Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncolytic virotherapy with an armed vaccinia virus in an orthotopic model of renal carcinoma is associated with modification of the tumor microenvironment

ABSTRACT Oncolytic virotherapy is an emergent promising therapeutic approach for the treatment of cancer. We have constructed a vaccinia virus (WR strain) deleted for thymidine kinase (TK) and ribonucleotide reductase (RR) genes that expressed the fusion suicide gene FCU1 derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. We evaluated this construct (VV-FCU1) in the orthotopic model of renal carcinoma (RenCa). Systemic administration of VV-FCU1 resulted in orthotopic tumor growth inhibition, despite temporary expression of viral proteins. VV-FCU1 treatment was associated with an infiltration of tumors by CD8+ T lymphocytes and a decrease in the proportion of infiltrating Tregs, thus modifying the ratio of CD8+/CD4+ Treg in favor of CD8+cytotoxic T cells. We demonstrated that VV-FCU1 treatment prolonged survival of animals implanted with RenCa cells in kidney. Depletion of CD8+ T cells abolished the therapeutic effect of VV-FCU1 while depletion of CD4+ T cells enhanced its protective activity. Administration of the prodrug 5-fluorocytosine (5-FC) resulted in a sustained control of tumor growth but did not extend survival. This study shows the importance of CD4+ and CD8+ T cells in vaccinia virus-mediated oncolytic virotherapy and suggests that this approach may be evaluated for the treatment of human renal cell carcinoma.
Recognition of Sulfation Pattern of Chondroitin Sulfate by Uronosyl 2-O-Sulfotransferase*

We have shown previously that a highly sulfated sequence, GalNAc(4,6-SO4)-GlcA(2SO4)-GalNAc(6SO4), is present at the nonreducing terminal of chondroitin sulfate (CS), and this structure was synthesized from a unique sequence, GalNAc(4SO4)-GlcA(2SO4)-GalNAc(6SO4), by sulfation with N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase. Uronosyl 2-O-sulfotrasferase (2OST), which transfers sulfate from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to position 2 of the GlcA residue of CS, is expected to be involved in synthesis of these structures; however, the specificity of 2OST concerning recognition of the sulfation pattern of the acceptor has largely remained unclear. In the present study, we examined the specificity of 2OST in terms of recognition of the sulfation pattern around the targeting GlcA residue. The recombinant 2OST could sulfate CS-A, CS-C, and desulfated dermatan sulfate. When [35S]glycosaminoglycans formed from CS-A after the reaction with the recombinant 2OST and [35S]PAPS were subjected to limited digestion with chondroitinase ACII, a radioactive tetrasaccharide (Tetra A) was obtained as a sole intermediate product. The sequence of Tetra A was found to be ΔHexA-GalNAc(4SO4)-GlcA(2SO4)-GalNAc(6SO4) by enzymatic and chemical reactions. These observations indicate that 2OST transfers sulfate preferentially to the GlcA residue located in a unique sequence, -GalNAc(4SO4)-GlcA-GalNAc(6SO4)-. When oligosaccharides with different sulfation patterns were used as the acceptor, GalNAc(4SO4)-GlcA-GalNAc(6SO4) and GlcA-GalNAc(4SO4)-GlcA-GalNAc(6SO4) were the best acceptors for 2OST among trisaccharides and tetrasaccharides, respectively. These results suggest that 2OST may be involved in the synthesis of the highly sulfated structure found in CS-A.
Highly active antiretroviral therapy enhances regression of cervical intraepithelial neoplasia in HIV-seropositive women

