Miracle-dz/UniFAR-FTUs huggingface dataset:
Mdm2 and Mdm4 Loss Regulates Distinct p53 Activities

Mutational inactivation of p53 is a hallmark of most human tumors. Loss of p53 function also occurs by overexpression of negative regulators such as MDM2 and MDM4. Deletion of Mdm2 or Mdm4 in mice results in p53-dependent embryo lethality due to constitutive p53 activity. However, Mdm2−/− and Mdm4−/− embryos display divergent phenotypes, suggesting that Mdm2 and Mdm4 exert distinct control over p53. To explore the interaction between Mdm2 and Mdm4 in p53 regulation, we first generated mice and cells that are triple null for p53, Mdm2, and Mdm4. These mice had identical survival curves and tumor spectrum as p53−/− mice, substantiating the principal role of Mdm2 and Mdm4 as negative p53 regulators. We next generated mouse embryo fibroblasts null for p53 with deletions of Mdm2, Mdm4, or both; introduced a retrovirus expressing a temperature-sensitive p53 mutant, p53A135V; and examined p53 stability and activity. In this system, p53 activated distinct target genes, leading to apoptosis in cells lacking Mdm2 and a cell cycle arrest in cells lacking Mdm4. Cells lacking both Mdm2 and Mdm4 had a stable p53 that initiated apoptosis similar to Mdm2-null cells. Additionally, stabilization of p53 in cells lacking Mdm4 with the Mdm2 antagonist nutlin-3 was sufficient to induce a cell death response. These data further differentiate the roles of Mdm2 and Mdm4 in the regulation of p53 activities. (Mol Cancer Res 2008;6(6):947–54)
Study on Binding Affinity of a Glutathione S-Transferase (GST) Fusion Protein to DNA Probe

The aims of this work were to: i) purify GST-fusion protein from bacterial cell extracts of Escherichia coli; ii) quantify the protein by SDS PAGE and Bradford assay; iii) determine protein-DNA interaction of the purified protein by Electrophoretic Mobility Shift Assay. Bacterial culture prepared by inoculation of a single E. coli colony that had a GST fusion protein (gst: six-X10 hd) constructed by ligation of the six-7-hd (X10) sequence into the BamHI and EcoRI sites of the vector pGEX-2T, grown overnight, was sonicated using Cole-Palmer Ultrasonic Homogenizer. Fusion protein was eluted from the beads with Tris-glutathione buffer (50 mM Tris [pH 8.1], 20 mM glutathione), which contained reduced Glutathione. SDS-PAGE was used to calculate the extracted bound protein. Total protein quantification was then estimated by the Bradford assay. Bovine Serum Albumin (BSA) absorbance values were used to plot the standard curve used to calculate the concentrations of the sample proteins. Nylon membrane was used for the electrophoretic transfer; membrane was cross linked and detected by Pierce’s Chemiluminescent Nucleic Acid Detection module. Results showed that X10 gave a strong band shift observed in Lanes 6 and 7 for both 200 ng and 400 ng elute 1 samples; however, there was no shift in the bands for the wild-type, positive control. The concentration of the elute 1 was obtained by the Bradford assay as 242.52 ng/μl and that of elute 2 was 106.30 ng/μl. Similarly, the result obtained by gel analysis was 300 ng/μl (0.3 μg/μl) and 150 ng/μl (0.15 μg/μl) for elutes 1 and 2 respectively.
The donor chromosome breakpoint for a jumping translocation is associated with large low-copy repeats in 21q21.3

Jumping translocations (JTs) are very rare chromosome aberrations, usually identified in tumors. We report a constitutional JT between donor chromosome 21q21.3→qter and recipients 13qter and 18qter, resulting in an ∼15.5-Mb proximal deletion 21q in a girl with mild developmental delay and minor dysmorphic features. Using fluorescence in situ hybridization (FISH) studies, we identified an ∼550-kb complex inter- and intra-chromosomal low-copy repeat (LCR) adjacent to the 21q21.3 translocation breakpoint. On the recipient chromosomes 13qter and 18qter, the telomeric sequences TTAGGG were retained. Genotyping revealed that the deletion was of maternal origin. We propose that genome architecture involving LCRs may be a major mechanism responsible for the origin of jumping translocations.
Production, solubility and antioxidant activity of curcumin nanosuspension

