Miracle-dz/UniFAR-FTUs huggingface dataset:
Spontaneous Ha‐ras Gene Activation in Cultured Primary Murine Keratinocytes: Consequences of Ha‐ras Gene Activation in Malignant Conversion and Malignant Progression

The activation of the c‐Ha‐ras gene and its contribution to the tumorigenic phenotype were examined in cultured mouse keratinocytes and squamous tumors using transfection into NIH 3T3 cells and nucleic acid hybridization. When normal keratinocytes were cultured in medium with 0.05 mM Ca2+ (low Ca2+ medium), many cells died within 2–3 wk, while others formed rapidly growing foci that could be subcultured. These rapidly growing cells produced benign tumors when grafted to nude mice and possessed a heterozygous mutation in the c‐Ha‐ras gene with an A‐>T transversion in codon 61. Fibroblast‐conditioned low Ca2+ medium prevented cell death, focus formation, c‐Ha‐ras gene mutation, and tumorigenicity. Thus, suboptimal culture conditions favored a spontaneous mutation in codon 61 of the c‐Ha‐ras gene of keratinocytes. When a v‐Ha‐ras gene was introduced into normal keratinocytes by a replication‐defective retrovirus, the recipient cells produced papillo‐mas in vivo, and after 2 mo, 60% of the tumors converted to squamous cell carcinomas. None of the 22 converted tumors had an endogenous c‐Ha‐ras gene mutation at codon 61. However, the A‐>T transversion mutation developed when these carcinoma cells were cultured in low Ca2+ medium but not in fibroblast‐conditioned medium. Cells with both an exogenous v‐Ha‐ras and an activated c‐Ha61‐ras gene produced undifferentiated, rapidly lethal carcinomas, while cells with only v‐Ha‐ras maintained the squamous carcinoma phenotype. Undifferentiated carcinomas also developed when the v‐Ha‐ras gene was introduced into papilloma cells with a chemically induced endogenous c‐Ha61‐ras gene mutation. These results suggest that mutation in the c‐Ha‐ras gene can contribute to initiation, malignant conversion, and malignant progression in skin carcinogenesis, and gene dosage may determine the phenotype expressed.
Open Reduction and Internal Fixation of Humeral Nonunions: A Biomechanical and Clinical Study

Background: Several studies have compared different methods for fixation of the midpart of the humeral shaft, but there are only scattered data regarding which type of plate construct provides the best fixation for humeral nonunion. The objectives of this study were (1) to obtain objective data on the performance of four different plate constructs used for fixation of humeral nonunion, and (2) to report our clinical experience with plate fixation of thirty-seven nonunions of the midpart of the humeral shaft.Methods: In the first part of the study, four plate constructs were compared in a Sawbones model. The groups consisted of (1) a posterior limited-contact dynamic compression plate alone; (2) a posterior limited-contact dynamic compression plate and an interfragmentary screw; (3) a posterior limited-contact dynamic compression plate, a lateral 3.5-mm reconstruction plate, and an interfragmentary screw; and (4) a posterior limited-contact dynamic compression plate and a lateral 3.5-mm reconstruction plate. Tests were performed with use of an MTS Bionix machine in anterior-posterior four-point bending, medial-lateral four-point bending, and external rotation torque.In the second part of the study, the charts of thirty-seven consecutive patients in whom a nonunion of the midpart of the humeral shaft had been treated with plate fixation were reviewed retrospectively. The average age of the patients was forty-eight years (range, thirteen to seventy-eight years). Nineteen patients were treated with a single posterior plate, and eighteen were treated with a two-plate construct with the plates parallel and lying at 90° to each other. All of the nonunions were treated with bone-grafting, and an interfragmentary screw was used in thirty-six of the thirty-seven patients. Radiographs and the clinical status were evaluated at an average of thirteen months postoperatively.Results: The biomechanical testing showed that the two-plate constructs were significantly stiffer than the single-plate constructs in all test modes (p < 0.05). In the clinical part of the study, thirty-four (92%) of the nonunions healed without complications at an average of 4.8 months. Two nonunions treated with the two-plate construct and one treated with one plate failed to heal.Conclusions: No significant difference in the healing rate was found between the two clinical groups (p = 0.4, &bgr; = 0.9), and the overall healing rate was 92%. However, a two-plate construct with the plates at right angles is mechanically stiffer than a single-plate construct, which might be helpful if rigid stabilization of the humerus at the midshaft level is needed.
Effect of small intestinal nutrient infusion on appetite, gastrointestinal hormone release, and gastric myoelectrical activity in young and older men

