Miracle-dz/UniFAR-FTUs huggingface dataset:
Flux of Ca2+ across the sarcoplasmic reticulum of guinea‐pig cardiac cells during excitation‐contraction coupling.

1. A method has been developed for calculating the flux of Ca2+ across the sarcoplasmic reticulum (SR) during excitation‐contraction coupling in mammalian heart cells. FSR will symbolize the net rate of movement of Ca2+, per litre of accessible cytoplasm, into or out of the sarcoplasmic reticulum. FSR has the units MS‐1. 2. A theory of the cytoplasmic [Ca2+]i transient in mammalian heart cells is presented in which the [Ca2+]i transient results from the various cellular processes that tend to increase or decrease cytoplasmic [Ca2+]i. According to the theory, FSR can be calculated if all cellular processes that contribute to the [Ca2+]i transient (other than Ca2+ fluxes across the SR) are either eliminated or are known quantitatively. 3. To obtain the measurements required to apply this theory, [Ca2+]i transients and membrane currents were recorded in guinea‐pig single ventricular myocytes subjected to whole‐cell voltage clamp and internal perfusion. [Ca2+]i transients were recorded through the use of the Ca2+ indicator, Fura‐2 (pentapotassium salt). 4. Ca2+ fluxes through the sodium‐calcium exchanger were eliminated in all experiments, by perfusing the cells, internally and externally with Na(+)‐free solutions. Ca2+ flux through the sarcolemmal L‐type Ca2+ channel was measured as the verapamil‐sensitive current. Influx of Ca2+ through all other voltage‐dependent pathways was found to be negligible for the calculation of FSR over the time course of a single [Ca2+]i transient. 5. In the combined absence of Ca2+ current, Na(+)‐Ca2+ exchange and fluxes across the SR (10 mM‐caffeine), the net rate of removal of Ca2+ from the cytoplasm, which includes presumed contributions from sarcolemmal Ca(2+)‐ATPase and mitochondrial Ca2+ transport, was found to be a negligible quantity in the calculation of FSR, over the time course of a single [Ca2+]i transient. 6. Calculation of FSR requires that the Ca(2+)‐binding capacity of cytoplasm be known. [Ca2+]i transients recorded during measurable total Ca2+ influx into the cytoplasm (verapamil‐sensitive current in the absence of fluxes across the SR) were compared with theoretical Ca2+ transients computed on the assumption that the entering Ca2+ could bind only to intracellular ligands (values for ligands taken from literature) and to Fura‐2 (30 microM). The slope of the regression line relating calculated total change in [Ca2+]i to the measured total Ca2+ influx was 0.99, not different from the perfect theoretical slope of 1.0 (correlation coefficient, 0.81; standard deviation of slope, 0.14; n = 7). 4+ the SR and FSR had a similar time course to that on depolarization. 10. The unidirectional efflux of Ca2+ from the SR, symbolized FSR, rel was calculated utilizing assumed characteristics of the Ca2+ pump of the SR. The value of FSR, rel was not affected by repolarization from voltage‐clamp pulses greater than 150 ms in duration. (ABSTRACT TRUNCATED AT 400 WORDS)
A single center analysis of nucleophosmin in acute myeloid leukemia: value of combining immunohistochemistry with molecular mutation analysis

Mutations of nucleophosmin 1 are frequently found in acute myeloid leukemia and lead to aberrant cytoplasmic accumulation of nucleophosmin protein. Immunohistochemical staining is therefore recommended as the technique of choice in front-line screening. In this study, we assessed the sensitivity and specificity of immunohistochemistry on formalin-fixed bone marrow biopsies compared with gold standard molecular analysis to predict nucleophosmin 1 mutation status in 119 patients with acute myeloid leukemia. Discrepant cases were further characterized by gene expression analyses and fluorescence in situ hybridization. A large overlap between both methods was observed. Nevertheless, nine patients demonstrated discordant results at initial screening. Five cases demonstrated nuclear staining of nucleophosmin 1 by immunohistochemistry, but a nucleophosmin 1 mutation by molecular analysis. In two cases this could be attributed to technical issues and in three cases minor subpopulations of myeloblasts had not been discovered initially. All tested cases exhibited the characteristic nucleophosmin-mutated gene expression pattern. Four cases had cytoplasmic nucleophosmin 1 staining and a nucleophosmin-mutated gene expression pattern without a detectable nucleophosmin 1 mutation. In two of these cases we found the chromosomal translocation t(3;5)(q25;q35) encoding the NPM-MLF1 fusion protein. In the other discrepant cases the aberrant cytoplasmic nucleophosmin staining and gene expression could not be explained. In total six patients (5%) had true discordant results between immunohistochemistry and mutation analysis. We conclude that cytoplasmic nucleophosmin localization is not always caused by a conventional nucleophosmin 1 mutation and that in the screening for nucleophosmin 1 abnormalities, most information will be obtained by combining immunohistochemistry with molecular analysis.
Inherited Variability of the Mitochondrial Genome and Successful Aging in Humans