ObjectiveThis study was undertaken to investigate the impact of highly active antiretroviral therapy (HAART) on the regression of cervical intraepithelial neoplasia (CIN) in HIV-infected women. DesignProspective study of 168 HIV-infected women with evidence of CIN until regression to a lower grade or to normality (end-point) or until surgical treatment or last visit. Ninety-six patients received HAART. MethodsWomen were examined every 6 months by Papanicolaou smears, colposcopy, and biopsy if required. The probability of CIN regression was calculated using survival analysis. HAART was entered as a time-dependent covariate according to the date of first prescription. ResultsRegression of CIN was observed in 67 (39.9%) women. The probability of regression at 12 months was significantly higher for high-grade CIN [23.8%; 95% confidence interval (CI), 14.2–33.5] than for low-grade lesions (14.8%; 95% CI, 7.0–22.6) (P = 0.04). The risk of regression of CIN was twice as high in women receiving HAART as compared with women not receiving HAART (relative hazard of regression, 1.93; 95% CI, 1.14–3.29). There was a trend for a larger increase in CD4 cell counts among those women taking HAART and who showed regression as compared with those who did not regress. ConclusionThe positive impact of HAART on CIN regression may be associated with some restoration of specific immune reactivity. This is not sufficient enough, however, to modify the gynecological follow-up of HIV-infected women.
A polymorphism of the mu-opioid receptor gene (OPRM1) and sensitivity to the effects of alcohol in humans.

BACKGROUND Recent research has implicated the endogenous opioid system in the development of alcohol use disorders. The A118G polymorphism of the OPRM1 gene has been shown to confer functional differences to mu-opioid receptors, such that the G variant binds beta-endorphin three times more strongly than the A variant. The goal of this study was to test whether the A118G polymorphism is associated with sensitivity to the effects of alcohol. METHODS Participants who were either homozygous for the A allele (n = 23) or heterozygous (n = 15) received intravenous doses of alcohol designed to reach three target levels of breath alcohol concentration: 0.02, 0.04, and 0.06. The testing procedure consisted of measures of subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three target breath alcohol concentrations. RESULTS The results suggested that individuals with the G allele reported higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared with participants with the A allele. Furthermore, participants with the G allele were almost three times more likely to report a positive family history of alcohol use disorders than participants with the A allele. CONCLUSIONS These findings may help to explain previous research suggesting that naltrexone is more effective among individuals with the G allele. A medication that reduces feelings of euphoria after alcohol consumption may be more successful among individuals with a genetic predisposition to greater feelings of euphoria after consuming alcohol.
Combination therapy of low-dose medroxyprogesterone acetate and oral estrogen does not affect endothelial function in the forearms of postmenopausal women

ObjectiveWe investigated whether low-dose medroxyprogesterone acetate (MPA) combined with oral estrogen had adverse effects on endothelial function compared with oral estrogen alone in postmenopausal women with mild hypercholesterolemia. DesignSubjects were divided into two groups. One group received conjugated equine estrogen (CEE, 0.625 mg daily) orally for the first 3 months, followed by estrogen combined with MPA (2.5 mg daily) orally for an additional 3 months (n = 26). The other group received no treatment (control group, n = 12). Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. Nitrite/nitrate, angiotensin-converting enzyme, and lipid concentrations were measured in the serum. ResultsBoth CEE and CEE combined with MPA significantly increased the FBF during reactive hyperemia. This increase was similar in both active treatment phases. No changes were seen in controls. FBF after sublingual nitroglycerin did not change over 6 months in either group. Significant and similar increases in serum concentration of nitrite/nitrate and plasma renin activity as well as decreases in angiotensin-converting enzyme activity were found in both treatment phases. No such changes occurred in the control group. There was no significant increase in high-density lipoprotein cholesterol or decrease in low-density lipoprotein cholesterol between the treatment phases. Likewise, no such changes were observed in the control group. ConclusionsOur 6-month study suggests that the addition of low-dose MPA with CEE had no adverse effects on forearm resistance artery endothelial function compared with CEE alone.
Observer based reference current generation for a three-phase shunt active power filter

In this paper, a new observer-based method, which generates the current reference for a three-phase shunt active power filter (SAPF), is presented. This technique is useful for active power filters and capable to eliminate harmonics and compensate reactive power simultaneously. First, the fundamental active current to identify is modeled in the form of a generating process. The other harmonic components appearing in the load current, as well as the basic noises inherent with the signal measurements, are all considered as noises for the observer. The goal of the extraction consists in filtering the noise in order to recover the active fundamental current. The filtering is carried out using an observer on the generating model. The dynamics of the extraction will depend on the speed of convergence of the observer. Simulation results are presented, showing that the method is feasible and the results are acceptable.
Early stopping criterion for message-passing decoding of LDLC

