gebhart/patrepeval huggingface dataset:
Regulation of Progesterone-Binding Breast Cyst Protein GCDFP-24 Secretion by Estrogens and Androgens in Human Breast Cancer Cells: A New Marker of Steroid Action in Breast Cancer* (1990)

We have previously demonstrated that androgens are potent inhibitors of breast cancer cell proliferation under both basal and estrogen-induced incubation conditions, while they suppress expression of the estrogen and progesterone receptors. To better understand the mechanisms responsible for the antagonism between androgens and estrogens in breast cancer and to obtain a new tumor marker for the actions of these two steroids, we have investigated the effects of androgens and estrogens on expression of the major protein found in human breast gross cystic disease fluid, namely GCDFP-24. This study was performed in ZR-75-1 and MCF-7 human breast cancer cells. After a 9-day incubation period, physiological concentrations of 17 beta-estradiol stimulated proliferation of ZR-75-1 and MCF-7 cells by 2- to 3.5-fold while simultaneously exerting a marked 70-90% inhibition of GCDFP-24 secretion. The estrogenic effects on GCDFP-24 secretion and cell proliferation were both competitively blocked by simultaneous incubation with the new steroidal pure antiestrogen EM-139. On the other hand, a maximal concentration (10 nM) of the nonaromatizable androgen dihydrotestosterone decreased by 50% the proliferation of ZR-75-1 cells; the half-maximal inhibitory effect was exerted at 0.01 nM. The androgen exerted a 3- to 4-fold stimulatory effect on GCDFP-24 secretion at an EC50 value of 0.01 nM. The effect of dihydrotestosterone on these parameters was competitively blocked by simultaneous incubation with the pure antiandrogen OH-flutamide. The present data show that the effects of estrogens and androgens in ZR-75-1 cells on GCDFP-24 secretion and cell growth are opposite. Similarly, in MCF-7 cells, estrogens stimulate cell growth, while GCDFP-24 secretion is inhibited. The present data also suggest that GCDFP-24 could well be a good biochemical marker for monitoring the response to androgenic and antiestrogenic compounds in the therapy of advanced breast cancer.
Detection of lipocortin 1 in human lung lavage fluid: lipocortin degradation as a possible proteolytic mechanism in the control of inflammatory mediators and inflammation. (1990)

Lipocortins are structurally related, glucocorticoid-inducible proteins that inhibit phospholipase A2 (PLA2), thereby reducing the liberation of arachidonic acid from phospholipids and so limiting the synthesis of eicosanoid inflammatory mediators. This study is the first demonstration of one lipocortin, lipocortin 1 (Lc 1; 37 kDa), in human lung lavage supernatants. In lavage fluid from healthy volunteers, a higher percentage (greater than 70%) of the detected Lc 1 was in its native form, compared to that from patients with abnormal lungs. In patients' lavage fluids, Lc 1 was more likely to be partially degraded (34 kDa). In abnormal bronchoalveolar lavage fluid (BALF), the more polymorphonuclear neutrophils (PMN)/lavage, the lower the proportion of Lc 1 in the native (37 kDa) form (n = 7 pairs, rs = -0.8214, p less than 0.05). Furthermore, when BALF cells were cultured and the harvested conditioned media incubated with pure human recombinant Lc 1, degradation of the 37 kDa form increased with the percentage of PMN (n = 10 pairs, s = -0.7200 after 1 hr; n = 6 pairs, rs = -0.9241 after 6 hr). These results suggest that factors released from the PMN are responsible for Lc 1 degradation in man. When recombinant human Lc 1 was incubated with human neutrophil elastase, the enzyme degraded Lc 1 in a dose-dependent way, suggesting that neutrophil elastase may be one such factor. Since PMNs are ubiquitous at sites of inflammation, it is possible that Lc 1 degradation is a permissive mechanism, which ensures that sufficient inflammation occurs to destroy the provocative stimulus. However, it is equally possible that, in some circumstances, the mechanism may be pathological and that the inactivation of Lc 1 leads to chronic, uncontrolled inflammation.
Two Independent Calcineurin-Binding Regions in the N-Terminal Domain of Murine NF-ATx1 Recruit Calcineurin to Murine NF-ATx1 (1999)

