Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensin II type 1 receptor antagonism improves endothelial vasodilator function in L-NAME-induced hypertensive rats by a kinin-dependent mechanism

Objective This study was designed to investigate the ability of a chronic blockade of angiotensin II type 1 receptors with losartan to reverse the endothelial dysfunction present in Nω-nitro-L-arginine methyl ester (L-NAME)-treated hypertensive rats and the possible dependence of this effect on bradykinin B2-receptor activation. Methods Rats treated with L-NAME alone (60 mg/kg per day for 8 weeks) or with L-NAME + losartan, L-NAME + icatibant (a bradykinin B2-receptor antagonist) and L-NAME + losartan + icatibant were studied. Losartan, icatibant or losartan + icatibant were co-administered with L-NAME during the last 4 weeks of the experiment. Endothelial nitric oxide synthase gene expression in aortic tissues, plasma nitrite/nitrate concentrations, the relaxant effect of acetylcholine on norepinephrine-precontracted aortic rings and 6-keto-PGF1α release from aortic rings were used as markers of the endothelial function. Results Rats treated with L-NAME alone and L-NAME + icatibant showed, as compared with untreated animals, a clear-cut increase in systolic blood pressure and a decrease of all the markers of endothelial function evaluated. In L-NAME-rats, administration of losartan reduced the systolic blood pressure and restored endothelial nitric oxide synthase gene expression, plasma nitrite/nitrate levels, the relaxant activity of acetylcholine on aortic rings and the generation of 6-keto-PGF1α from the aortic tissues. Co-administration of icatibant with losartan blunted the stimulatory effect of losartan on the markers of endothelial function evaluated. Conclusion These results demonstrated that losartan is capable of reversing the endothelial vasodilator dysfunction in L-NAME-induced hypertensive rats, and that the beneficial effect of losartan is mediated by bradykinin B2-receptor activation.
Crystallisation within transdermal rotigotine patch: is there cause for concern?

Rotigotine transdermal patch is the first transdermal non-ergot dopamine agonist, being a selective dopamine D 1 /D 2 /D 3 receptor agonist [1-4] . Rotigotine patch is effective over 24 h and provides a continuous dopaminergic stimulation (CDS) in ‘real life’ in patients with Parkinson’s disease (PD) and was approved for use in PD by the FDA and EMEA [1-4] . A total of 674 subjects have been evaluated in Phase I trials showing constant drug delivery to the skin, reproducible absorption and stable 24-h plasma levels [5-7] . In terms of composition, the drug is dispersed in a silicone adhesive and then spread evenly across a silicone backing to allow uniform and constant delivery of the drug [3,4] . The patch has been viewed as an advance in the therapeutic arena for PD exploiting the theoretical advantages of CDS and showing significant reduction of dyskinesias in animal models of PD [2-8] . In PD, doses used have been in the range of 2 – 16 mg/day, and patch sizes of 2, 4, 6 and 8 mg have been available for clinical use. In September 2008, rotigotine patch (2 – 4 mg) also received approval from the EMEA for use in moderate-to-severe restless legs syndrome (RLS), a condition that has a prevalence of about 8 – 12% in the Western population [9] . In PD, the promising clinical use of rotigotine was recently interrupted after healthcare professionals received notification regarding the rotigotine patch due to the appearance of ‘snowflake-like’ crystals within the patch ( Figure 1 ). This issue led to a specific batch recall in March 2008 in Europe; this resulted in a complete out-of-stock situation in the United States, where the drug is currently unavailable. There was at this time minimal disruption to supply in Europe; however, in May 2008 the EMEA directed that physicians in Europe should not start any new PD patients on rotigotine patch. At the same time, physicians, distributors, pharmacists and patients were advised to store the product in the refrigerator, and the patch was available only at 2 and 4 mg strengths for use in patients currently on rotigotine therapy.
Human Cytomegalovirus Interleukin-10 Polarizes Monocytes toward a Deactivated M2c Phenotype To Repress Host Immune Responses