Abstract: Increasing data indicate that polymorphic variants of nuclear loci can affect rate and quality of aging in humans. However, the mitochondrial genome is another good candidate, because of the central role played by mitochondrial genes in oxidative phosphorylation (OXPHOS) and cell metabolism. A characteristic of the mitochondrial genome (mtDNA) is the high level of interindividual variability that ensues from high mutation rate and unilinear inheritance. Related groups of germline/inherited mtDNA polymorphisms (haplogroups) have been identified as continent‐specific sets of stable/ancient/associated restriction fragment length polymorphisms in the mtDNA coding region, representing markers capable of exactly depicting the mtDNA pool of a specific population. The hypothesis can be put forward that mtDNA variants included in a haplogroup may have similar OXPHOS efficiency and therefore act as genetic factors predisposing to individual successful or unsuccessful aging. This idea can be explored by sampling groups of individuals of different ages from a well‐defined population and comparing the pools of mtDNA haplogroups between samples. The results obtained by screening mtDNA haplogroups in about 800 Italians of different ages, including more that 200 centenarians, agree with the hypothesis that the inherited variability of the mitochondrial genome is associated with the chance of successful aging and longevity in humans.
Verificación facial multimodal: 2D y 3D

Durante la segunda mitad del siglo XX, surgieron distintas tecnicas disenadas para reconocer a los individuos a partir de su imagen facial, es decir, informacion bidimensional. En los ultimos anos, han aparecido sensores capaces de adquirir no solo la informacion bidimensional de textura, sino tambien la forma de la cara, la informacion tridimensional. En la presente tesis doctoral se realiza una comparacion de la capacidad de reconocimiento facial de ambos tipos de informacion: 2D y 3D. Para ello, se han disenado tres sistemas verificadores diferentes, basados en distintas caracteristicas fisicas de acuerdo al tipo de informacion que tratan: imagen de textura (2D), imagen de profundidad (2.5D) y mallado tridimensional (3D). Los verificadores 2D y 2.5D se basan en la tecnica de Analisis de Componentes Principales y la clasificacion se realiza mediante Maquinas de Vectores Soporte. El verificador 3D se basa en la medida del ajuste de superficies faciales mediante el algoritmo Iterative Closest Point. Una de las principales ventajas del uso de informacion tridimensional es la posibilidad de realizar un proceso de normalizacion de los datos, para corregir giros faciales y correcciones en escala. Se han disenado tres metodos diferentes de normalizacion facial automatica: un metodo basado en la segmentacion de la superficie facial en funcion del valor de la curvatura media y gaussiana; un metodo tambien local, basado en la caracterizacion de puntos mediante Spin Images y una posterior clasificacion de estas mediante Maquinas de Vectores Soporte; un metodo global basado en el calculo de diferentes planos de regresion a partir del mallado tridimensional. Finalmente, se han fusionado los dos tipos de informacion 2D y 3D, para aprovechar las ventajas de cada una de ellas, obteniendo un sistema hibrido que mejora los verificadores individuales. La fusion se realiza a la altura del modulo de decision del sistema, realizando una combinacion lineal de las salidas o scores de cada uno de los clasificadores utilizados.
Mechanism of postsegregational killing by the hok gene product of the parB system of plasmid R1 and its homology with the relF gene product of the E. coli relB operon.

