Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrolyte-labile increase of oxygen affinity during in vivo aging of hemoglobin.

Normal human erythrocytes were separated according to in vivo age by ultracentrifugation. The "young" and "old" erythrocytes had mean cell ages of approximately 40 and 79 days, respectively. "Young" erythrocytes had a lower oxygen affinity and a higher heme-heme interaction than did "old" erythrocytes. This indicates an impairment of the oxygen-carrying function of erythrocyte hemoglobin with age. "Young" and "old" erythrocytes were hemolyzed yielding "young" and "old" hemoglobins. "Young" hemoglobin had a comparably lower oxygen affinity than did "old" hemoglobin when the hemolysates were dialyzed against electrolyte-free water. Exposure to sodium chloride completely obliterated this difference between the oxygen affinities and buffer values of "young" and "old" free hemoglobin. Similar exposure to potassium chloride resulted in partial obliteration of the difference between the oxygen affinities of "young" and "old" hemoglobin. Subsequent removal of sodium chloride by dialysis did not restore the pre-electrolyte differences between the oxygen affinities of "young" and "old" hemoglobin. This evidence indicates that in vivo aging is accompanied by a conformational change of the hemoglobin molecule, which is probably due to an alteration of electrostatic interactions involving the hemoglobin molecule and which is retained after hemolysis and dialysis against water but is obliterated by addition of electrolyte. It is not possible, however, to decide from the available evidence whether this molecular change occurs independently or as a result of influences by other substances, such as 2,3-diphosphoglycerate, which also change during in vivo aging of the erythrocyte.
Characterization of ocular hypertension induced by adenosine agonists.

PURPOSE Previous studies have shown that adenosine agonists may induce a rise in intraocular pressure (IOP), a reduction in IOP, or both. Although the reduction in IOP results from the activation of adenosine A1 receptors, the mechanisms responsible for the rise in IOP have not been investigated. This study examines the receptors and mechanisms responsible for the adenosine agonist-induced rise in IOP. METHODS The ocular effects of the nonselective adenosine agonist NECA, the relatively selective adenosine A2 agonist CV-1808, the A2a agonist CGS-21680, and the A1 agonist R-PIA were evaluated. RESULTS The topical administration of CV-1808 produced a rapid rise in IOP, with a maximum increase of 15.6 +/- 1.6 mm Hg. Dose-response curves demonstrated that each agonist produced a dose-related rise in IOP with the following rank order of potency: NECA > CV-1808 > > R-PIA = CGS-21680. At times corresponding to the rise in IOP, the administration of high doses of CV-1808 (165 micrograms) produced a significant increase in aqueous humor flow and protein concentration. Increases in IOP and aqueous humor protein levels induced by CV-1808 were blocked by pretreatment with the adenosine A2 antagonist DMPX. In vitro studies demonstrated that CV-1808 did not alter cyclic adenosine monophosphate production in the rabbit iris-ciliary body. In cats, topical administration of CV-1808 produced a rapid rise in IOP, with a maximum increase of 8.1 +/- 2.4 mm Hg and an ED50 of 73 +/- 2.9 micrograms. This rise in IOP was blocked by DMPX pretreatment. CONCLUSIONS These data demonstrate that adenosine receptor agonists can induce an acute rise in IOP in rabbits and cats. On the basis of pharmacologic characteristics, the rise in IOP is consistent with the activation of ocular adenosine A2 receptors. Functional studies indicate that at high doses, this rise in IOP involves an increase in aqueous flow and the breakdown of the blood-aqueous barrier.
The dependence of the pairwise velocity dispersion on galaxy properties