An early stopping criterion is proposed for low-density lattice codes (LDLC) to reduce the number of decoding iterations. The stopping criterion is based on a new metric which is used to predict the convergence of the iterative decoding algorithm for LDLC. Simulation results demonstrate that the proposed criterion can decrease the average iteration number considerably while the decoding performance degradation is within 0.2dB in the low symbol error rate region. Besides, the proposed criterion can provide a flexible tradeoff between performance and complexity.
Content Analysis of Sustainability Reporting on Malaysian Local Authority Websites

ABSTRACT This study examines the extent of sustainability reporting onMalaysian local authority websites. One hundred and thirty nineMalaysian local authority websites were analyzed using the contentanalysis technique. Findings revealed that the overall disclosurelevel is low despite the fact that websites have special interactivecapabilities, fast and an efficient way to report sustainabilityinformation. The websites were not employed as a strategic tool topromote stakeholder engagement with the community. The overallfindings may assist in the formulation of policies to encourage theuse of local authority websites to report sustainability informationto stakeholders. This paper adds to the limited literature on thewebsite sustainability reporting by the public sectors. Someimplications for promoting the use of website to disclosesustainability information are also provided in the paper. Keywords : content analysis, local authority, sustainability reporting,website Introduction The issue of sustainability has received considerable critical attention inMalaysia ranging from the government, society, media and Non-governmental Organizations (NGOs). Generally, sustainability consists
Promicromonospora vindobonensis sp. nov. and Promicromonospora aerolata sp. nov., isolated from the air in the medieval 'Virgilkapelle' in Vienna.

Two airborne bacterial isolates designated V45(T) and V54A(T) were characterized in order to determine their taxonomic position. 16S rDNA sequence analysis showed that the two isolates shared 98.1 % sequence similarity. Highest sequence similarities (98.0-98.5 %) were found to Promicromonospora citrea DSM 43110(T) and Promicromonospora sukumoe IFO 14650(T). Detection of a quinone system with the predominant compound MK-9(H(4)), a polar lipid pattern containing phosphatidylglycerol, a fatty acid profile with the predominant acids C(15 : 0) iso and C(15 : 0) anteiso and the diagnostic cell-wall diamino acid L-lysine supported the assignment of the novel isolates to the genus PROMICROMONOSPORA: The two isolates could be distinguished from P. sukumoe by the presence of glycine in the peptidoglycan, and the detection of the cell-wall sugar galactose differentiates them from the two established species of the genus PROMICROMONOSPORA: Each of the two isolates displayed a unique biochemical profile. Results from DNA-DNA hybridizations clearly demonstrated that V45(T) and V54A(T) represent separate species. Based on these data, it is proposed that V45(T) (=IFO 16525(T)=CCM 7044(T)) and V54A(T) (=IFO 16526(T) =CCM 7043(T)) be classified as the type strains of two novel Promicromonospora species, for which the names Promicromonospora vindobonensis sp. nov. and Promicromonospora aerolata sp. nov. are proposed.
Low-sensitivity, low-noise, band-rejection and all-pass active-RC filters

In this paper we introduce a new design procedure for low-sensitivity and low-noise filter biquads which have a symmetrical bridged-T passive-RC network. They are also low-power circuits, in that they use only one operational amplifier (opamp). The new design concept is based on the recently introduced "impedance tapering" method which was applied to allpole filters in G.S. Moschytz (1999), whereas in this paper it is extended to the design of filters with unite zeros. Thus, it is applied to two commonly used filter sections suitable for the realization of band-rejection and all-pass filters with low and medium pole-Q factors. In the new design procedure, the topology and component count remain the same; we just judiciously select the component values in order to reduce component tolerance sensitivity and improve noise performance. The sensitivity analysis is examined analytically and double-checked using PSpice Monte Carlo runs. In the PSpice noise analysis, a macro-model of the u uA741 opamp is used. It is found that the minimum-sensitivity and minimum-noise filters coincide.
How and why honorifics can signify dignity and elegance : The indexicality and reflexivity of linguistic rituals

