gebhart/patrepeval huggingface dataset:
Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression. (1993)

The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are phenotypically female at birth. Two striking and unexplained features of this disorder are that external genitalia of affected males undergo virilization during puberty and that these individuals have less temporal hair regression. The tissue-specific and developmental expression patterns of the 5 alpha-reductase isozymes were investigated by immunoblotting. The type 1 isozyme is not detectable in the fetus, is transiently expressed in newborn skin and scalp, and permanently expressed in skin from the time of puberty. There was no qualitative difference in 5 alpha-reductase type 1 expression between adult balding vs. nonbalding scalp. The type 2 isozyme is transiently expressed in skin and scalp of newborns. Type 2 is the predominant isozyme detectable in fetal genital skin, male accessory sex glands, and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues. Both isozymes are expressed in the liver, but only after birth. These results are consistent with 5 alpha-reductase type 1 being responsible for virilization in type 2-deficient subjects during puberty, and suggest that the type 2 isozyme may be an initiating factor in development of male pattern baldness.
The identification of the weak oestrogen equol [7-hydroxy-3-(4′-hydroxyphenyl)chroman] in human urine (1982)

The identification (by gas chromatography-mass spectrometry and n.m.r.) for the first time of the weak oestrogen equol [7-hydroxy-3-(4'-hydroxyphenyl)chroman] in human urine is described. Preliminary results of its quantitative excretion in urine are reported and the potential significance of the occurrence of this compound is discussed.
Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated 195-kDa protein with a large regulatory domain. (1996)

The coding sequence of rat MEK kinase 1 (MEKK1) has been determined from multiple, independent cDNA clones. The cDNA is full-length based on the presence of stop codons in all three reading frames of the 5' untranslated region. Probes from the 5' and the 3' coding sequences both hybridize to a 7-kb mRNA. The open reading frame is 4.5 kb and predicts a protein with molecular mass of 161,225 Da, which is twice the size of the previously published MEKK1 sequence and reveals 801 amino acids of novel coding sequence. The novel sequence contains two putative pH domains, two proline-rich regions, and a cysteine-rich region. Antisera to peptides derived from this new sequence recognize an endogenous protein in human and rodent cells of 195 kDa, consistent with the size of the expressed rat MEKK1 clone. Endogenous and recombinant rat MEKK1 are enriched in membranes; little of either is found in soluble fractions. Expression of recombinant rat MEKK1 leads to activation of three mitogen-activated protein kinase modules in the order c-Jun N-terminal kinase/stress-activated protein kinase > p38 mitogen-activated protein kinase = extracellular signal-regulated kinase 2.
O-GlcNAc Transferase Is in a Functional Complex with Protein Phosphatase 1 Catalytic Subunits (2004)

A hallmark of signal transduction is the dynamic and inducible post-translational modification of proteins. In addition to the well characterized phosphorylation of proteins, other modifications have been shown to be regulatory, including O-linked beta-N-acetylglucosamine (O-GlcNAc). O-GlcNAc modifies serine and threonine residues on a myriad of nuclear and cytosolic proteins, and for several proteins there appears to be a reciprocal relationship between phosphorylation and O-GlcNAc modification. Here we report further evidence of this yin-yang relationship by demonstrating that O-GlcNAc transferase, the enzyme that adds O-GlcNAc to proteins, exists in stable and active complexes with the serine/threonine phosphatases PP1beta and PP1gamma, enzymes that remove phosphate from proteins. The existence of this complex highlights the importance of understanding the dynamic relationship between O-GlcNAc and phosphate in modulating protein function in many cellular processes and disease states such as Alzheimer's disease and type II diabetes.
Predicting initiation and termination of atrial fibrillation from the ECG (2007)

Atrial fibrillation is the most common cardiac arrhythmia, affecting more than two million people in the US. Several therapies for patients with atrial fibrillation are available, but methods to help physicians select the optimal therapy for an individual patient are still required. Knowledge of whether a patient with a normal ECG will exhibit atrial fibrillation in the future, as well as whether atrial fibrillation will terminate spontaneously, would be very useful in clinical routine. The paper presents a software system for predicting the initiation and termination of atrial fibrillation from the ECG. The algorithms have been validated on ECGs from several signal databases. Prediction of the initiation of atrial fibrillation was achieved by detecting premature heart beats and analyzing the morphology of their P waves. Prediction of the termination of atrial fibrillation was based on calculation of the major atrial frequency. This frequency has been shown to decrease significantly prior to the termination of atrial fibrillation. Nevertheless, the effect is much less distinct in the large data set used for this study compared to previous studies. The initiation of atrial fibrillation, however, could be correctly predicted in approximately 75% of the data analyzed.
In Vivo Analysis of Autophagy in Response to Nutrient Starvation Using Transgenic Mice Expressing a Fluorescent Autophagosome Marker (2003)

