gebhart/patrepeval huggingface dataset:
Independent verification of circulating miRNA as diagnostic biomarkers for urothelial carcinoma (2022)

Urothelial carcinoma (UC) is an umbrella term for bladder cancers (BCa) and upper-tract urothelial carcinoma (UTUC), with BCa and UTUC sometimes detected concomitantly. The methods of detection for UC are often inaccurate or highly invasive, and, therefore, are thought to be unsatisfactory. Previously, we reported seven serum miRNAs as diagnostic markers for BCa. Here, we re-evaluated potential diagnostic miRNAs in different institutions. We prospectively analyzed serum samples obtained from 126 UC patients (BCa: 106 samples; UTUC: 14 samples; UTUC with BCa: six samples) and 50 noncancer controls by microarray analysis. We randomly assigned these samples into a training or a validation set. Biomarker candidate miRNAs were selected based on cross-validation scores in the training set of samples, with diagnostic power confirmed in the validation set. Among the diagnostic miRNAs identified in this way, miR-1343-5p and miR-6087 had been identified as potential diagnostic miRNAs in our previous study. In addition, we evaluated the association between the serum levels of identified miRNAs and the presence of UC risk conditions. The expression levels of several miRNAs correlate with the risk factors in participants without UC, which may be explained by the presence of a microscopic tumor or a precancerous lesion. In conclusion, we identified two robust miRNA diagnostic markers for UC detection. Further functional analysis is required to elucidate the mechanism by which alterations in the expression of these miRNAs occur.
Buffer and pH Effects on Propranolol Binding by Human Albumin and α1-Acid Glycoprotein (1988)

Propranolol binding to isolated human alpha-1-acid glycoprotein (AGP) and human albumin (HSA) was studied by equilibrium dialysis at 37 degrees C. With AGP (0.067%) and HSA (4%), total propranolol concentration was varied from 0.7 to 93,000 ng mL-1. Over this concentration range the percentage drug bound to HSA declined from 49 to 39% while that to AGP declined from 68 to 4%. Two classes of sites were identified on AGP with n1k1 = 8.50 X 10(4) M-1 and n2k2 = 3.12 X 10(4) M-1. With a pH 7.4 phosphate buffer, propranolol binding to AGP was greatest when the protein was initially dissolved in pH 7.4 water compared with pH 7.2 water or the phosphate buffer. Thus, the method of AGP solution preparation affected propranolol binding by this protein. For both AGP and HSA, greater drug binding was noted with phosphate buffers in comparison with a physiological buffer. With phosphate buffers, decreasing pH from 7.4 to 7.0 decreased propranolol binding by AGP, while decreasing pH from 7.7 to 7.4 had little effect. With HSA, the percent propranolol bound consistently decreased on lowering pH from 7.7 to 7.0.
Exploring Transcriptomic Landscapes in Red Blood Cells, in Their Extracellular Vesicles and on a Single-Cell Level (2022)

Being enucleated, RBCs lack typical transcriptomes, but are known to contain small amounts of diverse long transcripts and microRNAs. However, the exact role and importance of these RNAs are lacking. Shedding of extracellular vesicles (EVs) from the plasma membrane constitutes an integral mechanism of RBC homeostasis, by which RBCs remove unnecessary cytoplasmic content and cell membrane. To study this further, we explored the transcriptomes of RBCs and extracellular vesicles (EVs) of RBCs using next-generation sequencing. Furthermore, we performed single-cell RNA sequencing on RBCs, which revealed that approximately 10% of the cells contained detectable levels of mRNA and cells formed three subpopulations based on their transcriptomes. A decrease in the mRNA quantity was observed across the populations. Qualitative changes included the differences in the globin transcripts and changes in the expression of ribosomal genes. A specific splice form of a long non-coding RNA, Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1), was the most enriched marker in one subpopulation of RBCs, co-expressing with ribosomal structural transcripts. MALAT1 expression was confirmed by qPCR in CD71-enriched reticulocytes, which were also characterized with imaging flow cytometry at the single cell level. Analysis of the RBC transcriptome shows enrichment of pathways and functional categories required for the maturation of reticulocytes and erythrocyte functions. The RBC transcriptome was detected in their EVs, making these transcripts available for intercellular communication in blood.
Segregation analysis of complex phenotypes (1994)

