gebhart/patrepeval huggingface dataset:
Bone Marrow-Derived Mesenchymal Stromal Cells Express Cardiac-Specific Markers, Retain the Stromal Phenotype, and Do Not Become Functional Cardiomyocytes In Vitro (2008)

Although bone marrow-derived mesenchymal stromal cells (MSCs) may be beneficial in treating heart disease, their ability to transdifferentiate into functional cardiomyocytes remains unclear. Here, bone marrow-derived MSCs from adult female transgenic mice expressing green fluorescent protein (GFP) under the control of the cardiac-specific alpha-myosin heavy chain promoter were cocultured with male rat embryonic cardiomyocytes (rCMs) for 5-15 days. After 5 days in coculture, 6.3% of MSCs became GFP(+) and stained positively for the sarcomeric proteins troponin I and alpha-actinin. The mRNA expression for selected cardiac-specific genes (atrial natriuretic factor, Nkx2.5, and alpha-cardiac actin) in MSCs peaked after 5 days in coculture and declined thereafter. Despite clear evidence for the expression of cardiac genes, GFP(+) MSCs did not generate action potentials or display ionic currents typical of cardiomyocytes, suggesting retention of a stromal cell phenotype. Detailed immunophenotyping of GFP(+) MSCs demonstrated expression of all antigens used to characterize MSCs, as well as the acquisition of additional markers of cardiomyocytes with the phenotype CD45(-)-CD34(+)-CD73(+)-CD105(+)-CD90(+)-CD44(+)-SDF1(+)-CD134L(+)-collagen type IV(+)-vimentin(+)-troponin T(+)-troponin I(+)-alpha-actinin(+)-connexin 43(+). Although cell fusion between rCMs and MSCs was detectable, the very low frequency (0.7%) could not account for the phenotype of the GFP(+) MSCs. In conclusion, we have identified an MSC population displaying plasticity toward the cardiomyocyte lineage while retaining mesenchymal stromal cell properties, including a nonexcitable electrophysiological phenotype. The demonstration of an MSC population coexpressing cardiac and stromal cell markers may explain conflicting results in the literature and indicates the need to better understand the effects of MSCs on myocardial injury. Disclosure of potential conflicts of interest is found at the end of this article.
Deflecting Adversarial Attacks with Pixel Deflection (2018)

CNNs are poised to become integral parts of many critical systems. Despite their robustness to natural variations, image pixel values can be manipulated, via small, carefully crafted, imperceptible perturbations, to cause a model to misclassify images. We present an algorithm to process an image so that classification accuracy is significantly preserved in the presence of such adversarial manipulations. Image classifiers tend to be robust to natural noise, and adversarial attacks tend to be agnostic to object location. These observations motivate our strategy, which leverages model robustness to defend against adversarial perturbations by forcing the image to match natural image statistics. Our algorithm locally corrupts the image by redistributing pixel values via a process we term pixel deflection. A subsequent wavelet-based denoising operation softens this corruption, as well as some of the adversarial changes. We demonstrate experimentally that the combination of these techniques enables the effective recovery of the true class, against a variety of robust attacks. Our results compare favorably with current state-of-the-art defenses, without requiring retraining or modifying the CNN.
STEROIDAL PURE ANTIOESTROGENS (1987)

The effects of some novel 7 alpha-alkyl amide analogues of oestradiol on the rat and mouse uterus have been measured. The compound ICI 164,384 [N-n-butyl-N-methyl-11-(3,17 beta-dihydroxyoestra-1,3,5(10)-trien-7 alpha-yl) undecamide] was entirely devoid of oestrogenic activity in the rat and mouse uterus but completely blocked the uterine stimulatory effects of oestradiol and of tamoxifen. Biological activity was confined to 7 alpha-isomers. The affinity of ICI 164,384 for the rat uterus oestrogen receptor (0.19) was substantially greater than that of tamoxifen (0.025 c.f. oestradiol = 1). The compound inhibited oestradiol-induced growth of ZR-71-1 cells in a dose-dependent manner in vitro. ICI 164,384 thus has the characteristics of a pure antagonist of oestrogen action.
The survival motor neuron protein in spinal muscular atrophy (1997)

The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non-SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.
HeLa cell adherence, actin aggregation, and invasion by nonenteropathogenic Escherichia coli possessing the eae gene (1991)

