Miracle-dz/UniFAR-FTUs huggingface dataset:
Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant*

Exposure of the lung to concentrations of ozone found in ambient air is known to cause toxicity to the epithelial cells of the lung. Because of the chemical reactivity of ozone, it likely reacts with target molecules in pulmonary surfactant, a lipid-rich material that lines the epithelial cells in the airways. Phospholipids containing unsaturated fatty acyl groups and cholesterol would be susceptible to attack by ozone, which may lead to the formation of cytotoxic products. Whereas free radicalderived oxidized cholesterol products have been frequently studied for their cytotoxic effects, ozonized cholesterol products have not been studied, although they could reasonably play a role in the toxicity of ozone. The reaction of ozone with cholesterol yielded a complex series of products including 3β-hydroxy-5-oxo-5,6-secocholestan-6-al, 5-hydroperoxy-B-homo-6-oxa-cholestan-3β,7a-diol, and 5β,6β-epoxycholesterol. Mass spectrometry and radioactive monitoring were used to identify the major cholesterol-derived product during the reaction of 2 ppm ozone in surfactant as 5β,6β-epoxycholesterol, which is only a minor product during ozonolysis of cholesterol in solution. A dose-dependent formation of 5β,6β-epoxycholesterol was also seen during direct exposure of intact cultured human bronchial epithelial cells (16-HBE) to ozone. Studies of the metabolism of this epoxide in lung epithelial cells yielded small amounts of the expected metabolite, cholestan-3β,5α,6β-triol, and more abundant levels of an unexpected metabolite, cholestan-6-oxo-3β,5α-diol. Both 5β,6β-epoxycholesterol and cholestan-6-oxo-3β,5α-diol were shown to be cytotoxic to cultured 16-HBE cells. A possible mechanism for cytotoxicity is the ability of these oxysterols to inhibit isoprenoid-based cholesterol biosynthesis in these cells.
Thermal resistance of Bacillus subtilis var. niger in a closed system

The heat resistance of Bacillus subtilis var. niger has been measured from 85 to 125 degrees C using moisture levels of percent relative humidity (%RH) less than or equal to 0.001 to 100 in a closed system. Five curves have been presented to characterize the thermal destruction, using thermal death times defined as F values at a given combination of three moisture and temperature conditions. Reductions of 99.99% (4-log10 cycles) of the initial population were estimated for the three moisture conditions. At 110 degrees C, the expected time for a 4-log10 reduction was 1.1 h at %RH = 100, 3.1 h at %RH less than or equal to 0.1 and 54 h at %RH = 10.7. Goodness-of-fit tests to examine the adequacy of three polynomial models failed to indicate a trend. The linear model (from which estimates of D are obtained) was satisfactory for estimating the thermal death times (%RH less than or equal to 0.1) in the plate count range. The estimates based on observed thermal death times and D values for the %RH = 100 diverged so that D values generally gave a more conservative estimate over the temperature range 90 to 125 degrees C. Estimates of ZF and ZL ranged from 32.1 to 58.3 degrees C for the %RH less than or equal to 0.1 and 100. A ZD value of 30.0 was obtained for data observed at %RH less than or equal to 0.1. The ZF results were obtained from plotting observed log times to achieve a 99.99% reduction in the initial population versus temperature. Estimates of ZL and ZD were obtained by using linear estimates of L100 approximately equal to 4D and D values in a similar plot.
Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials

Background:In the week 48 primary analysis of ECHO and THRIVE, rilpivirine demonstrated noninferior efficacy and more favourable tolerability versus efavirenz in treatment-naive, HIV-1-infected adults. Pooled 96-week results are presented. Methods:Patients (N = 1368) received rilpivirine 25 mg once-daily (q.d.) or efavirenz 600 mg q.d. , with two background nucleoside/nucleotide reverse transcriptase inhibitors, in two randomized, double-blind, double-dummy Phase III trials. Results:At week 96, response rate (% confirmed viral load <50 copies/ml; intent-to-treat, time-to-loss-of-virologic response) was 78% in both groups. Responses were similar for both treatments by background regimen, sex, race, and in patients with more than 95% adherence (M-MASRI) or baseline viral load 100 000 copies/ml or less. Responses were lower and virologic failure higher for rilpivirine versus efavirenz in patients with 95% or less adherence or baseline viral load more than 100 000 copies/ml. Beyond week 48, the incidence of virologic failure was comparable (3 versus 2%) between treatment groups, rilpivirine resistance-associated mutations were consistent with those observed in year 1, there were few adverse events in both groups and no new safety concerns. Over 96 weeks, discontinuations due to adverse events (4 versus 9%), treatment-related grade 2–4 adverse events (17 versus 33%), rash (4 versus 15%), dizziness (8 versus 27%) and abnormal dreams/nightmares (8 versus 13%), and grade 2–4 lipid abnormalities were lower with rilpivirine than efavirenz. Only 2 and 4% of patients in the rilpivirine and efavirenz treatment groups, respectively, reported at least possibly treatment-related grade 2–4 adverse events during the second year of treatment. Conclusions:Rilpivirine 25 mg q.d. and efavirenz 600 mg q.d. had comparable responses at week 96. Rilpivirine had more virologic failures but improved tolerability versus efavirenz. The majority of virologic failures occurred in the first 48 weeks.
Chondroitin sulfate capsule system for efficient and secure gene delivery.

PURPOSE In this study, we developed various ternary complexes of encapsulated polyplexes and lipoplexes using chondroitin sulfate (CS) and investigated their universal usefulness for gene delivery. METHODS To prepare the cationic complexes, pDNA was mixed with some cationic vectors such as poly-L-arginine, poly-L-lysine, N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol liposomes, and DOTMA- dioleylphosphatidylethanolamine (DOPE) liposomes. CS was added to the cationic complexes for constructions of ternary complexes. We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of the ternary complexes. RESULT The cationic polymers and cationic liposomes bound to pDNA and formed stable cationic polyplexes and lipoplexes, respectively. Those cationic complexes showed high transgene efficiency in B16-F10 cells; however, they also had high cytotoxicity and strong agglutination with erythrocytes. CS could encapsulate the polyplexes and lipoplexes and form stable anionic particles without disrupting their structures. The ternary complexes encapsulated by CS showed high transgene efficiency in B16-F10 cells with low cytotoxicity and agglutination. As the result of animal experiments, the polyplexes had little transgene efficiency after intravenous administration in mice, whereas polyplexes encapsulated by CS showed specifically high transgene efficiency in the spleen. The capsulation of CS, however, reduced the high transgene efficiency of the lipoplexes. CONCLUSION These results indicate that CS can contribute to polyplex-mediated gene delivery systems for effective and safe gene therapy.
A Follow-up Study of Persons Found Not Criminally Responsible on Account of Mental Disorder in British Columbia

Objective: To describe the characteristics of individuals found not criminally responsible on account of mental disorder (NCRMD) after the 1992 Criminal Code amendments and to track their movement through the forensic system, as well as to unveil the changes to British Columbia's forensic psychiatric system that resulted from Bill C-30. Method: Profile information relating to persons found NCRMD between February 4, 1992, and February 4, 1998, in British Columbia was collected and analyzed. Community follow-up data was collected and analyzed for a 24-month period following a subject's discharge from hospital. Results: A substantially greater number of individuals entered the forensic psychiatric system in British Columbia after Bill C-30 was implemented. The post-1992 forensic psychiatric population contained fewer persons charged with serious index offences and a greater number of persons charged with relatively minor offences. The length of hospitalization for the NCRMD cohort decreased substantially after the 1992 Criminal Code amendments. Conclusion: The Bill C-30 provisions have made the NCRMD defence an attractive option for defendants and legal counsel.
Update on the pharmacology of REM sleep behavior disorder