Traditional models of the genetic transmission of human diseases have often assumed that the phenotype is a simple dichotomous trait, which is unrealistic for many psychiatric conditions, and may result in loss of valuable information. We describe a new model for complex phenotypes, implemented in the program COMDS, which subclassifies normal and affected individuals into polychotomies correlated with the underlying genetic liability to the disorder. The model is applied to 18 Scottish pedigrees ascertained for schizophrenia, in which auditory P300 latency had been measured as a possible correlate of the genetic predisposition to schizophrenia. The results suggest that there may be a major locus for schizophrenia, but that there are also other familial determinants, possibly a second modifier locus. In addition, the results indicate that auditory P300 latency may be a useful measure of the genetic predisposition to schizophrenia among asymptomatic relatives, although the relationship between P300 latency and the degree of genetic predisposition in clinical cases was not significant, presumably because other factors are operating on P300 latency. Because of the possible selection biases in this sample, there is a need to replicate these findings in systematically ascertained pedigrees.
Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion (2016)

Estrogen receptor (ER)-negative cancers have a poor prognosis, and few targeted therapies are available for their treatment. Our previous analyses have identified potential kinase targets critical for the growth of ER-negative, progesterone receptor (PR)-negative and HER2-negative, or "triple-negative" breast cancer (TNBC). Because phosphatases regulate the function of kinase signaling pathways, in this study, we investigated whether phosphatases are also differentially expressed in ER-negative compared to those in ER-positive breast cancers. We compared RNA expression in 98 human breast cancers (56 ER-positive and 42 ER-negative) to identify phosphatases differentially expressed in ER-negative compared to those in ER-positive breast cancers. We then examined the effects of one selected phosphatase, dual specificity phosphatase 4 (DUSP4), on proliferation, cell growth, migration and invasion, and on signaling pathways using protein microarray analyses of 172 proteins, including phosphoproteins. We identified 48 phosphatase genes are significantly differentially expressed in ER-negative compared to those in ER-positive breast tumors. We discovered that 31 phosphatases were more highly expressed, while 11 were underexpressed specifically in ER-negative breast cancers. The DUSP4 gene is underexpressed in ER-negative breast cancer and is deleted in approximately 50 % of breast cancers. Induced DUSP4 expression suppresses both in vitro and in vivo growths of breast cancer cells. Our studies show that induced DUSP4 expression blocks the cell cycle at the G1/S checkpoint; inhibits ERK1/2, p38, JNK1, RB, and NFkB p65 phosphorylation; and inhibits invasiveness of TNBC cells. These results suggest that that DUSP4 is a critical regulator of the growth and invasion of triple-negative breast cancer cells.
Activation of a murine T-cell hybridoma by cationized bacteria. (1989)

Cationic particles interact by electrostatic forces with membrane components of diverse cell types, including lymphocytes. Contact with cationized streptococci was shown to induce a murine T-cell hybridoma to transcribe lymphokine mRNA as well as secrete interleukin-2. This activation was accompanied by a rise in intracellular calcium. Cationized streptococci-induced activation of this T-cell hybridoma could be specifically inhibited by either chelating extracellular calcium or by treating with CD4 monoclonal antibody. These data indicate that the in vitro behaviour of T cells can be modulated by charged microbial particles; such interactions may have relevance for chronic inflammation associated with some bacterial infections.
Difficult wrist fractures. Perilunate fracture-dislocations of the wrist. (1987)