Enteropathogenic Escherichia coli (EPEC) produce diarrhea in humans by a mechanism that involves close adherence to epithelial cells in the intestine and colon. Close adherence is associated with effacement of microvilli and condensation of actin beneath the bacteria, a process termed attaching/effacing adherence. Attaching/effacing adherence of EPEC occurs in vitro in tissue culture, simplifying the study of the molecular genetics of this process. An EPEC gene (eae) necessary for attaching/effacing adherence was recently characterized. Enterohemorrhagic E. coli and the rabbit-specific RDEC-1 strain adhere in a like fashion in vivo and hybridize with eae. However, these strains adhere poorly to tissue culture cells, complicating the in vitro study of attaching/effacing adherence. In order to develop an in vitro model for the study of attaching/effacing activity of non-EPEC bacteria, a plasmid encoding the F1845 adhesin of an E. coli strain (C1845) isolated from a patient with diarrhea was transformed into RDEC-1 and enterohemorrhagic E. coli. The transformed strains adhered in a diffuse pattern to HeLa cells, and they aggregated HeLa cell actin at points of adherence in the fluorescein-isothiocyanate-labeled phalloidin assay. They also invaded HeLa cells in a gentamicin invasion assay, although not to the extent seen with EPEC. The construction of adherent non-EPEC strains facilitates the molecular study of the attaching/effacing properties and invasiveness of these strains in tissue culture models.
Silicon single-photon avalanche diodes with nano-structured light trapping (2017)

Silicon single-photon avalanche detectors are becoming increasingly significant in research and in practical applications due to their high signal-to-noise ratio, complementary metal oxide semiconductor compatibility, room temperature operation, and cost-effectiveness. However, there is a trade-off in current silicon single-photon avalanche detectors, especially in the near infrared regime. Thick-junction devices have decent photon detection efficiency but poor timing jitter, while thin-junction devices have good timing jitter but poor efficiency. Here, we demonstrate a light-trapping, thin-junction Si single-photon avalanche diode that breaks this trade-off, by diffracting the incident photons into the horizontal waveguide mode, thus significantly increasing the absorption length. The photon detection efficiency has a 2.5-fold improvement in the near infrared regime, while the timing jitter remains 25 ps. The result provides a practical and complementary metal oxide semiconductor compatible method to improve the performance of single-photon avalanche detectors, image sensor arrays, and silicon photomultipliers over a broad spectral range.The performance of silicon single-photon avalanche detectors is currently limited by the trade-off between photon detection efficiency and timing jitter. Here, the authors demonstrate how a CMOS-compatible, nanostructured, thin junction structure can make use of tailored light trapping to break this trade-off.
Optimization of immunofluorescence methods by quantitative image analysis. (1996)

There is a growing trend towards the objective quantification of immunohistochemical staining. However, quantification has not been used previously to optimize the original published immunohistochemical methods. We present a quantitative method for analyzing immunofluorescence staining employing the Applied Imaging MAGISCAN image analysis system, which has then been used to optimize major aspects of the standard immunofluorescent staining protocols. The optimization process resulted in a method that increased specific staining up to fivefold over typical published protocols, with no increase in nonspecific staining. The method is extremely reproducible. For slides stained by a single experimenter in one batch on one day, the coefficient of variation between replicate means is 1.2%. The image analysis protocol gave a linear response with increasing antigen concentration, as determined by using purified antigen dried onto slides. The revisions to the standard protocol presented here can also be applied to nonquantitative staining. It will help users of immunofluorescence to maximize their staining and may enable the detection of previously undetected antigens.
Inhibitory effect of fluvastatin on aortic intimal thickening in normocholesterolemic rabbits. (2000)

Proliferation of VSMC in the media and the migration to the intima can be inhibited, and apoptosis of VSMC be induced by short-term use of fluvastatin after balloon catheter denudation, independent of serum lipid change. The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.
The role of receptor tyrosine kinase inhibition in treating gastrointestinal malignancy (2003)

Tyrosine kinase receptors are proteins that transduce the signal from many growth factor and cytokine ligands to produce intracellular responses. As such they can activate multiple signalling cascade pathways and influence cell division, migration and survival. Many show upregulation in certain malignancies, including those of the gastrointestinal tract, and are thought to play key roles in carcinogenesis. This makes them attractive targets for drug therapy and in recent years many inhibitors have been developed. This review discusses the current situation regarding the development of inhibitors with particular reference to the erbB family, the insulin-like growth factor receptor, the Met receptor, the receptor for vascular endothelial growth factor and the Kit receptor. The evidence will be related back to cancers of the gut lumen. Clinical effectiveness in this area seems to lie in using a combinatorial approach that inhibits multiple key signalling points, and the reasons for this will be discussed.
Simulation of auditory analysis of pitch: An elaboration on the DWS pitch meter (1983)