OBJECTIVE:The mechanisms responsible for the reduction in appetite and slowing of gastric emptying in older persons are poorly understood. The aim of this study was to evaluate the effects of aging on small intestinal regulation of appetite, GI hormone release, and gastric myoelectrical activity.METHODS:Thirteen older (65–84 yr) and 13 young (18–32 yr) healthy men received isovolumetric, intraduodenal (ID) infusions of saline (control), lipid, and glucose for 120 min, on separate days. The energy content of the lipid and glucose infusions was identical at 2.86 kcal/min. Immediately after the ID infusions, each subject was offered a buffet meal, and ad libitum food intake was quantified. Blood glucose and plasma insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide were measured. Gastric myoelectrical activity was measured by surface electrogastrography (EGG). RESULTS:ID lipid suppressed food intake in both the young and older men (p < 0.05), whereas ID glucose suppressed food intake only in the older men (p < 0.05). The blood glucose (p < 0.01) and insulin (p < 0.05) responses to ID glucose were greater in older than young men. However, there were no differences in glucagon-like peptide 1 or glucose-dependent insulinotropic peptide responses to any of the infusions. There was a greater increase in the EGG power ratio both during and after ID glucose infusion in the young (p < 0.05) than the older men, and an attenuation of EGG frequency by nutrient infusions in older, but not young, men.CONCLUSIONS:Our findings indicate that aging is associated with nutrient-specific changes in appetite, hormonal, and gastric myoelectrical (EGG) responses to ID nutrients. An enhanced satiating effect of small intestinal carbohydrates may potentially contribute to the anorexia of aging.
QUANTITATIVE GENETICS AT THE MOLECULAR LEVEL : A ROOT METABOLOMICS CASE STUDY

Over the last several years, a number of plant studies have utilized high throughput analysis methods, such as expression profiling, protein quantization, and metabolic profiling, on plants to obtain large data sets of molecular phenotypes on a variety of genetic backgrounds (see Young and Udvardi, 2008). For example, metabolic profiling has been used to observe the effects of mutated genes (Feihn et al., 2000) and genetically map quantitative metabolite traits in a population of introgression lines (Schauer et al., 2006). Despite such prevalence and interest in these approaches, there has been relatively little work to reconcile the kind of data obtained with these methods to plant breeding theory. There are many examples of breeding for traits identified with a rapid assay, such as spectroscopy or UV-chromatography, from the last several decades, but adaptation of the newer profiling approaches has not been intuitive. The molecular traits that should be improved are not initially defined, as they are generally not the desired end product themselves. In other words, the final overall desired phenotypes are known, but the quantitative molecular phenotypes that contribute to them are not, requiring some association between them to be made. The compensating advantage of profiling techniques is the ability to accurately determine the abundance and identity of a large variety of molecules, on the order of one hundred to tens of thousands, depending on the methods and molecules. The challenge is to discover ways to coherently interpret and apply these kinds of data, which are now a highly available resource. This will require basic research into the range and conditions of molecular variation, nature of inheritance, and their relationships to the traditional agronomic traits of interest.
A Simple Method to Identify Sleep Apnea Using Holter Recordings

Introduction: Despite its severe cardiovascular and other consequences, sleep apnea syndrome frequently is undiagnosed. Because apneas result in repeated autonomic arousals associated with cyclic variations in heart rate (CVHR), we hypothesized that sleep apnea syndrome could be identified from simple HR tachograms (graphs of HR vs time) derived from ECG monitoring.
Living Spirituality and Sexuality: A Comparison of Lesbian, Gay and Bisexual Christians in France and Britain

