Miracle-dz/UniFAR-FTUs huggingface dataset:
Testing for germ line p53 mutations in cancer families.

A workshop on germ line p53 testing in members of families with the Li-Fraumeni cancer syndrome was held at the National Institutes of Health, Bethesda, Maryland, May 8-9, 1991.2 The meeting was cosponsored by the National Cancer Institute and the National Center for Human Genome Research. Virtually all forms of cancer in humans show a tendency to aggregate in families. These aggregates can be due to the inheritance of a cancer susceptibility gene, although chance association and shared exposures to environmental carcinogens are alternative explanations. Advances in molecular genetics have revealed the chromosomal locations of many of these cancer genes. A few have been cloned, including the hereditary netinoblastoma gene, WTJ gene for Wilms’ tumor, neurofibromatosis type I gene, and p53 gene, which is altered in six reported families with Li-Fraumeni syndrome (1, 2). The work of the Human Genome Project can be expected to identify many more genes for inherited diseases, including cancer (3). The proper use of the genetic data is an issue of growing concern. To address the relevance of these issues to cancer genes, a workshop was held on testing for germ line p53 mutation in families with Li-Fraumeni syndrome. This autosomal dominant disorder predisposes to at least six forms of cancer. The syndrome might serve as a paradigm for future testing of clinically healthy individuals for a variety of site-specific cancer susceptibility genes. The participants in the workshop encompassed diverse fields of study including dincal medicine, laboratory sciences, epidemiology, biostatistics, medical ethics, law, psychology, and cancer control. Joseph F. Fraumeni, Jr. (National Cancer Institute, Bethesda, MD) noted that this syndrome was initially recognized through clinical observations at the bedside, followed by descriptive and analytic epidemiology studies of defined patient populations. The syndrome is a clinical diagnosis based on the aggregation of elements of at least six forms of cancer in young family members (4). In affected families, the cancers show no distinguishing clinical and histopathological features. However, 39% of these cancers in one series occurred before 20 years of age (Table 1). The most common childhood cancers
Breakage of bacterial DNA by nitrofuran derivatives.

Concentrations of nitrofuran derivatives which had little effect on viability caused single-strand breaks in the DNA of Escherichia coli B/r. The highly carcinogenic N -[4-(5-nitro-2-furyl)-2-thiazolyl]formamide was most effective, nitrofuraldehyde semicarbazone was intermediate, and N -(5-nitro-2-furfurylidine)-1-aminohydantoin was least effective. DNA from treated cells that had been reincubated in drug-free medium was indistinguishable from that of untreated cells, suggesting repair of nitrofuran-induced breaks. No detectable breaks resulted when an E. coli mutant lacking soluble “nitrofurazone-reductase” activity was exposed to these agents. The carcinogenic N -[4-(5-nitro-2-furyl)-2-thiazolyl] formamide was found to be a specific inhibitor of DNA synthesis in E. coli B.
Anti-inflammatory and anticancer activities of ( )-zeylenol from stems of Uvaria grandiflora

Uvaria grandiflora has stimulated rigorous phytochemical investigation aimed at determining chemical structures and biological activities. In recent years, many polyoxygenated cyclohexenes have been isolated from this genus. This study reports that zeylenol isolated from the stems of U. grandiflora possess potential anti-inflammatory, anticancer, and caspase-3 activities. The structure of this compound was elucidated from spectroscopic analysis, particularly 2D NMR techniques. The anti-inflammatory effect and toxicity of zeylenol were evaluated in animal models and compared to that of reference drugs. In addition, the cytotoxicity of the isolated compound against human breast cancer MDA-MB231 and hepatocellular carcinoma HepG2 cell lines were studied. The test ( )-zeylenol at the dose of 1 mg/ear significantly inhibited oedema formation by 90%, 69%, 52%, and 52% after 15, 30, 60, and 120 min, respectively. Zeylenol was found to be toxic to both MDA-MB231 and HepG2 cells in a dose response manner with IC50 values of 54 10 and > 80 µM, respectively. The compound induced MDA-MB231 cell apoptosis via caspase-3 activation. Zeylenol probably possesses anti-inflammatory activity by inhibiting the synthesis or release of various inflammatory mediators and might be used to induce human breast cancer MDA-MB231 cell apoptosis.
Hypomethylation of the interferon‐γ gene correlates with its expression by primary T‐lineage cells

