Miracle-dz/UniFAR-FTUs huggingface dataset:
A proposed clinical test for monitoring fluoropyrimidine therapy: Detection and stability of thymidylate synthase ternary complexes

5-fluorouracil forms classic (covalent, ternary) complexes consisting of thymidylate synthase, fluoro-deoxyuridine monophosphate, and 5,10-methylene tetrahydrofolate. Despite a high pharmacologic interest in the classic complexes formed in cells treated with fluorouracil anticancer agents, the in vivo stability of the complexes and the possible interference in complex formation by other co-administered compounds have not been adequately described. We visualized classic complexes unaccompanied by unbound thymidylate synthase, inferring complete enzymatic inhibition, in 5-fluorouracil-treated S. cerevisiae and cancer cells in vitro and in murine tumors in vivo treated with 5-fluorouracil. Classic complexes persisted 13 days in cancer cells after a pulse of 5-fluorouracil. Classic complexes were reduced to absent in cancer cells in which the older antifolates methotrexate and aminopterin, or the modern antifolates pemetrexed and tomudex, were co-administered with 5-fluorouracil. Classic complexes were, however, detected when an alternate drug, 5-fluorodeoxyuridine, was administered with methotrexate. We visualized classic complexes at fifteen minutes to seven days after an acute single dose of 5-fluorouracil in mouse tumor models, in tumors and normal tissues. Using the same assay, we detected unbound thymidylate synthase in untreated human tissues, supporting the future use of this assay in evaluating the most appropriate dose of fluoropyrimidine and co-administered agents in clinical settings.
The DIRECT Project: Catalogs of Stellar Objects in Nearby Galaxies. I. The Central Part of M33

The DIRECT project aims to determine direct distances to two important galaxies in the cosmological distance ladder—M31 and M33—using detached eclipsing binaries (DEBs) and Cepheids. The search for these variables requires time-series photometry of large areas of the target galaxies and yields magnitudes and positions for tens of thousands of stellar objects, which may be of use to the astronomical community at large. During the first phase of the project, between 1996 September and 1997 October, we were awarded 95 nights on the F. L. Whipple Observatory 1.2 m telescope and 36 nights on the Michigan-Dartmouth-MIT 1.3 m telescope to search for DEBs and Cepheids in the M31 and M33 galaxies. This paper, the first in our series of stellar catalogs, lists the positions, three-color photometry, and variability indices of 57,581 stars with 14.4 < V < 23.6 in the central part of M33. The catalog is available from our FTP site.
Evolution and Structural Organization of the C Proteins of Paramyxovirinae

The phosphoprotein (P) gene of most Paramyxovirinae encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT. Overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. The C proteins cluster in three groups, comprising measles, Nipah, and Sendai virus. We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, α-helical C-terminus. We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group). We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin. Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization. Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated de novo by overprinting PNT in the ancestor of Paramyxovirinae. Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently. This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt. The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations.
Multiple extrahepatic portosystemic shunts in dogs: 30 cases (1981-1993).

OBJECTIVE To describe the long-term outcome in dogs with naturally developing multiple extrahepatic portosystemic shunts (PSS). DESIGN Retrospective case series. ANIMALS 30 dogs with multiple PSS. PROCEDURE Medical records of dogs with multiple PSS were reviewed. Follow-up data were obtained by 1 or more of the following methods: recheck at the veterinary teaching hospital (n = 6) or telephone contact with the referring veterinarian (n = 18) or owner (n = 10). The chi 2 or Mann-Whitney rank sum test was used to determine the association of clinical factors with long-term outcome. Survival curves were generated by the Kaplan-Meier product limit method. RESULTS Median age at diagnosis was 1 year. Findings on exploratory surgery in 25 dogs included ascites; numerous tortuous vessels connecting the portal vein with systemic veins; a small, misshapen liver; and an enlarged portal vein. The most common lesions on histologic evaluation of hepatic tissue specimens were hepatocellular atrophy, portal vascular duplication, cirrhosis, inflammation, and bile duct proliferation. Twelve dogs were treated surgically with vena caval banding, whereas 13 dogs were treated conservatively with dietary restriction of protein and administration of antibiotics, diuretics, and other drugs. Long-term survival and quality of life were similar in dogs from both treatment groups. Median follow-up interval in dogs that survived hospitalization was 24 months (range, 1 to 54 months). CLINICAL IMPLICATIONS On the basis of these findings, vena caval banding in dogs with multiple PSS is not superior to medical and nutritional treatment.
Microstructural instability of a welded joint in P91 steel during creep at 600°C

