Miracle-dz/UniFAR-FTUs huggingface dataset:
Intranasal Immunization with Pneumococcal Polysaccharide Conjugate Vaccines with Nontoxic Mutants of Escherichia coliHeat-Labile Enterotoxins as Adjuvants Protects Mice against Invasive Pneumococcal Infections

ABSTRACT Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) ofEscherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.
The Binary Pulsar PSR 1908+00 in NGC 6760

We present orbital parameters of the 3.6 ms binary pulsar 1908 +00 in the globular cluster NGC 6760. The orbital period is 3.4 hr, and the mass function is 3 x 10^6 M_⊙ , implying a minimum companion mass of 0.018 M_⊙ . The companion is probably degenerate; and if it is hydrogen, it is close to overflowing its Roche lobe. The only other millisecond binary radio pulsar systems with orbital period < 10 hr and mass function below 10-3 M_⊙ are the eclipsing pulsar 1957+20 and 1744-24A, and the very low mass binary 0021-721. These pulsars are ablating their companions and may be the progenitors of isolated millisecond pulsars. PSR 1908+00 shows no evidence for long-duration eclipses as are seen in 1744-24A, but short-duration eclipses as in 1957 + 20 are not excluded.
An Ecological Study of Anterior Cruciate Ligament Reconstruction, Part 1

Background: Additional high-quality prospective studies are needed to better define the objective criteria used in relation to return-to-sport decisions after synthetic (ligament advanced reinforcement system [LARS]) and autograft (hamstring tendon [2ST/2GR]) anterior cruciate ligament (ACL) reconstruction in active populations. Purpose: To prospectively investigate and describe the recovery of objective clinical outcomes after autograft (2ST/2GR) and synthetic (LARS) ACL reconstructions, as well as to investigate the relationship between these clinimetric test outcomes and return-to-sport activity (Tegner activity scale [TAS] score) at 12 and 24 months postoperatively. Study Design: Case series; Level of evidence, 4. Methods: A total of 64 patients who underwent ACL reconstruction (32 LARS, 32 2ST/2GR autograft) and 32 healthy reference participants were assessed for joint laxity (KT-1000 arthrometer), clinical outcome (2000 International Knee Documentation Committee [IKDC] knee examination), and activity (TAS score) preoperatively and at 12, 16, 20, and 24 weeks and 12 and 24 months postoperatively. Results: There was no significant correlation observed between clinical results using the 2000 IKDC knee examination and TAS score at 24 months (r s = 0.188, P = .137), nor were results for side-to-side difference (r s = 0.030, P = .814) or absolute KT-1000 arthrometer laxity of the surgical leg at 24 months postoperatively (r s = 0.076, P = .553) correlated with return-to-sport activity. Nonetheless, return-to-sport rates within the surgical cohort were 81% at 12 months and 83% at 24 months, respectively. No statistically significant differences were observed between physiological laxity of the uninjured knee within the surgical group compared with healthy knees within the reference group (P = .522). Conclusion: The results indicate that although relatively high levels of return-to-sport outcomes were achieved at 24 months compared with those previously reported in the literature, correlations between objective clinical tests and return-to-sport outcomes may not occur. Clinical outcome measures may provide suitable baseline information; however, the results of this study suggest that clinicians may need to place greater emphasis on other outcome measures when seeking to objectively promote safe return to sport.
So-called "nervous habits".

Summary The so-called “nervous habits” of 198 students were assessed by time-sampling 22 movement categories. Concentration of manipulatory behavior in the head and hand areas suggested that the stimulation generated by these activities is of some importance. Compared to men, women showed less facial manipulation and less leg and foot movement, but compensated, particularly by more nail-biting and manicure. Category scores did not have significant linear correlations with either Extraversion or Neuroticism scores on the Eysenck Personality Inventory (EPI). This may be due to idiosyncrasies in movement patterns.
Sequential Analysis: Design Methods and Applications Nearly Minimax One-sided Mixture-based Sequential Tests Nearly Minimax One-sided Mixture-based Sequential Tests

This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Abstract: We focus on one-sided, mixture-based stopping rules for the problem of sequential testing a simple null hypothesis against a composite alternative. For the latter, we consider two cases—either a discrete alternative or a continuous alternative that can be embedded into an exponential family. For each case, we find a mixture-based stopping rule that is nearly minimax in the sense of minimizing the maximal Kullback–Leibler information. The proof of this result is based on finding an almost Bayes rule for an appropriate sequential decision problem and on high-order asymptotic approximations for the performance characteristics of arbitrary mixture-based stopping times. We also evaluate the asymptotic performance loss of certain intuitive mixture rules and verify the accuracy of our asymptotic approximations with simulation experiments.
Chemokine ligand 20 enhances progression of hepatocellular carcinoma via epithelial-mesenchymal transition.

