Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical outcome in stage I to III breast carcinoma and eIF4E overexpression.

OBJECTIVE The objective of this study is to determine if high eukaryotic initiation factor 4E (eIF4E) overexpression (sevenfold elevation or more over benign breast tissue) is associated with a worse clinical outcome. SUMMARY BACKGROUND DATA Dysregulation of cellular functions by selective overexpression of specific proteins can lead to malignant transformation. The overexpression of eIF4E preferentially increases translation of mRNAs with long, G-C rich 5'-untranslated regions. Selective gene products, such as tumor neoangiogenic factors, ornithine decarboxylase, and cyclin D1, are upregulated. METHODS One hundred fourteen breast specimens were analyzed and eIF4E overexpression was quantified by Western blot analysis. Quantification for eIF4E protein level was accomplished using a rabbit anti-eIF4E antibody and colorimetric development of Western blots using nitro blue tetrazolium and 5-bromo-4-chloro-3-indolyl phosphate. The blots were scanned and analyzed by densitometry. Treatment, pathologic, and clinical outcome data variables were analyzed. Statistical analysis was performed to determine if eIF4E overexpression is associated with breast cancer clinical outcome. RESULTS In the 55 benign specimens, the mean eIF4E expression was 1.1+/-0.4 fold (mean +/- standard deviation). All 59 malignant breast carcinoma specimens were noted to have eIF4E overexpression (range, 1.9-fold to 30.6-fold), with a mean overexpression of 10.8+/-6.3-fold. The mean level of eIF4E expression in malignant specimens was higher than benign specimens (p < 0.05, unpaired t test). The degree of eIF4E overexpression appears to be independent of T and N stage. In the 21 patients with eIF4E overexpression of less than sevenfold, there was one cancer recurrence but no cancer-related deaths. In the 38 patients with high eIF4E overexpression (sevenfold or more), 14 patients had breast cancer recurrences (p = 0.03, log rank test), of whom 11 have died from the disease (p = 0.04, log rank test). The average follow-up interval in this study was 40 months. CONCLUSIONS Patients with stage I to III breast cancer and high eIF4E overexpression had a higher rate of cancer recurrence and a higher rate of cancer-related death when compared to similar-stage breast cancer patients with low eIF4E overexpression. Therefore, eIF4E protein overexpression may be of prognostic value in stage I to III breast carcinoma.
Translocation of the C Terminus of a Tail-anchored Protein across the Endoplasmic Reticulum Membrane in Yeast Mutants Defective in Signal Peptide-driven Translocation*

C-tail-anchored proteins are defined by an N-terminal cytosolic domain followed by a transmembrane anchor close to the C terminus. Their extreme C-terminal polar residues are translocated across membranes by poorly understood post-translational mechanism(s). Here we have used the yeast system to study translocation of the C terminus of a tagged form of mammalian cytochromeb 5, carrying an N-glycosylation site in its C-terminal domain (b 5-Nglyc). Utilization of this site was adopted as a rigorous criterion for translocation across the ER membrane of yeast wild-type and mutant cells. The C terminus of b 5-Nglyc was rapidly glycosylated in mutants where Sec61p was defective and incapable of translocating carboxypeptidase Y, a well known substrate for post-translational translocation. Likewise, inactivation of several other components of the translocon machinery had no effect onb 5-Nglyc translocation. The kinetics of translocation were faster for b 5-Nglyc than for a signal peptide-containing reporter. Depletion of the cellular ATP pool to a level that retarded Sec61p-dependent post-translational translocation still allowed translocation ofb 5-Nglyc. Similarly, only low ATP concentrations (below 1 μm), in addition to cytosolic protein(s), were required for in vitro translocation ofb 5-Nglyc into mammalian microsomes. Thus, translocation of tail-anchoredb 5-Nglyc proceeds by a mechanism different from that of signal peptide-driven post-translational translocation.
Clones identification of Sequoia sempervirens (D. Don) Endl. in Chile by using PCR-RAPDs technique