Intracellular calcium regulates events controlling nuclear translocation of nuclear factor of activated T cells (NF-AT). Calcium-dependent phosphatase calcineurin (CN) plays a central role in this process. Structural and functional analyses of the N-terminal domain of murine NF-ATx1, a member of the NF-AT family, have defined two distinct CN binding regions (CNBRs), CNBR1 and CNBR2, which are located in the region preceding the SP boxes of serine/proline-rich sequences and the region between the SP boxes and Rel similarity domain, respectively. The binding of murine NF-ATx1 (mNF-ATx1) to CN was abolished by deletion of these two regions, yet was unaffected by the individual deletion. In contrast, the nuclear translocation of mNF-ATx1 was much reduced when only CNBR2 was removed. Luciferase assay revealed that both regions are required for mNF-ATx1-dependent activation of the murine IL-2 promoter. Most importantly, recombinant CNBR2 bound CN with a higher affinity, and when expressed in Jurkat cells, it functioned as a dominant negative mutant that prevented the transcription driven by exogenous mNF-ATx1, probably by interfering with the function of CN. We propose that activation of mNF-ATx1 can be modulated through two distinct CN target regions. Our findings provide a new opportunity for pharmacological intervention with Ca2+-dependent signaling events.
Arthrobacter aurescens TC1 Metabolizes Diverse s -Triazine Ring Compounds (2002)

Arthrobacter aurescens strain TC1 was isolated without enrichment by plating atrazine-contaminated soil directly onto atrazine-clearing plates. A. aurescens TC1 grew in liquid medium with atrazine as the sole source of nitrogen, carbon, and energy, consuming up to 3,000 mg of atrazine per liter. A. aurescens TC1 is metabolically diverse and grew on a wider range of s-triazine compounds than any bacterium previously characterized. The 23 s-triazine substrates serving as the sole nitrogen source included the herbicides ametryn, atratone, cyanazine, prometryn, and simazine. Moreover, atrazine substrate analogs containing fluorine, mercaptan, and cyano groups in place of the chlorine substituent were also growth substrates. Analogs containing hydrogen, azido, and amino functionalities in place of chlorine were not growth substrates. A. aurescens TC1 also metabolized compounds containing chlorine plus N-ethyl, N-propyl, N-butyl, N-s-butyl, N-isobutyl, or N-t-butyl substituents on the s-triazine ring. Atrazine was metabolized to alkylamines and cyanuric acid, the latter accumulating stoichiometrically. Ethylamine and isopropylamine each served as the source of carbon and nitrogen for growth. PCR experiments identified genes with high sequence identity to atzB and atzC, but not to atzA, from Pseudomonas sp. strain ADP.
Branched-DNA Assay for Detection of the mecA Gene in Oxacillin-Resistant and Oxacillin-Sensitive Staphylococci (1998)

The identification of methicillin-resistant staphylococcus isolates in the clinical laboratory has typically been performed by using methods that detect phenotypic expression of resistance determinants. However, these methods may be difficult to interpret and some isolates do not express resistance until selective pressure is administered. Assays that detect genetic determinants are not subject to these limitations and have been effective in distinguishing isolates that are capable of expressing the resistance phenotype. In this study, a novel branched-DNA (bDNA) hybridization assay was used to test for the mecA gene in 416 clinical staphylococcal isolates. The results were compared with those obtained by a PCR-based assay and oxacillin disk diffusion. For 155 Staphylococcus aureus and 261 coagulase-negative Staphylococcus isolates, the bDNA assay and PCR results were 100% concordant. Among the S. aureus isolates, 20 were MecA+ and 135 were MecA-. For the coagulase-negative staphylococci, 150 were MecA+ and 111 were MecA-. The results from the genotypic detection methods were compared with those obtained by oxacillin disk diffusion. No discrepancies were detected among the S. aureus isolates; however, 10 coagulase-negative isolates were MecA+ but oxacillin sensitive and 1 isolate was MecA- but oxacillin resistant. Oxacillin resistance was induced in 6 of the 10 MecA+ isolates previously classified as oxacillin sensitive. These results suggest that the bDNA method described here is a sensitive and efficient method for detection of methicillin resistance in staphylococci and that genetic detection methods may be useful for detection of potential methicillin resistance in the clinical laboratory.
The control of electromagnetic scattering by impedance loading (1965)