Perilunate dislocations of the wrist have a common pathway of disruption that occurs from extensive dorsiflexion injuries. Open reduction and internal fixation of these injuries is required to provide accurate alignment and the option for ligament repair. Both dorsal and palmar surgical incisions may be indicated. Associated injuries to the median nerve must be recognized. Treatment includes scaphoid and radial styloid stabilization with multiple K-wires or internal compression screw (Herbert or Association for the Study of Internal Fixation [ASIF] screws). In these injuries, the lunate must be reduced first and stabilized. The scaphoid proximal segment follows the lunate unless the scapholunate (SL) ligament is torn. The distal scaphoid fragment, capitate, and triquetrum are reduced and aligned with the lunate and need to be held with K-wires. Ligament repair and augmentation may be necessary at both scapholunate and lunotriquetal areas if there has been serious ligament injury. Palmar ligament repair is often required, and we recommend a palmar exploration in most patients along with release of the median nerve. Surgical treatment results of perilunate fracture-dislocations of the wrist appear better than conservative treatment methods, but complications following both indicate the need for improved internal fixation and fracture-dislocation realignment. These fractures are a real challenge to the treating surgeon who must use patience, precise surgical techniques, and careful roentgenographic study (including tomograms and traction views) to assure the best result.
Lectin Chromatography/Mass Spectrometry Discovery Workflow Identifies Putative Biomarkers of Aggressive Breast Cancers (2012)

We used a lectin chromatography/MS-based approach to screen conditioned medium from a panel of luminal (less aggressive) and triple negative (more aggressive) breast cancer cell lines (n=5/subtype). The samples were fractionated using the lectins Aleuria aurantia (AAL) and Sambucus nigra agglutinin (SNA), which recognize fucose and sialic acid, respectively. The bound fractions were enzymatically N-deglycosylated and analyzed by LC-MS/MS. In total, we identified 533 glycoproteins, ∼90% of which were components of the cell surface or extracellular matrix. We observed 1011 glycosites, 100 of which were solely detected in ≥3 triple negative lines. Statistical analyses suggested that a number of these glycosites were triple negative-specific and thus potential biomarkers for this tumor subtype. An analysis of RNaseq data revealed that approximately half of the mRNAs encoding the protein scaffolds that carried potential biomarker glycosites were up-regulated in triple negative vs luminal cell lines, and that a number of genes encoding fucosyl- or sialyltransferases were differentially expressed between the two subtypes, suggesting that alterations in glycosylation may also drive candidate identification. Notably, the glycoproteins from which these putative biomarker candidates were derived are involved in cancer-related processes. Thus, they may represent novel therapeutic targets for this aggressive tumor subtype.
Beyond U0126. Dianion Chemistry Leading to the Rapid Synthesis of a Series of Potent MEK Inhibitors. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Towards an autonomous decentralized orchestration system (2015)

Summary Orchestrating workflows needed for modern scientific data analysis presents a significant research challenge: they are typically executed in a centralized manner such that all data pass through a single compute server known as the engine, which causes unnecessary network traffic that leads to a performance bottleneck. This paper presents a scalable decentralized orchestration system that relies on a functional, high‐level data coordination language for executing workflows. This system consists of distributed execution engines, each of which is responsible for executing part of the overall workflow. It exploits parallelism in the workflow by partitioning it into smaller sub‐workflows and determines the most appropriate engines to execute them using network resource monitoring and placement analysis. This permits the computation logic of the workflow to be moved towards the services providing the data, which improves the overall execution time. The system supports data‐driven execution that allows each sub‐workflow to be executed as soon as the data needed for its execution become available from other sources. Therefore, a scheduling mechanism is not required to manage the order in which the sub‐workflows are orchestrated. This paper provides an evaluation of the proposed system, which demonstrates that decentralized orchestration provides scalability over centralized orchestration. Copyright © 2015 John Wiley &amp; Sons, Ltd.
The Direct Antiviral Cytotoxicity by Bovine Lymphocytes Is Not Restricted by Genetic Incompatibility of Lymphocytes and Target Cells (1977)

Experiments were designed to determine if in the ox a requirement for genetic compatibility between antiviral cytotoxic cells and target cells was needed for cytotoxicity to occur. Unrelated bovine animals were immunized with vaccinia or IBR virus (a herpesvirus), and PBL were collected at various times for measurement of their cytotoxicity against autologous or heterologous uninfected or virus-infected fibroblasts. In all instances, cytotoxicity was expressed against heterologous as well as autologous targets and in most cases there was no evidence of enhanced killing of autologous cells. The cytotoxicity was shown to be direct, presumably T cell mediated, and was not attributable to ADCC. The likelihood of the animals under investigation sharing histocompatibility antigens was considered extremely remote but was not formally excluded.
Nietzsche contra Wagner (1889)

