gebhart/patrepeval huggingface dataset:
A rapid, PCR based test for differential molecular diagnosis of Prader-Willi and Angelman syndromes. (1998)

Approximately 98% of Prader-Willi syndrome (PWS) and 80% of Angelman syndrome (AS) cases have deletions at a common region in chromosome 15q11-13, uniparental disomy for chromosomes 15 (UPD15), or mutations affecting gene expression in this region. The resulting clinical phenotype (PWS or AS) in each class of mutation depends upon the parent of origin. Both disorders are characterised at the molecular level by abnormal methylation of imprinted genes at 15q11-q13 including the small nuclear ribonucleoprotein N gene (SNRPN). Current diagnostic strategies include high resolution cytogenetics, fluorescence in situ hybridisation (FISH), Southern blot hybridisation, or microsatellite typing. We have developed a novel and rapid diagnostic test for PWS and AS based on differential digestion of expressed (paternally imprinted) SNRPN sequences by the methylation sensitive endonuclease NotI or repressed (maternally imprinted) SNRPN sequences by the methylation requiring nuclease McrBC, followed by PCR amplification of the SNRPN promoter. We have evaluated this test by blinded analysis of 60 characterised DNA samples (20 PWS, 20 AS, and 20 unaffected controls). SNRPN sequences could not be amplified from PWS patient DNA which had been digested with McrBC, nor from AS patient DNA which had been digested with NotI. We were able to make a correct diagnosis of PWS, AS, or unaffected in all 60 samples tested. This novel test is rapid and has a high specificity and sensitivity for deletion and UPD15 cases. These features make this new test suitable as the initial step in a molecular diagnostic strategy for PWS/AS.
A single external enzyme confers alternative NADH:ubiquinone oxidoreductase activity in Yarrowia lipolytica (1999)

NADH:ubiquinone oxidoreductases catalyse the first step within the diverse pathways of mitochondrial NADH oxidation. In addition to the energy-conserving form commonly called complex I, fungi and plants contain much simpler alternative NADH:ubiquinone oxido-reductases that catalyze the same reaction but do not translocate protons across the inner mitochondrial membrane. Little is known about the distribution and function of these enzymes. We have identified YLNDH2 as the only gene encoding an alternative NADH:ubiquinone oxidoreductase (NDH2) in the obligate aerobic yeast Yarrowia lipolytica. Cells carrying a deletion of YLNDH2 were fully viable; full inhibition by piericidin A indicated that complex I activity was the sole NADH:ubiquinone oxidoreductase activity left in the deletion strains. Studies with intact mitochondria revealed that NDH2 in Y. lipolytica is oriented towards the external face of the mitochondrial inner membrane. This is in contrast to the situation seen in Saccharomyces cerevisiae, Neurospora crassa and in green plants, where internal alternative NADH:ubiquinone oxidoreductases have been reported. Phylogenetic analysis of known NADH:ubiquinone oxidoreductases suggests that during evolution conversion of an ancestral external alternative NADH:ubiquinone oxidoreductase to an internal enzyme may have paved the way for the loss of complex I in fermenting yeasts like S. cerevisiae.
Digital Optical Logic Using A Pulsed Sagnac Interferometer Switch (1986)

The use of a new Sagnac interferometer switch (SIS) to perform digital optical logic is described. The optical logic switch consists of a Sagnac interferometer with an optical nonlinear material in its loop. Both the SIS input and output logic variables are optical pulses. The output SIS state is a function of the initial mirror alignment and the state of the inducing light beam. Using various SIS interconnections, all 16 two-variable binary logic functions can be implemented. Parallel logic processing of different logic functions can be performed using a single Sagnac interferometer. Since SIS elements are cascadable, sequential operation is also possible. As an example, an implementation of the SIS optical binary full adder is illustrated. If one input is a cw analog signal and another input is an ultrafast optical pulse train, the SIS can also be used as an ultrafast optical sampling device. Conditions for proper optical sampling frequency are presented.
Cloning, Sequencing, Heterologous Expression, Purification, and Characterization of Adenosylcobalamin-dependentd-Ornithine Aminomutase from Clostridium sticklandii (2001)

