gebhart/patrepeval huggingface dataset:
Computerized textural analysis of DCE-MRI to enable identification of HER2-enriched breast cancers. (2016)

598 Background: HER2+ breast cancer is biologically and clinically heterogeneous. PAM50 profiling of HER2+ breast cancer reliably identifies the HER2-Enriched (HER2-E) subtype as most responsive to HER2-targeted antibody therapy (trastuzumab). As this subtype is currently only identifiable using molecular profiling of breast tumor tissue, a non-invasive HER2-E identification method could reduce future patient morbidity. We present initial findings involving a new computational imaging feature (CIF) that captures the disorder among pixel level gradient directions on dynamic contrast-enhanced (DCE) MRI. We show that this CIF is able to discriminate between HER2-E and other HER2+ breast cancer subtypes on DCE-MRI. Methods: 25 baseline DCE-MRI HER2+ breast cancer cases were split into two cohorts by PAM50-confirmed subtype (10 HER2-E, 15 non-HER2-E). 13 CIFs were computed on peak contrast image within expert-annotated lesions. This feature set was narrowed down to the 8 most differentially expressed features. Pharmacokinetic (PK) parameters (Kep, Ktrans, Ve), which quantify tumor-associated permeability changes, were also computed using Toft’s model. Consensus clustering was performed using 1) CIFs and 2) PK parameters and peak intensities. Results: Results of 2-group consensus clustering are shown in Table 1. CIFs yielded two distinct clusters, corresponding to HER2-E and non-HER2-E groups, with 70% sensitivity and 60% specificity. Studies sorted to the HER2-E cluster were characterized by under-expression of entropy and over-expression of texture homogeneity features relative to those of the non-HER2-E cluster. In contrast, PK parameters and peak intensities produced poorly defined groups that were uncorrelated with HER2 subtypes. Conclusions: CIFs more accurately identified HER2-E status compared with standard PK parameters on DCE-MRI. CIF expression patterns in HER2-E tumors suggest a less disordered imaging phenotype than other HER2+ tumors. Future validation studies of the HER2-E CIF signature identified here could potentially enable non-invasive prediction of response to trastuzumab. Feature Set Cluster % HER2-E Present % Non-HER2-E Present CIF A 70 40 B 30 60 PK + Intensity A 40 20 B 60 80
Conditional Antibody Expression to Avoid Central B Cell Deletion in a Humanized HIV-1 Vaccine Mouse Models (2020)

Abstract HIV-1 vaccine development aims to elicit broadly neutralizing antibodies (bnAbs) against diverse viral strains. In some HIV-1 infected individuals, bnAbs evolve from precursor antibodies through affinity maturation. To induce bnAbs, a vaccine must mediate a similar process of antibody maturation. One way to test vaccination strategies is to immunize mouse models that express human bnAb precursors. Such immunization experiments can assess whether the vaccine can convert precursor antibody into bnAb. A major problem with such mouse models is that bnAb expression often hinders B cell development in the bone marrow. Such developmental blocks may be attributed to unusual properties of bnAb variable regions, such as poly-reactivity and long antigen-binding loops, which are often under negative selection during primary B cell development. To address this problem, we devised a method to circumvent B cell developmental block by expressing bnAbs conditionally in mature B cells. We validated this method by expressing the unmutated common ancestor (UCA) of the human VRC26 bnAb in transgenic mice. Constitutive expression of combined immunoglobulin heavy and light chains of VRC26UCA led to developmental arrest of B cell progenitors in the bone marrow; poly-reactivity of VRC26UCA and poor pairing of VRC26UCA IgH chain with mouse surrogate light chain may contribute to the phenotype. The conditional expression strategy circumvented this developmental impediment, allowing the VRC26UCA to be expressed in mature peripheral B cells. This method should be generally applicable for expressing other antibodies that are under negative selection during B cell development. Significance statement Mouse models can provide fast and cost-effective systems to test HIV-1 vaccine candidates at the pre-clinical stage. To serve this purpose, mouse models are engineered to express the precursors of human bnAbs against diverse HIV-1 strains. Immunization of such mouse models can evaluate the ability of vaccines to mature the precursor antibodies into bnAbs. However, due to unusual properties of bnAbs, mouse models expressing their precursors often have B cell developmental defects. In this study, we devised and validated a strategy to address this problem. This method could also facilitate the expression of other clinically relevant antibodies in mature B cells in transgenic mice; immunization of such mice could be used to generate novel antibodies with desirable properties.
Complexity of Visual Icons Studied via Signal Detection Theory (2007)