To determine the potential role of methylation in the regulation of interferon‐γ (IFN‐γ) gene transcription by T cells, primary T‐lineage cell populations were analyzed for the extent of methylation of three CpG sites within or near transcriptional activator elements in the 5′ flank and first intron of the human IFN‐γ gene. A striking correlation was observed between the capacity of the IFN‐γ gene to be expressed and the degree of hypomethylation. The IFN‐γ gene was virtually completely methylated at all sites in thymocytes, neonatal T cells, and adult CD45RAhiCD45R0lo (antigenically naive) CD4 T cells, cell types that all have a low or undetectable capacity to express the IFN‐γ gene. In contrast, there was substantial hypomethylation in T‐lineage cell types with relatively high capacities to express the IFN‐γ gene, including adult CD8 T cells and adult CD45RAloCD45R0hi (memory/effector) CD4 T cells. These results suggest that hypomethylation of the IFN‐γ genetic locus may be an important determinant of IFN‐γ gene expression in vivo by T‐lineage cells.
Monitoring Collagen Synthesis in Fibroblasts Using Fluorescently Labeled tRNA Pairs

There is a critical need for techniques that directly monitor protein synthesis within cells isolated from normal and diseased tissue. Fibrotic disease, for which there is no drug treatment, is characterized by the overexpression of collagens. Here, we use a bioinformatics approach to identify a pair of glycine and proline isoacceptor tRNAs as being specific for the decoding of collagen mRNAs, leading to development of a FRET‐based approach, dicodon monitoring of protein synthesis (DiCoMPS), that directly monitors the synthesis of collagen. DiCoMPS aimed at detecting collagen synthesis will be helpful in identifying novel anti‐fibrotic compounds in cells derived from patients with fibrosis of any etiology, and, suitably adapted, should be widely applicable in monitoring the synthesis of other proteins in cells. J. Cell. Physiol. 229: 1121–1129, 2014. © 2014 Wiley Periodicals, Inc.
FORMULATION DEVELOPMENT AND EVALUATION OF DICLOFENAC SODIUM GEL USING WATER SOLUBLE POLYACRYLAMIDE POLYMER

High molecular weights water soluble homopolymer of acrylamide are reported to possess very high viscosity in low concentration, transparency, film forming properties and are useful in formation of gel. The diclofenac sodium gels were prepared by using different concentration of polyacrylamide for topical drug delivery with an objective to increase transparency and spreadability. These preparations were further compared with marketed diclofenac sodium gel. Spreadability and consistency of polyacrylamide gel containing diclofenac sodium (F9) were 6.5g. cm/sec and 5mm as compared to 5.5g. cm/sec and 10mm respectively of marketed gel, indicating good spreadability and consistency of the prepared gel (F9). The transparency of prepared batch F9 was good as compared to the marketed gel. The percent drug release was 97.11 and 98.66 from F9 and marketed gel respectively. No irritation was observed by skin irritation test. Stability studies under accelerated condition showed satisfactory results. It can be concluded that polyacrylamide gel containing diclofenac sodium showed good consistency, homogeneity, spreadability and stability and has wider prospect for topical preparations.
k‐space analysis of point‐resolved spectroscopy (PRESS) with regard to spurious echoes in in vivo 1H MRS

The spurious echo artefact, not uncommon in 1H MRS in the brain, comes from refocusing outer volume signal. Application of MRS in small volumes in susceptibility‐affected regions often results in large shim gradients. The artefact problem is accentuated when the global effect of the shim gradient shifts the water resonance outside the water suppression band in the outer volume. This scenario brings the issue of spurious echoes once again to the fore. In this paper, spurious signals of the point‐resolved spectroscopy (PRESS) sequence are analysed using the concept of k‐space. This new approach facilitates a more geometrical view of the problem, well suited for studying the effect of gradient spoiling and refocusing of signal. Several spoiling options are shown, and the probability of the global effects of shimming being a primary cause of the artefact is discussed. Fourier transform analysis of realistic slice profiles, combined with the k‐space description of spurious echoes, shows that unsuppressed water signal in outer regions greatly increases the demands on spoiling. Gradient spoiling adequate for artefact suppression at a given size of MRS volume may not be sufficient at a smaller size. Several ways to improve PRESS measurements with regard to suppression of spurious signal are discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Détection binaire distribuée sous contraintes de communication