Curcumin is a powerful bioactive agent and natural antioxidant, but it is practically water-insoluble and has low bioavailability; a possible solution to this obstacle would be formulations of curcumin nanoparticles. Surfactants such as tween 80 can be used to stabilize low-solubility molecules preventing particle aggregation. The objectives of this study were the preparation of a suspension with curcumin nanoparticles in tween 80, the testing of pure curcumin solubility and of a simple mixture of curcumin with tween 80 and nanosuspension in water and ethanol as solvents, and finally the assessment of the antioxidant activity. We prepared the nanosuspension by injecting a curcumin solution in dichloromethane at low flow in water with tween 80 under heating and ultrasound. The analysis of particles size was conducted through dynamic light scattering; the non-degradation of curcumin was verified through thin-layer chromatography. The analyses of antioxidant activity were carried out according to the DPPH method. The method applied to reduce the particles size was efficient. Both the curcumin suspension and nanosuspension in tween 80 increased its solubility. Curcumin and the formulations presented antioxidant activity.
Dissipation of herbicides chlorsulfuron and imazosulfuron in the soil and the effects on the soil bacterial community

Dissipation of Sulfonylurea herbicides has rarely been studied due to their low application dosage. In this study, two herbicides, chlorsulfuron and imazosulfuron, were applied to both Podu (Pu) and Wolylin (Wl) soils at concentrations of 10 mg kg−1 or 50 mg kg−1 with soils at filled water holding capacity and incubation under 30°C. Changes in the soil bacterial community were examined with denaturing gradient gel electrophoresis (DGGE), whereas the residue of the herbicides was measured by high performance liquid chromatography (HPLC). The dissipation mechanisms of the two herbicides were both chemical and biological. The half-life of chlorsulfuron is 6.8–28.4 days and that of imazosulfuron is 6.4–14.6 days. These both dissipate faster in a more acidic soil. A higher dosage inhibited 48 % of the dissipation of the chlorsulfuron in Wl soil. However, larger differences were not observed in other treatments. The half-lives of both herbicides for 10 mg kg−1 or 50 mg kg−1 concentrations were less than one month. The microbial community was changed after the chlorsulfuron and imazosulfuron were spiked. Two sulfonylurea herbicides changed the soil bacterial composition after they were amended, and the change was larger with imazosulfuron under 50 mg kg−1 of concentration.
Nasal continuous positive airway pressure: experiences with a new technical approach

Since the early 197Os, when continuous positive airways pressure (CPAP) was introduced as a method of treatment of neonatal respiratory distress, many technical approaches have been suggested (1, 2). Much of the CPAP provided today is via ventilator and endotracheal tube, but there are problems with these methods in the form of mechanical impedance. This is often inherent in the ventilator design, even though the most significant impedance to natural breathing is caused by the endotracheal tube. Nasally applied CPAP is another widely used technique, particularly in Scandinavia. The advantages of a nasal technique are obvious in clinical use. Nasal prongs are very easy to apply and comparatively non-invasive to the airways. The patient can still be nursed and handled with uninterrupted CPAP. Less obvious are the problems due to the performance of this technique. During CPAP, a pressure level ideally equal to the end-expiratory level should be maintained throughout the respiratory cycle. The constancy of airway opening pressure is a fundamental feature for avoiding an increase in the work of breathing (3-1 I ) . In 1979 Goldman and co-workers reported an almost l O O % increase in the work of breathing during nasal CPAP compared with CPAP breathing through a face mask (12). The explanation for this was mainly flow resistance within the nasal attachment. Furthermore, during clinical use leakage of breathing gas from the nasal attachment or through the patient’s mouth is
Atmospheric Chemistry and Physics Discussions Interactive comment on “ Atmospheric effects of volcanic eruptions as seen by famous artists and depicted in their paintings ” by