REM sleep behavior disorder (RBD) is characterized by complex behavioral manifestations in response to dream content that may cause sleep disruption or injuries to the patient or the bed partner. In this case, the patients need treatment to control their symptoms. Pharmacologic agents have been reported to have positive and negative impacts on REM sleep muscle atonia and the motor behaviors associated with RBD. Clonazepam is efficacious and well tolerated by the majority of patients afflicted by RBD and should be considered as initial treatment. In patients at risk of falls who have cognitive impairment or who have obstructive sleep apneas, melatonin may be a good alternative to clonazepam. Anticholinesterase inhibitors and dopaminergic agents are not of clear benefit. Monoamine oxidase inhibitors, tricyclic antidepressants, serotonergic synaptic reuptake inhibitors, and noradrenergic antagonists can induce or aggravate RBD symptoms and should be avoided in patients with RBD. When these agents are prescribed to patients with neurodegenerative disorders or narcolepsy who are at risk of developing RBD, systematic follow-up may be warranted to detect the emergence of RBD symptoms.
Unraveling pleiotropic functions of A-To-I RNA editing in Drosophila

In metazoan cells, transcripts that fold into double-strand RNA structures are endowed with the capacity to undergo A-to-I RNA editing, during which adenosines are catalytically deaminated to inosines by a class of enzymes known as ADARs (adenosine deaminases acting on RNA). In Drosophila, a wide range of coding mRNAs associated with signaling in the nervous system undergo A-to-I editing, and loss of editing results in extreme behavioral defects. Furthermore, there are indications that the precursors of endogenous small interfering RNAs also undergo editing. However, the mechanism by which A-to-I editing is related to ethology in Drosophila is unclear, as are the precise cell-types and developmental stages in which editing is most crucial. We have investigated these issues by altering small RNA production in flies lacking ADAR, and modulating editing levels in both time and space through a variety of transgenic techniques. Our results indicate that genetic re-coding in the nervous system is likely to be the primary pathway through which editing affects behavioral outputs, and further suggest that editing is required to 'fine-tune' neuro-transmission in the adult brain.
An overview of current issues in the uptake of atmospheric trace gases by aerosols and clouds

Abstract. A workshop was held in the framework of the ACCENT (Atmospheric Composition Change – a European Network) Joint Research Programme on "Aerosols" and the Programme on "Access to Laboratory Data". The aim of the workshop was to hold "Gordon Conference" type discussion covering accommodation and reactive uptake of water vapour and trace pollutant gases on condensed phase atmospheric materials. The scope was to review and define the current state of knowledge of accommodation coefficients for water vapour on water droplet and ice surfaces, and uptake of trace gas species on a variety of different surfaces characteristic of the atmospheric condensed phase particulate matter and cloud droplets. Twenty-six scientists participated in this meeting through presentations, discussions and the development of a consensus review. In this review we present an analysis of the state of knowledge on the thermal and mass accommodation coefficient for water vapour on aqueous droplets and ice and a survey of current state-of the-art of reactive uptake of trace gases on a range of liquid and solid atmospheric droplets and particles. The review recommends consistent definitions of the various parameters that are needed for quantitative representation of the range of gas/condensed surface kinetic processes important for the atmosphere and identifies topics that require additional research.
Biological Populations with Nonoverlapping Generations: Stable Points, Stable Cycles, and Chaos

Some of the simplest nonlinear difference equations describing the growth of biological populations with nonoverlapping generations can exhibit a remarkable spectrum of dynamical behavior, from stable equilibrium points, to stable cyclic oscillations between 2 population points, to stable cycles with 4, 8, 16, . points, through to a chaotic regime in which (depending on the initial population value) cycles of any period, or even totally aperiodic but boundedpopulation fluctuations, can occur. This rich dynamical structure is overlooked in conventional linearized analyses; its existence in such fully deterministic nonlinear difference equations is a fact of considerable mathematical and ecological interest.
Irreversible color vision losses in patients with chronic mercury vapor intoxication