AIM To identify the mechanisms of chemokine ligand 20 (CCL20)-induced hepatocellular carcinoma (HCC) metastasis and evaluate it as a prognostic marker. METHODS Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues from 62 patients who underwent curative resection. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of HCC patients. The expression levels of epithelial-mesenchymal transition (EMT)-and signaling pathway-related proteins were evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide (MTT) and Transwell assays. RESULTS CCL20 immunoreactivity was detected in all 62 patient specimens. CCL20 expression was associated with preoperative alpha-fetoprotein level (P = 0.043), tumor size (P = 0.000), tumor number (P = 0.008), vascular invasion (P = 0.014), and tumor differentiation (P = 0.007). Patients with high CCL20 expression had poorer recurrence-free and overall survivals compared to those with low CCL20 expression (both P < 0.001). CCL20 induced EMT-like changes in HCC cells and increased their proliferation and migration ability (P < 0.05). Western blotting and immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in HCC cells, and increased expression of phosphorylated AKT, β-catenin and vimentin, and decreased E-cadherin expression (P < 0.05). The correlation analysis revealed that high CCL20 expression in HCC tissue specimens was negatively correlated with E-cadherin expression (13.33%, 4/30), and positively correlated with vimentin (90.0%, 27/30), β-catenin (96.67%, 29/30) and p-AKT (76.67%, 23/30) expression. CONCLUSION CCL20 expression is associated with HCC recurrence and patient survival and promotes HCC cell proliferation and migration by inducing EMT-like changes via PI3K/AKT and Wnt/β-catenin pathways.
Elicited by the “ Binge ” Administration of Methamphetamine

Methamphetamine (METH) abuse is often characterized by a repeated pattern of frequent drug administrations (binge) followed by a period of abstinence. The effect of this pattern of METH use on cardiovascular function has not been characterized. Radiotelemetry was used to record the cardiovascular responses elicited during three successive METH binges (3 mg/kg, b.i.d. for 4 days) in conscious rats. Each binge was followed by a 10-day METH-free period. The effects of METH administration on vascular reactivity, Bezold-Jarisch reflex function, and cardiac morphology were also evaluated. The pressor responses elicited by the first three doses of METH in the second and third binges were significantly larger than those elicited by the corresponding doses in the first binge. The heart rate (HR) responses elicited by METH were similar within and among the three binges. Ten days after the last binge, the depressor responses elicited by the i.v. injection of sodium nitroprusside, isoproterenol, and acetylcholine were significantly smaller than those elicited before each binge. The arterial pressure and HR responses elicited by phenylephrine were unchanged. Bezold-Jarisch reflex function evoked by i.v. serotonin (10 g/kg) was significantly altered. The hearts from treated rats showed focal inflammatory infiltrates with abundant monocytes and occasional necrotic foci. These results indicate that this binge pattern of METH administration can significantly alter cardiovascular function and cardiovascular reflex function and produce serious cardiac pathology. The illicit use of methamphetamine (METH) has dramatically increased during the past several years, as has the number of clinical reports detailing serious and sometimes fatal cardiovascular toxicity associated with the use of this drug (Hong et al., 1991; Karch et al., 1999). Despite the potential dangers posed by METH, the cardiovascular effects of this drug have not been well characterized. Most experimental and clinical studies examining the cardiovascular actions of METH have focused on the acute arterial pressure (AP) and heart rate (HR) effects of the drug (Martin et al., 1971; Schindler et al., 1992). However, METH abuse typically involves a pattern of repeated drug administration. Only a handful of studies have looked at the cardiovascular responses elicited by repeated METH administration. For example, in humans given daily oral doses of METH, tolerance develops to the tachycardic but not the pressor actions of the drug (Perez-Reyes et al., 1991). In hypertensive dogs, daily oral administration of METH lowers resting AP but does not alter the magnitude of the pressor response elicited by METH (Vidrio, 1982). Conversely, in normotensive dogs the magnitude of the pressor response, but not the baseline AP, is lowered by the same dosing regime (Vidrio, 1982). In rats given single, intermittent i.p. doses of METH (six doses spaced 3–4 days apart), there is sensitization to the pressor effects of METH; however, the tachycardic responses and baseline cardiovascular parameters are not altered (Yoshida
In vivo footprinting and high-resolution methylation analysis of the mouse hypoxanthine phosphoribosyltransferase gene 5' region on the active and inactive X chromosomes