The authors’ idea to use paintings to reconstruct time series of volcanic eruptions is highly ingenious. It is probably one of the most interesting applications of libRadtran so far and I admire the amount of work put into this analysis, by collecting this huge number of paintings and retrieving ancillary information such as the solar zenith angle etc. For the analysis the authors calculated red/green (R/G) irradiance ratios and compared them to values derived from paintings. The model-calculated R/G ratios were systematically lower than the observed ones (Figure 3 of Zerefos et al (2007)) in fact, the modelled ratio was almost always smaller than 1, indicating a blue or grey color rather than red. For that reason, the observed R/G values had to be reduced by 30% to be comparable with the model. On the other hand, the retrieval procedure (Figure
The evolution of a high mutation rate and declining fitness in asexual populations

Simulations of asexual populations undergoing continual adaptation present a definite prediction: mutator hitchhiking should drive the mutation rate upwards in an asexual population until it reaches an intolerable level, at which point the population will be driven extinct. Experimental studies have shown that a mutator allele can readily hitchhike to fixation with beneficial mutations in an asexual population having a low, wildtype mutation rate. Using Eshcerichia coli, I show that a genotype bearing two mutator alleles can supplant an asexual population already fixed for one mutator allele. My results provide experimental support for recent theory predicting that mutator alleles will tend to accumulate in asexual populations by hitchhiking with beneficial mutations, causing an ever-higher genomic mutation rate. Interestingly, results from recent simulations also suggest that the deleterious mutational load which accompanies an increased mutation rate is not immediately incurred. The delay in accruing a mutational load may potentially allow a succession of mutator hitch hiking events to occur before the cost of the initial hitchhiking event is incurred. Ultimately, mutation rates in asexual populations may evolve upwards to a rate that threatens extinction due to overwhelming mutational pressure. To test this prediction, I established independent populations of E. coli bearing either a singleor double-mutator genotype and propagated them for several thousand generations. At the conclusion of the experiment, the growth rate of the single-mutator populations had risen substantially, consistent with the substitution of beneficial mutations; in contrast, the growth rate of the double-mutator populations had fallen significantly, consistent with erosion of fitness by deleterious mutations. In addition, both sets of populations had maintained the mutation rate present at the outset of the experiment. Strikingly, the experiment seems to have provided evidence of mutation-driven fitness decline in the double-mutator populations despite the presence of beneficial mutations. I address the experimental results in the context of theoretical predication of fitness decline at a high mutation rates. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Biology First Advisor Paul Sniegowski
Optimization of the acquisition parameters for a SPET system dedicated to breast imaging

This work is developed within the framework of a larger project, which aims to develop a multimodal CT-SPET system dedicated to breast imaging. The goal of this paper is to optimize the choice of the various parameters involved in the design of a SPET system dedicated to breast imaging. In particular, we simulated different collimators, different tumor to background (T/B) ratios for two different spherical tumors with diameters of 5 mm and 8 mm. The performance of the explored cameras were analyzed in terms of SNR and image contrast (IC) values, calculated on the reconstructed images. In addition, we investigated the visibility limits of the system, by modifying the tumor size, the T/B value, and the diameter of the breast phantom (8 cm, 10 cm, and 13 cm). As a general tendency, we found out that a high-resolution camera is preferable, in terms of image contrast. On the other hand, the general purpose collimator seems to give a smoother image, giving rise to SNR values comparable to those obtained with the high-resolution collimator, even with a reduced contrast. High-sensitivity collimators seem to give a worse response on the reconstructed images. The 8 mm tumor is clearly visible for all the simulated conditions, even if it could be very close to the visibility limit for the high-sensitivity collimator. The 5 mm tumor is close to the visibility limit for general purpose and high-resolution collimators, for a T/B ratio equal to 10:1 and is not visible with high-sensitivity collimator. The smaller tumor is almost obscured by the background with the thickest breast (13 cm diameter).
Adaptive modulation based MC-CDMA systems for 4G wireless consumer applications