Honorifics are known as politeness markers in the languages that have them. However, the descriptions in the Western literature on the functions of honorifics were not felt by speakers of languages that employ honorifics to be satisfactory, either for academic or for general understanding. The goal of this paper is to try to make sense of the use and function of honorifics as fully as possible so as to explain how and why they can signify not only politeness but also the speaker's dignity and/or elegance. It is claimed that the indexing and reflexive functions of honorifics according to wakimae use have to be understood in a high context culture where the speaker's viewpoint and the organization of speaking is different from what has been generally assumed in the discipline to date.
Concurrent inspiratory muscle and cardiovascular training differentially improves both perceptions of effort and 5000 m running performance compared with cardiovascular training alone

Objective: To examine whether inspiratory muscle training (IMT) is a useful additional technique with which to augment cardiovascular exercise training adaptations. Methods: 16 healthy untrained males agreed to participate in the study and were randomly assigned to training (TRA; n = 8) and placebo (PLA; n = 8) groups. Pre- and post-training measurements of spirometry and maximal inspiratory mouth pressure (MIP) were taken in addition to i) maximal aerobic power (VO2max) and ii) 5000 m run time-trial. All subjects completed the same 4 week cardiovascular training programme which consisted of three running sessions (CV1: 5×1000 m, CV2: 3×1600 m, SP1: 20 min run) in each of the 4 weeks. IMT was performed daily by both groups using an inspiratory muscle trainer (POWERbreathe). TRA completed 30 maximal inspirations while PLA inspired 30 times against a negligible resistance. Results: Mean MIP increased significantly in both groups (TRA: 14.5 (SD 6.8)% change, PLA: 7.8 (7.4)% change) from pre- to post-training (p<0.01) but was not significantly related to changes in running performance. Mean CV1 training-repetition runs improved similarly in both groups, but RPE evaluations were significantly reduced in TRA (15.7 (0.7)) compared with PLA (16.6 (0.8)) at week 4 (p<0.05). Pre- to post-training changes in VO2max were well-matched between both TRA (+2.1 (2.3)%) and PLA (+1.3 (2.4)%) while post-intervention 5000 m performance was significantly augmented in TRA compared with PLA (TRA: 4.3 (1.6)%, PLA: 2.2 (1.9)%, p<0.05). Conclusions: The addition of IMT to a cardiovascular training programme augments 5000 m running performance but exerts no additional influence over VO2max compared with a cardiovascular-training group. This is probably due to IMT-induced reduction in perceived effort at high ventilatory rates, which is of greater consequence to longer duration time-trial performances than incremental tests of VO2max.
THE INTRINSIC PROPERTIES OF AN IN SITU PERFUSED CROCODILE HEART

An in situ perfused crocodile (Crocodylus porosus) heart preparation was developed to investigate the effects of input and output pressure on cardiac dynamics and to determine the conditions that lead to a right-to-left cardiac shunt. The pericardium was kept intact, both the left and right atria were perfused and all three outflow tracts (right aortic, left aortic and pulmonary) were cannulated, enabling pressures and flows to be monitored. The perfused heart preparation had an intrinsic heart rate of 34 beats min-1 and generated a physiological power output. Both the left and right sides of the heart were sensitive to filling pressure. Increasing the filling pressure to both atria resulted in an increase in stroke volume and cardiac output (Frank­Starling effect). Increasing the filling pressure to the right atrium also had a positive chronotropic effect. Large right ventricular stroke volumes initiated a right-to-left shunt, despite the left aorta having a pressure 1.5 kPa higher than the pulmonary output pressure. The left ventricle was able to maintain its output and stroke volume up to an output pressure of approximately 8 kPa. However, the right ventricle was significantly weaker. Right ventricular output and stroke volume showed a marked decrease when the output pressure was increased above 5 kPa. A right-to-left shunt occurred when pulmonary output pressure was increased. Surprisingly, a shunt occurred into the left aorta before the pressure in the pulmonary artery became greater than that in the left aorta. Once the pressure in the pulmonary artery exceeded the left aortic pressure, pulmonary artery flow ceased and right ventricular output was solely via the left aorta. A right-to-left shunt could also be initiated by increasing the filling pressure to the left atrium.
Drug use, health and social outcomes of hard-to-treat heroin addicts receiving supervised injectable opiate treatment: secondary outcomes from the Randomized Injectable Opioid Treatment Trial (RIOTT).