Two investigations on how humans perceive information from visually rendered complex objects, such as military icons (glyphs) were conducted. A signal detection theory framework was employed to evaluate the sensitivity and specificity of human subject performance. The 6 adults tested showed that as complexity increased, their accuracy in performance decreased. Study 1 showed that complex dimensions (features) could not be assigned arbitrarily. Study 2 developed a rank ordering for features of an iconic object.
MiR‐9 downregulates CDX2 expression in gastric cancer cells (2011)

Ectopic expression of CDX2, a caudal-related homeobox protein, is known to be associated with the development of intestinal metaplasia in the stomach and gastric carcinogenesis. Previously, we reported that DNA methylation was partly responsible for CDX2 silencing in gastric cancer (GC). However, the mechanism underlying the aberrant expression of CDX2 during malignant transformation remained unclear. MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators. To elucidate the role of miRNAs in CDX2 downregulation in GC cells, putative miRNAs, such as miR-9, were computationally predicted. After exogenous pre-miR-9 precursor transfection, the luciferase activity of a reporter vector containing a part of the 3'-UTR of CDX2 was downregulated in HEK-293T cells. The inverse correlation between the miR-9 and CDX2 protein levels was demonstrated in GC cell lines. By means of miR-9 overexpression and knockdown techniques, the expression levels of the CDX2 protein and downstream target genes (p21, MUC2 and TFF3) were responsively altered in MKN45 and NUGC-3 cells. Transfection of an anti-miR-9 molecule significantly inhibited cell growth by promoting G(1) cell cycle arrest in MKN45 cells similarly to the effect of CDX2 overexpression. Moreover, examination of the miR-9 levels in primary GC tissues revealed that the amounts of miR-9 in the CDX2-negative group were significantly higher than those in the CDX2-positive group (p = 0.004). Therefore, miR-9 might repress CDX2 expression via the binding site in the 3'-UTR, resulting in the promotion of cell proliferation in GCs.
Understanding the TXA seizure connection (2012)

Transexamic acid (TXA) is an antifibrinolytic that has been used successfully to prevent blood loss during major surgery. However, as its usage has increased, there have been growing reports of postsurgical seizure events in cardiac surgery patients. In this issue of the JCI, Lecker et al. explore this connection and suggest that TXA-mediated inhibition of glycine receptors may underlie the effect. This finding prompted the authors to explore the preclinical efficacy of common anesthetics that function by reducing the TXA-mediated inhibition to prevent or modify postsurgical seizures.
Hydroxyalkenal Formation Induced by Advanced Glycosylation of Low Density Lipoprotein (1996)

Advanced glycosylation end products (AGEs) have been identified to be present on both the apolipoprotein and lipid components of low density lipoprotein (LDL) and to act to prevent its recognition and uptake by high affinity, tissue LDL receptors. Lipid-linked AGEs form readily in vitro by the covalent addition of glucose to the amine-containing head groups of phospholipids. This process is accompanied by oxidation of the unsaturated fatty acid side chains and occurs in the absence of exogenously added transition metals or free radical generating systems, suggesting that AGE formation may contribute significantly to lipid oxidation in vivo. To assess more precisely the chemical basis of AGE-induced oxidative modification, we performed gas chromatography-mass spectrometry analysis of the lipid products which form over time during LDL-advanced glycosylation in vitro. Negative ion chemical ionization mass spectroscopy of two major compounds that were identified were consistent with the structures of the fatty acid oxidation products 4-hydroxyhexenal and 4-hydroxynonenal. These data support the concept that AGE formation in close proximity to unsaturated fatty acyl groups leads to lipid oxidation and provide additional evidence that advanced glycosylation is an important pathogenic modification of the LDL particle in vivo.
Stereospecific syntheses of both diastereomers of (.+-.)-2-amino-4-methyl-5-hexenoic acid (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereospecific syntheses of both diastereomers of (.+-.)-2-amino-4-methyl-5-hexenoic acidBarry B. Snider and John V. DunciaCite this: J. Org. Chem. 1981, 46, 16, 3223–3226Publication Date (Print):July 1, 1981Publication History Published online1 May 2002Published inissue 1 July 1981https://pubs.acs.org/doi/10.1021/jo00329a015https://doi.org/10.1021/jo00329a015research-articleACS PublicationsRequest reuse permissionsArticle Views324Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Electronic structure via the auxiliary-field Monte Carlo algorithm (1995)