D-Ornithine aminomutase from Clostridium sticklandii catalyzes the reversible rearrangement of d-ornithine to (2R,4S)-2,4-diaminopentanoic acid. The two genes encoding d-ornithine aminomutase have been cloned, sequenced, and expressed in Escherichia coli. The oraS gene, which encodes a protein of 121 amino acid residues with M(r) 12,800, is situated upstream of the oraE gene, which encodes a protein of 753 amino acid residues with M(r) 82,900. The holoenzyme appears to comprise a alpha(2)beta(2)-heterotetramer. OraS shows no significant homology to other proteins in the Swiss-Prot data base. The deduced amino acid sequence of OraE includes a conserved base-off/histidine-on cobalamin-binding motif, DXHXXG. OraE was expressed in E. coli as inclusion bodies. Refolding experiments on OraE indicate that the interactions between OraS and OraE and the binding of either pyridoxal phosphate or adenosylcobalamin play important roles in refolding process. The K(m) values for d-ornithine, 5'-deoxyadenosylcobalamin (AdoCbl), and pyridoxal 5'-phosphate (PLP) are 44.5 +/- 2.8, 0.43 +/- 0.04, and 1.5 +/- 0.1 microm, respectively; the k(cat) is 6.3 +/- 0.1 s(-1). The reaction was absolutely dependent upon OraE, OraS, AdoCbl, PLP, and D-ornithine being present in the assay; no other cofactors were required. A red-shift in UV-visible absorption spectrum is observed when free adenosylcobinamide is bound by recombinant D-ornithine aminomutase and no significant change in spectrum when free adenosylcobinamide is bound by mutant OraE-H618G, demonstrating that the enzyme binds adenosylcobalamin in base-off/histidine-on mode.
Association of Testosterone, Insulin-Like Growth Factor-I, and C-Reactive Protein with Metabolic Syndrome in Chinese Middle-Aged Men with a Family History of Type 2 Diabetes (2005)

Clustering of FH, hormonal abnormalities, and high hs-CRP is associated with MES in Chinese middle-aged men.
A hard-core predicate for all one-way functions (1989)

A central tool in constructing pseudorandom generators, secure encryption functions, and in other areas are “hard-core” predicates b of functions (permutations) ƒ, discovered in [Blum Micali 82]. Such b(x) cannot be efficiently guessed (substantially better than 50-50) given only ƒ(x). Both b, ƒ are computable in polynomial time.
Macrophages prevent human red blood cell reconstitution in immunodeficient mice (2011)

An animal model supporting human erythropoiesis will be highly valuable for assessing the biologic function of human RBCs under physiologic and disease settings, and for evaluating protocols of in vitro RBC differentiation. Herein, we analyzed human RBC reconstitution in NOD/SCID or NOD/SCID/γc(-/-) mice that were transplanted with human CD34+ fetal liver cells and fetal thymic tissue. Although a large number of human CD45- CD71+ nucleated immature erythroid cells were detected in the bone marrow, human RBCs were undetectable in the blood of these mice. Human RBCs became detectable in blood after macrophage depletion but disappeared again after withdrawal of treatment. Furthermore, treatment with human erythropoietin and IL-3 significantly increased human RBC reconstitution in macrophage-depleted, but not control, humanized mice. Significantly more rapid rejection of human RBCs than CD47-deficient mouse RBCs indicates that mechanisms other than insufficient CD47-SIRPα signaling are involved in human RBC xenorejection in mice. All considered, our data demonstrate that human RBCs are highly susceptible to rejection by macrophages in immunodeficient mice. Thus, strategies for preventing human RBC rejection by macrophages are required for using immunodeficient mice as an in vivo model to study human erythropoiesis and RBC function.
Investigation on diversity and population succession dynamics of endophytic bacteria from seeds of maize (Zea mays L., Nongda108) at different growth stages (2012)