Drawing upon two conceptually and methodologically related projects in France and Britain, the authors illuminate lesbian, gay and bisexual Christians’ religious orientations, beliefs and practices. The samples demonstrated striking similarities and differences. Participants generally strongly disagreed with the Church’s censorious teachings on non-heterosexuality, but the British sample appeared more critical. The French sample also experienced a greater degree of psychological and social dissociation. Nevertheless, some participants across samples stayed within homophobic religious structures because of their commitment to integrating their sexuality and spirituality, and to making religious communities more inclusive. This commitment was buttressed by: (1) their conceptualization of the all-loving God and of Jesus Christ as a transgressive champion of social justice; (2) positive personal experiences; (3) the marginalization of church authority in their moral universe; and (4) increasing theological, social and political capital. Theoretically, the authors contribute to debates on contemporary religious and spiritual landscape and identity. S’appuyant sur deux enquêtes identiques, conceptuellement et méthodologiquement parlant, menées en Grande-Bretagne et en France, les auteurs éclairent les croyances, les pratiques et les orientations religieuses de gays, lesbiennes et bisexuel/les chrétiens. Les échantillons présentent quelques différences et similitudes remarquables. Si les participants sont généralement tout à fait en désaccord avec les positions officielles des Églises sur l’homosexualité et la bisexualité, l’échantillon britannique semble plus critique. Les enquêtés français vivent un niveau plus élevé de dissociation psychologique et sociale. Quelques personnes des deux échantillons restent toutefois au sein de structures religieuses homophobes, en tentant, d’une part, d’intégrer leur sexualité et leur spiritualité et, d’autre part, de faire évoluer celles-ci de l’intérieur vers une plus grande inclusivité. Leur effort pour intégrer foi et sexualité s’étaye sur (1) l’idée d’un Dieu aimant chacune de ses créatures et de Jésus-Christ comme un champion de justice sociale; (2) un vécu personnel positif; (3) une certaine délégitimation de l’autorité de l’Église dans l’univers moral individuel; et (4) l’augmentation du capital théologique, social et politique. Les auteurs contribuent aux débats théoriques sur l’identité et le paysage religieux et spirituel contemporains.
A biophysical model of heat sensitivity in nociceptive C-fiber neurons

The ability to detect noxious stimuli and evoke a defensive response is made possible by specialized peripheral sensory neurons called nociceptors that respond to stimuli such as extreme temperature, pressure and injury. A number of experimental studies have been done on nociceptors at various range of temperatures in order to understand the underlying biophysical mechanisms. Simple models for describing temperature sensitivity are available, such as the Hodgkin and Huxley model for squid giant axon. However, to our knowledge there are no existing models for temperature sensitive nociceptive C-fiber DRG neurons with multiple ion channels that have also been validated against experimental findings for different temperatures. Here, we report a biophysical model for temperature dependence in nociceptors, more precisely for C-fibers. We validate the model using action potentials recorded at different temperatures. The resulting action potentials from the simulation show that the model satisfactorily replicates the key features of the experimentally obtained results paving the way for further studies.
Real-time discrimination of broadcast speech/music

We describe a technique which is successful at discriminating speech from music on broadcast FM radio. The computational simplicity of the approach could lend itself to wide application including the ability to automatically change channels when commercials appear. The algorithm provides the capability to robustly distinguish the two classes and runs easily in real time. Experimental results to date show performance approaching 98% correct classification.
Tension Performance of Metal-Plate Connected Joints of Chinese Larch Dimension Lumber

Tension tests of metal-plate connected (MPC) joints for Chinese larch (Larix gmelinii (Rupr.) Rupr. ) were conducted in four orientations. Load-deflection curves were obtained for each MPC jointed specimen. Ultimate tension load, translation stiffness, stiffness at large slip, and failure modes for each specimen were obtained. A Foschi 3-parameter model was found to fit the load-deflection curves very well. Wood grain, and MPC length and loading directions had significant effects on elastic deformation and stiffness at large slip of the MPC joints. Load parallel to the grain with MPC length parallel to load (AA) represented the highest elastic deformation, while load perpendicular to the grain and MPC parallel to load (AE) showed the lowest. Load perpendicular to grain with MPC length perpendicular to load (EE) presented the highest stiffness at large slip, AA the second, load parallel to grain-MPC length perpendicular to load (EA) the third, and AE the lowest. The translation stiffness and tension load showed similar trends in terms of the effect of test orientations. The ultimate tension load was reduced by 18.9% from AA to EA, 34.2% from AA to AE, and 36.8% from AA to EE. Multiple failure modes occurred at the MPC joint, including MPC shear failure, tooth withdrawal, and wood failure.
The implementation of Restoring Health – a chronic disease model of care to decrease acute health care utilization

