Miracle-dz/UniFAR-FTUs huggingface dataset:
Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma and its precursor lesions

Oestrogen receptor alpha (ER) plays a critical, diverse and not fully understood role in endometrial carcinoma. Most endometrial carcinomas express ER and some of these tumours respond favourably to anti‐oestrogen therapy. On the other hand, tamoxifen therapy constitutes a major risk factor for endometrial carcinoma development. Amplification of the ESR1 gene encoding ER was recently shown to constitute a mechanism for ER over‐expression in breast carcinoma. This study was designed to determine the potential role of ESR1 amplifications in endometrial carcinoma. Tissue microarrays of 368 endometrial carcinomas and large sections of 43 cases of endometrial hyperplasia were analysed for ESR1 gene amplification and ER protein expression by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. FISH revealed ESR1 amplification in 40/176 (23%) cancers, 6/19 (32%) atypical complex hyperplasias, 3/10 (30%) complex hyperplasias without atypia and 2/14 (14%) simple hyperplasias without atypia. Strong ER protein expression was significantly linked to ESR1 amplification in endometrial carcinoma (p = 0.0036). These data indicate that ESR1 amplification might be one mechanism for ER over‐expression in endometrial carcinoma, and suggest an early role for ESR1 amplification in the development of a significant fraction of endometrial carcinoma. Given the predictive role of ESR1 amplification for tamoxifen response in breast carcinoma, it will be interesting to investigate the response of ESR1‐amplified endometrial cancers to anti‐oestrogenic drugs. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity.

We have used multiple-amino acid replacement mutagenesis to examine the roles of the TCR homologues of Ig complementarity-determining regions (CDR) and framework sequences in Ag-MHC and Staphylococcus aureus enterotoxin reactivity. In the three cases examined, transplantation of Ig CDR3 homologues between I-Ek-restricted TCR that recognize distinct peptides did not result in transfer of peptide reactivity. Thus the structural context of the CDR3 loops, e.g., both neighboring CDR and the V beta structure, must play a crucial, albeit supporting, role in ligand recognition. The extreme lability of this context was also shown by the fact that transplantation of the CDR1, -2, and -3 loops from the beta chain of 5C.C7 onto a V beta 1 framework failed to transfer MHC-peptide specificity even when the TCR-alpha chains were identical. In contrast, superantigen reactivity was readily transferred in several cases, with CDR2 transplants conferring strong staphylococcal enterotoxin B and A reactivity and CDR1 transplants yielding weak reactivities. This suggests that bacterial (and perhaps other) superantigens bind to many of the same regions of the TCR V beta that are believed to interact with MHC molecules. These regions of V beta may be ideal targets for superantigen binding precisely because they interact with MHC molecules and thus may be relatively conserved.
Protein Mobilization in Germinating Mung Bean Seeds Involves Vacuolar Sorting Receptors and Multivesicular Bodies1[W][OA]

Plants accumulate and store proteins in protein storage vacuoles (PSVs) during seed development and maturation. Upon seed germination, these storage proteins are mobilized to provide nutrients for seedling growth. However, little is known about the molecular mechanisms of protein degradation during seed germination. Here we test the hypothesis that vacuolar sorting receptor (VSR) proteins play a role in mediating protein degradation in germinating seeds. We demonstrate that both VSR proteins and hydrolytic enzymes are synthesized de novo during mung bean (Vigna radiata) seed germination. Immunogold electron microscopy with VSR antibodies demonstrate that VSRs mainly locate to the peripheral membrane of multivesicular bodies (MVBs), presumably as recycling receptors in day 1 germinating seeds, but become internalized to the MVB lumen, presumably for degradation at day 3 germination. Chemical cross-linking and immunoprecipitation with VSR antibodies have identified the cysteine protease aleurain as a specific VSR-interacting protein in germinating seeds. Further confocal immunofluorescence and immunogold electron microscopy studies demonstrate that VSR and aleurain colocalize to MVBs as well as PSVs in germinating seeds. Thus, MVBs in germinating seeds exercise dual functions: as a storage compartment for proteases that are physically separated from PSVs in the mature seed and as an intermediate compartment for VSR-mediated delivery of proteases from the Golgi apparatus to the PSV for protein degradation during seed germination.
of Peritonitis an Inflammatory Response in a Sterile Model Macrophages and Granulocytes and Mount GM-CSF, and M-CSF) Still Produce Colony-Stimulating Factors (G-CSF, Mice Lacking Three Myeloid