Macroautophagy mediates the bulk degradation of cytoplasmic components. It accounts for the degradation of most long-lived proteins: cytoplasmic constituents, including organelles, are sequestered into autophagosomes, which subsequently fuse with lysosomes, where degradation occurs. Although the possible involvement of autophagy in homeostasis, development, cell death, and pathogenesis has been repeatedly pointed out, systematic in vivo analysis has not been performed in mammals, mainly because of a limitation of monitoring methods. To understand where and when autophagy occurs in vivo, we have generated transgenic mice systemically expressing GFP fused to LC3, which is a mammalian homologue of yeast Atg8 (Aut7/Apg8) and serves as a marker protein for autophagosomes. Fluorescence microscopic analyses revealed that autophagy is differently induced by nutrient starvation in most tissues. In some tissues, autophagy even occurs actively without starvation treatments. Our results suggest that the regulation of autophagy is organ dependent and the role of autophagy is not restricted to the starvation response. This transgenic mouse model is a useful tool to study mammalian autophagy.
Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer. (1999)

Epithelial ovarian cancer (EOC) remains localized within the peritoneal cavity in a large number of patients, lending itself to i.p. approaches of therapy. In the present study, we investigated the effect of replication-selective herpes simplex virus-1 (HSV-1) used as an oncolytic agent against EOC and the use of human teratocarcinoma PA-1 as carrier cells for i.p. therapy. HSV-1716, a replication-competent attenuated strain lacking ICP34.5, caused a direct dose-dependent oncolytic effect on EOC cells in vitro. A single i.p. administration of 5 x 10(6) plaque-forming units resulted in a significant reduction of tumor volume and tumor spread and an increase in survival in a mouse xenograft model. PA-1 cells supported HSV replication in vitro and bound preferentially to human ovarian carcinoma surfaces compared with mesothelial surfaces in vitro and in vivo. In comparison with the administration of HSV-1716 alone, irradiated PA-1 cells, infected at two multiplicities of infection with HSV-1716 and injected i.p. at 5 x 10(6) cells/animal, led to a significant tumor reduction in the two models tested and the significant prolongation of mean survival in one model. Histological evaluation revealed extensive necrosis in tumor areas infected by HSV-1716. Immunohistochemistry against HSV-1 revealed areas of viral infection within tumor nodules, which persisted for several weeks after treatment. Administration of HSV-infected PA-1 carrier cells resulted in larger areas of tumor infected by the virus. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on EOC, which may be further enhanced by the utilization of a delivery system with carrier cells, based on amplification of the viral load and possibly on preferential binding of carrier cells to tumor surfaces.
A model for multi-perspective opinion inferences (2016)

A text might give rise to various projections: a writer, a text and a reader projection.Given the (proclaimed) factuality of a text, the overt or hidden attitudes between the various referents can be inferred, as well as the writers opinion and -given the reader's preferences -his or her perception of the whole.Moreover, some sentences might even indicate controversial topics if viewed from a common sense perspective.We introduce an approach based on Description Logics that integrates these various perspectives into a joint model.
Plasminogen Activator Inhibitor 1 Functions as a Urokinase Response Modifier at the Level of Cell Signaling and Thereby Promotes Mcf-7 Cell Growth (2001)