To investigate potential mechanisms regulating the hypoxanthine phosphoribosyltransferase (HPRT) gene by X-chromosome inactivation, we performed in vivo footprinting and high-resolution DNA methylation analysis on the 5' region of the active and inactive mouse HPRT alleles and compared these results with those from the human HPRT gene. We found multiple footprinted sites on the active mouse HPRT allele and no footprints on the inactive allele. Comparison of the footprint patterns of the mouse and human HPRT genes demonstrated that the in vivo binding of regulatory proteins between these species is generally conserved but not identical. Detailed nucleotide sequence comparison of footprinted regions in the mouse and human genes revealed a novel 9-bp sequence associated with transcription factor binding near the transcription sites of both genes, suggesting the identification of a new conserved initiator element. Ligation-mediated PCR genomic sequencing showed that all CpG dinucleotides examined on the active allele are unmethylated, while the majority of CpGs on the inactive allele are methylated and interspersed with a few hypomethylated sites. This pattern of methylation on the inactive mouse allele is notably different from the unusual methylation pattern of the inactive human gene, which exhibited strong hypomethylation specifically at GC boxes. These studies, in conjunction with other genomic sequencing studies of X-linked genes, demonstrate that (i) the active alleles are essentially unmethylated, (ii) the inactive alleles are hypermethylated, and (iii) the high-resolution methylation patterns of the hypermethylated inactive alleles are not strictly conserved. There is no obvious correlation between the pattern of methylated sites on the inactive alleles and the pattern of binding sites for transcription factors on the active alleles. These results are discussed in relationship to potential mechanisms of transcriptional regulation by X-chromosome inactivation.
Multiple Independent Genetic Variants in the 8q24 Region Are Associated with Prostate Cancer Risk

Recently, the 8q24 region has been identified as a prostate cancer susceptibility locus in a genome-wide scan of prostate cancer families in Iceland and an admixture scan of African Americans. Further investigations of variants at 8q24 have shown the existence of additional single nucleotide polymorphisms (SNPs) that enhance prostate cancer risk, suggesting the possibility of multiple regions harboring variants for the disease. In the present population-based study of Caucasians (1,308 cases and 1,266 controls) and African Americans (149 cases and 85 controls), we tested the association between prostate cancer and 23 SNPs in the 8q24 region. Fourteen SNPs in Caucasians and 5 SNPs in African Americans were significantly associated with risk of prostate cancer after adjusting for multiple comparisons; of these, 5 SNPs in Caucasians and 3 in African Americans were independently associated with risk. The strongest association was for rs6983561 (carriers of any C allele) with an odds ratio of 1.6 (95% confidence interval, 1.1-2.1) in Caucasians; variants in rs979200, rs1016343, rs7837328, and rs10090154 were also independently associated with risk. In African Americans, the strongest association was for rs7000448 (carriers of any T allele) with an odds ratio of 3.4 (95% confidence interval, 1.3-8.7). In addition, two SNPs that extend the boundaries of the 8q24 region were significantly associated with risk: rs979200 at the centromeric boundary and rs3891248, located in the first intron of the c-MYC gene (IVS1-355), which identifies a new telomeric boundary. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1203–13)
The theory-practice gap: impact of professional-bureaucratic work conflict on newly-qualified nurses.

AIM This paper reports the findings from a naturalistic enquiry undertaken in the United Kingdom into the extent to which the ideals and values of the preregistration nursing course are adopted by individual newly educated Registered Nurses. BACKGROUND Research in several countries provides consistent evidence of the existence of a theory-practice gap in nursing. Clear disparities have been demonstrated between the best practice ideals and values that are taught and those actually encountered in everyday practice. Nurse education 'Project 2000' reforms in the United Kingdom were designed, in part, to address this issue. Few studies to date have examined the impact of these reforms on newly qualified Registered Nurses' ability to translate theory into practice. METHODS A longitudinal study was carried out in three educational institutions in the United Kingdom from 1997 to 2000. Final year nursing students (n = 72) in three colleges of nursing completed questionnaires to elicit views on their ideals and values for practice. In-depth interviews with a purposive subsample of 26 participants (at 4-6 and 11-15 months postqualification) indicated the extent to which these ideals and values were adopted in practice. Interviews were tape-recorded, transcribed, and data were analysed using constant comparison and negative case analysis. FINDINGS Although new nurses emerged from their programmes with a strong set of nursing values, a number of professional and organizational factors effectively sabotaged implementation. Professional sabotage includes obeying covert rules, lack of support and poor nursing role models. Organizational sabotage includes structural and organizational constraints such as time pressures, role constraints, staff shortages and work overload. CONCLUSION The disparity between nursing as taught and as practised may have profound implications for the future of the profession both in the United Kingdom and internationally, in terms of morale, job satisfaction and retention. Measures to improve resources and reduce the professional-bureaucratic work conflict are discussed.
Reopening of L-type calcium channels in human ventricular myocytes during applied epicardial action potentials.