Electromagnetic scattering from a conducting object can be controlled by loading portions of its surface with distributed or lumped impedances. The scattered field from a loaded object is expressed as a superposition of fields scattered by the unloaded object and fields reradiated by the loading. The interference of these fields can be used to produce the required scatter control. Techniques for evaluating the reradiated field are discussed. A general form for the scattered field as a function of load impedance is shown, and techniques for studying this form are discussed. Theoretical and experimental results for thin, impedance loaded dipoles are compared. For dipole lengths not much greater than λ/2, broadside backscatter can be reduced 30 to 40 dB with a passive center load. Greater lengths and other aspects require multiple passive loads. Backscatter reduction of up to 20 dB has been reported for thick dipoles at broadside incidence, planar surfaces at normal incidence, and long thin objects near end-on incidence.
Potential for genetic manipulation of mammals. (1989)

The development of a new mammalian genetics in which specifically designed gene alterations of pre-existing endogenous genetic loci may be achieved via tissue culture of stem cells is described. At present this technology is rapidly emerging for mice by gene targeting in cultured embryonic stem cells, isolation of the desired cell clone and re-constitution of germ-line chimaeric animals. Results to date and strategies for gene targeting and isolation of the required cell clones are discussed. This new genetic technology is likely to have a major impact both in genetic studies and, especially if it can be extended to larger mammalian species, in practical applications.
Early findings from a community‐based, cluster‐randomized, controlled oral cancer screening trial in Kerala, India (2000)

BACKGROUND.Oral cancer satisfies the criteria for a suitable disease for screening, and oral visual inspection is a suitable test for oral cancer screening.The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated.The authors describe a cluster-randomized, controlled oral cancer screening trial in southern India and its early results. METHODS.Apparently healthy subjects age 35 years or older in 13 clusters called panchayaths were randomized to either an intervention group (n ϭ 7) or a control group (n ϭ 6).Subjects in the intervention group will receive 3 rounds of screening consisting of oral visual inspection by trained health workers at 3-year intervals.The first round of screening was carried out between October 1995 and May 1998.Participants were visited in their homes and interviewed for sociodemographic details, tobacco-smoking and alcohol-drinking habits, and personal medical history.Those with tobacco or alcohol habits were advised to stop those habits.Subjects in the intervention group were offered screening, and those with lesions suggestive of oral leukoplakia, submucous fibrosis, or oral cancer were referred for examination by physicians.Confirmed leukoplakias were excised whenever possible, others were kept on follow-up, and those with confirmed oral cancers were referred for treatment.Data on oral cancer incidence, stage distribution, survival, and mortality in the study groups are obtained by record linkage with the Trivandrum population-based cancer registry and municipal death registration systems. RESULTS.There were 59,894 eligible subjects in the intervention group and 54,707 in the control group; 31.4% of the former group reported no tobacco or alcohol habits, compared with 44.1% of the latter.The distribution of age, education, occupation, income, and socioeconomic status were similar in the two groups.Of 3585 subjects in the intervention group referred, 52.4% were examined by physicians; 36 subjects with oral cancers and 1310 with oral precancers were diagnosed.Of the 63 oral cancers recorded in the cancer registry, 47 were in the intervention group and 16 were in the control group, yielding incidence rates of 56.1 and 20.3 per 100,000 person-years in the intervention and control groups, respectively.The program sensitivity for detection of oral cancer was 76.6% and the specificity 76.2%; the positive predictive value was 1.0% for oral cancer.In the intervention group, 72.3% of the cases were in Stages IϪII, as opposed to 12.5% in the control 664
Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets (2002)

