Miracle-dz/UniFAR-FTUs huggingface dataset:
Fructose-1,6-bisphosphate improves efficiency of work in isolated perfused rat hearts.

The purpose of this study was to determine whether exogenous fructose-1,6-bisphosphate (F-1,6-P2) directly affects myocardial hemodynamics and certain metabolic parameters. Isolated working rat hearts were perfused for 30 min with 10 mM glucose (+insulin) as the exclusive exogenous substrate followed by 15 min with glucose plus one of the following concentrations (in mM) of F-1,6-P2: 1.25, 2.5, 5, or 10, and finally returned to the glucose only buffer. Additions of 2.5 and 5 mM F-1,6-P2 decreased (P less than 0.01) oxygen consumption (VO2) by 10.8 and 17.0% and coronary flow by 8.3 and 10.3%, respectively. No changes were observed in lactate release, cardiac output (CO), peak systolic pressure, heart rate, or pressure work (PW). Efficiency, expressed as PW divided by VO2, increased with F-1,6-P2 by 8.6% with 1.25 mM (P less than 0.05), 13.2% with 2.5 mM (P less than 0.01), and 16.9% with 5 mM (P less than 0.01). F-1,6-P2 at 10 mM produced no further improvements in VO2 or efficiency but was associated with declines (P less than 0.05) in CO and PW. Glucose plus 10 mM fructose had no effects on any of the above parameters, indicating that the F-1,6-P2-induced changes were not due to changes in osmolarity or to end products of F-1,6-P2 hydrolysis. Some chelation of buffer calcium by F-1,6-P2 occurred, but when free calcium was equalized in glucose and glucose plus 5 mM F-1,6-P2 buffers, the decline in VO2 (11.5%) was still far greater than could be explained by exogenous F-1,6-P2 metabolism in the glycolytic pathway. (ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Sequential and Simultaneous Applications of Bacteriophages on Populations of Pseudomonas aeruginosa In Vitro and in Wax Moth Larvae

ABSTRACT Interest in using bacteriophages to treat bacterial infections (phage therapy) is growing, but there have been few experiments comparing the effects of different treatment strategies on both bacterial densities and resistance evolution. While it is established that multiphage therapy is typically more effective than the application of a single phage type, it is not clear if it is best to apply phages simultaneously or sequentially. We tried single- and multiphage therapy against Pseudomonas aeruginosa PAO1 in vitro, using different combinations of phages either simultaneously or sequentially. Across different phage combinations, simultaneous application was consistently equal or superior to sequential application in terms of reducing bacterial population density, and there was no difference (on average) in terms of minimizing resistance. Phage-resistant bacteria emerged in all experimental treatments and incurred significant fitness costs, expressed as reduced growth rate in the absence of phages. Finally, phage therapy increased the life span of wax moth larvae infected with P. aeruginosa, and a phage cocktail was the most effective short-term treatment. When the ratio of phages to bacteria was very high, phage cocktails cured otherwise lethal infections. These results suggest that while adding all available phages simultaneously tends to be the most successful short-term strategy, there are sequential strategies that are equally effective and potentially better over longer time scales.
Caregivers' Communication with Patients about Illness and Death: Initial Validation of a Scale

Caregivers of terminal cancer patients experience substantial communication difficulties with their loved ones about their illness. Existing communication scales focus on communication as perceived by the patient and do not include items that refer to his close death. The current study describes the development and initial validation of an instrument aimed at measuring caregivers' communication with patients about their illness and death. Two hundred thirty-six bereaved primary caregivers of cancer patients were recruited over a period of 18 months. The psychometric properties of the scale were explored by confirmatory factor analysis. Results provided support for a one factor solution. The discriminant and convergent validity of the responses to the scale were also supported. Future studies should further establish the validity of the scale with larger sample sizes and different populations of caregivers of patients with other terminal diseases.
Higher incorporation of heterologous chicken immunoglobulin Y compared with homologous quail immunoglobulin Y into egg yolks of Japanese quail (Coturnix japonica).