AIMS Present study was performed to compare the dynamics of human L-type calcium current (ICa,L) flowing during rectangular voltage pulses, voltage ramps, and action potentials (APs) recorded from epicardiac and endocardiac canine ventricular cells. METHODS ICa,L was recorded in single myocytes isolated from undiseased human hearts using the whole cell voltage clamp technique. RESULTS The decay of ICa,L was monotonic when using rectangular pulses or endocardial APs as voltage commands, whereas the current became double-peaked (displaying a second rise and fall) during epicardial (EPI) APs or voltage ramps used to mimic EPI APs. These ICa,L profiles were associated with single-hooked and double-hooked phase-plane trajectories, respectively. No sustained current was observed during the AP commands. Kinetics of deactivation and recovery from inactivation of human ICa,L were determined using twin-pulse voltage protocols and voltage ramps, and the results were similar to those obtained previously in canine cells under identical experimental conditions. CONCLUSIONS ICa,L can inactivate partially before and deactivate during the phase-1 repolarization of the epicardiac AP, and reopening of these channels seems to be associated with formation of the dome.
Genetic Ablation of Bcl-x Attenuates Invasiveness without Affecting Apoptosis or Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Cancer

Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-xL, demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic β-cell-specific knockout of both alleles of Bcl-x using the Cre-LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, suggestive of redundancy without compensatory transcriptional up-regulation. Interestingly, the incidence of invasive carcinomas was reduced, and tumor cells lacking Bcl-x were impaired in invasion in a two-chamber trans-well assay under conditions mimicking hypoxia. Thus, while the function of Bcl-x in suppressing apoptosis and thereby promoting tumor growth is evidently redundant, genetic ablation implicates Bcl-x in selectively facilitating invasion, consistent with a recent report documenting a pro-invasive capability of Bcl-xL upon exogenous over-expression.
Hypolipidemic and Antioxidative Effects of the Plant Glycoprotein (36 kDa) from Rhus verniciflua Stokes Fruit in Triton WR-1339-Induced Hyperlipidemic Mice

We investigated the hypolipidemic and antioxidative effects on male ICR mice of a glycoprotein isolated from Rhus verniciflua Stokes (RVS) fruit. The administration of the RVS glycoprotein (100 mg/kg) for two weeks resulted in a significant decrease in such plasma lipid levels as total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL). The levels of TC, TG and LDL in the hyperlipidemic model were significantly increased, whereas the high-density lipoprotein (HDL) level was considerably decreased. The 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity and the level of thiobarbituric acid-reactive substances (TBARS) were significantly elevated, whereas the production of nitric oxide (NO) was diminished. Moreover, the administration of the RVS glycoprotein prior to inducing hyperlipidemic mice suppressed the increase in the plasma lipid levels (TC, TG and LDL), and decrease in the HDL level in Triton WR-1339-induced hyperlipidemic mice. Furthermore, the RVS glycoprotein significantly inhibited the activity of HMG-CoA reductase and the levels of TBARS in the hyperlipidemic mice. In addition, the activities of detoxicant enzymes [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were gradually augmented after a supplement with the RVS glycoprotein. The results suggest that the RVS glycoprotein would be effective in preventing an increase in the plasma lipid levels and in improving the antioxidant levels. This protein might be useful as a therapeutic agent.
Methyl 2-oxo-2H-chromene-3-carboxylate

The title compound, C11H8O4, features an almost planar molecule (r.m.s. deviation = 0.033 Å for all non-H atoms). In the crystal, the molecules are linked via C—H⋯O hydrogen bonds, forming two-dimensional networks lying parallel to (1-21).