Ces dernieres annees, l'interet scientifique porte aux differents aspects des systemes autonomes est en pleine croissance. Des voitures autonomes jusqu'a l'Internet des objets, il est clair que la capacite de systemes a prendre des decision de maniere autonome devient cruciale. De plus, ces systemes opereront avec des ressources limitees. Dans cette these, ces systemes sont etudies sous l'aspect de la theorie de l'information, dans l'espoir qu'une comprehension fondamentale de leurs limites et de leurs utilisations pourrait aider leur conception par les futures ingenieurs.Dans ce travail, divers problemes de decision binaire distribuee et collaborative sont consideres. Deux participants doivent "declarer" la mesure de probabilite de deux variables aleatoires, distribuees conjointement par un processus sans memoire et designees par $vct{X}^n=(X_1,dots,X_n)$ et $vct{Y}^n=(Y_1,dots,Y_n)$. Cette decision et prise entre deux mesures de probabilite possibles sur un alphabet fini, designes $P_{XY}$ et $P_{bar{X}bar{Y}}$. Les prelevements marginaux des variables aleatoires, $vct{X}^n$ et $vct{Y}^n$ sont supposes a etre disponibles aux differents sites . Il est permis aux participants d'echanger des quantites limitees d'information sur un canal parfait avec un contraint de debit maximal. Durant cette these, la nature de cette communication varie. La communication unidirectionnelle est consideree d'abord, suivie par la consideration de communication bidirectionnelle, qui permet des echanges interactifs entre les participants.
On the mechanism of glucose-beta-phosphate oxidation in cell-free extracts of Xanthomonas phaseoli (XP8).

Extracts of the plant pathogenic organism Xanthomonas phaseoli contain both TPN- and DPN-linked glucose-6-phosphate dehydrogenases as well as a DPN-specific glyceraldehyde phosphate dehydrogenase. DPNH oxidase is very active and sensitive to high concentrations of cyanide. No evidence could be found for the presence of pyridine nucleotide transhydrogenase.Ribose-5-phosphate is metabolized via the pentose cycle; sedoheptulose phosphate is an intermediate and other criteria of the functioning of the pentose cycle are met when ribose-5-phosphate is the substrate. The same system also functions with 6-phosphogluconate as substrate but at a level which suggests that this pathway is not of great significance.The Entner–Doudoroff 6-phosphogluconate-splitting pathway is the major avenue of hexosephosphate utilization in cell-free extracts. Pyruvate formation and utilization are discussed in relation to function and cofactor requirements.While phosphoglucose isomerase, aldolase, triosephosphate isomerase, and the .
Infertility and preterm delivery, birthweight, and Caesarean section: a study within the Danish National Birth Cohort.

BACKGROUND More than 10% of babies are born to couples taking >1 year to conceive (a common definition of infertility). Some evidence indicates that such pregnancies are at increased risk of preterm delivery and other adverse birth outcomes, but the problem has rarely been addressed in large, longitudinal studies enrolling couples irrespective of infertility treatment. METHODS We used data from the Danish National Birth Cohort: 55 906 singleton live births from women who reported their waiting time to pregnancy (TTP) and other covariates in an interview during the 2nd trimester of pregnancy. RESULTS A TTP >1 year was associated with an increased risk of all outcomes studied, including preterm birth [odds ratios and 95% confidence intervals were 1.5 (1.2, 1.8) among primiparas and 1.9 (1.5, 2.4) among multiparas]. Odds ratios for preterm remained elevated after adjustment for covariates. Among couples with a TTP >1 year, infertility treatment was associated with added risk only among multiparas. CONCLUSION Infertile women are at higher risk of adverse birth outcomes even if they conceive without treatment. With >10% of babies born to infertile couples, it is important to consider this group as potentially high risk when providing prenatal care.
Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial.