The parB region of plasmid R1 encodes two genes, hok and sok, which are required for the plasmid‐stabilizing activity exerted by parB. The hok gene encodes a potent cell‐killing factor, and it is regulated by the sok gene product such that cells losing a parB‐carrying plasmid during cell division are rapidly killed. Coinciding with death of the host cell, a characteristic change in morphology is observed. Here we show that the killing factor encoded by the hok gene is a membrane‐associated polypeptide of 52 amino acids. A gene located in the Escherichia coli relB operon, designated relF, is shown to be homologous to the hok gene. The relF gene codes for a polypeptide of 51 amino acids, which is 40% homologous to the hok gene product. Induced overexpression of the hok and relF gene products results in the same phenomena: loss of cell membrane potential, arrest of respiration, death of the host cell and change in cell morphology. The parB region and the relB genes were cloned into unstably inherited oriC minichromosomes. Whereas the parB region also conferred a high degree of genetic stability to an oriC minichromosome, the relB operon (with relF) did not; therefore the latter does not appear to ‘stabilize’ its replicon (the chromosome). The function of the relF gene is not known.
Invasion-Inhibitory Antibodies Elicited by Immunization with Plasmodium vivax Apical Membrane Antigen-1 Expressed in Pichia pastoris Yeast

ABSTRACT In a recent vaccine trial performed with African children, immunization with a recombinant protein based on Plasmodium falciparum apical membrane antigen 1 (AMA-1) conferred a significant degree of strain-specific resistance against malaria. To contribute to the efforts of generating a vaccine against Plasmodium vivax malaria, we expressed the ectodomain of P. vivax AMA-1 (PvAMA-1) as a secreted soluble protein in the methylotrophic yeast Pichia pastoris. Recognized by a high percentage of sera from individuals infected by P. vivax, this recombinant protein was found to have maintained its antigenicity. The immunogenicity of this protein was evaluated in mice using immunization protocols that included homologous and heterologous prime-boost strategies with plasmid DNA and recombinant protein. We used the following formulations containing different adjuvants: aluminum salts (Alum), Bordetella pertussis monophosphoryl lipid A (MPLA), flagellin FliC from Salmonella enterica serovar Typhimurium, saponin Quil A, or incomplete Freund's adjuvant (IFA). The formulations containing the adjuvants Quil A or IFA elicited the highest IgG antibody titers. Significant antibody titers were also obtained using a formulation developed for human use containing MPLA or Alum plus MPLA. Recombinant PvAMA-1 produced under “conditions of good laboratory practice” provided a good yield, high purity, low endotoxin levels, and no microbial contaminants and reproduced the experimental immunizations. Most relevant for vaccine development was the fact that immunization with PvAMA-1 elicited invasion-inhibitory antibodies against different Asian isolates of P. vivax. Our results show that AMA-1 expressed in P. pastoris is a promising antigen for use in future preclinical and clinical studies.
Thermodynamic Integration in 3n Dimensions without Biases or Alchemy for Protein Interactions

Thermodynamic integration (TI), a powerful formalism for computing the Gibbs free energy, has been implemented for many biophysical processes characterized by one-dimensional order parameters with alchemical schemes that require delicate human efforts to choose/design biasing potentials for sampling the desired biophysical events and to remove their artifactitious consequences afterwards. Theoretically, an alchemical scheme is exact but practically, it causes error amplification. Small relative errors in the interaction parameters can be amplified many times in their propagation into the computed free energy [due to subtraction of similar numbers such as (105 ± 5) − (100 ± 5) = 5 ± 7], which would render the results significantly less accurate than the input interaction parameters. In this paper, we present an unsophisticated implementation of TI in 3n dimensions (3nD) (n=1,2,3…) without alchemy or biasing potentials. In TI3nD, the errors in the interaction parameters will not be amplified and human efforts are not required to design biasing potentials that generate unphysical consequences. Using TI3nD, we computed the standard free energies of three protein complexes: trometamol in Salmonella effector SpvD (n=1), biotin in avidin (n=2), and Colicin E9 endonuclease with cognate immunity protein Im9 (n=3) and the hydration energies of ten biologically relevant compounds (n=1 for water, acetamide, urea, glycerol, trometamol, ammonium and n=2 for erythritol, 1,3-propanediol, xylitol, biotin). The computed results all agree with available experimental data. Each of the 13 computations is accomplishable within two (for a hydration problem) to ten (for the protein-recognition problem) days on an inexpensive workstation (two Xeon E5-2665 2.4GHz CPUs and one nVidia P5000 GPU).
An Introduction to Buddhism: Teachings, History and Practices