A model was developed for estimating the pitch of complex sounds that are partially masked by background sound. Our ultimate aim is to obtain a model that can separate two simultaneous sounds on the basis of the harmonic structure of at least one of the sounds. The MDWS model is an extension of the Duifhuis, Willems, and Sluyter pitch meter (DWS) [J. Acoust. Soc. Am. 71, 1568-1580 (1982)] which is a practical implementation of Goldstein's optimum processor theory of pitch perception [J. Acoust. Soc. Am. 54, 1496-1516 (1973)]. The main modifications incorporated in MDWS consist of a more faithful modeling of auditory frequency analysis and of an alteration to the criterion used to decide which fundamental best fits a set of resolved components. Effects of the latter modification were investigated in a comparison between model estimates of the pitch of inharmonic complex signals and results obtained for humans. Furthermore, the accuracy of model estimates of the pitch of periodic signals (among which were synthesized vowel sounds), partially masked by noise, was compared with the just noticeable difference of fundamental frequency of these sounds for human observers. The results of these two tests show that the model estimates come close to human perception.
Kenya - export prospects and problems (2005)

This report examines reasons why Kenya and other African trade did not provide the engine of growth that it did elsewhere. During the last quarter century many Sub-Saharan African countries non-oil exports either declined in absolute terms, or expanded at a slower pace than world trade. Evidence suggests African countries, including Kenya, experienced serious supply constraints that limited their ability to capitalize on opportunities of international production sharing in foreign markets. Inappropriate governance policies, and a general unfavorable commercial environment, were largely responsible for Africa's supply problems. In addition, a decomposition of recent trade changes into supply and demand factors shows that, with two important exceptions (cut flowers and apparel exports) Kenya experienced a general erosion of its US and EU import market shares. These findings support the conclusion of the recent Africa Competitiveness Report that concludes Kenya is at a competitive disadvantage vis-a-vis more than one half the other African countries surveyed.
Origin of a T cell clone with a mismatched combination of MHC restriction and coreceptor expression. (1994)

Although the existence of a large number of CD8+ class II MHC-specific CTLs had long been noticed, the origin of such T cells with a discordant combination of specificity and phenotype has been a mystery in the positive selection model. Recent reports suggesting the independency of the positive selection of T cells from coreceptor-mediated signals raised a possibility that they might be the progeny of putative transitional, mismatched, single-positive cells appearing before positive selection as proposed in the stochastic/selective model. By developing transgenic mice carrying TCR alpha and beta chain genes of a CD8+ class II MHC Ag-specific allogeneic CTL clone QM11, the origin of such T cells with mismatched TCR specificity and coreceptor expression was studied. The results indicate that QM11 belongs to a conventional CD8+ T cell population whose maturation is dependent on a class I (or class I-like) MHC product. Consequently, the reactivity of QM11 to I-Ak can be considered to be an accidental cross-reaction.
Modification of non-protein thiols contents in transgenic tobacco plants producing bacterial enzymes of cysteine biosynthesis pathway. (2001)

Conditions of achieving the maximal accumulation of sulfhydryl metabolites in the leaves of tobacco were explored. Simultaneous production of bacterial O-acetylserine (thiol)-lyase and serine acetyltransferase resulted in the increased thiols contents as compared to single transformants and controls. However, leaf discs feeding experiments differently affected thiols concentration in different plant groups and suggested that the most promising strategy to obtain plants with a high level of non-protein thiol-containing compounds might be sulfate feeding to plants overproducing serine acetyltransferase.
15‐Deoxy‐Δ12,14‐PGJ2, but not troglitazone, modulates IL‐1β effects in human chondrocytes by inhibiting NF‐κB and AP‐1 activation pathways (2001)

The activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the production and the effects of proinflammatory cytokines. Since interleukin-1beta (IL-1beta) directly mediates cartilage degradation in osteoarthritis, we investigated the capability of PPARgamma ligands to modulate IL-1beta effects on human chondrocytes. RT-PCR and Western blot analysis revealed that PPARgamma expression was decreased by IL-1beta. 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), in contrast to troglitazone, was highly potent to counteract IL-1beta-induced cyclooxygenase-2 and inductible nitric oxide synthase expression, NO production and the decrease in proteoglycan synthesis. Western blot and gel-shift analyses demonstrated that 15d-PGJ2 inhibited NF-kappaB activation, while troglitazone was ineffective. Although 15d-PGJ2 attenuated activator protein-1 binding on the DNA, it potentiated c-jun migration in the nucleus. The absence or the low effect of troglitazone suggests that 15d-PGJ2 action in human chondrocytes is mainly PPARgamma-independent.
Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives:  Potent and Selective A2AAdenosine Antagonists (1996)