BACKGROUND Perioperative epirubicin, cisplatin and fluorouracil (ECF) chemotherapy improves survival in operable oesophago-gastric cancer [Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) trial HR 0.75 (0.6-0.93)]. HER2 amplification is reported to predict enhanced benefit from anthracyclines in breast cancer. We sought to define whether HER2 predicts benefit from ECF in oesophago-gastric cancer. PATIENTS AND METHODS Diagnostic biopsies and/or resection specimens were collected from 415 of 503 MAGIC trial patients (82.5%). HER2 was evaluated by immunohistochemistry (IHC) and brightfield dual in situ hybridisation (BDISH) in tissue microarrays. The prognostic and predictive impact of HER2 status was investigated. RESULTS Concordance between HER2 over-expression (IHC3+) and amplification was 96%. Results of HER2 assessment in biopsy and resection specimens were concordant in 92.9% (145/156). HER2 positive rate (IHC3+, or IHC2+/BDISH positive) was 10.9% in the whole cohort and 10.4% in resection specimens. A further 4.0% of resections were IHC negative/BDISH positive. HER2 status was neither prognostic, nor (in pre-treatment biopsies) predicted enhanced benefit from chemotherapy [HER2 positive HR 0.74 (0.14-3.77); HER2 negative HR 0.58 (0.41-0.82), interaction P = 0.7]. However, the power of the predictive analysis was limited by the small number of HER2 positive pre-treatment biopsies. CONCLUSIONS HER2 status is not an independent prognostic biomarker in early oesophago-gastric adenocarcinoma.
Enhancing supervised learning with complex aggregate features and context sensitivity. (Amélioration de l'apprentissage supervisé par l'utilisation d'agrégats complexes et la prise en compte du contexte)

In this thesis, we study model adaptation in supervised learning. Firstly, we adapt existing learning algorithms to the relational representation of data. Secondly, we adapt learned prediction models to context change.In the relational setting, data is modeled by multiples entities linked with relationships. We handle these relationships using complex aggregate features. We propose stochastic optimization heuristics to include complex aggregates in relational decision trees and Random Forests, and assess their predictive performance on real-world datasets.We adapt prediction models to two kinds of context change. Firstly, we propose an algorithm to tune thresholds on pairwise scoring models to adapt to a change of misclassification costs. Secondly, we reframe numerical attributes with affine transformations to adapt to a change of attribute distribution between a learning and a deployment context. Finally, we extend these transformations to complex aggregates.
The Term Structure of Interbank Risk

We infer a term structure of interbank risk from spreads between rates on interest rate swaps indexed to the London Interbank Offered Rate (LIBOR) and overnight indexed swaps. We develop a tractable model of interbank risk to decompose the term structure into default and non-default (liquidity) components. From August 2007 to January 2011, the fraction of total interbank risk due to default risk, on average, increases with maturity. At short maturities, the non-default component is important in the first half of the sample period and is correlated with measures of funding and market liquidity. The model also provides a framework for pricing, hedging, and risk management of interest rate swaps in the presence of significant basis risk.
PHOTIC INDUCTION OF Fos IN THE SUPRACHIASMATIC NUCLEUS OF AFRICAN MOLE-RATS: RESPONSES TO INCREASING IRRADIANCE