ABSTRACT Several human cytomegalovirus (HCMV) genes encode products that modulate cellular functions in a manner likely to enhance viral pathogenesis. This includes UL111A, which encodes homologs of human interleukin-10 (hIL-10). Depending upon signals received, monocytes and macrophages become polarized to either classically activated (M1 proinflammatory) or alternatively activated (M2 anti-inflammatory) subsets. Skewing of polarization toward an M2 subset may benefit the virus by limiting the proinflammatory responses to infection, and so we determined whether HCMV-encoded viral IL-10 influenced monocyte polarization. Recombinant viral IL-10 protein polarized CD14+ monocytes toward an anti-inflammatory M2 subset with an M2c phenotype, as demonstrated by high expression of CD163 and CD14 and suppression of major histocompatibility complex (MHC) class II. Significantly, in the context of productive HCMV infection, viral IL-10 produced by infected cells polarized uninfected monocytes toward an M2c phenotype. We also assessed the impact of viral IL-10 on heme oxygenase 1 (HO-1), which is an enzyme linked with suppression of inflammatory responses. Polarization of monocytes by viral IL-10 resulted in upregulation of HO-1, and inhibition of HO-1 function resulted in a loss of capacity of viral IL-10 to suppress tumor necrosis factor alpha (TNF-α) and IL-1β, implicating HO-1 in viral IL-10-induced suppression of proinflammatory cytokines by M2c monocytes. In addition, a functional consequence of monocytes polarized with viral IL-10 was a decreased capacity to activate CD4+ T cells. This study identifies a novel role for viral IL-10 in driving M2c polarization, which may limit virus clearance by restricting proinflammatory and CD4+ T cell responses at sites of infection.
Autoimmune liver disease and rheumatic manifestations

Purpose of reviewTo review studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate shared pathogenic pathways, and encourage innovative site-specific therapies. Recent findingsAutoimmune hepatitis has clinical manifestations, serological markers, pathogenic mechanisms, genetic predispositions, and therapies similar to the rheumatic diseases. The rheumatic manifestations may mask the underlying liver disease and vice versa. Variations in clinical phenotype and outcome for the autoimmune liver diseases may reflect host-specific and region-specific factors, and defects in counter-regulatory suppressor functions by regulatory T cells may facilitate cell-mediated cytotoxicity and autoreactivity. Mixed syndromes with hallmark features of one disease in another probably reflect a genetic predisposition for immune expression that is shared among the diseases. Mycophenolate mofetil, budesonide, rapamycin, and 6-thioguanine are promising treatments, and de-novo autoimmune hepatitis after liver transplantation suggests that the calcineurin inhibitors may have paradoxical effects on self-tolerance. SummaryClinical phenotypes of autoimmune hepatitis commonly include rheumatic manifestations that can mask the liver disease. Defects in counter-regulatory functions enhance cell-mediated cytotoxicity, and pharmacological interventions that promise site-specific actions affecting immunocyte differentiation and proliferation are feasible.
Impact of HIV on Genomic Variability in the 5′UTR of HCV in Indian Patients with HCV/HIV Co-Infection

Background: The impact of HIV on hepatitis C virus (HCV) genome during HCV/HIV co-infection is poorly understood. The present study was intended to unveil nucleotide sequence variability in the 5′-untranslated region (5′UTR) of HCV in co-infected cases. Methods: Automated nucleotide sequencing of the 5′UTR of HCV from both mono- and co-infected cases was performed. Results: Data analysis revealed deletion of a continuous stretch of 12 nucleotides (nt 240–251) from domain IIIc in 20% co-infected cases, but no long-stretch deletion was observed in HCV from mono-infected cases. On the contrary, there was no insertion in the 5′UTR of HCV from co-infectedcases, but there were insertions in domain II and III (3 mononucleotides and 2 dinucleotides) of the 5′UTR in mono-infected cases. Conclusion: Since domain III is known to be important for binding of 40S ribosomal subunit, deletion of a single stretch of 12 nucleotides in HCV from co-infected cases observed in the present study may have implications during HCV replication with or without HIV infection. Although this is the first report on genomic heterogeneity in the 5′UTR of HCV from HCV/HIV co-infected Indian patients, it would be worthwhile to study if similar changes are observed in other genes of HCV during co-infection.
Individually-secure multi-source multicast