Adaptive modulation based MC-CDMA systems can play a vital role in future generation consumer communication electronics. Adaptive modulation, combined with MC-CDMA based transmission technology, is a promising way to increase the data rate that can be reliably transmitted over the wireless radio channels. For 4G wireless networks, which demand very high data rate up to 100 Mbits/s with the constraints limiting higher data rate being severe ISI due to multipath and limited spectrum, such kind of adaptive modulation based multi-carrier systems applied to a wide-area environment, can achieve very large average user throughputs. In this paper, adaptive modulation based M-ary PSK, M-ary QAM, M-ary CPM, M-ary MHPM and GMSK systems applied to a turbo coded MC-CDMA system in a Rayleigh fast fading channel environment have been investigated and the BER performance of all these digital modulation techniques have been compared. Results of the comparative study indicate that the continuous phase modulation schemes like CPM, MHPM, and GMSK gives better performance as compared to PSK and QAM schemes. At most of the time, the MHPM systems outperforms both GMSK and CPM. The PSK and QAM based systems perform well till the number of users are around 10. As a whole, the adaptive MHPM system is found to give the optimum performance among the considered digital modulation schemes for the MC-CDMA system in a 4G environment.
Imaging Through Random Discrete-Scatterer Dispersive Media

Abstract : The objective of the effort was to develop a methodology which would allow enhanced signal transmission, high resolution range imaging and/or target detection through optically obscuring, dilute, discrete-scatterer media such as clouds, fog, dust and other aerosols. (A) Properties of chirped-train waveforms such as their multi-band power spectra and the resulting point spread and ambiguity functions were analyzed. Advantages of the utilization of chirped trains in multi-spectralimaging (i.e., imaging based on frequency sub-bands of the chirped train signal) allowing extraction of frequency dependent information with improved signal-to-noise ratio was observed. (B) Propagation of short infrared/optical pulses in dilute random media consisting of large, compared to the wavelength, scatterers was analyzed. A rigorous approach based on analytic complex-contour integration of numerically determined cut and pole singularities of the radiative transport equation solution in the Fourier space was developed. It was found that the intensity of a propagating pulse, in addition to the coherent (ballistic) contribution and a long late-time diffusive tail, also exhibits a sharply rising early-time component that (i) can be attributed to the small-angle diffractive part of the scattering cross-section on medium particles, (ii) is attenuated proportionally to the nondiffractive rather than total cross-section, and (iii) can be extracted by high-pass filtering of the received pulse.
NTT Data: Description of the Erie System Used for MUC-6

Erie is a name recognition system developed for the Multilingual Entity Task (MET) in MUC-6. The pattern matching engine recognizes organization, person, and place names along with time and numeric expressions in Japanese text. Although our previous information extraction system Tex-tract performed well in MUC-5, the pattern matching engine, which was written in AWK language, was slow[2]. System maintenance was also difficult, since the patterns were defined in both the matching engine and the pattern files. Erie solves these problems by generating a pattern matching engine in C language directly from the defined patterns.
Behavioural profiles of inbred mouse strains used as transgenic backgrounds. II: cognitive tests

One of the characteristic manifestations of several neurodegenerative diseases is the progressive decline in cognitive ability. In order to determine the suitability of six mouse strains (129S2/Sv, BALB/c, C3H/He, C57BL/6j, CBA/Ca and DBA/2) as transgenic background strains, we investigated the performance on a variety of tasks designed to identify subtle changes in cognition. In addition, a test of exploratory behaviour was used to probe the level of underlying anxiety in these mouse strains, as anxiety can be a confounding factor on behavioural performance generally. The C3H/He mice exhibited the least anxiogenic behavioural profile spending most time on the open arms of the maze, in contrast to the 129S2/Sv mice which spent the least amount of time in this location and were the quickest to move into a closed arm. The C3H/He mouse strain failed to acquire a visual discrimination task and failed to demonstrate learning on a water maze spatial learning task, in contrast to the CBA/Ca, DBA/2 and C57BL/6j strains which demonstrated a degree of learning in both tasks. No significant strain differences were identified on the object recognition task. These data, taken together, suggest that care must be taken when choosing cognitive tasks to be used with particular mouse strains and that task sensitivity must be considered as a critical element to research protocols with regard to these mouse strains.
Striving for Better and Earlier Movement Prediction by Postprocessing of Classification Scores