A protocol of polymerase chain reaction-random amplified polymorphic DNAs (PCR-RAPDs) was established to analyse the gene diversity and genotype identification for clones of Sequoia sempervirens (D. Don) Endl. in Chile. Ten (out of 34) clones from introduction trial located in Voipir-Villarrica, Chile, were studied. The PCR-RAPDs technique and a modified hexadecyltrimethylammonium bromide (CTAB) protocol were used for genomic DNA extraction. The PCR tests were carried out employing 10-mer random primers. The amplification products were detected by electrophoresis in agarose gels. Forty nine polymorphic bands were obtained with the selected primers (BG04, BF07, BF12, BF13, and BF14) and were ordered according to their molecular size. The genetic similarity between samples was calculated by the Jaccard index and a dendrogram was constructed using a cluster analysis of unweighted pair group method using arithmetic averages (UPGMA). Of the primers tested, 5 (out of 60) RAPD primers were selected for their reproducibility and high polymorphism. A total of 49 polymorphic RAPD bands were detected out of 252 bands. The genetic similarity analysis demonstrates an extensive genetic variability between the tested clones and the dendrogram depicts the genetic relationships among the clones, suggesting a geographic relationship. The results indicate that the RAPD markers permitted the identification of the assayed clones, although they are derived from the same geographic origin.
Fuzzy Based Blood Image Segmentation for Automated Leukemia Detection

Acute lymphoblastic leukemia (ALL) are a group of hematological neoplasia of childhood which is characterized by a large number of lymphoid blasts in the blood stream. ALL makes around 80% of childhood leukemia and it mostly occur in the age group of 3-7. The nonspecific nature of the signs and symptoms of ALL often leads to wrong diagnosis. Diagnostic confusion is also posed due to imitation of similar signs by other disorders. Careful microscopic examination of stained blood smear or bone marrow aspirate is the only way to effective diagnosis of leukemia. Techniques such as fluorescence in situ hybridization (FISH), immunophenotyping, cytogenetic analysis and cytochemistry are also employed for specific leukemia detection. The need for automation of leukemia detection arises since the above specific tests are time consuming and costly. Morphological analysis of blood slides are influenced by factors such as hematologists experience and tiredness, resulting in non standardized reports. A low cost and efficient solution is to use image analysis for quantitative examination of stained blood microscopic images for leukemia detection. A fuzzy based two stage color segmentation strategy is employed for segregating leukocytes or white blood cells (WBC) from other blood components. Discriminative features i.e. nucleus shape, texture are used for final detection of leukemia. In the present paper two novel shape features i.e., Hausdorff Dimension and contour signature is implemented for classifying a lymphocytic cell nucleus. Support Vector Machine (SVM) is employed for classification. A total of 108 blood smear images were considered for feature extraction and final performance evaluation is validated with the results of a hematologist.
Use of digoxigenin-labelled oligonucleotide DNA probes for VT2 and VT2 human variant genes to differentiate Vero cytotoxin-producing Escherichia coli strains of serogroup O157

Digoxigenin-labelled oligonucleotide DNA probes specific for B-subunit genes of Vero cytotoxin 2 (VT2) and a variant of VT2 (VT2vha) were used to differentiate 116 strains of Escherichia coli serogroup O157 belonging to phage types 1, 2, 4, 8, 14, and 49. Of these strains, 38% had sequences for both VT2 and VT2vha, 38% had sequences for VT2 only, and 24% had sequences for VT2vha only. Oligonucleotide probe hybridization subdivided strains of all of the phage types except phage type 1. The greatest variation in toxin gene pattern was observed with strains of phage type 14, for which there were six distinct patterns when the presence or absence of VT1 genes was also considered. Two strains from each phage type group were examined for bacteriophages encoding VT production. Two of the six VT2vha-producing strains carried phage from which DNA hybridized with the VT2vha-specific probe. Phages were not detected in the remaining four VT2vha strains, suggesting that genes may be chromosomally located or associated with a defective prophage. In contrast, seven of the eight VT2 strains carried phages from which DNA hybridized with the VT2-specific probe. Two strains of E32511 (O157:H-) were also investigated. One strain (E32511A) possessed gene sequences for both VT2 and VTvha and was shown to carry phage possessing gene sequences for VT2. With strain E32511B, however, phages were not detected and DNA hybridized only with the VT2vha probe. Analysis of total genomic DNA digested with restriction endonuclease EcoRI showed that polymorphisms were seen with VT2 strains and not with VT2vha strains.
Molecular mapping of alzheimer‐type dementia in Down's syndrome