To assess the combined role of G-CSF, GM-CSF, and M-CSF in myeloid cell production, mice deﬁcient in all three myeloid CSFs were generated (G (cid:1) / (cid:1) GM (cid:1) / (cid:1) M (cid:1) / (cid:1) mice). G (cid:1) / (cid:1) GM (cid:1) / (cid:1) M (cid:1) / (cid:1) mice share characteristics found in mice lacking individual cytokines: they are toothless and osteopetrotic and furthermore acquire alveolar proteinosis that is more severe than that found in either GM (cid:1) / (cid:1) or G (cid:1) / (cid:1) GM (cid:1) / (cid:1) mice. G (cid:1) / (cid:1) GM (cid:1) / (cid:1) M (cid:1) / (cid:1) mice have a signiﬁcantly reduced lifespan, which is prolonged by antibiotic administration, suggesting compromised ability to control bacterial infection. G (cid:1) / (cid:1) GM (cid:1) / (cid:1) M (cid:1) / (cid:1) mice have circulating neutrophils and monocytes, albeit at signiﬁcantly reduced numbers compared with wild-type mice, but surprisingly, have more circulating monocytes than M (cid:1) / (cid:1) mice and more circulating neutrophils than G (cid:1) / (cid:1) GM (cid:1) / (cid:1) mice. Due to severe osteopetrosis, G (cid:1) M / mice show diminished numbers of myeloid cells, myeloid progenitors, and B lymphocytes in the bone marrow, but have signiﬁcantly enhanced compensatory splenic hemopoiesis. Although G M / mice have a profound deﬁciency of myeloid cells in the resting peritoneal cavity, the animals mount a moderate cellular response in a model of sterile peritonitis. These data establish that in the absence of G-CSF, GM-CSF, and M-CSF, additional growth factor(s) can stimulate myelopoiesis and acute inﬂammatory responses. The Journal of Immunology, 2007, 178: 6435–6443.
Sleeve Lobectomy as an Alternative Procedure to Pneumonectomy for Non-small Cell Lung Cancer

Introduction: The aim of this study is to compare the outcomes of sleeve lobectomy (SL) and pneumonectomy (PN) and to determine which one is more acceptable standard procedure for patients with non-small cell lung cancer. Methods: From 1996 to 2005, 424 patients underwent SL (n = 157) and PN (n = 267) in our institution. Propensity score matching analysis was performed to compare these two groups for mortality, morbidity, survival, recurrence, and postoperative pulmonary function. Results: In each group, 105 patients were eligible for analysis. The operative mortality was lower in the SL group (1.0%) than the PN group (8.6%), (p < 0.0001). The morbidity was similar (33.4% versus 29.5%, p = 0.376). The 5-year survival was lower in the PN group (PN, 32.14% versus SL, 58.43%, p = 0.0002). The recurrence pattern (locoregional versus distant) did not differ between two groups (p = 0.180). The mean actual postoperative first second forced expiratory volume in the patients underwent SL was 2.05 ± 0.55 liter, which increased by 7.9% compared with the predicted-postoperative first second forced expiratory volume. Conclusions: Our results showed that the SL can be performed with low operative risk and may offer superior survival and better postoperative pulmonary function compared with the PN in selected patients. If anatomically feasible, a SL must be considered as a favorable alternative to PN in patients with non-small cell lung cancer.
Roles of oxidative stress and glutathione depletion in JP-8 jet fuel-induced apoptosis in rat lung epithelial cells.