In avian species, blood IgY is selectively incorporated into the yolks of maturing oocytes, although the precise mechanism is poorly understood. Our previous study showed that 22% of i.v. -injected heterologous chicken IgY (cIgY) was incorporated into egg yolks of Japanese quail (Coturnix japonica). However, it is not known whether homologous quail IgY (qIgY) can be more efficiently incorporated into quail egg yolks than cIgY. Therefore, we compared the uptakes of qIgY and cIgY i.v. administered into quail egg yolks and further characterized the uptakes of these 2 antibodies into quail ovarian follicles. Quail IgY and cIgY purified from the blood of the respective bird were labeled with digoxigenin, and their uptakes into quail egg yolks were determined by ELISA. Unexpectedly, total incorporation of the injected qIgY was only one-third of that of cIgY, although much more qIgY was left in blood compared with cIgY, suggesting that qIgY is the less preferable antibody as a transport ligand into quail egg yolks. On the other hand, deposition of the qIgY into heart, lung, liver, spleen, kidney, and ovarian follicular membrane was markedly higher than that of cIgY. Amino acid sequence analysis of 3 peptides derived from the trypsin-digested qIgY heavy chain revealed low homology between qIgY and cIgY. In conclusion, our results show that heterologous cIgY is more efficiently incorporated into quail egg yolks than homologous qIgY, possibly due to a distinctive antibody transport system existing in oocytes. The present results also may provide a new strategy for delivering useful proteinaceous substances into egg yolks in an attempt to produce designer eggs.
Predicting the impact of measles vaccination in England and Wales: model validation and analysis of policy options

Summary Measles incidence in England and Wales has fallen to an all-time low. Attention is now focused on preventing local outbreaks, and, in the long run, on the elimination of indigenous measles. A realistic age-structured (RAS) mathematical model of measles transmission is used to reconstruct the impact of measles vaccination in England and Wales from 1968 to the present and to evaluate the merits of future policy options. In general, the predictions of the model show good agreement with long-term age stratified case reports and seroprevalence surveys. The model underestimates the proportion of cases that are notified in 0–2-year-old children. However, recent work suggests a high degree of misdiagnosis in this age group. Projections on the basis of the existing vaccination strategy in the UK suggest that the present level of measles vaccine coverage will be insufficient to eliminate small seasonal outbreaks of measles. This result is, however, sensitive to the assumed level of vaccine efficacy. Explorations of a variety of changes to current vaccination strategy favour a 2-dose schedule with the second dose administered at age 4 years irrespective of vaccination history. A vaccination campaign in school-age children, to reduce deficits in herd immunity, would accelerate progress towards measles elimination.
Heart valve replacement: a statistical review of 35 years' results.

BACKGROUND AND AIMS OF THE STUDY Having performed our first heart valve replacement in 1960, we began a prospective lifetime follow up service for all patients, contacting them at least annually to determine survivorship and heart valve complications. METHODS We reviewed isolated aortic (AVR) and mitral (MVR) valve replacements from 1960 to 1993, with follow up to 1998. In total, 2,942 AVR and 1,579 MVR were performed, with 21,742 and 12,142 patient-years of follow up, respectively. Analysis of the results affords an opportunity to demonstrate the usefulness and necessity of certain statistical methods, including multivariable event-free analyses and cumulative incidence functions. RESULTS The survival rate was 8% at 30 years for both valve positions. However, an overall survival curve is an artificial composite of patients of increasingly higher risk being served during increasingly safer years of calendar time. One result is that, for AVR, age is not a significant univariate risk factor for operative mortality, but is highly significant after accounting for date of surgery using logistic regression. Long-term mortality is higher for tissue valves than for mechanical valves; but mean age is greater (74 versus 57 years), and after accounting for age using Cox regression, mortality is similar for both valve types. Kaplan-Meier analysis estimates thromboembolism occurrences of 85% for AVR and 95% for MVR at 35 and 34 years, respectively, but the cumulative incidence estimates are only 32% and 41%, respectively. CONCLUSIONS Prospective follow up for over 35 years has provided an opportunity to illustrate important statistical issues: Multivariate analyses are essential to avoid being misled by excluding important risk factors or including artifactual ones, and the cumulative incidence estimates the percentage of patients who will actually experience a complication.
Survival Comparison of Allograft and Autograft Anterior Cruciate Ligament Reconstruction at the United States Military Academy