The Restoring Health Program, a multi-disciplinary model of care for patients with chronic lung diseases, heart failure, and diabetes, was established to improve the quality of life and function for patients with these target chronic diseases, while reducing their disproportionately high demand on acute health care services. Acute health care utilization at St Vincent’s Hospital Melbourne for all patients recruited between February 2003 and June 2005 (n = 351) was analyzed using within-subjects paired sample t-tests to compare the 6 months of pre-recruitment with 6 months of post-recruitment. Analysis showed statistically significant decreases in emergency department presentations (P < 0.001), hospital admissions (P < 0.001), and length of stay (P < 0.001). This article describes the current model of care, the program’s enablers, and its impact on health service demand after the first 4 years of implementation.
Replication of Epstein-Barr virus: ultrastructural and immunofluorescent studies of P3HR1-superinfected Raji cells

We have studied by means of electron microscopy and immunofluorescence the different steps of the replication of the P3HR1 strain of Epstein-Barr virus in Raji cells. The virus entered the cell by fusion of the viral envelope with the plasma membrane, followed by the disintegration of the capsid. In some cases, the migration of nucleocapsids toward the nuclear membrane was observed. The synthesis of new virions began as early as 7 h after infection (in the case of a high multiplicity of infection [MOI]-800 particles per cell) and took place in low-electron-density areas of the nucleus. A viral envelope was acquired by budding either through the nuclear membrane or more often through membranes of the Golgi apparatus or cytoplasmic vacuoles. Comparing immunofluorescence and electron microscopic data a good correlation was found between the presence of early antigen and ultrastructurally altered cells, as well as between the presence of viral capsid antigen and virus-producing cells. With different MOIs, different types of viral cycles were observed: at a low MOI (less than or equal to 50 particles per cell), a nonproducer cycle was induced, with early antigen synthesis only; at a higher MOI (100 particles per cell), a transient production of a small amount of virions was observed, and at a high MOI (greater than or equal to 300 particles per cell), a productive cycle was the rule.
p27kip1 Deficiency Impairs G2/M Arrest in Response to DNA Damage, Leading to an Increase in Genetic Instability

ABSTRACT p27kip1 is a cyclin-dependent kinase inhibitor and a tumor suppressor. In some tumors, p27 suppresses tumor growth by inhibition of cell proliferation. However, this is not universally observed, implying additional mechanisms of tumor suppression by p27. p27-deficient mice are particularly susceptibility to genotoxin-induced tumors, suggesting a role for p27 in the DNA damage response. To test this hypothesis, we measured genotoxin-induced mutations and chromosome damage in p27-deficient mice. Both p27+/− and p27−/− mice displayed a higher N-ethyl-N-nitrosourea-induced mutation frequency in the colon than p27+/+ littermates. Furthermore, cells from irradiated p27-deficient mice exhibited a higher number of chromatid breaks and showed modestly increased micronucleus formation compared to cells from wild-type littermates. To determine if this mutator phenotype was related to the cell cycle-inhibitory function of p27, we measured cell cycle arrest in response to DNA damage. Both normal and tumor cells from p27-deficient mice showed impaired G2/M arrest following low doses of ionizing radiation. Thus, p27 may inhibit tumor development through two mechanisms. The first is by reducing the proliferation of cells that have already sustained an oncogenic lesion. The second is by transient inhibition of cell cycle progression following genotoxic insult, thereby minimizing chromosome damage and fixation of mutations.
The hormone regulatory element of mouse mammary tumour virus mediates progesterone induction.