A series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives (10a-o,q,r), bearing alkyl and aralkyl chains on positions 7 and 8, were synthesized in the attempt to obtain potent and selective antagonists for the A(2A) adenosine receptor subtype. The compounds were tested in binding and functional assays to evaluate their potency for the A(2A) compared with the A1 adenosine receptor subtype. In binding studies in rat brain membranes, most of the compounds showed affinity for A(2A) receptors in the low nanomolar range with a different degree of A(2A) versus A1 selectivity. Comparison of N(7) (10a-d,h-o)- and N(8) (10e-g)-substituted pyrazolo derivatives indicates that N(7) substitution decreases the A1 affinity with the concomitant increase of A(2A) selectivity. Specifically, the introduction of a 3-phenylpropyl group at pyrazolo nitrogen in position 7 (101) increased significantly the A(2A) selectivity, being 210-fold, while the A(2A) receptor affinity remained high (Ki=2.4 nM). With regards to the affinity for A(2A) receptors, also the compound 10n, bearing in the 7-position a beta-morpholin-4-ylethyl group, deserves attention (Ki=5.6 nM) even though the A2A selectivity (84-fold) was not as high as that of 101. Conversely, the compound 10m (N(7)-4-phenylbutyl derivative) showed a remarkable selectivity (A1/a(2A) ratio = 129) associated with lower A(2A) affinity (Ki = 21 nM). In functional studies, most of the compounds examined reversed 5'-(N-ethylcarbamoyl) adenosine-induced inhibition of rabbit platelet aggregation inhibition which is a biological response mediated by the A2A receptor subtype. The compounds are potent and selective A2A antagonists which can be useful to elucidate the pathophysiological role of this adenosine receptor subtype. These compounds deserve to be further developed to assess their potential for treatment of neurodegenerative disorders such as Parkinson's disease.
Effect of blueberry feeding on plasma lipids in pigs (2007)

Two feeding trials were conducted with pigs to determine the effects of blueberry supplementation on plasma lipid levels and other indices of cardiovascular benefit. In the first trial, where basal diets contained a high level of plant-based components (70 % soya, oats and barley), supplementation with 1, 2 and 4 % blueberries resulted in a decrease in total, LDL- and HDL-cholesterol. The greatest reduction was observed in the 2 % blueberry-fed pigs, where total, LDL- and HDL-cholesterol were reduced 11.7, 15.1 and 8.3 %, respectively. In the second trial where basal diets contained only 20 % (w/w) of soya, oats and barley, the lipid-modulating effect of blueberries was attenuated, so that supplementation with 1.5 % blueberries reduced total cholesterol by 8 %, which occurred only in pigs whose diets had been supplemented with cholesterol (0.08 %), NaCl (0.11 %) and fructose (9 %). In the first feeding trial, blueberry supplementation had no effect on blood platelet activity. Blueberry supplementation also had no effect on the susceptibility of leucocyte DNA to oxidation in the first trial and no effect on the susceptibility of LDL to oxidation in the second trial. Results of these two feeding trials are discussed in relation to the effects of basal diet composition on lipid-modulating effects of blueberries.
DNA sequence-selective binding of head-to-tail linked bis-lexitropsins: relation of phasing to cytotoxic potency. (1993)

A series of polymethylene, -(CH2)n-tether-linked head-to-tail bislexitropsins (n = 1-7) have been synthesized in order to assess the effect on DNA binding of phasing, that arises because of lack of dimensional correspondence between oligopeptides and oligonucleotides. Binding constants to poly(dA-dT), estimated from ethidium displacement, are from 0.55 to 16.66 x 10(8) M-1. Comparable Ka values for calf thymus DNA and for poly(dG-dC) are approximately 10(6) and approximately 10(5) M-1, respectively reflecting the anticipated AT preference. Sequence-selective binding was examined by reflecting the anticipated AT preference. Sequence-selective binding was examined by methylethidium propyl ethylenediamine tetraacetic acid (MPE) complementary strand footprinting on an EcoRI/HindIII restriction fragment of pBR322 DNA with r = 0.08 and 0.32. Ligands bearing N-methylpyrrole dipeptide moieties linked by -(CH2)n, where n = 2, 4 or 6, give evidence of bidentate binding in (AT)n-rich sequences from footprinting at r = 0.32. By contrast, those ligands linked by (CH2)n, where n = 1, 3, 5 or 7, bind in a predominantly monodentate fashion. Cystostatic activity against KB human nasopharyngeal cancer cells has shown enhanced potency, compared with distamycin, for those linked bis-lexitropsins with n = 2, 4 and 6. That the increased potency may be attributed to more effective DNA binding in the latter cases is indicated by the fact that the n = 1, 3, 5 and 7 ligand homologues do not exhibit comparable enhanced cytotoxic potency.