Background: There is recent evidence that use of allograft tendons for anterior cruciate ligament (ACL) reconstruction in young patients may result in increased failure rates compared with autologous grafts. Hypothesis: Allograft ACL reconstruction will result in higher failure rates in young athletes compared with autograft reconstruction. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective cohort study of cadets at the United States Military Academy (USMA) was performed to assess performance of ACL reconstructions performed before entrance to service. Members of the classes of 2007 through 2013 who had undergone prior ACL reconstruction were identified through the Department of Defense Medical Evaluation Review Board reporting and waiver process and evaluated on the first day of matriculation. These participants were followed during their tenure at the academy with revision ACL reconstruction as the primary outcome measure of interest. Kaplan-Meier survival analysis was performed for all graft types using STATA with significance set as P < . 05. Results: A total of 120 cadets underwent 122 ACL reconstructions (2 bilateral) before matriculation and compose the prospective cohort. This cohort included 30 female and 90 male cadets. Of these 122 knees with prior ACL reconstructions, the grafts used were 61 bone–patellar tendon–bone (BTB), 45 hamstring, and 16 allograft. A total of 20 failures occurred among this cohort at an average of 545 days from matriculation. Of the failures requiring revision, 7 were BTB (11% of all BTB), 7 were allograft (44% of all allograft), and 6 were hamstring (13% of all hamstring). There was no significant difference in the graft failure between the BTB and hamstring autograft groups. In contrast, those who entered the USMA with an allograft were 7.7 times more likely to experience a subsequent graft failure during the follow-up period when compared with the BTB autograft group (hazard ratio = 7.74; 95% confidence interval [CI], 2.67-22.38; P < .001). When allografts were compared with all autografts combined, a similar increase failure was noted in the allograft group (hazard ratio = 6.71; 95% CI, 2.64-17.06; P < .001). Conclusion: In this young active cohort, individuals having undergone an allograft ACL reconstruction were significantly more likely to experience clinical failure requiring revision reconstruction compared with those who underwent autologous graft reconstruction. The authors recommend the use of autograft in ACL reconstruction in young athletes.
Genetic structure in the nonrewarding, bumblebee-pollinated orchid Calypso bulbosa

Among- and within-population variation at neutral loci is governed by an interaction between stochastic processes and gene flow. A previous study of pollen dispersal in which the transfer of individually marked pollinia was monitored, indicated not only that populations of the nonrewarding, bumblebee-pollinated orchid Calypso bulbosa are connected by substantial levels of gene flow, but also that seed production may be the result of self-fertilization to a considerable extent. We examined the genetic structure of 21 C. bulbosa populations in northern Sweden by F-statistics analyses of variation at three polymorphic allozyme loci. Four populations each consisted of two or three distinct patches, which also allowed us to evaluate among-patch differentiation. The inbreeding coefficient over all loci within populations was high (FIS=0.283). F-statistics indicated that the level of genetic differentiation among patches within populations varied among populations. FST among patches within populations ranged between −0.021 and 0.119 and was significantly different from zero in two of the populations. There was low to moderate genetic differentiation among populations (FST=0.072). A Mantel test indicated a positive correlation between geographical and genetic distances among populations, but this correlation was dependent on the difference in allele frequencies between the southernmost population sampled and all other populations. Self-fertilization and substructuring within sampling units (within patches and populations) may have contributed to the high inbreeding coefficients observed in many C. bulbosa populations. Long-distance seed and pollen dispersal may account for the low to moderate genetic differentiation among populations.
Analysis of pH‐dependent elements in proteins: Geometry and properties of pairs of hydrogen‐bonded carboxylic acid side‐chains