In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to pancreatic beta cells, causing impaired insulin secretion. IL-1beta is a proinflammatory cytokine acting during the autoimmune process of type 1 diabetes. IL-1beta inhibits beta cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor NF-kappaB. Recently, we have shown that increased glucose concentrations also induce Fas expression and beta cell apoptosis in human islets. The aim of the present study was to test the hypothesis that IL-1beta may mediate the deleterious effects of high glucose on human beta cells. In vitro exposure of islets from nondiabetic organ donors to high glucose levels resulted in increased production and release of IL-1beta, followed by NF-kappaB activation, Fas upregulation, DNA fragmentation, and impaired beta cell function. The IL-1 receptor antagonist protected cultured human islets from these deleterious effects. beta cells themselves were identified as the islet cellular source of glucose-induced IL-1beta. In vivo, IL-1beta-producing beta cells were observed in pancreatic sections of type 2 diabetic patients but not in nondiabetic control subjects. Similarly, IL-1beta was induced in beta cells of the gerbil Psammomys obesus during development of diabetes. Treatment of the animals with phlorizin normalized plasma glucose and prevented beta cell expression of IL-1beta. These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1beta/NF-kappaB pathway as a target to preserve beta cell mass and function in this condition.
Working‐memory fMRI reveals cingulate hyperactivation in euthymic major depression (2008)

While cognitive impairments are well documented for the acute episode of major depressive disorder (MDD), less is known about cognitive functioning in the euthymic state. For working memory, dysfunctional activation of lateral prefrontal and cingulate cortex has been reported in the acute episode. This study investigates working-memory function and its neurobiological correlate in euthymic MDD patients, particularly whether dysfunctional activation persists when depressive symptoms improve. We investigated 56 subjects with functional magnetic resonance imaging (fMRI) at 3 Tesla. To challenge working-memory function, a classical verbal n-back task (0-, 1-, and 2-back) was used in 28 well-characterized, euthymic, unipolar MDD patients and 28 healthy control subjects matched according to age, sex, and educational level. Data were analyzed using SPM5. In the absence of significant behavioral differences, we observed comparable overall patterns of brain activation in both groups. As expected, both groups showed stronger activation of the typical working-memory network with increasing memory load. However, significant hyperactivation of the cingulate cortex was observed in euthymic patients, while lateral prefrontal activation was comparable between patients and controls. Working-memory challenge in the euthymic state of MDD revealed a dissociation of lateral prefrontal and cingulate brain function. Cingulate function, which is important for both emotional and cognitive processing and their integration, is still abnormal when mood is restored. This could reflect a different speed of normalization in prefrontal and limbic cortices, persistent systematic changes in neuronal networks after an episode of MDD, or a compensatory mechanism to maintain working-memory performance.
A possible role for Ca2+-ATPase in human sperm capacitation (1994)