The principal mission of Multi-Source Multicast (MSM) is to disseminate all messages from all sources in a network to all destinations. MSM is utilized in numerous applications. In many of them, securing the messages disseminated is critical. A common secure model is to consider a network where there is an eavesdropper which is able to observe a subset of the network links, and seek a code which keeps the eavesdropper ignorant regarding all the messages. While this is solved when all messages are located at a single source, Secure MSM (SMSM) is an open problem, and the rates required are hard to characterize in general. In this paper, we consider Individual Security, which promises that the eavesdropper has zero mutual information with each message individually. We completely characterize the rate region for SMSM under individual security, and show that such a security level is achievable at the full capacity of the network, that is, the cut-set bound is the matching converse, similar to non-secure MSM. Moreover, we show that the field size is similar to non-secure MSM and does not have to be larger due to the security constraint.
Separability of different negative components of the event-related potential associated with auditory stimulus processing.

The lateral scalp distribution of the early negative selective-attention effect on auditory eventrelated potentials (ERPs) was compared to the distribution of the midline-negative N1 component inverting in polarity at the scalp area below the Sylvian fissure. No such polarity inversion was observed for the selective-attention effect at the N1 latency. This result supports the proposal that another component, the processing negativity (PN), overlaps (summates to) the exogenous N1 in the ERPs to attended stimuli. A subsequent experiment demonstrated that the mismatch negativity (MMN: peaking at 150–200 ms), an ERP component automatically elicited by deviant stimuli presented among homogenous repetitive stimuli, had opposite polarities above and below the Sylvian fissure. Thus, the MMN at least partly emanates from a cerebral generator which considerably overlaps that of the N1. The results are discussed in terms of separability of the brain mechanisms involved in the voluntary and involuntary processing of auditory stimuli reflected by the PN and MMN, respectively.
Depression and neurocognitive performance in individuals with HIV/AIDS: 2‐year follow‐up

The aims of this study were to follow a cohort of HIV‐infected individuals for 2 years to assess changes in depression and neuropsychological performance over time, to explore the relationship between depression, HIV illness and neuropsychological performance, and to examine the natural history of the effect of highly active antiretroviral therapy (HAART) on depression and neurocognitive performance.
Photodynamic therapy in chronic central serous chorioretinopathy.

Chronic central serous chorioretinopathy (CCSC) occurs in patients over the age of 50 and is clinically characterized by neurosensory detachment associated with areas of retinal pigment epithelium (RPE) atrophy, pigment mottling, and fluorescein angiography (FA) evidence of uneven hyperfluorescence with subtle leaks.1,2 The end stage of the disease can lead to RPE atrophy within the macular region with severe visual impairment. Laser photocoagulation directed to focal leaks has been reported to be useful for selected cases.1,2 The present case report describes results of photodynamic therapy (PDT) with verteporfin in a case of CCSC.
Middle School Physical Education Physical Activity Quantification

The objective of the study was to improve physical activity (PA) surveillance of the Healthy People 2010 Objective 22:10 (i.e., 50% of the lesson time engaged in PA) by establishing a pedometer steps/min guideline to quantify time engaged in PA during physical education. A sample of 180 middle school students had their PA measured via pedometry (steps/min) and behavioral observation (PA time). Factorial analyses of variance were used to examine PA differences. Linear and logistic regression, decision accuracy, and receiver-operating-characteristic (ROC) statistics were used to test steps/min cut points against the 50% PA recommendation. PA differences were not found (p > .01). Steps/min was a significant (p ≤ .01) predictor of PA time, and the binary outcome of meeting or not meeting the PA recommendation. A steps/min interval of 82–88 was an accurate indicator of the 50% PA recommendation. The ROC statistic was . 97 (p ≤ .01), suggesting steps/min was an excellent discriminator of the binary outcome. Pedometer steps/min is a valid, objective, and practical approach for surveillance of physical education PA, a key physical education and public health outcome.
On the FDTD Formulations for Modeling Wideband Lorentzian Media