A rather frequent but so far little discussed observation is that pairs of carboxylic acid side‐chains in proteins can share a proton in a hydrogen bond. In the present article, quantum chemical calculations of simple model systems for carboxyl–carboxylate interactions are compared with structural observations from proteins. A detailed structural analysis of the proteins deposited in the PDB revealed that, in a subset of proteins sharing less than 90% sequence identity, 19% (314) contain at least one pair of carboxylic acids with their side‐chain oxygen atoms within hydrogen‐bonding distance. As the distance between those interacting oxygen atoms is frequently very short (∼2.55 Å), many of these carboxylic acids are suggested to share a proton in a strong hydrogen bond. When situated in an appropriate structural environment (low dielectric constant), some might even form a low barrier hydrogen bond. The quantum chemical studies show that the most frequent geometric features of carboxyl–carboxylate pairs found in proteins, and no or symmetric ligation, are also the most stable arrangements at low dielectric constants, and they also suggest at medium and low pH a higher stability than for isosteric amide–carboxylate pairs. The presence of these pairs in 119 different enzymes found in the BRENDA database is set in relation to their properties and functions. This analysis shows that pH optima of enzymes with carboxyl–carboxylate pairs are shifted to lower than average values, whereas temperature optima seem to be increased. The described structural principles can be used as guidelines for rational protein design (e.g., in order to improve pH or temperature stability). Proteins 2005. © 2004 Wiley‐Liss, Inc.
A Modified Dynamic Synchrophasor Estimation Algorithm Considering Frequency Deviation

When the power system is suffered from disturbances, such as unbalance, load variation, and fault occurrence, not only the phase and magnitude of the power signal will change but also the fundamental frequency can deviate away from the nominal one up to 5 Hz as per IEEE standard C37.118. As large frequency deviation will lead to great errors on Taylor approximation, the accuracy can be improved by expanding the dynamic characteristics in form of Taylor series near real fundamental frequency of supplied signals instead of nominal frequency (50/60 Hz). The corresponding coefficient against the different frequency estimations is applied to the dynamic phasor estimator to yield accurate synchrophasor estimation with the consideration of large frequency deviation. First, raw phasors attained by short time Fourier transform, are employed to provide the frequency estimation. Then, according to the frequency estimation, the coefficient matrix calculated off-line in form of lookup table is selected to calculate phasor estimation at the center of data window. Finally, a shift process is taken to give phasor estimation at report time. Simulated signals, PSCAD-generated signal, RTDS-generated data, and field data are employed to evaluate the performance of the proposed algorithm. The results show that the proposed algorithm can get more accurate phasor estimations than our previous work at most of the time with the cost of minor increase of computational power.
Subunit Interactions in Yeast Transcription/Repair Factor TFIIH

A yeast strain harboring a temperature-sensitive allele of TFB3 (tfb3 ts ), the 38-kDa subunit of the RNA polymerase II transcription/nucleotide excision repair factor TFIIH, was found to be sensitive to ultraviolet (UV) radiation and defective for nucleotide excision repair in vitro. Interestingly, tfb3 ts failed to grow on medium containing caffeine. A comprehensive pairwise two-hybrid analysis between yeast TFIIH subunits identified novel interactions between Rad3 and Tfb3, Tfb4 and Ssl1, as well as Ssl2 and Tfb2. These interactions have facilitated a more complete model of the structure of TFIIH and the nucleotide excision repairosome.
A multiple electrode cochlear implant