Plant seeds are carriers of both beneficial bacteria and pathogens. Using the 16S rRNA gene clone library technique, we conducted a preliminary study on the community diversity and population succession dynamics of endophytic bacteria in seeds of reciprocal cross hybrid maize at different seed developmental stages. In both hybrid lines (108A and 108B), more types of endophytic bacteria were found at the proembryo-forming stage than in the other two stages, including 29 and 23 bacterial operational taxonomic units (OTUs), respectively. Undibacterium (39.20 and 30.00 % in 108A and 108B, respectively) was the first dominant bacterium to appear. At the milky stage, fewer types of endophytic bacteria in 108A and 108B appeared, including 18 and 16 OTUs, respectively, and the abundance of the dominant genus Burkholderia in the two seed samples reached 73.38 and 80.43 %, respectively. Limnobacter appeared as the second and third endophytic dominant bacterium in 108A (4.55 %) and 108B (5.07 %), respectively, in both seed samples. At the dough stage, the abundance of the first dominant bacterium, Burkholderia, in 108A and 108B was 78.26 and 84.80 %, respectively. Pantoea appeared as the second endophytic dominant bacterium in the both seeds (9.42 and 4.80 % in 108A and 108B, respectively). This is the first study on endophytic bacteria present during several crucial stages of the dynamic grain growth process of plant seeds conducted using culture-independent methods.
PRELIMINARY VALIDITY OF “INTEGNEUROTM”: A NEW COMPUTERIZED BATTERY OF NEUROCOGNITIVE TESTS (2005)

The purpose of this study was to examine the preliminary validity of a newly developed battery of computerized cognitive measures, IntegNeuro. This standardized and semi-automated computerized battery assesses sensori-motor function, attention, new learning and memory, language fluency, executive function, and estimated intelligence. A total of 50 healthy individuals (aged 22-80 years) were included in the study. Correlational analyses revealed highly significant associations between the two cognitive batteries. These results support the use of IntegNeuro as a computerized cognitive system. Additional studies are needed to examine the clinical utility of the battery.
IL15 polymorphism is associated with advanced fibrosis, inflammation‐related biomarkers and virological response in human immunodeficiency virus/hepatitis C virus coinfection (2016)

The presence of IL15 rs10833 AA genotype in HIV-/HCV-co-infected patients was associated with advanced liver fibrosis, inflammation-related biomarkers and increased rates of SVR to pegIFN-alpha/RBV therapy.
Sequential Projection Pursuit Principal Component Analysis – Dealing with Missing Data Associated with New -Omics Technologies (2013)

Principal Component Analysis (PCA) is a common exploratory tool used to evaluate large complex data sets. The resulting lower-dimensional representations are often valuable for pattern visualization, clustering, or classification of the data. However, PCA cannot be applied directly to many -omics data sets generated by newer technologies such as label-free mass spectrometry due to large numbers of non-random missing values. Here we present a sequential projection pursuit PCA (sppPCA) method for defining principal components in the presence of missing data. Our results demonstrate that this approach generates robust and informative low-dimensional data representations compared to commonly used imputation approaches.
Comparison of Reagents for Determining the Activated Partial Thromboplastin Time (1978)

Six commercially available reagents for the determination of the activated partial thromboplastin time have been evaluated and compared with respect to their sensitivity to the coagulation factors VIII, IX and XI and to their response to heparin. Some variation was observed among the reagents regarding their sensitivity to factor XI and even greater differences were obtained with factors VIII and IX. It was also clear that none of the reagents was sensitive to the same extent to the factors tested. The sensitivity to heparin shows considerable variation, in terms of time as well as mode of response to increasing heparin levels. In four reagents this response is linear, it is logarithmic in one and the remaining one is yet again different. It seems unlikely that any standardization of the APTT determination is at present possible with the reagents studied.
Analysis of false alarm distributions in the development and evaluation of hyperspectral point target detection algorithms (2007)

We analyze the efficacy of various point target detection algorithms for hyperspectral data. We present a novel way to measure the discrimination capability of a target detection algorithm; we avoid being critically dependent on the particular placement of a target in the image by examining the overall ability to detect a target throughout the various backgrounds of the cube. We first demonstrate this approach by analyzing previously published algorithms from the literature; we then present two new dissimilar algorithms that are designed to eliminate false alarms on edges. Trade-offs between the probability of detection and false alarms rates are considered. We use our metrics to quantify the improved capability of the proposed algorithms over the standard algorithms.
Epstein–Barr virus vaccines (2015)