Plasminogen activator inhibitor 1 (PAI-1) is a major inhibitor of urokinase-type plasminogen activator (uPA). In this study, we explored the role of PAI-1 in cell signaling. In MCF-7 cells, PAI-1 did not directly activate the mitogen-activated protein (MAP) kinases, extracellular signal-regulated kinase (ERK) 1 and ERK2, but instead altered the response to uPA so that ERK phosphorylation was sustained. This effect required the cooperative function of uPAR and the very low density lipoprotein receptor (VLDLr). When MCF-7 cells were treated with uPA-PAI-1 complex in the presence of the VLDLr antagonist, receptor-associated protein, or with uPA-PAI-1(R76E) complex, which binds to the VLDLr with greatly decreased affinity, transient ERK phosphorylation (<5 min) was observed, mimicking the uPA response. ERK phosphorylation was not induced by tissue-type plasminogen activator-PAI-1 complex or by uPA-PAI-1 complex in the presence of antibodies that block uPA binding to uPAR. uPA-PAI-1 complex induced tyrosine phosphorylation of focal adhesion kinase and Shc and sustained association of Sos with Shc, whereas uPA caused transient association of Sos with Shc. By sustaining ERK phosphorylation, PAI-1 converted uPA into an MCF-7 cell mitogen. This activity was blocked by receptor-associated protein and not observed with uPA-PAI-1(R76E) complex, demonstrating the importance of the VLDLr. uPA promoted the growth of other cells in which ERK phosphorylation was sustained, including beta3 integrin overexpressing MCF-7 cells and HT 1080 cells. The MEK inhibitor, PD098059, blocked the growth-promoting activity of uPA and uPA-PAI-1 complex in these cells. Our results demonstrate that PAI-1 may regulate uPA-initiated cell signaling by a mechanism that requires VLDLr recruitment. The kinetics of ERK phosphorylation in response to uPAR ligation determine the function of uPA and uPA-PAI-1 complex as growth promoters.
Control of mucin-type O-glycosylation: A classification of the polypeptide GalNAc-transferase gene family (2011)

Glycosylation of proteins is an essential process in all eukaryotes and a great diversity in types of protein glycosylation exists in animals, plants and microorganisms. Mucin-type O-glycosylation, consisting of glycans attached via O-linked N-acetylgalactosamine (GalNAc) to serine and threonine residues, is one of the most abundant forms of protein glycosylation in animals. Although most protein glycosylation is controlled by one or two genes encoding the enzymes responsible for the initiation of glycosylation, i.e. the step where the first glycan is attached to the relevant amino acid residue in the protein, mucin-type O-glycosylation is controlled by a large family of up to 20 homologous genes encoding UDP-GalNAc:polypeptide GalNAc-transferases (GalNAc-Ts) (EC 2.4.1.41). Therefore, mucin-type O-glycosylation has the greatest potential for differential regulation in cells and tissues. The GalNAc-T family is the largest glycosyltransferase enzyme family covering a single known glycosidic linkage and it is highly conserved throughout animal evolution, although absent in bacteria, yeast and plants. Emerging studies have shown that the large number of genes (GALNTs) in the GalNAc-T family do not provide full functional redundancy and single GalNAc-T genes have been shown to be important in both animals and human. Here, we present an overview of the GalNAc-T gene family in animals and propose a classification of the genes into subfamilies, which appear to be conserved in evolution structurally as well as functionally.
Femtosecond laser-assisted deep anterior lamellar keratoplasty in phototherapeutic keratectomy versus the big-bubble technique in keratoconus (2018)

Patients with keratoconus treated with FSL-assisted DALK performed using the big-bubble technique fare better than treated with FSL-assisted DALK associated with PTK.
Cdc42 and RhoA have opposing roles in regulating membrane type 1-matrix metalloproteinase localization and matrix metalloproteinase-2 activation (2008)

Proteolysis of the basement membrane and interstitial matrix occurs early in the angiogenic process and requires matrix metalloproteinase (MMP) activity. Skeletal muscle microvascular endothelial cells exhibit robust actin stress fibers, low levels of membrane type 1 (MT1)-MMP expression, and minimal MMP-2 activation. Depolymerization of the actin cytoskeleton increases MT1-MMP expression and MMP-2 activation. Rho family GTPases are regulators of actin cytoskeleton dynamics, and their activity can be modulated in response to angiogenic stimuli such as vascular endothelial growth factor (VEGF). Therefore, we investigated their roles in MMP-2 and MT1-MMP production. Endothelial cells treated with H1152 [an inhibitor of Rho kinase (ROCK)] induced stress fiber depolymerization and an increase in cortical actin. Both MMP-2 and MT1-MMP mRNA increased, which translated into greater MMP-2 protein production and activation. ROCK inhibition rapidly increased cell surface localization of MT1-MMP and increased PI3K activity, which was required for MMP-2 activation. Constitutively active Cdc42 increased cortical actin polymerization, phosphatidylinositol 3-kinase activity, MT1-MMP cell surface localization, and MMP-2 activation similarly to inhibition of ROCK. Activation of Cdc42 was sufficient to decrease RhoA activity. Capillary sprout formation in a three-dimensional collagen matrix was increased in cultures treated with RhoAN19 or Cdc42QL and, conversely, decreased in cultures treated with dominant negative Cdc42N17. VEGF stimulation also induced activation of Cdc42 while inhibiting RhoA activity. Furthermore, VEGF-dependent activation of MMP-2 was reduced by inhibition of Cdc42. These results suggest that Cdc42 and RhoA have opposing roles in regulating cell surface localization of MT1-MMP and MMP-2 activation.
The Actions of Propofol on γ-Aminobutyric Acid-A and Glycine Receptors in Acutely Dissociated Spinal Dorsal Horn Neurons of the Rat (2002)