AIMS The Randomized Injectable Opioid Treatment Trial (RIOTT) compared supervised injectable heroin (SIH) and supervised injectable methadone (SIM) with optimized oral methadone (OOM) (ISRCTN0133807). Heroin addicts (previously unresponsive to treatment) made significant reductions in street heroin use at 6 months when treated with SIH. We now examine secondary outcomes. DESIGN Multi-site randomized controlled trial (RCT) comparing SIH versus OOM and SIM versus OOM. SETTING Three supervised injectable opiate clinics in England. PARTICIPANTS Chronic refractory heroin addicts continuing to inject street heroin virtually daily despite oral substitution treatment (n = 127), randomized to either SIH(n = 43), SIM(n = 42) or OOM(n = 42). All received high levels of medical and psychosocial support. MEASUREMENTS SECONDARY OUTCOMES wider drug use, crime, health and social functioning at 6 months. FINDINGS At 6 months, no significant differences were found between treatment groups in wider drug use (crack/cocaine, benzodiazepines, alcohol), physical and mental health (SF-36) or social functioning. Within each treatment group, significant reductions were observed in crime [SIH = odds ratio (OR) 0.05; P < 0.001; SIM = OR 0.11; P = 0.002; OOM = OR 0.11; P = 0.003] and money spent per week on illicit drugs (SIH = mean change £-289.43; P < 0.001; SIM = mean change £-183.41; P < 0.001; OOM = mean change £-162.80; P < 0.001), with SIH significantly more likely to have reduced money spent on illicit drugs versus OOM (mean difference £-92.04; P < 0.001). Significant improvements were seen in physical health for SIH and SIM (SIH = mean change 3.97; P = 0.008; SIM = mean change 4.73; P = 0.002) and mental health for OOM (mean change 6.04; P = 0.013). CONCLUSIONS Supervised injectable heroin treatment and supervised injectable methadone treatment showed no clearly identified benefit over optimized oral methadone in terms of wider drug use, crime, physical and mental health within a 6-month period, despite reducing street heroin use to a greater extent. However, all interventions were associated with improvements in these outcomes.
Ectopic expression of a novel OsExtensin‐like gene consistently enhances plant lodging resistance by regulating cell elongation and cell wall thickening in rice

Summary Plant lodging resistance is an important integrative agronomic trait of grain yield and quality in crops. Although extensin proteins are tightly associated with plant cell growth and cell wall construction, little has yet been reported about their impacts on plant lodging resistance. In this study, we isolated a novel extensin‐like (OsEXTL) gene in rice, and selected transgenic rice plants that expressed OsEXTL under driven with two distinct promoters. Despite different OsEXTL expression levels, two‐promoter‐driven OsEXTL‐transgenic plants, compared to a rice cultivar and an empty vector, exhibited significantly reduced cell elongation in stem internodes, leading to relatively shorter plant heights by 7%–10%. Meanwhile, the OsEXTL‐transgenic plants showed remarkably thickened secondary cell walls with higher cellulose levels in the mature plants, resulting in significantly increased detectable mechanical strength (extension and pushing forces) in the mature transgenic plants. Due to reduced plant height and increased plant mechanical strength, the OsEXTL‐transgenic plants were detected with largely enhanced lodging resistances in 3 years field experiments, compared to those of the rice cultivar ZH11. In addition, despite relatively short plant heights, the OsEXTL‐transgenic plants maintain normal grain yields and biomass production, owing to their increased cellulose levels and thickened cell walls. Hence, this study demonstrates a largely improved lodging resistance in the OsEXTL‐transgenic rice plants, and provides insights into novel extensin functions in plant cell growth and development, cell wall network construction and wall structural remodelling.