Auxiliary-field Monte Carlo (AFMC) is an exact approach for calculating the ground state of a system of fermions (or bosons) interacting by pair-potentials. The method uses the Hubbard–Stratonovich transformation to replace the exact imaginary-time propagator by an average over an ensemble of propagators for independent particles in the presence of a varying external field, so that the calculation of the exact energy is reduced to multiple independent calculations, each of which costs essentially the same as one Hartree–Fock iteration. Here we consider the application of AFMC to calculate molecular structure, and present preliminary simulations on He and Be. We develop two simple methods to partially alleviate a ‘‘sign-problem’’ in AFMC through restriction of the length of the imaginary-time propagation, by either a simultaneous propagation of several initial states followed by subspace-diagonalization or by incorporation of information from all propagated time steps. The first method is tested and found to yield significant improvement in accuracy. For the present simulations, the single-particle orbitals are expanded in a given set of primitive orbitals. The resulting spectral-AFMC method yields, for sufficiently converged ensembles, the full-CI energy associated with a given basis. The developments reported here, and in particular the demonstration of subspace-diagonalization, have however general validity independent of whether a basis set or a grid representation is used for the single-particle orbitals (in the first case a full-CI result is obtained in the given basis, while a converged grid representation would yield the exact result).
TDANet: An Efficient Solution For Short-Term Mobile Traffic Forecasting (2023)

Mobile traffic forecasting is crucial for optimizing the network configuration and improving Quality-of-Service (QoS); accurate mobile traffic predictions can help the network operators better configure the network and adapt to the trend of mobile demand. However, improving mobile traffic forecasting is challenging as traffic patterns exhibit strong periodicity while also retaining a certain level of randomness; this makes it difficult to model the sequence correlation. To obtain better mobile traffic predictions, we proposed a deep learning-based predictor called Temporal Dynamics Aware Network (TDANet). TDANet is carefully designed to extract both the global and the local temporal patterns employing recurrent and attention components; a linear module is employed to make the predictions more sensitive to the magnitude of mobile traffic, which makes the model better able to capture fast dynamics. Extensive experiments are conducted on a real-world mobile traffic dataset, and the results show that TDANet outperforms all the baseline models on all evaluation metrics, including both accuracy and complexity.
Reversible Ammonia Sorption on Carbon for the Primary Life Support System (PLSS) (2012)

Results are presented on the development of regenerable trace-contaminant (TC) sorbents for use in Extravehicular Activities (EVAs), and more specifically in the Primary Life Support System (PLSS). Since ammonia is the most important TC to be captured, data presented in this paper are limited to ammonia sorption, with results relevant to other TCs to be reported at a later time. The currently available TC-control technology involves the use of a packed bed of acid-impregnated granular charcoal. The sorbent is non-regenerable, and its use is associated with appreciable pressure drop, i.e. power consumption. The objective of this work is to demonstrate the feasibility of using vacuum-regenerable carbon sorbents for PLSS application. In this study, several carbon monoliths were fabricated and tested. Multiple adsorption/vacuum-regeneration cycles were demonstrated at room temperature, as well as carbon surface conditioning that enhances ammonia sorption without impairing sorbent regeneration. Depending on sorbent monolith geometry, the reduction in pressure drop with respect to granular sorbent was found to be between 50% and two orders of magnitude.
Degradation of extracellular ATP by the retinal pigment epithelium (2005)