Previous research has hypothesized an association between Alzheimer's disease and the amyloid precursor protein (APP) gene found on chromosome 21. We report the case of a 78‐year‐old woman with Down's syndrome with partial trisomy 21 [46,XX,rec(21)dup q, inv(21) (p12q22.1)]. No evidence of Alzheimer's disease was found on neuropsychological, magnetic resonance imaging, and neuropathological assessment. The gene sequence for APP was present in only two copies. This case further supports the hypothesis that Alzheimer's disease is associated with trisomy for proximal chromosome 21q, including the APP gene.
Caenorhabditis elegans SUR-5, a Novel but Conserved Protein, Negatively Regulates LET-60 Ras Activity during Vulval Induction

ABSTRACT The let-60 ras gene acts in a signal transduction pathway to control vulval differentiation in Caenorhabditis elegans. By screening suppressors of a dominant negativelet-60 ras allele, we isolated three loss-of-function mutations in the sur-5 gene which appear to act as negative regulators of let-60 ras during vulval induction.sur-5 mutations do not cause an obvious mutant phenotype of their own, and they appear to specifically suppress only one of the two groups of let-60 ras dominant negative mutations, suggesting that the gene may be involved in a specific aspect of Ras activation. Consistent with its negative function, overexpressing sur-5 from an extragenic array partially suppresses the Multivulva phenotype of an activatedlet-60 ras mutation and causes synergistic phenotypes with a lin-45 raf mutation. We have clonedsur-5 and shown that it encodes a novel protein. We have also identified a potential mammalian SUR-5 homolog that is about 35% identical to the worm protein. SUR-5 also has some sequence similarity to acetyl coenzyme A synthetases and is predicted to contain ATP/GTP and AMP binding sites. Our results suggest thatsur-5 gene function may be conserved through evolution.
Perceptual Stability Analysis of a Graph Model System

Perceptual graph model systems are designed to be employed when there are discrepancies in decision makers' (DMs) perceptions of a conflict, which may be caused, for instance, by the presence of negative emotion or asymmetric information among DMs. In this case, conventional stability analysis cannot be used; perceptual stability analysis is proposed as a new theoretical procedure that extends existing stability algorithms to situations when DMs have independent perceptions or awarenesses of a conflict. The overriding objective of perceptual stability analysis is to predict possible resolutions, and unveil the dependence of these predictions on variability in a DM's awareness. Perceptual stability analysis takes a two-phase approach. In Phase 1, individual stability analysis is applied to each DM's graph model (a perceptual graph model) from the point of view of the owner of the model, for each DM in the model, using standard or perceptual solution concepts, depending on the owner's awareness of others' perceptions. Then, in Phase 2, metastability analysis is employed to consolidate the stability assessments of a state in all perceptual graph models and across all variants of awareness-i.e., in all possible graph model systems. The distinctive modes of equilibria thus defined reflect the incompatibilities in DMs' perceptions and viewpoints, but nonetheless provide important insights into possible resolutions of the conflict. To demonstrate the practical application of these new developments, a model of the conflict in Chechnya is presented and analyzed.
Insufficiency of transformation by simian virus 40, polyomavirus, EJ-ras, or v-myc oncogenes for conversion of ethanolamine-responsive mammary cells to ethanolamine-nonresponsive cells