Brain-computer interfaces that enable movement prediction are useful for many application fields from telemanipulation to rehabilitation. Current systems still struggle with a level of unreliability that requires improvement. Here, we investigate several postprocessing methods that operate on the classification outcomes. In particular, the data was classified after preprocessing using a support vector machine (SVM). The output of the SVM, i.e. the raw score values, were postprocessed using previously obtained scores to account for trends in the classification result. The respective methods differ in the way the transformation is performed. The idea is to use trends, like the rise of the score values approaching an upcoming movement, to yield a better prediction in terms of detection accuracy and/or an earlier time point. We present results from different subjects where upcoming voluntary movements of the right arm were predicted using the lateralized readiness potential from the EEG. The results illustrate that better and earlier predictions are indeed possible with the suggested methods. However, the best postprocessing method was rather subject-specific. Depending on the requirements of the application at hand, postprocessing the classification scores as suggested here can be used to find the best compromise between prediction accuracy and time point.
Design and Function: A Physical and Electrical Description of the 3M House Cochlear Implant System

A patient-wearable, single-electrode cochlear implant was first used by a patient in 1972 at the House Ear Institute. Since early 1982, a redesigned version of this system has been in clinical use. This new system, called the 3M House cochlear implant system, consists of an implanted receiver and a patient-worn signal processor, transmitter, and microphone. Also available are instruments to assist the audiologist and patient in proper fitting and testing of the equipment. Physical and electrical characteristics of the devices are described, with attention given to improvements over the older system and features important to the use in children.
Deposited in DRO : 21 May 2015 Version of attached le : Published Version Peer-review status of attached

Vaccination is one of the most effective ways of reducing childhood mortality. Despite global uptake of childhood vaccinations increasing, rates remain sub-optimal, meaning that vaccine-preventable diseases still pose a public health risk. A range of interventions to promote vaccine uptake have been developed, although this range has not specifically been reviewed in early childhood. We conducted a systematic review and meta-analysis of parental interventions to improve early childhood (0–5 years) vaccine uptake. Twenty-eight controlled studies contributed to six separate meta-analyses evaluating aspects of parental reminders and education. All interventions were to some extent effective, although findings were generally heterogeneous and random effects models were estimated. Receiving both postal and telephone reminders was the most effective reminder-based intervention (RD = 0.1132; 95% CI = 0.033–0.193). Sub-group analyses suggested that educational interventions were more effective in lowand middle-income countries (RD = 0.13; 95% CI = 0.05–0.22) and when conducted through discussion (RD = 0.12; 95% CI = 0.02–0.21). Current evidence most supports the use of postal reminders as part of the standard management of childhood immunisations. Parents at high risk of noncompliance may benefit from recall strategies and/or discussion-based forums, however further research is needed to assess the appropriateness of these strategies. © 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by-nc-sa/4.0/).
Construction du profil social de l'utilisateur dans un contexte dynamique. Application d'une méthode de pondération temporelle

Les mecanismes d’adaptation de l’information (personnalisation, recommandation) s’appuient tous sur un profil utilisateur. Une des difficultes majeures est la construction de ce profil dont la pertinence vis-a-vis des besoins/interets de l’utilisateur joue un role important dans la qualite des adaptations produites. Les reseaux sociaux numeriques (RSN) sont une source d’informations tres riche sur l’utilisateur. Nous nous interessons au processus de construction du profil utilisateur a partir de son RSN appele « profil social ». Nous proposons dans ce travail d’integrer des criteres temporels dans le processus de construction du profil de l’utilisateur. Le poids « temporel », qui reflete la pertinence d’un interet a un instant donne, est calcule, d’une part, a partir de la pertinence des individus du reseau egocentrique de l’utilisateur en prenant en compte « la fraicheur » de leurs liens avec l’utilisateur et, d’autre part, a partir de la pertinence des informations qu’ils partagent en prenant en compte la « fraicheur » de ces informations. Cet article est une version etendue de celui presente a Inforsid 2015 (Canut et al., 2015) en proposant un etat de l’art plus complet, la description et l’analyse d’experimentations plus poussees.