[This corrects the article DOI: 10.1038/cti.2014.27.].
Human pancreatic beta-like cells converted from fibroblasts (2016)

Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro. Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes.
Quantification of Cell-Free DNA in Normal and Complicated Pregnancies: Overcoming Biological and Technical Issues (2014)

The characterization of cell-free DNA (cfDNA) originating from placental trophoblast in maternal plasma provides a powerful tool for non-invasive diagnosis of fetal and obstetrical complications. Due to its placental origin, the specific epigenetic features of this DNA (commonly known as cell-free fetal DNA) can be utilized in creating universal 'fetal' markers in maternal plasma, thus overcoming the limitations of gender- or rhesus-specific ones. The goal of this study was to compare the performance of relevant approaches and assays evaluating the amount of cfDNA in maternal plasma throughout gestation (7.2-39.5 weeks). Two fetal- or placental-specific duplex assays (RPP30/SRY and RASSF1A/β-Actin) were applied using two technologies, real-time quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Both methods revealed similar performance parameters within the studied dynamic range. Data obtained using qPCR and ddPCR for these assays were positively correlated (total cfDNA (RPP30): R = 0.57, p = 0.001/placental cfDNA (SRY): R = 0.85, p<0.0001; placental cfDNA (RASSF1A): R = 0.75, p<0.0001). There was a significant correlation in SRY and RASSF1A results measured with qPCR (R = 0.68, p = 0.013) and ddPCR (R = 0.56, p = 0.039). Different approaches also gave comparable results with regard to the correlation of the placental cfDNA concentration with gestational age and pathological outcome. We conclude that ddPCR is a practical approach, adaptable to existing qPCR assays and well suited for analysis of cell-free DNA in plasma. However, it may need further optimization to surpass the performance of qPCR.
Imaging Mouse Retinal Ganglion Cells and Their Loss In Vivo by a Fundus Camera in the Normal and Ischemia-Reperfusion Model (2008)

purpose. To visualize retinal ganglion cells (RGCs) and their gradual loss in the living mouse. methods. With the use of B6.Cg-Tg(Thy1-CFP)23Jrs/J mice, which express cyan fluorescent protein (CFP) in RGCs, and a commercially available mydriatic retinal camera attached with a 5 million-pixel digital camera to visualize RGCs in vivo, the authors recorded fundus photographs longitudinally in the ischemia reperfusion model group and the untreated group to evaluate longitudinal changes in the number of RGCs in experimental models. Moreover, RGCs expressing CFP were evaluated histologically by a retrograde-labeling method and retinal whole mount or sections. results. The authors devised an in vivo imaging technique using a conventional retinal camera and visualized RGCs at the single-cell level. In the ischemia reperfusion model, a longitudinal reduction in the number of RGCs was demonstrated in each mouse eye. The number of RGCs and the fluorescence intensity of the nerve fiber decreased considerably during the first week. The percentages of RGCs decreased to 34.2% ± 7.5%, 24.1% ± 9.1%, 23.0% ± 9.3%, and 22.2% ± 8.4% (mean ± SD, n = 5) of the percentages before injury at 1, 2, 3, and 4 weeks after injury, respectively (P < 0.001). In this transgenic mouse, 97% of CFP-expressing cells were RGCs and 73% of RGCs expressed CFP. conclusions. This in vivo technique allows noninvasive, repeated, and longitudinal evaluation of RGCs for investigation of retinal neurodegenerative diseases and new therapeutic modalities for them.
Construction and characterization of Escherichia coli strains deficient in multiple secreted proteases: protease III degrades high-molecular-weight substrates in vivo (1991)