Abstract The martensitic 10CrMoVNb 91 (P91) steel has been developed for applications under high ultra supercritical pressure for steam power plants. The creep rupture strength of welded joints of this steel is limited by the fine grained region of its heat affected zone (HAZ). The microstructural changes occurring in this region during long term creep tests at 600°C and 70 MPa were examined using optical microscopy and scanning and transmission electron microscopy for comparison with the microstructure of this region after post-weld heat treatment. The factors which result in the reduction of creep rupture strength of the fine grained region of HAZ are discussed. It was found that the most effective factors reducing the creep rupture strength of the fine grained region of the HAZ of a welded joint in P91 steel, in comparison with the coarse grained region of the HAZ and the base metal of the welded joint, are the finer prior austenite grain size of the fine grained region, which accelerates the rate of growth of martensite lath subgrains and enhances creep cavitation, and also the lower peak temperature during welding, which results in a softer martensite matrix.
Axion string constraints.

We study the production of cosmological axions in the standard scenario in which a global string network forms at the Peccei-Quinn phase transition. We make detailed calculations of the axions produced by string loops, comparing these with estimates of other contributions from long strings and domain walls. We delineate key uncertainties in string network evolution, the chief of which is the magnitude of radiative backreaction. We conclude that axions produced by these topological contributions provide the significant cosmological constraint on the symmetry breaking scale [ital f][sub [ital a]] and the axion mass [ital m][sub [ital a]].
Physical properties and compact analysis of commonly used direct compression binders

This study investigated the basic physico-chemical property and binding functionality of commonly used commercial direct compression binders/fillers. The compressibility of these materials was also analyzed using compression parameters derived from the Heckel, Kawakita, and Cooper-Eaton equations. Five classes of excipients were evaluated, including microcrystalline cellulose (MCC), starch, lactose, dicalcium phosphate (DCP), and sugar. In general, the starch category exhibited the highest moisture content followed by MCC, DCP, lactose, and finally sugars; DCP displayed the highest density, followed by sugar, lactose, starch, and MCC; the material particle size is highly processing dependent. The data also demonstrated that MCC had moderate flowability, excellent compressibility, and extremely good compact hardness; with some exceptions, starch, lactose, and sugar generally exhibited moderate flowability, compressibility, and hardness; DCP had excellent flowability, but poor compressibility and hardness. This research additionally confirmed the binding mechanism that had been well documented: MCC performs as binder because of its plastic deformation under pressure; fragmentation is the predominant mechanism in the case of lactose and DCP; starch and sugar perform by both mechanism.
Responses of a Thermophilic Synechococcus Isolate from the Microbial Mat of Octopus Spring to Light

ABSTRACT Thermophilic cyanobacteria of the genus Synechococcus are major contributors to photosynthetic carbon fixation in the photic zone of microbial mats in Octopus Spring, Yellowstone National Park. Synechococcus OS-B′ was characterized with regard to the ability to acclimate to a range of different light irradiances; it grows well at 25 to 200 μmol photons m−2 s−1 but dies when the irradiance is increased to 400 μmol photons m−2 s−1. At 200 μmol photons m−2 s−1 (high light [HL]), we noted several responses that had previously been associated with HL acclimation of cyanobacteria, including cell bleaching, reduced levels of phycobilisomes and chlorophyll, and elevated levels of a specific carotenoid. Synechococcus OS-B′ synthesizes the carotenoids zeaxanthin and β,β-carotene and a novel myxol-anhydrohexoside. Interestingly, 77-K fluorescence emission spectra suggest that Synechococcus OS-B′ accumulates very small amounts of photosystem II relative to that of photosystem I. This ratio further decreased at higher growth irradiances, which may reflect potential photodamage following exposure to HL. We also noted that HL caused reduced levels of transcripts encoding phycobilisome components, particularly that for CpcH, a 20.5-kDa rod linker polypeptide. There was enhanced transcript abundance of genes encoding terminal oxidases, superoxide dismutase, tocopherol cyclase, and phytoene desaturase. Genes encoding the photosystem II D1:1 and D1:2 isoforms (psbAI and psbAII/psbAIII, respectively) were also regulated according to the light regimen. The results are discussed in the context of how Synechococcus OS-B′ may cope with high light irradiances in the high-temperature environment of the microbial mat.
Phosphorylation of Rubella Virus Capsid Regulates Its RNA Binding Activity and Virus Replication