The toxic jet fuel JP-8 induces morphological and biochemical changes characteristic of apoptosis in rat lung epithelial (RLE-6TN) cells. The mechanism of JP-8 toxicity in these cells was further investigated in an attempt to identify potential therapeutic interventions. Given that oxidative stress and changes in the concentrations of endogenous antioxidants, such as glutathione (GSH), have been associated with the cellular damage elicited by numerous toxicants, the possibility that JP-8 induces cellular oxidative stress was investigated. Experimentally induced depletion of intracellular GSH or exposure of cells to a low concentration of H(2)O(2) markedly enhanced JP-8-induced cell death. A significant reduction in intracellular concentrations of GSH was noted in RLE-6TN cells shortly after exposure to JP-8. Furthermore, JP-8 induced the generation of reactive oxygen species (ROS) in RLE-6TN cells. Consistent with the notion that JP-8 toxicity is mediated by generation of ROS and depletion of intracellular GSH, JP-8-induced cell death was inhibited by exogenous GSH or the thiol-containing antioxidant N-acetyl-cysteine. This protective effect was associated with marked inhibition of both the activation of caspase-3 and the loss of the mitochondrial membrane potential induced by JP-8. Inhibition of the JP-8-induced activation of poly(ADP-ribose) polymerase by 3-aminobenzamide did not protect cells against JP-8 toxicity. Together, these results indicate that thiol antioxidants are highly effective in rescuing cells from JP-8-induced cell death and that they may provide a basis for new therapeutic approaches to counteract JP-8 toxicity.
Approximate dynamic programming based supplementary frequency control of thermal generators in power systems with large-scale renewable generation integration

Intermittent electricity generation from renewable sources is characterized by a wide range of fluctuations in frequency spectrum. The medium-frequency component of 0.01 Hz-1 Hz cannot be filtered out by system inertia and automatic generation control (AGC) and thus it results in deterioration of frequency quality. In this paper, an approximate dynamic programming (ADP) based supplementary frequency controller for thermal generators is developed to attenuate renewable generation fluctuation in medium-frequency range. A policy iteration based training algorithm is employed for online and model-free learning. Our simulation results demonstrate that the proposed supplementary frequency controller can effectively adapt to changes in the system and provide improved frequency control. Further sensitivity analysis validates that the supplementary frequency controller significantly attenuates the dependence of frequency deviation on the medium-frequency component of renewable generation fluctuation.
Experimental conduction block induced by serum from a patient with anti‐GM1 antibodies

Increased titers of antibodies to GM1 ganglioside in humans are associated with lower motor neuron disease and predominantly motor neuropathy with or without conduction block. To investigate the possible mechanism of these antibodies, we injected the serum of a patient with anti‐GM1 antibodies who had motor neuron disease and multifocal motor conduction block, into rat sciatic nerve. When injected with fresh human complement, the serum‐induced conduction block with temporal dispersion and deposits of immunoglobulin were detected at the nodes of Ranvier. Electron microscopic studies revealed demyelination in 6.5% of the fibers. After preabsorbtion with GM1, the serum had no effect, suggesting that the anti‐GM1 antibodies were responsible for the conduction abnormalities.
Cellular Localization and Trafficking of the Human ABCA1 Transporter* 210

ABCA1, the ATP-binding cassette protein mutated in Tangier disease, mediates the efflux of excess cellular sterol to apoA-I and thereby the formation of high density lipoprotein. The intracellular localization and trafficking of ABCA1 was examined in stably and transiently transfected HeLa cells expressing a functional human ABCA1-green fluorescent protein (GFP) fusion protein. The fluorescent chimeric ABCA1 transporter was found to reside on the cell surface and on intracellular vesicles that include a novel subset of early endosomes, as well as late endosomes and lysosomes. Studies of the localization and trafficking of ABCA1-GFP in the presence of brefeldin A or monensin, agents known to block intracellular vesicular trafficking, as well as apoA-I-mediated cellular lipid efflux, showed that: (i) ABCA1 functions in lipid efflux at the cell surface, and (ii) delivery of ABCA1 to lysosomes for degradation may serve as a mechanism to modulate its surface expression. Time-lapse fluorescence microscopy revealed that ABCA1-GFP-containing early endosomes undergo fusion, fission, and tubulation and transiently interact with one another, late endocytic vesicles, and the cell surface. These studies establish a complex intracellular trafficking pathway for human ABCA1 that may play important roles in modulating ABCA1 transporter activity and cellular cholesterol homeostasis.
Evolution of Human Intelligence: The Roles of Brain Size and Mental Construction