African mole-rats (family Bathyergidae) are strictly subterranean rodent species that are rarely exposed to environmental light. Morphological and physiological adaptations to the underground environment include a severely reduced eye size and regressed visual system. Responses of the circadian system to light, however, appear to be intact, since mole-rats are able to entrain their circadian activity rhythms to the light-dark cycle and light induces Fos expression in the suprachiasmatic nucleus (SCN). Social organization varies from solitary species to highly elaborated eusocial structures, characterized by a distinct division of labor and in which one reproductive female regulates the behavior and reproductive physiology of other individuals in the colony. The authors studied light-induced Fos expression in the SCN to increasing light intensities in four mole-rat species, ranging from strictly solitary to highly social. In the solitary Cape mole-rat, light induces significant Fos expression in the SCN, and the number of Fos-immunopositive cells increases with increasing light intensity. In contrast, Fos induction in the SCN of social species was slightly greater than, but not statistically different from, the dark-control animals as is typical of most rodents. One species showed a trend for an increase in expression with increased light, whereas a second species showed no trend in expression. In the naked mole-rat, Fos expression appeared higher in the dark-controls than in the animals exposed to light, although the differences in Fos expression were not significant. These results suggest a gradient in the sensitivity of the circadian system to light in mole-rats, with a higher percentage of individuals that are unresponsive to light in correlation with the degree of sociality. In highly social species, such as the naked mole-rat that live in a relatively stable subterranean milieu in terms of food availability, temperature, constant darkness, and devoid of 24-h cyclic environmental cues, the temporal coordination of rest-wake activities may be dependent on social interactions and social status rather than on photic regulation of the circadian timing system. (Author correspondence: moosthuizen@zoology.up.ac.za)
Partial Match of 3D Faces using Facial Curves between SIFT Keypoints

In this work, we propose and experiment an original solution to 3D face recognition which supports partial matching of facial scans as occurs in the case of missing parts and occlusions. In the proposed approach, distinguishing traits of the face are captured by first extracting SIFT keypoints on the face scan and then measuring how the face changes along facial curves defined between pairs of keypoints. Facial curves are also associated with a measure of salience so as to distinguish curves that model characterizing traits of some subjects from curves that are frequently observed in the face of many different subjects. The recognition accuracy of the approach has been experimented on the Face Recognition Grand Challenge dataset.
Pathophysiology of Glaucomatous Optic Neuropathy: Role of Optic Nerve Head Vascular Insufficiency

In 1970, based on my experimental and clinical studies, I defined glaucoma as: “a disease wherein the normal balance between the intraocular pressure and the blood pressure in the choroidal vessels supplying the optic disc and retrolaminar part of the optic nerve is disturbed, resulting in vascular insufficiency in the optic disc and retrolaminar part of the optic nerve, and hence in visual field defects and pathological changes in the optic disc and optic nerve. ”1 Since the conventional wisdom at that time was that glaucoma was essentially mechanical in nature, caused solely by high intraocular pressure (IOP), this concept was received with marked skepticism. Since then, however, evidence that vascular insufficiency in the optic nerve head (ONH) plays an important role in pathogenesis of glaucomatous optic neuropathy has progressively accumulated; so that now its vasogenic origin is widely accepted.2 To understand the vasogenic mechanism of glaucomatous optic neuropathy, it is crucial to have a good understanding of the following: 1. Blood supply of the ONH. 2. The various factors that influence the ONH circulation. 3. Evaluation of the ONH circulation.
Intravenous Lidocaine Does Not Attenuate the Cardiovascular and Catecholamine Response to a Rapid Increase in Desflurane Concentration

This study was designed to investigate the effect of intravenous lidocaine on the sympathetic activity after a rapid increase in desflurane concentration.Twenty ASA grade I and II patients, were allocated randomly to a control group (C) and a lidocaine group (L). After induction of anesthesia with intravenous propofol 2 mg/kg and muscle relaxation with intravenous vecuronium 0.1 mg/kg, desflurane was given to achieve an end-tidal minimum alveolar anesthetic concentration (MAC) of 0.7. Group L received 1.5 mg/kg lidocaine intravenously, while Group C received an equal volume of 0.9% sodium chloride solution intravenously. These solutions were prepared and coded by a colleague who took no further part in the study. The concentration of desflurane was then abruptly increased to 1.5 MAC. Heart rate and mean arterial pressure were noted every half minute. Blood samples were taken for plasma catecholamines at rest, 0.7 MAC, and at 1-min intervals for 5 min after the increase in desflurane concentration. There was a significant increase in heart rate and mean arterial pressure in both groups. The increase in heart rate was significantly less in Group L from 0.5 until 2.5 min (P < 0.05). There was no difference in mean arterial pressure between the groups except at 4.5 and 5.0 min (P < 0.05). Plasma catecholamines were not significantly different between the groups. Intravenous lidocaine did not attenuate the sympathetic response to a rapid increase in desflurane concentration. It is unlikely that airway irritation is the cause of this phenomenon. (Anesth Analg 1996;82:358-61)