Bevat tevens: Het geval Wagner / Friedrich Nietzsche. - Vert. van: Der Fall Wagner. Nietzsche in de dagboeken van Cosima Wagner. - Vert. van een keuze uit: Die Tagebucher. - Munchen [etc.], 1976, 1977
History and future of auditory filter models (2010)

Auditory filter models have a history of over a hundred years, with explicit bio-mimetic inspiration at many stages along the way. From passive analogue electric delay line models, through digital filter models, active analogue VLSI models, and abstract filter shape models, these filters have both represented and driven the state of progress in auditory research. Today, we are able to represent a wide range of linear and nonlinear aspects of the psychophysics and physiology of hearing with a rather simple and elegant set of circuits or computations that have a clear connection to underlying hydrodynamics and with parameters calibrated to human performance data. A key part of the progress in getting to this stage has been the experimental clarification of the nature of cochlear nonlinearities, and the modelling work to map these experimental results into the domain of circuits and systems. No matter how these models are built into machine-hearing systems, their bio-mimetic roots will remain key to their performance. In this paper we review some of these models, explain their advantages and disadvantages and present possible ways of implementing them. As an example, a continuous-time analogue CMOS implementation of the One Zero Gammatone Filter (OZGF) is presented together with its automatic gain control that models its level-dependent nonlinear behaviour.
Determination of the bioenergy production capacity from biochemical profiles of some aquatic phytoremediation plants. Energy while cleaning. (2014)

This study aims to research the possibilities of converting some hydrophytes into energy by revaluating them after the harvesting process. These hydrophytes used in the phytoremediation studies disperse naturally in aquatic mediums, sometimes even revealing themselves as invasive species. Chosen hydrophytes samples (Eichornia crassipes, Cyperus alternifolius, Lemna minor, Pistia stratiotes, Typha latifolia, Nasturtium officinale , Houttonia cordata) are analysed in terms of oil rate, biochemical profiles which include elaeostearic compositions, COI/T.20/Doc No 17 (capillary column gas chromatography) and in-house methods. The obtained data are analysed in comparison to the elaeostearics rate and compositions of the plants used in biodiesel procurement (canola, soy, palm, sunflower, Botryococcus and Chlorella oils). As a result, it is found that linolenic acid and linoleic acid percentages especially stand forth in the plants Eichornia sp., Cyperus sp., Lemna sp., the stearic and oleic acid percentages are significantly high in Pistia sp., and palmitic elaeostearic percentage is higher in the plants of Houttonia sp. and Nasturtium sp. than the plants currently used in biodiesel procurement, yet the oil rate within their system is lower than these plants. Moreover, it is thought that the plant waste obtained after the harvest carried out in order to ensure the water quality of the systems may in the least meet this deficit.
Flow method and apparatus for screening chemicals using micro x-ray fluorescence (2023)

Method and apparatus for screening chemicals using micro x-ray fluorescence. A method for screening a mixture of potential pharmaceutical chemicals for binding to at least one target binder involves flow-separating a solution of chemicals and target binders into separated components, exposing them to an x-ray excitation beam, detecting x-ray fluorescence signals from the components, and determining from the signals whether or not a binding event between a chemical and target binder has occurred.
ON THE OBSERVATION OF ACOUSTO-ELASTIC HYSTERESIS IN KINKING NONLINEAR ELASTIC SOLIDS (2009)

Using bulk acoustic waves we studied the nonlinear mechanical properties and hysteresis of the acousto‐elastic effect in kinking nonlinear elastic, KNE, solids. The experiments reviewed here present direct observation of nonlinear hysteretic scattering and attenuation of ultrasonic waves in Ti3SiC2 and Ti3AlC2, representatives of KNE solids, as a function of quasi‐static cyclic compressive stresses. We attribute this dynamic behavior to the interaction of the acoustic waves with dislocation in incipient kink bands. The relevance of these findings to possible sensor applications of hysteretic KNE solids is briefly discussed.
Analysis, design, and performance of micropower circuits for a capacitive pressure sensor IC (1986)