Sequences within the long terminal repeat region (LTR) of mouse mammary tumour virus (MMTV) confer progestin inducibility to either the tk‐promoter or the MMTV‐promoter in T47D cells, a human mammary tumour cell line which possesses high constitutive levels of progesterone receptor. In a clone of MCF7 cells, another human mammary tumour cell line with a low level of progesterone receptor, as well as in rat fibroblasts, glucocorticoid but not progestin induction is observed. The effect of the progesterone analogue R5020 is much more pronounced than the effect of dexamethasone, and at the concentrations required for maximal induction, R5020 does not significantly compete with binding of dexamethasone to the glucocorticoid receptor. In conjunction with previous results on the DNA binding of the glucocorticoid and progesterone receptors, these data show that two different steroid hormones, acting through their respective receptors, can mediate the induction of gene expression by interacting with the same DNA sequences. Our results suggest that the hormone regulatory element of MMTV may primarily be a progesterone‐responsive element in mammary cells.
Priming effect of luteinizing hormone releasing factor elicited by preoptic stimulation and by intravenous infusion and multiple injections of the synthetic decapeptide.

We have investigated whether the priming effect of LH-RF can be elicited by electrical stimulation of the medial preoptic area, or by i.v. infusion or multiple i.v. injections of the synthetic decapeptide. All experiments were carried out on animals anaesthetized with sodium pentobarbitone at 13.30 h. In pro-oestrous rats, the LH response to the second of two electrical stimuli, 15 min in duration and separated by 60 min, was significantly greater than the response to the first stimulus. When synthetic LH-RF was infused at a constant rate for 90 min, plasma LH increased gradually for the first 45-60 min after which it increased markedly. This enhanced secretion of LH did not occur in rats which were infused with the same total dose of LH-RF, either 15 or 75 ng/100 g body wt, over periods of 45 min or less. When a dose of 15 ng LH-RF/100 g body wt was administered in six divided doses by i.v. injections, each separated by 15 min, there was a marked increase in plasma LH after 75 min. The profile of the mean plasma LH concentration in rats subjected to preoptic stimulation for 90 min was similar to that in rats infused for 90 min with LH-RF, but the variation in response was much greater in the stimulated rats. These results indicate that the priming effect can be elicited by endogenous as well as synthetic LH-RF, and that whether LH-RF reaches the pituitary at a constant rate or in a pulsatile manner the factor is capable of significantly increasing the responsiveness of the gonadotrophs. The relevance of these findings with respect to the development of the spontaneous preovulatory LH surge is discussed. A priming effect could not be elicited by constant LH-RF infusion in dioestrous rats; this supports the view that steroid hormones, especially oestradiol-17phi, determine the magnitude of the effect. The LH response in male rats subjected to i.v. infusion of LH-RF was much lower than in females. Pre-treatment with oestradiol benzoate did not increase the response significantly, suggesting that this sex difference cannot be ascribed simply to low levels of plasma oestrogen in the male.
Preparation and Characterization of Non-Stoichiometric Yttrium Aluminum Garnet (YAG) with Antisite Defects as a Potential Scintillator

Non-stoichiometric YAG powder samples were prepared via a simple sol-gel combustion method by introducing antisite defects YAl,16a intentionally. The investigation of structure and luminescence properties confirmed that the antisite defects with different concentrations can be created through adjusting the composition in YAG at relatively low (1000°C) temperature. The X-ray excited luminescence and vacuum ultra-violet spectroscopies show that the luminescence intensity of non-stoichiometric YAG increases with increasing antisite defects concentration, which is much stronger than that of the stoichiometric counterpart under the same conditions. It indicates that non-stoichiometric YAG with antisite defects YAl,16a might be used as a potential candidate for scintillator.
Using Topic-Specific Ranks to Personalize Web Search

This chapter introduces a personalized ranking function as a means of offering Web information seekers with search results that satisfy their particular interests. It argues that users’ preferences can be accurately identified based on the semantic analysis of their previous searches and that learnt user preferences can be fruitfully employed for personalizing search results. In this respect, we introduce a ranking formula that encapsulates the user’s interests in the process of ordering retrieved results so as to meet the user’s needs. For carrying out our study we relied on a lexical ontology that encodes a number of concepts and their interrelations and which helps us determine the semantics of both the query keywords and the query matching pages. Based on the correlation between the query and document semantics, our model decides upon the ordering of search results so that these are personalized.