This longitudinal study addresses the reversibility of color vision losses in subjects who had been occupationally exposed to mercury vapor. Color discrimination was assessed in 20 Hg-exposed patients (mean age = 42.4 ± 6.5 years; 6 females and 14 males) with exposure to Hg vapor during 10.5 ± 5.3 years and away from the work place (relative to 2002) for 6.8 ± 4.2 years. During the Hg exposure or up to one year after ceasing it, mean urinary Hg concentration was 47 ± 35.4 μg/g creatinine. There was no information on Hg urinary concentration at the time of the first tests, in 2002 (Ventura et al., 2005), but at the time of the follow-up tests, in 2005, this value was 1.4 ± 1.4 μg/g creatinine for patients compared with 0.5 ± 0.5 μg/g creatinine for controls (different group from the one in Ventura et al. (2005)). Color vision was monocularly assessed using the Cambridge Colour Test (CCT). Hg-exposed patients had significantly worse color discrimination (p < 0.02) than controls, as evaluated by the size of MacAdam's color discrimination ellipses and color discrimination thresholds along protan, deutan, and tritan confusion axes. There were no significant differences between the results of the study in Ventura et al. (2005) and in the present follow-up measurements, in 2005, except for worsening of the tritan thresholds in the best eye in 2005. Both chromatic systems, blue-yellow and red-green, were affected in the first evaluation (Ventura et al., 2005) and remained impaired in the follow-up testing, in 2005. These findings indicate that following a long-term occupational exposure to Hg vapor, even several years away from the source of intoxication, color vision impairment remains irreversible.
Characterization of a Protective Monoclonal AntibodyRecognizing Staphylococcus aureus MSCRAMM ProteinClumping FactorA

ABSTRACT The Staphylococcus aureus MSCRAMM (microbial surface components recognizing adhesive matrix molecules) protein clumping factor A (ClfA) has been shown to be a critical virulence factor in several experimental models of infection. This report describes the generation, characterization, and in vivo evaluation of a murine monoclonal antibody (MAb) against ClfA. Flow cytometric analysis revealed that MAb 12-9 recognized ClfA protein expressed by all of the clinical S. aureus strains obtained from a variety of sources. In assays measuring whole-cell S. aureus binding to human fibrinogen, MAb 12-9 inhibited S. aureus binding by over 90% and displaced up to 35% of the previously adherent S. aureus bacteria. Furthermore, a single infusion of MAb 12-9 was protective against an intravenous challenge with a methicillin-resistant strain of S. aureus in a murine sepsis model (P< 0.0001). These data suggest that anti-ClfA MAb 12-9 should be further investigated as a novel immunotherapy for the treatment and prevention of life-threatening S. aureus infections.
Review : Restoring Sinus Rhythm in Patients with Atrial Flutter and Fibrillation: Pharmacologic or Electrical Cardioversion?

Atrial fibrillation and atrial flutter, the most frequently encountered tachyarrhythmias requir ing treatment, have become a major focus for clinical and basic research in recent years. Restoration and maintenance of sinus rhythm, having been shown to improve exercise capac ity, alleviate symptoms, and reduce the incidence of thromboembolic events, may be the opti mal management strategy. Identification of the safest, most efficacious and cost-effective means of restoring sinus rhythm is necessary prior to the institution of optimal antiarrhyth mic therapy to maintain sinus rhythm. Potential advantages of pharmacologic compared with electrical cardioversion include lack of need for general anesthesia and likely lower cost. Pharmacologic conversion has been accomplished with drugs that prolong atrial refractori ness, including class Ia (quinidine, procainamide, disopyramide), class Ic (flecainide, propafenone), and class III (sotalol, amiodarone) compounds. The so-called pure class III agents were created to overcome the blocker side effects of sotalol and the complex pharma codynamic profile of amiodarone. Two such agents are dofetilide, which selectively blocks the rapid component of the delayed rectifier current (Ikr) and ibutilide, which augments the slow inward sodium current, with a smaller component of action mediated by the block of Ikr. Reported overall conversion rates for recent onset atrial fibrillation and atrial flutter were 31 % and 54% for dofetilide, respectively, and 29-31 % and 38-63%, respectively, for ibu tilide. Proarrhythmia, manifested as polymorphic ventricular tachycardia requiring cardiover sion, was a significant early side effect of both agents. Data from clinical trials with these new agents, combined with increasing knowledge of the electrophysiologic substrate for these arrhythmias, has renewed interest in the development of safer, more efficacious class III drugs for atrial fibrillation and atrial flutter conversion.
Differential effects of nitric oxide synthase modulation on porcine systemic and pulmonary circulation in vivo.

