential may have contributed as well. We conclude that the decrease in the excitability of principal neurons in the MNTB matches the increase of the strength of the synaptic inputs resulting from the formation and maturation of the calyx of Held synapse during the first postnatal week. This decrease in excitability will make it progressively more difficult for non‐calyceal inputs to trigger action potentials. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 284–295, 2011
Pharmacology of potent and selective S2-serotonergic antagonists.

Ketanserin is the prototype of a new series of serotonergic antagonists that competitively and selectively block 5-hydroxytryptamine (S2) serotonergic receptors. Ketanserin and its analogues antagonize the events mediated by this receptor, i.e., serotonin-induced vasoconstriction, bronchoconstriction, and platelet aggregation, irrespective of whether serotonin acts directly or amplifies the effect of vasoconstrictors or platelet aggregating agents. The antagonism is pure because compounds such as ketanserin are devoid of agonistic activity. The actions of ketanserin are mainly peripheral, whereas other members of the series, e.g., ritanserin, act on the brain and are potent antagonists of lysergic acid diethylamide and other centrally acting serotonomimetic drugs. The different pharmacological profiles of the new S2-serotonergic antagonists and the evidence already available on their clinical effects prompt a further exploration of these agents in a large range of cardiovascular and other diseases.
Effect of impurities on the oxidation mechanism of nickel at 800°C

Abstract The effect of impurities on the oxidation mechanism of nickel was studied on commercial nickel grades compared to a pure nickel. On the basis of oxidation kinetics, SEM and STEM microstructural and analytical investigations allowed us to identify the oxidation mechanism for both types of nickel at 800°C. The morphology of the oxide scale notably differs according to the purity of the nickel. For oxidised commercial grades, a duplex structure was observed with an outer columnar layer and an inner layer made of equiaxed grains. The inner NiO/outer NiO interface is planar without any segregation, while the NiO/Ni interface is convoluted with large cavities. Mn, Ti and sometimes also silicon impurities were detected at this latter interface. Below the NiO/Ni interface, in the underlying nickel, large internal oxidation was observed. The observed microstructure was quite different for the pure nickel. A single porous NiO layer, composed of equiaxed grains, was observed. The NiO/Ni interface was facetted and no porosity was detected. The presence and localisation of impurities, as well as morphological changes through the scale in the nickel grades, were taken into account to explain the modification of oxidation kinetics with substrate purity.
Current and Emerging Biologics for Ulcerative Colitis

Conventional medical treatment for ulcerative colitis can have limited efficacy or severe adverse reactions requiring additional treatment or colectomy. Hence, different biological agents that target specific immunological pathways are being investigated for treating ulcerative colitis. Anti-tumor necrosis factor (TNF) agents were the first biologics to be used for treating inflammatory bowel disease. For example, infliximab and adalimumab, which are anti-TNF agents, are being used for treating ulcerative colitis. Recently, golimumab, another anti-TNF agent, and vedolizumab, an anti-adhesion therapy, have been approved for ulcerative colitis by the U.S. Food and Drug Administration. In addition, new medications such as tofacitinib, a Janus kinase inhibitor, and etrolizumab, another anti-adhesion therapy, are emerging as therapeutic agents. Therefore, there is a need for further studies to select appropriate patient groups for these biologics and to improve the outcomes of ulcerative colitis treatment through appropriate medical usage.
The Compensatory Growth in Juveniles of Sea Bass

The aim of this work was to investigate the distribution of regulative molecules in the stomach of juvenile Dicentrarchus labrax during compensatory growth, using immunohistochemical methods. Antisera against galanin, neuropeptide Y, ghrelin, leptin, and serotonin were used on fasted and refed D. labrax. The results show a characteristic distributive pattern for the sought molecules in fish refed after 35 days of fasting, with a high increased presence of both ghrelin and leptin.
Specificity of the MMPI–2 Fake Bad Scale as a Marker for Personal Injury Malingering

Psychologists who evaluate patients in medicolegal contexts should utilize objective assessment data with empirically established sensitivity and specificity for identifying negative response bias. The purpose of this study was to investigate the specificity of the Fake Bad Scale for identifying negative response bias in personal injury claimants. The cutoff scores proposed by Lees-Haley and colleagues were applied to inmate volunteers from a federal prison, medical outpatients, and patients from an inpatient substance abuse unit. Half of the inmates were given instructions to malinger psychopathology to affect the adjudication process, and the remaining inmates and all of the hospital patients were given standard instructions. The original cutoff scores correctly identified the majority of inmates instructed to malinger psychopathology, but these scores resulted in unacceptably high rates of false positive classifications. The revised cutoff scores resulted in fewer false positives, i.e., 8%–24%.
Heart disease in patients with seropositive rheumatoid arthritis; a controlled autopsy study and review.

Chronic pericarditis was the most common rheumatoid lesion of the heart in 47 autopsied patients with seropositive rheumatoid arthritis; it was uncommon in an equal number of matched controls. This lesion, almost always benign, is often associated with electrocardiogram changes, long duration of arthritis, and severe musculoskeletal disability, and rarely with constrictive pericarditis. Myocarditis and rheumatoid granulomas are less frequent but also characteristic. Myocarditis was found more frequently in patients with severe osteoporosis. Whether rheumatoid coronary arteritis is a clinically significant entity remains unsettled. Functionally important valvular disease is rare, though cases of granulomatous valvulitis and valvular insufficiency are documented. Nonspecific endocarditis is frequent, but not more so than in a control population. Most, but not all, heart disease related to rheumatoid arthritis is innocuous.