Two competing philosophical paradigms characterize approaches to the evolution of the human mind. One postulates continuity between animal and human behavioral capacities. The other assumes that humans and animals are separated by major qualitative behavioral and mental gaps. This paper presents a continuity model that suggests that expanded human mental capacities primarily reflect the increased information processing capacities of the enlarged human brain including the enlarged neocortex, cerebellum, and basal ganglia. These increased information processing capacities enhance human abilities to combine and recombine highly differentiated actions, perceptions, and concepts in order to construct larger, more complex, and highly variable behavioral units in a variety of behavioral domains including language, social intelligence, tool-making, and motor sequences. Environmental input, including self-generated input, interacts with mental constructional capacities to assure that developing humans acquire species-typical and culturally-specific behavioral patterns. This mental constructional model is compatible with our current understanding of differences between human and non-human primate brains, of human brain plasticity, and of the minimal genetic differences between humans and chimpanzees.
Multiple-dose pharmacokinetics of fluvoxamine in children and adolescents.

OBJECTIVE To determine the pharmacokinetics of fluvoxamine in children and adolescents and to compare pharmacokinetic data from adolescents to adults from a previous study. METHOD Fluvoxamine was titrated to a target dose of 100 mg b.i. d. in children (6-11 years) and 150 mg b.i. d. in adolescents (12-17 years) with obsessive-compulsive disorder or other disorder requiring fluvoxamine treatment. Serum samples were collected over 12 hours after 12 or more consecutive doses of 25, 50, 100, and 150 mg. RESULTS Sixteen children (seven females, nine males) and 18 adolescents (nine females, nine males) were included in the pharmacokinetic analyses. Children demonstrated higher mean peak plasma concentration, higher mean area under the plasma concentration-time curve, and lower apparent oral clearance compared with adolescents. Compared with male children, female children had higher mean area under the plasma concentration-time curve, higher mean peak plasma concentration, and more reports of adverse events. However, the area under the plasma concentration-time curve was not directly correlated with frequency or severity of adverse events. Pharmacokinetics were nonlinear over the dose range studied. No pharmacokinetic differences were apparent between adolescents and adults on 150 mg b.i. d. CONCLUSIONS These pharmacokinetic results suggest that children (especially females) have a higher exposure to fluvoxamine than adolescents, whereas adolescents and adults appear to have similar exposure to fluvoxamine.
Solar power prediction with data source weighted nearest neighbors

We consider the task of predicting the half-hourly solar PhotoVoltaic (PV) power output for the next day from three sources: previous solar power, previous weather data and weather forecasts. We propose DWkNN, a data source weighed nearest neighbor method that considers the importance of the different data sources and learns the best weights for them. We evaluate its performance using Australian PV and weather data for one year. Our results show that DWkNN is more accurate than the standard nearest neighbor and other machine learning, statistical and persistence methods used for comparison. We assess the importance of the three data sources to predict the PV power output and show that the most useful information source is the weather forecast, followed by the previous weather and previous PV power data. The addition of the daily average solar irradiance forecast for the next day, when this information is available, considerably improves the accuracy.
Avian Influenza Outbreaks in Chickens, Bangladesh

To determine the epidemiology of outbreaks of avian influenza A virus (subtypes H5N1, H9N2) in chickens in Bangladesh, we conducted surveys and examined virus isolates. The outbreak began in backyard chickens. Probable sources of infection included egg trays and vehicles from local live bird markets and larger live bird markets.
Aspiration and ingestion in dental practice: a 10-year institutional review.