Normal mammary epithelial cells (ethanolamine responsive) require ethanolamine to enable them to grow in defined culture medium because they cannot synthesize de novo a sufficient amount of phosphatidylethanolamine. Mammary tumor cells which retain properties of the normal tissue are also likely to be ethanolamine responsive, whereas dedifferentiated, highly tumorigenic mammary tumor cells are ethanolamine nonresponsive. The nonresponsive tumor cells are able to synthesize the necessary amount of phosphatidylethanolamine to sustain growth. Therefore, the progression of malignancy seems to convert ethanolamine-responsive mammary cells to ethanolamine-nonresponsive ones. In an attempt to prove the above assumption and to understand the mechanism responsible for the conversion during the progression of malignant transformation, mammary tumor cell line 64-24, which is typically ethanolamine responsive, was transfected with simian virus 40, polyomavirus, EJ-ras, or v-myc oncogenes, and the resulting transfectants were examined for their growth response to ethanolamine. Many of the transfectants exhibited typical transformed phenotypes; however, none of the transfectants converted to ethanolamine-nonresponsive cells. Some of the SV40 and polyomavirus transformants were able to grow in the absence of ethanolamine, although they grew better in the presence of ethanolamine, unlike typical ethanolamine-nonresponsive cells. These cells could grow in the absence of ethanolamine, even though their membrane phospholipid was phosphatidylethanolamine deficient. The present study indicates that the expression of any one of the four oncogenes tested, which allows the cells to exhibit transformed phenotypes in 64-24 cells, is not sufficient for the conversion of ethanolamine-responsive cells to -nonresponsive cells.
Heat and Dehydration Additively Enhance Cardiovascular Outcomes following Orthostatically-Stressful Calisthenics Exercise

Exercise and exogenous heat each stimulate multiple adaptations, but their roles are not well delineated, and that of the related stressor, dehydration, is largely unknown. While severe and prolonged hypohydration potentially “silences” the long-term heat acclimated phenotype, mild and transient dehydration may enhance cardiovascular and fluid-regulatory adaptations. We tested the hypothesis that exogenous heat stress and dehydration additively potentiate acute (24 h) cardiovascular and hematological outcomes following exercise. In a randomized crossover study, 10 physically-active volunteers (mean ± SD: 173 ± 11 cm; 72.1 ± 11.5 kg; 24 ± 3 year; 6 females) completed three trials of 90-min orthostatically-stressful calisthenics, in: (i) temperate conditions (22°C, 50% rh, no airflow; CON); (ii) heat (40°C, 60% rh) whilst euhydrated (HEAT), and (iii) heat with dehydration (no fluid ~16 h before and during exercise; HEAT+DEHY). Using linear mixed effects model analyses, core temperature (TCORE) rose 0.7°C more in HEAT than CON (95% CL: [0.5, 0.9]; p < 0.001), and another 0.4°C in HEAT+DEHY ([0.2, 0.5]; p < 0.001, vs. HEAT). Skin temperature also rose 1.2°C more in HEAT than CON ([0.6, 1.8]; p < 0.001), and similarly to HEAT+DEHY (p = 0.922 vs. HEAT). Peak heart rate was 40 b·min−1 higher in HEAT than in CON ([28, 51]; p < 0.001), and another 15 b·min−1 higher in HEAT+DEHY ([3, 27]; p = 0.011, vs. HEAT). Mean arterial pressure at 24-h recovery was not consistently below baseline after CON or HEAT (p ≥ 0.452), but was reduced 4 ± 1 mm Hg after HEAT+DEHY ([0, 8]; p = 0.020 vs. baseline). Plasma volume at 24 h after exercise increased in all trials; the 7% increase in HEAT was not reliably more than in CON (5%; p = 0.335), but was an additional 4% larger after HEAT+DEHY ([1, 8]; p = 0.005 vs. HEAT). Pooled-trial correlational analysis showed the rise in TCORE predicted the hypotension (r = −0.4) and plasma volume expansion (r = 0.6) at 24 h, with more hypotension reflecting more plasma expansion (r = −0.5). In conclusion, transient dehydration with heat potentiates short-term (24-h) hematological (hypervolemic) and cardiovascular (hypotensive) outcomes following calisthenics.
Long-term angiographic and clinical outcome of patients undergoing multivessel coronary stenting.