Protease III, the product of the ptr gene, is a 110-kDa periplasmic protease with specificity towards insulin and other low-molecular-weight substrates (less than 7,000 molecular weight) in vitro (Y.-S.E. Cheng and D. Zipser, J. Biol. Chem. 254:4698-4706, 1979). Escherichia coli strains deficient in protease III were constructed by insertional inactivation of the ptr gene. This mutation did not appear to affect the function of the adjoining recB and recC genes. Expression of protein A-beta-lactamase, a protease-sensitive secreted polypeptide, was increased approximately twofold in ptr cells. A comparable increase in the half-life of protein A-beta-lactamase was observed by pulse-chase experiments, suggesting that protease III is involved in the catabolism of high-molecular-weight substrates in vivo, ptr mutants exhibited no detectable phenotypic alterations except for a slight reduction in growth rate. When the ptr mutation was transferred to a strain deficient in the secreted protease DegP, a further decrease in growth rate, as well as an additive increase in the expression of the fusion protein, was observed. A ptr degP ompT mutant strain resulted in a further increase in expression in minimal medium but not in rich medium.
Size constraints for targeting post‐transcriptional gene silencing and for RNA‐directed methylation in Nicotiana benthamiana using a potato virus X vector (2001)

Using a recombinant potato virus X (PVX) vector, we investigated the relationship between the length of RNA sequence identity with a transgene and the ability to promote post-transcriptional gene silencing (PTGS) and transgene methylation. The lower size limit required for targeting reporter transgene mRNA de novo using PTGS was 23 nucleotides (nt) of complete identity, a size corresponding to that of small RNAs associated with PTGS in plants and RNA interference (RNAi) in animals. The size and sequence specificity were also explored for PTGS-associated transgene methylation and for the targeting of the vector RNA. The PTGS-competent short sequences resulted in similar patterns of methylation. In all cases, including specific sequences of 33 nt with or without symmetrical cytosine residues, the methylation was distributed throughout the transcribed region of the transgene. In contrast, short sequences lacking symmetrical cytosines were less efficient at promoting PTGS of the transgene mRNA. Short gfp sequences in the PVX vector provided as effective a target for the degradation of viral RNA as was found for PVX carrying the complete gfp cDNA. Short sequences were able to initiate PTGS of an endogenous gene, phyotene desaturase, although this occurred in the absence of DNA methylation. This experimental approach provides important insights into the relationship between short RNA sequences and PTGS.
Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation (2013)

Existing in vitro models of human intestinal function commonly rely on use of established epithelial cell lines, such as Caco-2 cells, which form polarized epithelial monolayers but fail to mimic more complex intestinal functions that are required for drug development and disease research. We show here that a microfluidic 'Gut-on-a-Chip' technology that exposes cultured cells to physiological peristalsis-like motions and liquid flow can be used to induce human Caco-2 cells to spontaneously undergo robust morphogenesis of three-dimensional (3D) intestinal villi. The cells of that line these villus structures are linked by tight junctions, and covered by brush borders and mucus. They also reconstitute basal proliferative crypts that populate the villi along the crypt-villus axis, and form four different types of differentiated epithelial cells (absorptive, mucus-secretory, enteroendocrine, and Paneth) that take characteristic positions similar to those observed in living human small intestine. Formation of these intestinal villi also results in exposure of increased intestinal surface area that mimics the absorptive efficiency of human intestine, as well enhanced cytochrome P450 3A4 isoform-based drug metabolizing activity compared to conventional Caco-2 cell monolayers cultured in a static Transwell system. The ability of the human Gut-on-a-Chip to recapitulate the 3D structures, differentiated cell types, and multiple physiological functions of normal human intestinal villi may provide a powerful alternative in vitro model for studies on intestinal physiology and digestive diseases, as well as drug development.
Intrauterine photoacoustic and ultrasound imaging probe (2018)

Intrauterine photoacoustic and ultrasound imaging are probe-based imaging modalities with translational potential for use in detecting endometrial diseases. This deep-tissue imaging probe design allows for the retrofitting of commercially available endometrial sampling curettes. The imaging probe presented here has a 2.92-mm diameter and approximate length of 26 cm, which allows for entry into the human endometrial cavity, making it possible to use photoacoustic imaging and high-resolution ultrasound to characterize the uterus. We demonstrate the imaging probes’ ability to provide structural information of an excised pig uterus using ultrasound imaging and detect photoacoustic signals at a radial depth of 1 cm.