Several popular numerical approaches for modeling the dispersion characteristics of complex media are applied to simulate the wave propagation in the wideband Lorentzian (WBL) media under the second-order or fourth-order accurate finite-difference time-domain (FDTD) formulation. Their implementing algorithms and work performance for this type of dispersive materials are studied and compared to each other. The coefficients of a general second-order discrete numerical model pertaining to each of these approaches are derived respectively and a unified set of FDTD updating equations for implementing them is presented. In light of the analytical results calculated from the given numerical dispersion equations that determines the effective permittivity and permeability of a corresponding artificial WBL medium and the simulation results from the practical FDTD simulations for an exemplified WBL medium, the modeling accuracy and stability limits of these approaches are presented by evaluating the absolute errors of both the propagation and transmission functions of a plane electromagnetic pulse wave propagating in the WBL material and transmitting through an interface between the vacuum and the WBL medium under the second-order or fourth-order FDTD formulation combined with each of the discussed approaches.
In Vitro Synergistic Activity of Combined Piperacillin and Tobramycin Against Clinical Strains of Achromobacter xylosoxidans

Corresponding author: Jean-Marie Duez; Laboratoire de Bactériologie Médicale, CHU de Dijon, BP 37013, 21070 Dijon Cedex (France). Tel +33 380 29 35 23; Fax +33 380 29 32 80; e-mail: jean-marie.duez@chu-dijon.fr Both antibiotics were separately diluted twofold and then distributed onto microplates with a Transtar-96® apparatus (Costar, Cambridge, MA, UsA). The inoculation was performed by suspending fresh bacterial colonies in sterile saline solution to obtain a density equivalent to a 0.5 McFarland standard. A tenfold dilution was used to inoculate the microplates with an MiC 2000 replicating apparatus (Dynatech Laboratories inc., Chantilly, VA, UsA) that plunged 96 pins into the diluted suspension, took off 1 to 2 microliters per pin and delivered them into each well. This inoculum was assessed as being in the range 105-106 CFU/ml. After inoculation, the plates were covered, sealed in bags to avoid dehydration, and incubated overnight at 37°C. Growth was observed with a magnifying mirror, recorded and subcultured by the replicator to assess viability and purity. The MiC of each antibiotic was assessed and the inhibitory activity of the combination was compared to the activity of the antibiotics alone. The fractional inhibitory concentration indexes (∑FiC) were calculated according to the usual formula:
Plk1 Phosphorylation of TRF1 Is Essential for Its Binding to Telomeres*

In a search for Polo-like kinase 1 (Plk1) interaction proteins, we have identified TRF1 (telomeric repeat binding factor 1) as a potential Plk1 target. In this communication we report further characterization of the interaction. We show that Plk1 associates with TRF1, and Plk1 phosphorylates TRF1 at Ser-435 in vivo. Moreover, Cdk1, serving as a priming kinase, phosphorylates TRF1 to generate a docking site for Plk1 toward TRF1. In the presence of nocodazole, ectopic expression of wild type TRF1 but not TRF1 with alanine mutation in the Plk1 phosphorylation site induces apoptosis in cells containing short telomeres but not in cells containing long telomeres. Unexpectedly, down-regulation of TRF1 by RNA interference affects cell proliferation and results in obvious apoptosis in cells with short telomeres but not in cells with long telomeres. Importantly, we observe that telomeric DNA binding ability of TRF1 is cell cycle-regulated and reaches a peak during mitosis. Upon phosphorylation by Plk1 in vivo and in vitro, the ability of TRF1 to bind telomeric DNA is dramatically increased. These results demonstrate that Plk1 interacts with and phosphorylates TRF1 and suggest that Plk1-mediated phosphorylation is involved in both TRF1 overexpression-induced apoptosis and its telomeric DNA binding ability.
Identification of a T-cell epitope adjacent to neutralization antigenic site 1 of poliovirus type 1