ABSTRACT Rubella virus is an enveloped positive-strand RNA virus of the family Togaviridae. Virions are composed of three structural proteins: a capsid and two membrane-spanning glycoproteins, E2 and E1. During virus assembly, the capsid interacts with genomic RNA to form nucleocapsids. In the present study, we have investigated the role of capsid phosphorylation in virus replication. We have identified a single serine residue within the RNA binding region that is required for normal phosphorylation of this protein. The importance of capsid phosphorylation in virus replication was demonstrated by the fact that recombinant viruses encoding hypophosphorylated capsids replicated at much lower titers and were less cytopathic than wild-type virus. Nonphosphorylated mutant capsid proteins exhibited higher affinities for viral RNA than wild-type phosphorylated capsids. Capsid protein isolated from wild-type strain virions bound viral RNA more efficiently than cell-associated capsid. However, the RNA-binding activity of cell-associated capsids increased dramatically after treatment with phosphatase, suggesting that the capsid is dephosphorylated during virus assembly. In vitro assays indicate that the capsid may be a substrate for protein phosphatase 1A. As capsid is heavily phosphorylated under conditions where virus assembly does not occur, we propose that phosphorylation serves to negatively regulate binding of viral genomic RNA. This may delay the initiation of nucleocapsid assembly until sufficient amounts of virus glycoproteins accumulate at the budding site and/or prevent nonspecific binding to cellular RNA when levels of genomic RNA are low. It follows that at a late stage in replication, the capsid may undergo dephosphorylation before nucleocapsid assembly occurs.
Nocturnal eating syndrome in adults.

Ten adult subjects were referred to our sleep disorders center complaining of difficulty in maintaining sleep due to frequent and recurrent awakenings to eat or drink. All patients manifested more than one episode per night, characterized by compulsive food seeking and a return to sleep only after adequate food intake. Food-seeking drive was described as an urgent abnormal need to swallow food and was associated with an absence of real hunger. Six subjects showed an elective nighttime intake of carbohydrates, and in all cases only edible substances were injected. The patients were always fully awake during the episodes and could clearly recall them in the morning. Polysomnographic investigation showed low levels of sleep efficiency, a high number of awakenings and a strict relation between nocturnal eating episodes and nonrapid eye movement (NREM) sleep. The average length of each episode was 3.5 minutes. The "eating latency", that is the interval between awakening and chewing start, was shorter than 30 seconds in 50% of the episodes. No medical, hormonal or neurological disorders were found during clinical and laboratory investigations. Body mass index was abnormally high in six patients. Anorexia nervosa and bulimia were carefully excluded. Various psychiatric disturbances were found in nine subjects, who were nevertheless well-functioning adults. Concurrent dyssomniac disorders, such as narcolepsy or periodic leg movements occasionally associated with restless legs syndrome, were diagnosed in five patients. (ABSTRACT TRUNCATED AT 250 WORDS)
Validity of the HSE stress tool: an investigation within four organizations by the Corporate Health and Performance Group.

AIM To examine the validity and accuracy of the HSE Management Standards Stress Tool. METHODS A cross-sectional questionnaire was administered to employees of the occupational health and human resource departments of four of the Corporate Health and Performance Group organizations. The relationship between the six first-pass stress filter questions and self-rated health were examined using the General Health Questionnaire (GHQ12) and the Short Form. The relationship between the filter questions and objective work characteristics such as sickness absence, self-rated performance and job satisfaction was also examined. RESULTS Two hundred and thirty-five employees participated, giving an overall response rate of 68%. The study sample met the proposed HSE of 85 and 65% pass rates and would not normally progress to further analysis. Almost 40% of the group were above threshold on the GHQ12; 19% rated their work as very or extremely stressful. While the filters were highly specific, they were insensitive and at best detected for less than 40% of those with psychological or work stress. All but one of the filters had less than 50% positive predictive value for work stress and the majority of those identified by the filters did not consider themselves stressed, either overall or by work. Five of the filter questions were significantly associated with self-rated performance, three with absence and two with other objective work indicators. CONCLUSIONS Further developmental work on these filter questions is indicated. Use of work absence as a measure of the impact or 'cost' of stress may lead to a significant underestimation of the 'true cost' of psychosocial hazards in the workplace.
Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis

ObjectiveThe ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined.MethodsThe amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls.ResultsThe mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.0005) and patients without infection (P = 0.040). Also, the mean ATP level in patients without infection was significantly lower than that in healthy controls (P = 0.012). There was no correlation between the ATP level and the Disease Activity Score in 28 joints.ConclusionImmuKnow assay results may be effective in identifying RA patients at increased risk of infection, but the results showed no correlation with RA activity. Larger studies are required to establish the clinical advantages of this assay in RA treatment.
Submicroscopic Deterministic Quantum Mechanics

So-called hidden variables introduced in quantum mechanics by de Broglie and Bohm have changed their initial enigmatic meanings and acquired quite reasonable outlines of real and measurable characteristics. The start viewpoint was the following: All the phenomena, which we observe in the quantum world, should reflect structural properties of the real space. Thus the scale 10^{-28} cm at which three fundamental interactions (electromagnetic, weak, and strong) intersect has been treated as the size of a building block of the space. The appearance of a massive particle is associated with a local deformation of the cellular space, i.e. deformation of a cell. The mechanics of a moving particle that has been constructed is deterministic by its nature and shows that the particle interacts with cells of the space creating elementary excitations called "inertons". The further study has disclosed that inertons are a substructure of the matter waves which are described by the orthodox wave \psi-function formalism. The concept has allowed resolving the spin problem. The theory, or more exactly, the existence of inertons, has been verified experimentally: in rarefied gases, inerton clouds of atoms' electrons interact with a strong laser pulse; in a solid, atom's inertons induce an additional harmonic potential that contributes to the interatomic interaction (metal specimens and the KIO_3*HIO_3 crystal).
On the derivation of propensity scales for predicting exposed transmembrane residues of helical membrane proteins

Helical membrane proteins (HMPs) play a crucial role in diverse physiological processes. Given the difficulty in determining their structures by experimental techniques, it is desired to develop computational methods for predicting the burial status of transmembrane residues. Deriving a propensity scale for the 20 amino acids to be exposed to the lipid bilayer from known structures is central to developing such methods. A fundamental problem in this regard is what would be the optimal way of deriving propensity scales. Here, we show that this problem can be reformulated such that an optimal scale is straightforwardly obtained in an analytical fashion. The derived scale favorably compares with others in terms of both algorithmic optimality and practical prediction accuracy. It also allows interesting insights into the structural organization of HMPs. Furthermore, the presented approach can be applied to other bioinformatics problems of HMPs, too. All the data sets and programs used in the study and detailed primary results are available upon request.
The Impact of the Unstructured Contacts Component in Influenza Pandemic Modeling

Background Individual based models have become a valuable tool for modeling the spatiotemporal dynamics of epidemics, e.g. influenza pandemic, and for evaluating the effectiveness of intervention strategies. While specific contacts among individuals into diverse environments (family, school/workplace) can be modeled in a standard way by employing available socio-demographic data, all the other (unstructured) contacts can be dealt with by adopting very different approaches. This can be achieved for instance by employing distance-based models or by choosing unstructured contacts in the local communities or by employing commuting data. Methods/Results Here we show how diverse choices can lead to different model outputs and thus to a different evaluation of the effectiveness of the containment/mitigation strategies. Sensitivity analysis has been conducted for different values of the first generation index G0 , which is the average number of secondary infections generated by the first infectious individual in a completely susceptible population and by varying the seeding municipality. Among the different considered models, attack rate ranges from 19.1% to 25.7% for G0 = 1.1, from 47.8% to 50.7% for G0 = 1.4 and from 62.4% to 67.8% for G0 = 1.7. Differences of about 15 to 20 days in the peak day have been observed. As regards spatial diffusion, a difference of about 100 days to cover 200 km for different values of G0 has been observed. Conclusion To reduce uncertainty in the models it is thus important to employ data, which start being available, on contacts on neglected but important activities (leisure time, sport mall, restaurants, etc.) and time-use data for improving the characterization of the unstructured contacts. Moreover, all the possible effects of different assumptions should be considered for taking public health decisions: not only sensitivity analysis to various model parameters should be performed, but intervention options should be based on the analysis and comparison of different modeling choices.
Higher order attribute grammars

A new kind of attribute grammars, called higher order attribute grammars, is defined. In higher order attribute grammars the structure tree can be expanded as a result of attribute computation. A structure tree may be stored in an attribute. The term higher order is used because of the analogy with higher order functions, where a function can be the result or parameter of another function. A relatively simple method, using OAGs, is described to derive an evaluation order on the defining attribute occurrences which comprises all possible direct and indirect attribute dependencies. As in OAGs, visit-sequences are computed from which an efficient algorithm for attribute evaluation can be derived.