We present measurements of the pairwise velocity dispersion (PVD) for different classes of galaxies in the Sloan Digital Sky Survey (SDSS). For a sample of about 200 000 galaxies with redshifts in the interval 0.01 < z < 0.3, and r-band magnitudes M-0.1r between - 16 and - 23, we study the dependence of the PVD on galaxy properties such as luminosity, stellar mass (M-*), colour (g - r), 4000-angstrom break strength (D-4000), concentration index (C), and stellar surface mass density (mu(*)). The luminosity dependence of the PVD is in good agreement with the results of Jing & Borner for the two-degree Field Galaxy Redshift Survey catalogue, once the photometric bandpass difference between the two surveys is taken into account. The value of sigma(12) measured at k = 1 h Mpc(-1) decreases as a function of increasing galaxy luminosity for galaxies fainter than L*, before increasing again for the most luminous galaxies in our sample. Each of the galaxy subsamples selected according to luminosity or stellar mass is divided into two further subsamples according to colour, D4000, C and mu(*). We find that galaxies with redder colours and higher D4000, C, and mu(*) values have larger PVDs on all scales and at all luminosities/stellar masses. The dependence of the PVD on the parameters related to recent star formation ( colour, D4000) is stronger than on the parameters related to galaxy structure (C, mu(*)), especially on small scales and for faint galaxies. The reddest galaxies and galaxies with high surface mass densities and intermediate concentrations have the highest pairwise peculiar velocities, that is, these move in the strongest gravitational fields. We conclude that the faint red population located in rich clusters is responsible for the high PVD values that are measured for low-luminosity galaxies on small scales.
Effects of regional phentolamine on hypoxic vasodilatation in healthy humans

1 Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of β‐adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2 We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation ∼85 %) in eight healthy men and women (18‐26 years) after selective α‐adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined α‐ and β‐adrenergic blockade (phentolamine and propranolol) and after combined α‐ and β‐adrenergic blockade coupled with NO synthase inhibition (NG‐monomethyl‐l‐arginine, l‐NMMA). 3 Hypoxia increased forearm vascular conductance by 49.0 ± 13.5 % after phentolamine (compared to +16.8 ± 7.0 % in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by ∼50 %, but dilatation was still present (+24.7 ± 7.0 %, P < 0.05 vs. normoxia). When l‐NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 ± 4.0 %, P < 0.05 vs. normoxia). 4 Thus, selective regional α‐adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by β‐adrenergic receptor‐mediated pathways. Finally, since considerable dilatation persists in the presence of both β‐adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.
Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: Role in vasculogenic mimicry

Tumor cell plasticity represents a significant clinical challenge in that the fate and function of tumor cells can be elusive until a tumor mass is evident. A remarkable example of plasticity is tumor cell vasculogenic mimicry, recently described in aggressive uveal and cutaneous melanoma, in addition to ovarian carcinoma, whereby tumor cells express endothelial‐associated genes and form de novo vasculogenic‐like networks in three‐dimensional (3‐D) culture. In the current investigation, we examined whether there is evidence for vasculogenic mimicry in heterogeneous prostatic neoplasms.
The Space‐Time Pattern of the Cochlear Microphonics (Guinea Pig), as Recorded by Differential Electrodes

Pairs of very small electrodes were placed in two or more turns of the cochlea of the guinea pig. The cochlear microphonic from a short segment (about 1 mm) of the cochlear partition can thus be recorded, and without contamination by action potentials. The outputs of the second, third, and fourth turns were compared with that of the first turn with respect to both amplitude and phase as a function of frequency. The space‐time pattern thus revealed is a traveling wave which passes up the cochlea to a distance that depends on the frequency. The pattern agrees well with that of mechanical movement (Bekesy) except that the cochlear microphonic shows relatively greater amplitude (voltage) in the basal turn. Low frequencies travel farther up the cochlea than do high. The velocity (for a 750 cps tone) is about 100 m/sec in the basal turn and about 2 m/sec in the fourth turn. Phase differences of as much as 5π were observed, by means of Lissajous patterns, between the responses of the first and the third turn. Ce.
Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure

Background—Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone (RAAS) cascade. This may overcome ACE inhibition but should be blocked by a direct renin inhibitor. We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure. Methods and Results—Patients with New York Heart Association class II to IV heart failure, current or past history of hypertension, and plasma brain natriuretic peptide (BNP) concentration >100 pg/mL who had been treated with an ACE inhibitor (or angiotensin receptor blocker) and β-blocker were randomized to 3 months of treatment with placebo (n=146) or aliskiren 150 mg/d (n=156). The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP (NT-proBNP). Patients’ mean age was 68 years, mean ejection fraction was 31%, and mean±SD systolic blood pressure was 129±17.4 mm Hg. Sixty-two percent of the patients were in New York Heart Association functional class II, and 33% were taking an aldosterone antagonist. Plasma NT-proBNP rose by 762±6123 pg/mL with placebo and fell by 244±2025 pg/mL with aliskiren (P=0.0106). BNP and urinary (but not plasma) aldosterone were also reduced by aliskiren. Clinically important differences in blood pressure and biochemistry were not seen between aliskiren and placebo. Conclusions—Addition of aliskiren to an ACE inhibitor (or angiotensin receptor blocker) and β-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated.
Psychosocial risk factors for chronic low back pain in primary care--a systematic review.

BACKGROUND Low back pain (LBP) is a major public health problem, often encountered in primary care. Guidelines recommend early identification of psychosocial factors that could prevent recovery from acute LBP. METHODS To review the evidence on the prognostic value of psychosocial factors on transition from acute to chronic non-specific LBP in the adult general population. Systematic review is the design of the study. A systematic search was undertaken for prospective studies dealing with psychosocial risk factors for poor outcome of LBP in primary care, screening PubMed, PsychInfo and Cochrane Library databases. The methodological quality of studies was assessed independently by two reviewers using standardized criteria before analysing their main results. RESULTS Twenty-three papers fulfilled the inclusion criteria, covering 18 different cohorts. Sixteen psychosocial factors were analysed in three domains: social and socio-occupational, psychological and cognitive and behavioural. Depression, psychological distress, passive coping strategies and fear-avoidance beliefs were sometimes found to be independently linked with poor outcome, whereas most social and socio-occupational factors were not. The predictive ability of a patient's self-perceived general health at baseline was difficult to interpret because of biomedical confounding factors. The initial patient's or care provider's perceived risk of persistence of LBP was the factor that was most consistently linked with actual outcome. CONCLUSION Few independent psychosocial risk factors have been demonstrated to exist. Randomized clinical trials aimed at modifying these factors have shown little impact on patient prognosis. Qualitative research might be valuable to explore further the field of LBP and to define new management strategies.
A Step-Up Switched-Capacitor Multilevel Inverter With Self-Voltage Balancing

The objective of this paper is to propose a new inverter topology for a multilevel voltage output. This topology is designed based on a switched capacitor (SC) technique, and the number of output levels is determined by the number of SC cells. Only one dc voltage source is needed, and the problem of capacitor voltage balancing is avoided as well. This structure is not only very simple and easy to be extended to a higher level, but also its gate driver circuits are simplified because the number of active switches is reduced. The operational principle of this inverter and the targeted modulation strategies are presented, and power losses are investigated. Finally, the performance of the proposed multilevel inverter is evaluated with the experimental results of an 11-level prototype inverter.
The Interplay between Cyclic AMP, MAPK, and NF-κB Pathways in Response to Proinflammatory Signals in Microglia