This book is a comprehensive introduction to the Buddhist tradition as it has developed in three major cultural areas in Asia, and also developed in the West. It is intended to be a textbook for students of religious and Asian studies respectively, but will also be of interest to those who want a general survey of Buddhism and its beliefs. Unlike many other general books about Buddhism, it not only explores Buddhist beliefs, but also seeks to show as a set of practices. It thus includes chapters on devotion, ethics, monastic practices and meditation. Such practices are related to Buddhist teachings and historical developments. Emphasising as it does the diversity found within different Buddhist traditions, the book aims to underline common threads of belief, practice and historical continuities which unify the Buddhist world. Dr Harvey has sought to answer questions that are often asked by people on first meeting the tradition, and in his section on Nirvana offers a novel interpretation of this ultimate, transcendent mystery.
Preparticipation Examination (Screening): Practical Issues as Determined by Sport: A United Kingdom Perspective

Objectives:Pre-participation examination, screening and health surveillance are part of the job specification for many roles within Sports Medicine. The type and scope of this activity varies enormously, with little consensus as to best evidence-based practice. The purpose of this work was to explore and understand the practical approaches to pre-participation examination, screening and health surveillance in two contrasting sport scenarios. Data Source:Team physicians for British Triathlon and Manchester United Football Club. Data synthesis/Methods:Information was gathered under the headings: why screen, screening objectives, practical issues and constraints? Results:The systems evolved within these two sports reflect their respective opportunities and constraints. Different systems, each with merit, have evolved with some generalizable concepts across sport. Conclusions:A perfect system for pre-participation examination, screening and health surveillance across all sport does not exist, however, within specific sport scenarios examples of good practice are demonstrated.
Symptom experiences: perceptual accuracy between advanced-stage cancer patients and family caregivers in the home care setting.

PURPOSE This study used a comparative descriptive design to compare family caregivers' and advanced-stage cancer patients' perceptions of patients' multidimensional symptom experiences on presence, frequency, severity, and distress. PATIENTS AND METHODS A convenience sample of 98 dyads, composed of advanced-stage heterogeneous cancer patients and their caregivers, completed the Memorial Symptom Assessment Scale in the home care setting on a one-time basis. This scale is a 32-item Likert-type scale for assessing the presence, frequency, severity, and distress arising from symptoms in cancer patients. RESULTS There was confirmation of trends previously described in related studies where, for example, caregivers tend to overreport on symptom experiences. However, the degree of absolute difference between patient and caregiver responses was normally around 1 unit (on a theoretical range of 0 to 4 units). Levels of patient-caregiver agreement were better on more concrete questions related to symptom frequency, severity, and distress than on broad questions related to the presence of a symptom. Patients and caregivers achieved better levels of agreement on physical versus psychological symptoms. CONCLUSION The findings indicated that family caregivers can provide reasonable proxy or complementary reports on patient symptom experiences of frequency, severity, and distress. However, family caregivers have greater difficulty in achieving high levels of accuracy on psychological versus physical symptoms.
Vitamin B12 Is a Strong Determinant of Low Methionine Synthase Activity and DNA Hypomethylation in Gastrectomized Rats