The University of Melbourne Departments of Otolaryngology and Electrical Engineering (UMDOLEE) receiving and stimulating component of a multiple-electrode cochlear implant hearing prosthesis produces constant stimulation. It has a stimulating pulse shape that minimizes the production of toxic substances and loss of metal from the electrodes, and this is achieved with a biphasic rectangular waveform where the first phase is negative with respect to ground. The duration of each stimulus phase in 180 msec, which is long enough to allow low levels of current stimulation, and short enough to permit rates of 1000 pulses/second to be achieved. In order to be consistent with our present understanding of the perception of pitch, the device permits the independent stimulation of a number of electrodes. Furthermore, to electrically isolate the stimulus to small areas, there is the capacity to vary the current and set the threshold independently at individual electrodes. The phase and amplitude of the pulses to neighbouring electrodes with also be varied to assist in localizing the current flow. The pattern to stimulation to individual or groups of electrodes can also be altered to enable studies to be carried out to determine ways of conveying frequency and intensity information over a more normal dynamic range.
A New Function for the C-terminal Zinc Finger of the Glucocorticoid Receptor

Glucocorticoids inhibit NF-κB signaling by interfering with the NF-κB transcription factor RelA. Previous studies have identified the DNA-binding domain (DBD) in the glucocorticoid receptor (GR) as the major region responsible for this repressive activity. Using GR mutants with chimeric DBDs the repressive function was found to be located in the C-terminal zinc finger. As predicted from these results the mineralocorticoid receptor that contains a C-terminal zinc finger identical to that of the GR was also able to repress RelA-dependent transcription. Mutation of a conserved arginine or a lysine in the second zinc finger of the GR DBD (Arg-488 or Lys-490 in the rat GR) abolished the ability of GR to inhibit RelA activity. In contrast, C-terminal zinc finger GR mutants with mutations in the dimerization box or mutations necessary for full transcriptional GR activity were still able to repress RelA-dependent transcription. In addition, we found that the steroid analog ZK98299 known to induce GR transrepression of AP-1 had no inhibitory effect on RelA activity. In summary, these results demonstrate that the inhibition of NF-κB by glucocorticoids involves two critical amino acids in the C-terminal zinc finger of the GR. Furthermore, the results from the use of mineralocorticoid receptor and anti-glucocorticoids suggest that the mechanisms for GR-mediated repression of NF-κB and AP-1 are different.
Massive production of butanediol during plant infection by phytopathogenic bacteria of the genera Dickeya and Pectobacterium

Plant pathogenic bacteria of the genera Dickeya and Pectobacterium are broad‐host‐range necrotrophs which cause soft‐rot diseases in important crops. A metabolomic analysis, based on 13C‐NMR spectroscopy, was used to characterize the plant‐bacteria interaction. Metabolic profiles revealed a decline in plant sugars and amino acids during infection and the concomitant appearance of a compound identified as 2,3‐butanediol. Butanediol is the major metabolite found in macerated tissues of various host plants. It is accumulated during the symptomatic phase of the disease. Different species of Dickeya or Pectobacterium secrete high levels of butanediol during plant infection. Butanediol has been described as a signalling molecule involved in plant/bacterium interactions and, notably, able to induce plant systemic resistance. The bud genes, involved in butanediol production, are conserved in the phytopathogenic enterobacteria of the genera Dickeya, Pectobacterium, Erwinia, Pantoea and Brenneria. Inactivation of the bud genes of Dickeya dadantii revealed that the virulence of budA, budB and budR mutants was clearly reduced. The genes budA, budB and budC are highly expressed during plant infection. These data highlight the importance of butanediol metabolism in limiting acidification of the plant tissue during the development of the soft‐rot disease caused by pectinolytic enterobacteria.
Systematic review: patient‐reported outcomes in chronic hepatitis C ‐ the impact of liver disease and new treatment regimens

Treatment for chronic hepatitis C (CH‐C) is rapidly changing and moving away from an interferon and ribavirin‐based therapy to interferon‐free ribavirin‐free all oral regimens. These regimens are simpler and shorter to administer with very high efficacy rates and better side effect profiles. As advances in the treatment of CH‐C occur, it is imperative to capture both clinical outcomes (efficacy and safety) as well as patient‐reported outcomes (PROs). In fact, PROs assesses and quantifies the impact of these regimens on patient experience. PROs assess patients' health‐related quality of life (HRQOL) especially in the realms of fatigue and neuropsychiatric issues such as depression which can affect treatment adherence and work productivity.