Cyclic AMP is an important intracellular regulator of microglial cell homeostasis and its negative perturbation through proinflammatory signaling results in microglial cell activation. Though cytokines, TNF-α and IL-1β, decrease intracellular cyclic AMP, the mechanism by which this occurs is poorly understood. The current study examined which signaling pathways are responsible for decreasing cyclic AMP in microglia following TNF-α stimulation and sought to identify the role cyclic AMP plays in regulating these pathways. In EOC2 microglia, TNF-α produced a dramatic reduction in cyclic AMP and increased cyclic AMP-dependent PDE activity that could be antagonized by Rolipram, myristoylated-PKI, PD98059, or JSH-23, implicating a role for PDE4, PKA, MEK, and NF-κB in this regulation. Following TNF-α there were significant increases in iNOS and COX-2 immunoreactivity, phosphorylated ERK1/2 and NF-κB-p65, IκB degradation, and NF-κB p65 nuclear translocation, which were reduced in the presence of high levels of cyclic AMP, indicating that reductions in cyclic AMP during cytokine stimulation are important for removing its inhibitory action on NF-κB activation and subsequent proinflammatory gene expression. Further elucidation of the signaling crosstalk involved in decreasing cyclic AMP in response to inflammatory signals may provide novel therapeutic targets for modulating microglial cell activation during neurological injury and disease.
Monitoring HIV Drug Resistance Early Warning Indicators in Cameroon: A Study Following the Revised World Health Organization Recommendations

Background The majority (>95%) of new HIV infection occurs in resource-limited settings, and Cameroon is still experiencing a generalized epidemic with ~122,638 patients receiving antiretroviral therapy (ART). A detrimental outcome in scaling-up ART is the emergence HIV drug resistance (HIVDR), suggesting the need for pragmatic approaches in sustaining a successful ART performance. Methods A survey was conducted in 15 ART sites of the Centre and Littoral regions of Cameroon in 2013 (10 urban versus 05 rural settings; 8 at tertiary/secondary versus 7 at primary healthcare levels), evaluating HIVDR-early warning indicators (EWIs) as-per the 2012 revised World Health Organization’s guidelines: EWI1 (on-time pill pick-up), EWI2 (retention in care), EWI3 (no pharmacy stock-outs), EWI4 (dispensing practices), EWI5 (virological suppression). Poor performance was interpreted as potential HIVDR. Results Only 33.3% (4/12) of sites reached the desirable performance for “on-time pill pick-up” (57.1% urban versus 0% rural; p<0.0001) besides 25% (3/12) with fair performance. 69.2% (9/13) reached the desirable performance for “retention in care” (77.8% urban versus 50% rural; p=0.01) beside 7.7% (1/13) with fair performance. Only 14.4% (2/13) reached the desirable performance of “no pharmacy stock-outs” (11.1% urban versus 25% rural; p=0.02). All 15 sites reached the desirable performance of 0% “dispensing mono- or dual-therapy”. Data were unavailable to evaluate “virological suppression” due to limited access to viral load testing (min-max: <1%-15%). Potential HIVDR was higher in rural (57.9%) compared to urban (27.8%) settings, p=0.02; and at primary (57.9%) compared to secondary/tertiary (33.3%) healthcare levels, p=0.09. Conclusions Delayed pill pick-up and pharmacy stock-outs are major factors favoring HIVDR emergence, with higher risks in rural settings and at primary healthcare. Retention in care appears acceptable in general while ART dispensing practices are standard. There is need to support patient-adherence to pharmacy appointments while reinforcing the national drug supply system.
Expression, and Molecular and Enzymatic Characterization of Cu-Containing Nitrite Reductase from a Marine Ammonia-Oxidizing Gammaproteobacterium, Nitrosococcus oceani

Ammonia-oxidizing bacteria (AOB) remove intracellular nitrite to prevent its toxicity by a nitrifier denitrification pathway involving two denitrifying enzymes, nitrite reductase and nitric oxide reductase. Here, a Cu-containing nitrite reductase from Nitrosococcus oceani strain NS58, a gammaproteobacterial marine AOB, was expressed in Escherichia coli and purified to homogeneity. Sequence homology analysis indicated that the nitrite reductase from N. oceani was phylogenetically closer to its counterparts from denitrifying bacteria than that of the betaproteobacterium Nitrosomonas europaea. The recombinant enzyme was a homotrimer of a 32 kDa subunit molecule. The enzyme was green in the oxidized state with absorption peaks at 455 nm and 575 nm. EPR spectroscopy indicated the presence of type 2 Cu. Molecular activities and the affinity constant for the nitrite were determined to be 1.6×103 s−1 and 52 μM, respectively.
Flexibility within the Rotor and Stators of the Vacuolar H+-ATPase