The spinal cord plays an important role in modulating anesthetic-induced suppression of nociceptive transmission. To gain some insight into the anesthetic mechanisms of propofol at the spinal level, we investigated the direct action of propofol and its modulation on the γ-aminobutyric acid-A receptor (GABAAR) and the glycine receptor (GlyR) in acutely dissociated rat spinal dorsal horn neurons by using whole-cell patch-clamp electrophysiology. Propofol induced Cl− currents (ICl), which were sensitive to bicuculline and, to a lesser extent, to strychnine. The activation, desensitization, and deactivation of propofol-induced ICl were slower than those of GABA- and glycine-induced ICl. In addition, this study revealed similar modulatory actions of propofol on GABAAR and GlyR. Propofol potentiated both GABA- and glycine-induced ICl at small con-centrations and inhibited both GABA- and glycine-induced ICl at large concentrations. The potentiation of propofol on ICl was caused by slowing current desensitization and deactivation, whereas the inhibition actions might be involved in the cross-desensitization between GABA- and propofol-induced ICl and the cross-inhibition between the GABAAR and GlyR. The results suggest that propofol facilitation of GABAAR and GlyR at the spinal level could contribute significantly to general anesthetic-induced analgesia and anesthesia.
Development of a sensitive multi-well colorimetric assay for active NFkappaB (2001)

The transcription factor nuclear factor kappaB (NFkappaB) is a key factor in the immune response triggered by a wide variety of molecules such as inflammatory cytokines, or some bacterial and viral products. This transcription factor represents a new target for the development of anti-inflammatory molecules, but this type of research is currently hampered by the lack of a convenient and rapid screening assay for NFkappaB activation. Indeed, NFkappaB DNA-binding capacity is traditionally estimated by radioactive gel shift assay. Here we propose a new DNA-binding assay based on the use of multi-well plates coated with a cold oligonucleotide containing the consensus binding site for NFkappaB. The presence of the DNA-bound transcription factor is then detected by anti-NFkappaB antibodies and revealed by colorimetry. This assay is easy to use, non-radioactive, highly reproducible, specific for NFkappaB, more sensitive than regular radioactive gel shift and very convenient for high throughput screening.
Risk Factor Analysis of Permanent Pacemaker Infection (2007)

Background. Several host- and procedure-related factors have been reported to increase the risk of permanent pacemaker (PPM) infection on the basis of descriptive analyses of case series. The purpose of this study is to assess the risk factors for PPM infection using case-control study methods.Methods. All patients who had a PPM implanted at our institution from January 1991 to December 2003 were retrospectively reviewed. Each patient who experienced a PPM infection was matched with 2 control subjects by age, sex, year of implantation, and duration of follow-up. Univariate and multivariable analyses were performed to identify significant risk factors for PPM infection.Results. Twenty-nine case patients and 58 control subjects met inclusion criteria. The majority (83%) of case patients presented with a pocket infection; a minority (10%) had PPM-related endocarditis. Staphylococcus species (69%) were the most common pathogens. On univariate analysis, previous PPM infection, malignancy, long-term corticosteroid use, multiple device revisions, a permanent central venous catheter, the presence of >2 pacing leads, and a lack of antibiotic prophylaxis at the time of PPM placement were associated with an increased risk of PPM infection. A multivariable logistic regression model identified long-term corticosteroid use (odds ratio [OR], 13.90; 95% confidence interval [CI], 1.27-151.7; P=.03) and the presence of >2 pacing leads versus 2 leads (OR, 5.41; 95% CI, 1.44-20.29; P=.01) as independent risk factors for PPM infection. In contrast, use of antibiotic prophylaxis prior to PPM implantation had a protective effect (OR, 0.087; 95% CI, 0.016-0.48; P=.005).Conclusions. These findings should assist clinicians in identifying patients who are at increased risk of PPM infection, as well as in developing strategies to minimize the modifiable risks.
siRNA-mediated knockdown of aryl hydrocarbon receptor nuclear translocator 2 affects hypoxia-inducible factor-1 regulatory signaling and metabolism in human breast cancer cells (2011)