Mammalian spermatozoa require extracellular Ca2+, some of which must be internalized, to undergo capacitation and acrosomal exocytosis. The mechanisms controlling the intracellular Ca2+ concentration are unclear, but current evidence suggests that a Ca(2+)-ATPase may be involved. Using treatments that potentially modulate enzyme activity, we investigated this possibility in human spermatozoa; the capacitation state and acrosomal integrity were monitored by chlortetracycline fluorescence. Incubation of cells in the presence of quercetin, a Ca(2+)-ATPase inhibitor, significantly accelerated the transition from the uncapacitated F pattern of chlortetracycline fluorescence to the capacitated, acrosome-intact B pattern within 1 h. This was followed by an increase in the number of cells displaying the capacitated, acrosome-reacted AR pattern. Since most Ca(2+)-ATPases in somatic cells are sensitive to calmodulin, we also investigated the effect of the calmodulin antagonist W-7 on chlortetracycline patterns. At 1-125 mumol l-1, W-7 significantly stimulated capacitation and acrosomal exocytosis. Furthermore, W-7 at 1 mumol l-1 proved to be more effective than W-5, a less potent antagonist, suggesting that the observed responses in human spermatozoa did reflect a calmodulin-sensitive mechanism. When the glucose concentration in the culture medium was varied (from 0 to 5.56 mmol l-1) to alter the availability of ATP for enzyme activity, it was found that a reduced concentration of glucose promoted capacitation more rapidly than did the standard concentration of 5.56 mmol glucose l-1. However, maximal changes, particularly in promoting the shift from the B to the AR pattern of chlortetracycline fluorescence, required millimolar concentrations of glucose during the last few minutes before assessment. Finally, the addition of partially purified mouse sperm decapacitation factor (proposed to activate a Ca(2+)-ATPase and thus maintain a low intracellular Ca2+ concentration) to capacitated human sperm suspensions caused a significant reversal in the capacitation state of cells (from the B to the F pattern). The F pattern of chlortetracycline fluorescence predominates in conditions favouring low concentrations of intracellular Ca2+. From these results, we suggest that a Ca(2+)-ATPase may play an important role during human sperm capacitation. A time-dependent decrease in endogenous enzyme activity would allow the intracellular concentration of Ca2+ to rise to a critical value necessary for initiation acrosomal exocytosis and subsequent successful fertilization.
Ceramic-Based Nanoparticles Entrapping Water-Insoluble Photosensitizing Anticancer Drugs:  A Novel Drug−Carrier System for Photodynamic Therapy (2003)

A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drug-carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter approximately 30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.
GANs Trained by a Two Time-Scale Update Rule Converge to a Nash Equilibrium (2017)

Generative Adversarial Networks (GANs) excel at creating realistic images with complex models for which maximum likelihood is infeasible. However, the convergence of GAN training has still not been proved. We propose a two time-scale update rule (TTUR) for training GANs with stochastic gradient descent on arbitrary GAN loss functions. TTUR has an individual learning rate for both the discriminator and the generator. Using the theory of stochastic approximation, we prove that the TTUR converges under mild assumptions to a stationary local Nash equilibrium. The convergence carries over to the popular Adam optimization, for which we prove that it follows the dynamics of a heavy ball with friction and thus prefers flat minima in the objective landscape. For the evaluation of the performance of GANs at image generation, we introduce the Frechet Inception Distance (FID) which captures the similarity of generated images to real ones better than the Inception Score. In experiments, TTUR improves learning for DCGANs and Improved Wasserstein GANs (WGAN-GP) outperforming conventional GAN training on CelebA, CIFAR-10, SVHN, LSUN Bedrooms, and the One Billion Word Benchmark.
Zur Kenntnis homologer Alkohole der Terpen‐ und Sesquiterpenreihe X. Synthese Des (+)‐3‐Hydroxymethyl‐Δ4‐Carens (1958)

Abstract Es wird die Synthese des (+)‐3‐Hydroxymethyl‐Δ 4 ‐carens (II) durch säurekatalysierte Addition von (+)‐Δ 3 ‐Caren (I) an Formaldehyd beschrieben. Die katalytische Hydrierung von II führt zum (‐)‐3‐Hydroxymethylcaran (III), das als Ausgangsmaterial für Synthesen in der Caran‐Reihe verwendet wird. Es werden die IR‐Spektren der neuen Verbindungen angegeben und die Zuordnungsmöglichkeiten von Absorptionsbanden zum vollständig substituierten Cyclopropanring diskutiert.