An integrated circuit has been designed, built, and testing as part of a capacitive pressure transducer. High-accuracy compact micropower circuits utilizing a standard bipolar IC process without any special components or trimming are used. The key circuits for achieving this performance are a Schmitt trigger oscillator and a bandgap voltage reference. The sensor circuits consume 200 /spl mu/W at 3.5 V, can resolve capacitance changes of 300 p.p.m., measure temperature to /spl plusmn/0.1/spl deg/C over a limited temperature range, and presently occupy 4 mm/SUP 2/ on a 2 mm/spl times/6 mm implantable monolithic silicon pressure sensor. Further scaling of the sensor is discussed showing that a reduction of area by a factor of 4 is achievable.
Neurotrophin Regulation of the Developing Nervous System: Analyses of Knockout Mice (1997)

The neurotrophins, NGF, BDNF, NT3 and NT4, are one family in a growing repertoire of neurotrophic factors. The neurotrophins have long been implicated in neuronal survival and recent studies from mice with targeted disruptions of the neurotrophin genes confirm this role, but also reveal that the action of the neurotrophins is more complex, and in some instances more interactive, than originally envisaged. Lack of functional NGF, BDNF and NT3 genes results in severe neuronal deficits and an early postnatal death. However, NT4 is unique among the neurotrophins and while the absence of NT4 does result in limited sensory neuron loss these mice do not die early, suggesting that NT4-dependent neurons are not critical for survival. Phenotypic analyses of mice lacking neurotrophin receptors, TrkA, B and C, confirm that TrkA is the functional receptor for NGF, TrkB acts as the primary receptor for BDNF and NT4, and NT3 signals primarily through TrkC. However, the finding that TrkC mutant mice have a less dramatic phenotype than their NT3 counterparts implicates NT3 in signaling via receptors other than TrkC. Further studies, using combinatorial Trk and neurotrophin deletions, reveal that while BDNF and NT4 subserve distinct neuron populations in most cases, other neuron sub-populations can be supported by either BDNF or NT4, providing evidence for compensatory actions between neurotrophins. As a mechanism to explain programmed cell death that occurs in the developing nervous system, recent studies examining neurotrophin gene-dosage effects suggest that the availability of neurotrophins, NGF, BDNF and NT3, may be limiting for some neuron populations. In addition, the proposed switch in neurotrophin dependency for some neuron populations is now being determined using neurotrophin mutant mice. We discuss these and other recent findings on neurotrophin requirements for the developing nervous system.
Regional Restriction of Alcohol/Retinol Dehydrogenases along the Mouse Gastrointestinal Epithelium (1997)

The gastrointestinal tract is a major site of alcohol dehydrogenase (ADH) activity in humans and rodents. Because class IADH (ADH-I) and class IV ADH (ADH-IV), but not class III ADH (ADH-III), function as retinol dehydrogenases in vitro and may thus participate in retinoid signaling needed for epithelial differentiation, the aim of this study was to determine the localization of these enzymes along the gastrointestinal tract. Specific antibodies were used to examine the tissue distribution of all three known classes of mouse ADH by Western blotting, and cellular localization was determined by immunohistochemistry. ADH-I was detected primarily in the intestine, liver, kidney, adrenal, and uterus, with detection of ADH-III in all tissues examined, and detection of ADH-IV primarily in the esophagus, stomach, adrenal, skin, ovary, and epididymis. Along the gastrointestinal tract, ADH-III was not specifically localized, whereas ADH-I was localized exclusively in the villus epithelium of the small intestine and absorptive epithelium of the large intestine, with ADH-IV being localized exclusively in the basal and suprabasal epithelial cells of the esophagus and gastric pit surface epithelium of the stomach. The ADH localization patterns observed are consistent with ADH-I and ADH-IV, but not ADH-III, functioning physiologically in retinol metabolism needed for epithelial differentiation. Our results further suggest that the functions of ADH-I and ADH-IV are regionally restricted to the lower and upper components, respectively, of the gastrointestinal epithelium, a finding that may relate to the different efficiencies of these two enzymes for retinol oxidation, as well as to the different susceptibilities of the upper and lower digestive tracts for ethanol-induced cancers.
Multilevel array decomposition algorithm for fast statistical characterization of conformal arrays in the presence of excitation errors (2009)

International audience