Recent human studies found that the mRNA expression level of aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) was positively associated with the prognosis of breast cancer. In this study, we used small interfering RNA techniques to knockdown ARNT2 expression in MCF7 human breast cancer cells, and found that an almost 40% downregulation of ARNT2 mRNA expression increased the expression of sensitive to apoptosis gene (3.36-fold), and decreased the expression of von Hippel-Lindau (0.27-fold) and matrix metalloproteinase-1 (0.35-fold). The metabolite analysis revealed the contents of glucose, glycine, betaine, phosphocholine, pyruvate and lactate involved in the hypoxia-inducible factor (HIF)-1-dependent glycolytic pathway were significantly lower in cells treated with siARNT2. Our results suggested that ARNT2 might play an important role in the modulation of HIF-1-regulated signaling and metabolism.
A PHYSIOLOGICAL STUDY OF EPILEPTIC SEIZURES FOLLOWING CORTICAL STIMULATION IN ANIMALS AND ITS APPLICATION TO HUMAN CLINICS (1952)

1. Nicotinization (as well as picrotoxinization and metrazolization) applied to grey matters of the cerebral cortex, thalamus, midbrain, and cerebellar cortex produces selectively generalized clonic convulsion in dogs and apes; but that applied to the white matter or nerve causes no motor effects.2. By chemical stimulation and the method of elimination, the author confirmed the path of clonic convulsion as follows:thalamus (contralateral) thalamus (homolateral) Substantia nigra (contralateral) cerebrum→lenticular nuclei→Substantia nigra (homolateral)→(crossed)→anterior horn cell of spinal cord→skeletal muscle3. From the cerebellar cortex clonic convulsion was produced with or without cerebrum. The path passes through the thalamus to the lenticular nucleus, to the homolateral midbrain.4. After severing the lenticular nuclei of both sides, the clonic convulsion initiated in the cerebral cortex, thalamus, cerebellum or lenticular nucleus itself was completely abolished in dogs.5. Unitateral lenticotomy was applied to epileptic patients with partial success. Not only the fit of seizures, but also the fit of loss of consciousness was eradicated in successful cases. A very high cure rate is anticipated with bilateral lenticotomy.6. From the fact that cerebral clonic convulsion was produced in dogs in which the medullary pyramids had been severed, and that its path has several relay nuclei to the spinal cord, it must be considered that this system belongs to the extrapyramidal system.7. Some substances elicit tonic convulsions (TK) from the cerebrum and others alternating convulsions (LK). Thus the method of chemical stimulation can fractionate the action of the motor cells in experiments on the central nervous system, and elucidate the path of each system.
Multiple Functional Groups of Varying Ratios in Metal-Organic Frameworks (2010)

We show that metal-organic frameworks (MOFs) can incorporate a large number of different functionalities on linking groups in a way that mixes the linker, rather than forming separate domains. We made complex MOFs from 1,4-benzenedicarboxylate (denoted by "A" in this work) and its derivatives -NH2, -Br, -(Cl)2, -NO2, -(CH3)2, -C4H4, -(OC3H5)2, and -(OC7H7)2 (denoted by "B" to "I," respectively) to synthesize 18 multivariate (MTV) MOF-5 type structures that contain up to eight distinct functionalities in one phase. The backbone (zinc oxide and phenylene units) of these structures is ordered, but the distribution of functional groups is disordered. The complex arrangements of several functional groups within the pores can lead to properties that are not simply linear sums of those of the pure components. For example, a member of this series, MTV-MOF-5-EHI, exhibits up to 400% better selectivity for carbon dioxide over carbon monoxide compared with its best same-link counterparts.