BACKGROUND This article is an institutional retrospective review of incidents involving aspiration and ingestion of dental foreign objects at a large multidisciplinary dental educational facility. It was undertaken to determine which dental procedures were more likely to involve aspiration or ingestion, as well as to evaluate the outcome of these adverse incidents. METHODS The inclusion criteria involved all patients who were documented to have experienced loss of dental instruments or material behind the posterior pharynx during a 10-year consecutive period. The dental and medical records of these patients were analyzed, and the outcomes of the adverse events fell into three categories: aspiration, ingestion, or neither aspirated nor ingested. The authors also noted the type of dental instrument and the specialty or area of dentistry in which this event occurred. RESULTS There were 36 documented cases. Twenty-five of these were instances of ingestion and one was an aspiration. In 10 cases, aspiration and ingestion were ruled out through radiographic examination or the object was retrieved from the patient's mouth. CONCLUSIONS Fixed prosthodontic therapy had the highest number of incidents of adverse outcomes. Ingestion was a more prevalent outcome than aspiration. Dental procedures involving single-tooth cast or prefabricated restorations involving cementation have a higher likelihood of aspiration. CLINICAL IMPLICATIONS The implications for clinical practice include the recognition of risk that dental therapy demands in regard to the airway and posterior pharynx, documentation and follow-up of adverse outcomes, and the use of preventive measures such as rubber dams or gauze throat screens or floss ligatures.
AIDS‐related Kaposi's sarcoma: epidemiological, diagnostic, treatment and control aspects in sub‐Saharan Africa

Until the 1980s, little attention had been accorded to endemic Kaposi's sarcoma (KS), a neoplasm noted in several parts of Southern Europe and the African continent but with relatively slow progression, except in children and young adults. Furthermore, therapeutic approaches based on surgery, radiation and topical treatment were of limited efficacy, mostly used to overcome the disabling and stigmatizing effects of the disease. With the emergence of the HIV/AIDS epidemic, and the profound impact of KS on AIDS‐related mortality, the pathogenesis of KS has been better studied, and the realisation that a virus (KS‐associated Herpesvirus or Human Herpesvirus 8, or KSHV/HHV‐8), combined with immunosuppression and cytokine‐induced growth, was responsible for the development of this disease has led to novel therapeutic approaches. These are unfortunately still highly toxic, require careful monitoring, and are expensive, thus limiting their use in most parts of Africa. However, the use of highly active antiretroviral therapy (HAART), which has led to a considerable decline in KS incidence in populations of industrialized countries, constitutes the best hope for the control of this stigmatizing and lethal disease in Africa. Trials comparing different regimens of antiretroviral drugs in combination with systemic chemotherapeutic agents are urgently needed.
Obstacles to Implementing the Strategic Action Plan in the Light of Performance Evaluation at College of Education in Jeddah University

The present study aims to investigate the obstacles to implementing the strategic action plan in the light ofperformance evaluation at the College of Education, Jeddah University. The author adopted the descriptive analyticalapproach. The population comprised all forms and documents relevant to the domains, namely learning andeducation, post-graduate studies, social responsibility, and funding. The results showed that the achievement rate ofthe domains was 40%, 18%, 0.04%, and 73%, respectively. The obstacles to learning and education related toawareness of the course and its design, difficulty of students’ interaction, and form filling objectively. The obstaclesto post-graduate studies domain were relevant to publishing in reviewed and standardized journals due to JeddahUniversity, lack of action handbook for mission and, post-graduate studies based on mission regulation of the SaudiUniversities. The obstacles to social responsibility were relevant to funding in terms of allocating a budget foractivating the social responsibility projects and upgrading the college’s infrastructure. The obstacles to funding andinvestment were based on the needs of civil society associations to launch new programs that meet their needs andprovide the College of Education with investment return.