Background/Aims: The respective influence of folate and vitamin B12 deficiency on MTR activity and transcription, and on DNA methylation is not clearly established. The aim of this study was to assess the respective influence of folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA methylation. Methods: Sixty-one rats were administered normal diet or diet deficient in choline, methionine, folic acid and vitamin B12. Forty-seven of them underwent total gastrectomy or ileal resection. Results: Low vitamin B12 was observed only in gastrectomized rats. Low folate was observed in rats under deficient diet. Total MTR activity (holo- + apoenzyme) was lowered only with vitamin B12 level <200 pmol/l (p = 0.0002), while the ratios of total vs. holo-MTR activity and of transcripts MTR vs. GAPDH (RT-PCR) were unchanged. Vitamin B12 was the single determinant of low MTR (lower quartile, odds ratio = 15.75, p = 0.0017). Low MTR and low vitamin B12 were the two determinants of DNA hypomethylation (lower quartile) (odds ratio = 17.07, p = 0.0006, and odds ratio = 7.31, p = 0.006, respectively). Conclusion: Vitamin B12 affects MTR expression by a non-transcriptional mechanism different from a protective effect on MTR proteolysis. It is also a strong determinant of DNA hypomethylation.
Nucleic acid stability in thermophilic prokaryotes: a review

In order to survive at temperatures of ≥60°C, thermophilic prokaryotes (Archaea and Eubacteria) have adopted different strategies. These strategies include high CG content in the coding sequences, nucleotide arrangement of purine-purine and pyrimidine-pyrimidine, methylation of nucleotides, histone/histone like proteins, reverse gyrase, cations, etc., also provide thermal stability to genome. Strategies adopted at the level of DNA are naturally, though not universally, reflected in RNA in thermophiles. Increased purine load (particularly of adenine), preferential codon usage, post-transcriptional modifications etc. provide thermal stability. All these factors may differ from taxa to taxa as no single or all the factors together can be universally attributed for providing thermal stability to nucleic acids.
A Simple, Fast, and Robust Open-Phase Fault Detection Technique for Six-Phase Induction Motor Drives

Fault tolerance is much appreciated at industry in applications with high-reliability requirements. Due to their inherent fault-tolerant capability against open-phase faults (OPFs), drives with multiple three-phase windings are ideal candidates in such applications and for this reason many efforts have been devoted to the development of different fault-tolerant control strategies. Fault detection is, however, a previous and mandatory stage in the creation of fault-tolerant drives, and the study of specific OPF detection methods for six-phase drives is still scarce. Taking advantage of the secondary currents (so called x-y currents) that are unique in multiphase machines, this study proposes new fault indices that detect and locate the OPFs without additional hardware. The method proves to be simple and independent of the operating point, control technique, and drive parameters. Comparative experimental results confirm the capability of the proposed method to achieve fast detection times with good robustness.
Shifts in leaf vein density through accelerated vein formation in C4 Flaveria (Asteraceae).

BACKGROUND AND AIMS Leaf venation in many C(4) species is characterized by high vein density, essential in facilitating rapid intercellular diffusion of C(4) photosynthetic metabolites between different tissues (mesophyll, bundle sheath). Greater vein density has been hypothesized to be an early step in C(4) photosynthesis evolution. Development of C(4) vein patterning is thought to occur from either accelerated or prolonged procambium formation, relative to ground tissue development. METHODS Cleared and sectioned tissues of phylogenetically basal C(3) Flaveria robusta and more derived C(4) Flaveria bidentis were compared for vein pattern in mature leaves and vein pattern formation in developing leaves. KEY RESULTS In mature leaves, major vein density did not differ between C(3) and C(4) Flaveria species, whereas minor veins were denser in C(4) species than in C(3) species. The developmental study showed that both major and minor vein patterning in leaves of C(3) and C(4) species were initiated at comparable stages (based on leaf length). An additional vein order in the C(4) species was observed during initiation of the higher order minor veins compared with the C(3) species. In the two species, expansion of bundle sheath and mesophyll cells occurred after vein pattern was complete and xylem differentiation was continuous in minor veins. In addition, mesophyll cells ceased dividing sooner and enlarged less in C(4) species than in C(3) species. CONCLUSIONS Leaf vein pattern characteristic to C(4) Flaveria was achieved primarily through accelerated and earlier offset of higher order vein formation, rather than other modifications in the timing of vein pattern formation, as compared with C(3) species. Earlier cessation of mesophyll cell division and reduced expansion also contributed to greater vein density in the C(4) species. The relatively late expansion of bundle sheath and mesophyll cells shows that vein patterning precedes ground tissue development in C(4) species.