Stimulation of ATP or adenosine receptors causes important physiological changes in retinal pigment epithelial (RPE) cells that may influence their relationship to the adjacent photoreceptors. While RPE cells have been shown to release ATP, the regulation of extracellular ATP levels and the production of dephosphorylated purines is not clear. This study examined the degradation of ATP by RPE cells and the physiological effects of the adenosine diphosphate (ADP) that result. ATP was readily broken down by both cultured human ARPE-19 cells and the apical membrane of fresh bovine RPE cells. The compounds ARL67156 and betagamma-mATP inhibited this degradation in both cell types. RT-PCR analysis of ARPE-19 cells found mRNA message for multiple extracellular degradative enzymes; ectonucleotide pyrophosphatase/phosphodiesterase eNPP1, eNPP2, and eNPP3; the ectoATPase ectonucleoside triphosphate diphosphohydrolase NTPDase2, NTPDase3, and some message for NTPDase1. Considerable levels of ADP bathed RPE cells, consistent with a role for NTPDase2. ADP and ATP increased levels of intracellular Ca(2+). Both responses were inhibited by thapsigargin and P2Y(1) receptor inhibitor MRS 2179. Message for both P2Y(1) and P2Y(12) receptors was detected in ARPE-19 cells. These results suggest that extracellular degradation of ATP in subretinal space can result in the production of ADP. This ADP can stimulate P2Y receptors and augment Ca(2+) signaling in the RPE.
The in vivo properties of STX243: a potent angiogenesis inhibitor in breast cancer (2008)

The steroidal-based drug 2-ethyloestradiol-3,17-O,O-bis-sulphamate (STX243) has been developed as a potent antiangiogenic and antitumour compound. The objective of this study was to ascertain whether STX243 is more active in vivo than the clinically relevant drug 2-methoxyoestradiol (2-MeOE2) and the structurally similar compound 2-MeOE2-3,17-O,O-bis-sulphamate (STX140). The tumour growth inhibition efficacy, antiangiogenic potential and pharmacokinetics of STX243 were examined using four in vivo models. Both STX243 and STX140 were capable of retarding the growth of MDA-MB-231 xenograft tumours (72 and 63%, respectively), whereas no inhibition was observed for animals treated with 2-MeOE2. Further tumour inhibition studies showed that STX243 was also active against MCF-7 paclitaxel-resistant tumours. Using a Matrigel plug-based model, in vivo angiogenesis was restricted with STX243 and STX140 (50 and 72%, respectively, using a 10 mg kg(-1) oral dose), thereby showing the antiangiogenic activity of both compounds. The pharmacokinetics of STX243 were examined at two different doses using adult female rats. The compound was orally bioavailable (31% after a single 10 mg kg(-1) dose) and resistant to metabolism. These results show that STX243 is a potent in vivo drug and could be clinically effective at treating a number of oncological conditions.
Weaning from mechanical ventilation (2014)

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Virus Zika et organes du tractus génital masculin : infection et réponse innée (2019)

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Competitive Inhibition of Choline Phosphotransferase by Geranylgeraniol and Farnesol Inhibits Phosphatidylcholine Synthesis and Induces Apoptosis in Human Lung Adenocarcinoma A549 Cells (1998)

We have previously shown that, among various isoprenoids, farnesol and geranylgeraniol specifically induced actin fiber disorganization, growth inhibition, and apoptosis in human lung adenocarcinoma A549 cells (Miquel, K., Pradines, A., and Favre, G. (1996) Biochem. Biophys. Res. Commun. 225, 869-876). Here we demonstrate that isoprenoid-induced apoptosis was preceded by an arrest in G0/G1 phase. The isoprenoid effects were independent of protein prenylation and of mitogen-activated protein kinase activity. Moreover, geranylgeraniol and farnesol induced a rapid inhibition of phosphatidylcholine biosynthesis at the last step of the CDP-choline pathway controlled by choline phosphotransferase and not at the level of CTP:phosphocholine cytidylyltransferase, the key enzyme of the pathway. Inhibition of choline phosphotransferase was confirmed by in vitro assays on microsomal fractions, which clearly showed that the isoprenoids acted by competitive inhibition with the diacylglycerol binding. Exogenous phosphatidylcholine addition prevented all the biological effects of the isoprenoids, including actin fiber disorganization and apoptosis, suggesting that inhibition of phosphatidylcholine biosynthesis might be the primary event of the isoprenoid action. These data demonstrate the molecular mechanism of geranylgeraniol and farnesol effects and suggest that the mevalonate pathway, leading notably to prenylated proteins, might be linked to the control of cell proliferation through the regulation of phosphatidylcholine biosynthesis.
Attenuation of an Avian Pathogenic Escherichia coli Strain Due to a Mutation in the rpsL Gene (2004)