BACKGROUND Randomized clinical trials have shown that multivessel coronary angioplasty is feasible and provides similar long-term survival as bypass surgery in selected patients. However, the higher need for repeat intervention, in particular, coronary artery bypass graft surgery, remains a problem. The objective of this study was to test the hypothesis that multivessel stenting is safe and effective in reducing the need for repeat interventions, in particular, the need for bypass surgery. METHODS AND RESULTS Between March 1993 and June 1995, 100 consecutive patients (243 lesions) had multivessel coronary stenting. High-pressure stent optimization was used in all patients. Procedural success was achieved in 97% of lesions; 2 patients (2%) required emergency bypass surgery. Angiographic follow-up was obtained in 89% of patients at 5.2+/-2.5 months. Angiographic restenosis occurred in 22% of the lesions, but 37% of patients had > or = 1 lesion with restenosis. Clinical follow-up was obtained in all patients at 21 +/- 10 months: target lesion revascularization was needed in 30 patients (30%), repeat angioplasty in 28 patients (28%) and coronary bypass surgery in 2 patients (2%); the overall survival rate was 96% (2% noncardiac death). CONCLUSIONS Multivessel coronary stenting can be performed with high success rate and low need for emergency bypass surgery. Compared with historical results with multivessel percutaneous transluminal coronary angioplasty, patients who undergo multivessel stenting need less repeat interventions, in particular, less coronary bypass surgery and have similar long-term survival.
Interactions between Carbon and Nitrogen Metabolism in Fibrobacter succinogenes S85: a 1H and13C Nuclear Magnetic Resonance and Enzymatic Study

ABSTRACT The effect of the presence of ammonia on [1-13C]glucose metabolism in the rumen fibrolytic bacterium Fibrobacter succinogenes S85 was studied by13C and 1H nuclear magnetic resonance (NMR). Ammonia halved the level of glycogen storage and increased the rate of glucose conversion into acetate and succinate 2.2-fold and 1.4-fold, respectively, reducing the succinate-to-acetate ratio. The13C enrichment of succinate and acetate was precisely quantified by 13C-filtered spin-echo difference1H-NMR spectroscopy. The presence of ammonia did not modify the 13C enrichment of succinate C-2 (without ammonia, 20.8%, and with ammonia, 21.6%), indicating that the isotopic dilution of metabolites due to utilization of endogenous glycogen was not affected. In contrast, the presence of ammonia markedly decreased the 13C enrichment of acetate C-2 (from 40 to 31%), reflecting enhanced reversal of the succinate synthesis pathway. The reversal of glycolysis was unaffected by the presence of ammonia as shown by 13C-NMR analysis. Study of cell extracts showed that the main pathways of ammonia assimilation in F. succinogenes were glutamate dehydrogenase and alanine dehydrogenase. Glutamine synthetase activity was not detected. Glutamate dehydrogenase was active with both NAD and NADP as cofactors and was not repressed under ammonia limitation in the culture. Glutamate-pyruvate and glutamate-oxaloacetate transaminase activities were evidenced by spectrophotometry and 1H NMR. When cells were incubated in vivo with [1-13C]glucose, only13C-labeled aspartate, glutamate, alanine, and valine were detected. Their labelings were consistent with the proposed amino acid synthesis pathway and with the reversal of the succinate synthesis pathway.
Clinical outcomes following percutaneous coronary intervention with drug-eluting stents versus bare metal stents in patients on chronic hemodialysis.

BACKGROUND Patients on chronic hemodialysis (HD) are recognized as a high-risk group for adverse events after percutaneous coronary intervention, and whether drug-eluting stents (DES) are associated with improved outcomes over bare metal stents (BMS) is still uncertain. The purpose of this study was to assess the efficacy of DES compared with BMS at short- and long-term follow-up (FU) in an unselected sample of HD patients. METHODS AND RESULTS In the time period 2005-2010, consecutive patients on chronic HD treated with percutaneous coronary intervention (PCI) and stent implantation were retrospectively selected and analyzed. A total of 169 patients were selected, 77 treated exclusively with BMS and 92 exclusively with DES. Baseline clinical characteristics were similar in the 2 groups as well as the number of treated vessels, treated lesions, and the stent per patient ratio. At longest available FU, no difference between the 2 study groups was found in terms of cardiac death (18.2% vs 16.3%, P=0.83), myocardial infarction (2.5% vs 8.6%, P=0.09), cerebrovascular accidents (0% vs 1.1%, P=0.98), and target vessel revascularization (TVR) (9.1% vs 16.3%, P=0.17). Major adverse cardiac and cerebrovascular events-free survival at 1,500 days in the BMS and DES groups was 57.6% and 50.9% (P=0.11), respectively. CONCLUSIONS PCI in patients on chronic HD treatment is associated with a high incidence of adverse events at FU, mainly represented by death. In our study, the use of DES was not associated with a reduction of target lesion revascularization (TLR) and TVR.