The V-ATPase is a membrane-bound protein complex which pumps protons across the membrane to generate a large proton motive force through the coupling of an ATP-driven 3-stroke rotary motor (V1) to a multistroke proton pump (Vo). This is done with near 100% efficiency, which is achieved in part by flexibility within the central rotor axle and stator connections, allowing the system to flex to minimise the free energy loss of conformational changes during catalysis. We have used electron microscopy to reveal distinctive bending along the V-ATPase complex, leading to angular displacement of the V1 domain relative to the Vo domain to a maximum of ~30°. This has been complemented by elastic network normal mode analysis that shows both flexing and twisting with the compliance being located in the rotor axle, stator filaments, or both. This study provides direct evidence of flexibility within the V-ATPase and by implication in related rotary ATPases, a feature predicted to be important for regulation and their high energetic efficiencies.
Bacteria associated with the gastric epithelium of neonatal pigs

Light and electron microscopy showed lactobacilli and, to a lesser degree, streptococci to be closely associated with the squamous area of the pig stomach known as the pars esophagea. Several different types of extracellular layers were seen on bacteria attached to the epithelial surface. The total number of bacteria per square centimeter did not change with age up to 10 days, and there was no effect of weaning at 2 days. Lactobacillus fermentum, L. salivarius, and Streptococcus salivarius were isolated more frequently from sucking pigs than from those that were early weaned, whereas the reverse was true of L. acidophilus and S. bovis. All isolates recovered from washed macerated pars esophagea adhered to pig esophageal epithelial cells when tested in vitro.
Time-Dependent Changes in Antioxidant Enzymes and Vascular Reactivity of Aorta in Streptozotocin-Induced Diabetic Rats Treated With Curcumin

In the present study changes in oxidative stress and vascular reactivity in aortic rings of chronic streptozotocin-diabetic (STZ-CON) and nondiabetic (ND-CON) rats is studied at 4 weekly intervals up to 24 weeks. The effect of chronic curcumin (200 mg/kg) treatment was also studied. Blood glucose and blood pressure levels were significantly higher in the STZ-CON group and curcumin administration had no significant effect on it. Superoxide dismutase and catalase activity were either unchanged or significantly increased during the early stage of diabetes whereas during the medium and late stage were significantly reduced. Reduced glutathione and lipid peroxidation levels significantly decreased as time after STZ administration increased. Phenylephrine (PE)-induced contraction was significantly (P < 0.05) increased during the early stage of diabetes, whereas it was significantly (P < 0.05) reduced at the medium and late stage of diabetes. Acetylcholine (Ach)-induced relaxation significantly decreased with respect to time after STZ administration. Sodium nitroprusside (SNP)-induced relaxation was unaltered up to initial stage but after medium stage there was a rightward shift and the pD2 value significantly decreased. Though curcumin treatment had no significant effect on superoxide dismutase, catalase, and reduced glutathione levels, it significantly reduced lipid peroxidation compared with diabetic control. Curcumin treatment attenuated the phenylephrine-induced increase in contraction during the early stage. However, curcumin treatment had no significant effect at the medium and late stage. Though curcumin administration improved Ach-induced relaxation it did not restore it to normal. Inability of curcumin to prevent oxidative stress during the late stage may be due to the fact that chronic diabetes (hyperglycemia) leads to excessive production of free radicals. Hence the present study shows that variations reported in antioxidant enzymes and vascular reactivity are due to the duration of diabetes or time after diabetes induction in STZ model and this can not be completely reversed by chronic treatment with curcumin.