OBJECTIVE To study and compare the effects of inhibiting endothelial nitric oxide synthase on systemic and pulmonary circulation in an in vivo model. DESIGN Prospective, randomized, controlled study. SETTING Laboratory for experimental surgery at a university medical center. SUBJECTS Seventeen anesthetized, mechanically ventilated pigs. INTERVENTIONS To produce a stable and continuous stimulation of endothelial nitric oxide synthase, an infusion of acetylcholine was given to one group of animals (n = 5) in a dose that decreased mean arterial pressure by 15%. After 45 mins, N(G)-monomethyl-L-arginine (L-NMMA) was given in a dose of 3 mg/kg for 5 mins in order to inhibit the enzyme. A second dose of 10 mg/kg was given 30 mins later. L-arginine was then given in a dose of 100 mg/kg to reverse the inhibition. One group of animals (n = 6) received a single dose of indomethacin (2.5 mg/kg) 15 mins after the start of acetylcholine infusion. L-NMMA and L-arginine were then given. In a control group (n = 5), the effects of L-NMMA and L-arginine were studied without acetylcholine. Circulatory parameters were monitored and resistance indices were calculated via arterial, central venous, and pulmonary artery catheters. MEASUREMENTS AND MAIN RESULTS In control animals, 3 and 10 mg/kg of L-NMMA induced an increase in mean arterial pressure of 14% and 25%, respectively, with similar increases in systemic vascular resistance. Mean pulmonary arterial pressure increased by 22% and 48%, respectively. Acetylcholine lowered mean arterial pressure by 15% and did not affect the relative changes induced by L-NMMA. Acetylcholine had no effect on pulmonary resting tone but enhanced the pulmonary hypertension and increase in resistance induced by L-NMMA. This enhancement was abolished by indomethacin, which produced systemic hypertension while no effect on pulmonary pressure was seen. CONCLUSIONS A basal release of nitric oxide contributes to the maintenance of normal vascular tone in the anesthetized pig. Stimulation of endothelial nitric oxide synthase by acetylcholine did not result in any further pulmonary vasodilation as was seen in the systemic circulation. Inhibition of nitric oxide synthase had a greater effect on pulmonary pressure than on systemic pressure. However, this difference was abolished by the administration of indomethacin. Increased nitric oxide release or acetylcholine itself seems to stimulate the production of a vasoconstricting prostanoid in the pulmonary circulation.
Origins and originators: lesbian couples negotiating parental identities and sperm donor conception

Donor conception challenges conventional kinship idioms: the involvement of a gamete donor culturally raises questions about parentage and also the meaning of genetic heritage. Although there is now a growing body of literature exploring how people resorting to donor conception negotiate kinship and connectedness, this predominantly focuses on heterosexual couples. Little is yet known about how lesbian couples navigate these processes. This paper builds on a qualitative interview study comprising 25 lesbian couples in England and Wales with experiences of pursuing donor conception in the context of their couple relationship to explore how these couples negotiate the contribution of the donor. It explores how couples negotiate meanings of parenthood, genetic origins and the bodily process of conception. The paper argues that lesbian couples negotiate parental identities, biogenetic relationships and also the meaning of conception by disassembling and reassembling the meaning of kinship, parenthood, creation, origin and originator. Findings suggest that lesbian couples weave together old and new understandings of relatedness in complex patterns and that this enables them to assert authority as parents.