Proliferative T-cell responses to poliovirus in various strains of mice have been analyzed by using either killed purified virus or capsid protein VP1 synthetic peptides. Following immunization of mice with inactivated poliovirus type 1 (PV1), a specific proliferative response of their lymph node CD4+ T cells was obtained after in vitro stimulation with purified virus. In mice immunized with PV1, PV2, or PV3, a strong cross-reactivity of the T-cell responses was observed after in vitro stimulation with heterologous viruses. By using various strategies, a dominant T-cell epitope was identified in the amino acid 103 to 115 region of capsid polypeptide VP1, close by the C3 neutralization epitope. The T-cell response to VP1 amino acids 103 to 115 is H-2 restricted: H-2d mice are responders, whereas H-2k and H-2b mice do not respond to this T-cell epitope. Immunization of BALB/c (H-2d) mice with the uncoupled p86-115 peptide, which represents VP1 amino acids 86 to 115 and contains both the T-cell epitope and the C3 neutralization epitope, induced poliovirus-specific B- and T-cell responses. Moreover, these mice developed poliovirus neutralizing antibodies.
Inclusion of the generalized Breit interaction in excitation of highly charged ions by electron impact.

The generalized Breit interaction is included in the scattering matrix elements when determining collision strengths for electron-impact excitation of highly charged ions. We use a relativistic distorted-wave approach that employs a Dirac-Fock-Slater potential to calculate the free-electron wave functions. This same potential is used to calculate the atomic-structure data. Collision strengths are presented for H-like, He-like, and Li-like ions for a range of [ital Z] values and impact-electron energies. Good agreement is obtained when comparing to the few existing calculations for hydrogenic ions. The effect of including the interaction is found to be small for ions with [ital Z][approx]26, but increases steadily with [ital Z]. Changes of nearly 70% are observed for [ital Z]=92. Effects for the more complex He-like and Li-like ions are greater than for the hydrogenic analogs for the entire range of [ital Z] values considered. The accuracy of some simpler forms of the Breit interaction is also discussed.
The chaperone function of DnaK requires the coupling of ATPase activity with substrate binding through residue E171.

Central to the chaperone function of Hsp70 stress proteins including Escherichia coli DnaK is the ability of Hsp70 to bind unfolded protein substrates in an ATP‐dependent manner. Mg2+/ATP dissociates bound substrates and, furthermore, substrate binding stimulates the ATPase of Hsp70. This coupling is proposed to require a glutamate residue, E175 of bovine Hsc70, that is entirely conserved within the Hsp70 family, as it contacts bound Mg2+/ATP and is part of a hinge required for a postulated ATP‐dependent opening/closing movement of the nucleotide binding cleft which then triggers substrate release. We analyzed the effects of dnaK mutations which alter the corresponding glutamate‐171 of DnaK to alanine, leucine or lysine. In vivo, the mutated dnaK alleles failed to complement the delta dnaK52 mutation and were dominant negative in dnaK+ cells. In vitro, all three mutant DnaK proteins were inactive in known DnaK‐dependent reactions, including refolding of denatured luciferase and initiation of lambda DNA replication. The mutant proteins retained ATPase activity, as well as the capacity to bind peptide substrates. The intrinsic ATPase activities of the mutant proteins, however, did exhibit increased Km and Vmax values. More importantly, these mutant proteins showed no stimulation of ATPase activity by substrates and no substrate dissociation by Mg2+/ATP. Thus, glutamate‐171 is required for coupling of ATPase activity with substrate binding, and this coupling is essential for the chaperone function of DnaK.
Large margin relative distance learning for person re-identification

Distance metric learning has achieved great success in person re-identification. Most existing methods that learn metrics from pairwise constraints suffer the problem of imbalanced data. In this study, the authors present a large margin relative distance learning (LMRDL) method which learns the metric from triplet constraints, so that the problem of imbalanced sample pairs can be bypassed. Different from existing triplet-based methods, LMRDL employs an improved triplet loss that enforces penalisation on the triplets with minimal inter-class distance, and this leads to a more stringent constraint to guide the learning. To suppress the large variations of pedestrian's appearance in different camera views, the authors propose to learn the metric over the intra-class subspace. The proposed method is formulated as a logistic metric learning problem with positive semi-definite constraint, and the authors derive an efficient optimisation scheme to solve it based on the accelerated proximal gradient approach. Experimental results show that the proposed method achieves state-of-the-art performance on three challenging datasets (VIPeR, PRID450S, and GRID).