The diseases caused by pathogenic Escherichia coli constitute a major economic loss to the poultry industry. The development of a live oral E. coli vaccine to prevent or reduce diseases in poultry had been the objective of our work. Four spontaneous streptomycin-dependent (str-dependent) mutants were generated from a virulent avian strain that contains a mutation in the fur region of the chromosome. Genetic analysis of the mutants indicated that the str-dependent phenotype was due to a base change of C --> T at base 272 in the rpsL gene. The mutants were tested for attenuation using the day-old chick model. Day-old birds, in groups of 20, were either challenged with 10(6) colony-forming units (CFU) of the str-dependent mutant, the parent strain (containing the fur mutation), or the wild-type strain without the fur mutation. The parent strain and the wild-type strain were highly virulent, and 80% or more of the birds died. None of the birds challenged with the str-dependent mutants died, indicating attenuation of the mutants. The protective effect of the mutant as a live vaccine against the challenge with 10(6) CFU of the wild-type strain EC317 was investigated. Vaccination by both aerosol (day 1) and oral (days 14 and 28) routes using 10(8) CFU of the str-dependent mutant (EC1598) had no effect on the occurrence of cellulitis in the birds. Two vaccinations given as aerosol on day 1 and given orally on day 14 also had no significant effect on the occurrence of systemic lesions. Three immunizations on days 1, 14, and 28 resulted in a significant reduction in the number of birds with systemic lesions. Antibody titers prior to challenge were not predictive of outcome of challenge.
Zinc in Alzheimer’s Disease: A Meta-Analysis of Serum, Plasma, and Cerebrospinal Fluid Studies (2015)

To evaluate whether zinc levels in serum, plasma, and cerebrospinal fluid are altered in Alzheimer’s disease (AD), we performed meta-analyses of 27 studies on the topic published from 1983 to 2014. The subjects’ sample obtained by merging studies was a pooled total of 777 AD subjects and 1,728 cont rols for serum zinc studies, 287 AD subjects and 166 controls for plasma zinc, and of 292 AD subjects and 179 controls for CSF zinc. The main result of this meta-analysis is the very high heterogeneity among the studies either in demographic terms or in methodological approaches. Although we considered these effects in our analyses, the heterogeneity persisted and it has to be taken into account in the interpretation of the results. Our meta-analysis indicated that serum zinc appears significantly decreased in AD patients compared with healthy controls, and this result is confirmed when serum and plasma studies were analyzed together. If we considered the age-matched studies, the meta-analysis carried out on only six studies showed no significant difference in zinc levels between AD and healthy controls (SMD =−0.55, 95% CI (−1.18; 0.09); p = 0.094; I2 = 91%). In the light of these findings, we speculated about the possibility that the decreases observed could indicate a possible dietary zinc deficiency and we suggested that the possible involvement of zinc alterations in AD may have an interplay with copper metabolism.
Appendix to A Field Study of Refactoring Rationale, Benefits, and Challenges at Microsoft (2012)

In order to understand practices at Microsoft, we sent a survey to 1290 engineers, whose change comments include a keyword, refactoring in the last 2 years for the five Microsoft products (Windows Phone, Exchange, Windows, Office Communication and Services, and Office). We purposely targeted the engineers who are already familiar with the term, refactor- ing, because our goal is to understand their own definition and their perception about the value of refactoring. This document contains the complete set of survey questions. The results of the survey will be published in a separate paper.