gebhart/patrepeval huggingface dataset:
Relation between aberrant α-catenin expression and loss of E-cadherin function in prostate cancer (1997)

It is now well documented that E-cadherin expression correlates inversely with tumor grade in various carcinomas including prostate cancer. We also demonstrated a statistically significant correlation between decreased E-cadherin expression and progression-free period in early stage patients treated by radical prostatectomy and decreased survival in patients with advanced stage disease. We now study the relationship between E cadherin and alpha-catenin expression, because in prostate cancer cell lines, mutational inactivation of the alpha-catenin gene can be the cause of the impaired E-cadherin function. Twenty patients treated by radical prostatectomy and 32 advanced stage patients were evaluated immunohistochemically for E-cadherin and alpha-catenin expression. The results were related to tumor grade and disease progression. Four patients in the radical prostatectomy group had aberrant E-cadherin and alpha-catenin expression and showed disease progression. The other 16 patients were free of progression and had normal E-cadherin and alpha-catenin expression. In the advanced stage group, 4 of 13 patients with normal E-cadherin staining showed aberrant alpha-catenin expression and 2 patients (50%) progressed, compared with only 22% progression in patients with both normal E-cadherin and alpha-catenin expression. The other 19 patients with aberrant E-cadherin and alpha-catenin staining had the poorest prognosis. Our results suggest that loss of alpha-catenin expression could be one of the mechanisms responsible for the loss of E-cadherin-mediated cell-cell adhesion in human prostate cancer and might in some cases provide prognostic information.
De Novo Adipose Tissue Generation through Long-Term, Local Delivery of Insulin and Insulin-Like Growth Factor-1 by PLGA/PEG Microspheres in an in Vivo Rat Model: A Novel Concept and Capability (2000)

This study was undertaken to characterize the duration of long-term growth factor delivery by poly(lactic-co-glycolic-acid)-polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long-term delivery of insulin and insulin-like growth factor-1 (IGF-1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF-1, separately, were produced by a double-emulsion solvent-extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin-containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF-1, insulin + IGF-1, and blank microspheres) (n = 4). Insulin and IGF-1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4-week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF-1, and insulin + IGF-1 microspheres. Such islands were not seen in the blank microsphere group. Hematoxylin and eosin-stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil-Red-O stained sections demonstrated that these cells contained lipid. Computer-aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of "ectopic" adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long-term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long-term local insulin and IGF-1 to induce adipogenic differentiation to mature lipid-containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks.
FK506, An Immunosuppressant Targeting Calcineurin Function (2000)

The macrolactam natural product, FK506 (Tacrolimus), acts as a powerful and clinically useful immnosuppressant through disruption of signaling events mediated by the calcium-dependent serine/threonine protein phosphatase, calcineurin (CaN), in T lymphocytes. Its mechanism of action involves the formation of a molecular complex with the intracellular FK506-binding protein-12 (FKBP12), thereby acquiring the ability to interact with CaN and to interfere with its access to and dephosphorylation of various substrates. Among the CaN substrates whose activity is altered by FK506, the nuclear factors of activated T cells (NFAT), a family of transcription factors regulating lymphokine gene expression, have been shown to play a prominent role in FK506-induced immunosuppression. Over the past few years, additional members of the FKBP and NFAT families of proteins have been identified, providing further insights into the complexity of FK506 biological effects. Furthermore, it has become clear that, predominantly as a result of CaN inhibition, FK506 alters multiple biochemical processes in a variety of cells besides lymphocytes. This may account for the adverse side effects of the drug, including neurotoxicity and nephrotoxicity. Extensive medicinal chemistry efforts have been devoted to the generation of analogs of FK506 with the hope of identifying compounds with an improved therapeutic index, that could have broader therapeutic utility than the parent drug. These efforts yielded several compounds with unique biochemical attributes, showing evidence for a dissociation between immunosuppressive and toxic properties, which may pave the way towards designing safer FK506-related immunosuppressants.
Short-Term Results of Intravitreal Bevacizumab for Macular Edema with Retinal Vein Obstruction and Diabetic Macular Edema (2007)

An intravitreal bevacizumab injection for ME caused by RVO and DME was safe and effective for improving visual acuity and reducing CRT.
Magnetic Nanoparticle-Enhanced Biosensor Based on Grating-Coupled Surface Plasmon Resonance (2011)

A highly sensitive surface plasmon resonance (SPR) biosensor employing magnetic nanoparticle (MNP) assays is presented. In the reported approach, MNPs simultaneously served as "vehicles" for rapid delivery of target analyte from a sample to the sensor surface and as labels increasing the measured refractive index changes that are associated with the binding of target analyte. An optical setup based on grating-coupled surface plasmon resonance (GC-SPR) was used with a magnetic field gradient applied through the sensor chip for manipulating with MNPs on its surface. Iron oxide MNPs and a sensor surface with metallic diffraction grating were modified with antibodies that specifically recognize different epitopes of the analyte of interest. The sensitivity of the biosensor was investigated as a function of mass transport of the analyte to the sensor surface driven by diffusion (free analyte) or by the magnetic field gradient (analyte bound to MNPs). Immunoassay-based detection of β human chorionic gonadotropin (βhCG) was implemented to evaluate the sensitivity of the MNP-enhanced GC-SPR biosensor scheme. The results reveal that the sensitivity of βhCG detection was improved by 4 orders of magnitude compared with the regular SPR sensor with direct detection format, and a limit of detection below pM was achieved.
Oncolytic Adenoviral Mutants with E1B19K Gene Deletions Enhance Gemcitabine-induced Apoptosis in Pancreatic Carcinoma Cells and Anti-Tumor Efficacy In vivo (2009)

Our data suggest that oncolytic mutants lacking the antiapoptotic E1B19K gene can improve efficacy of DNA-damaging drugs such as gemcitabine through convergence on cellular apoptosis pathways. These findings imply that less toxic doses than currently practiced in the clinic could efficiently target pancreatic adenocarcinomas when combined with adenoviral mutants.
Detection of cancer cells in the blood by FACS sorting of CD45- cells. (1998)

We describe a simple and sensitive method for detection of low number of cancer cells in the blood. The method is based on FACS sorting of leukocytes labelled with anti-CD45 monoclonal antibody and examining CD45- cells by conventional cytology and immunostaining for cytokeratin 18. In a model study, cancer cells seeded at the frequency of 1 per 106 and 1 per 107 leukocytes were detected in CD45- population. Sensitivity of this method was comparable to reverse transcription polymerase chain reaction (RT-PCR) used for detection of cancer cells expressing CD44 variants-mRNA. In a pilot study, cancer cells were also isolated from the blood of some patients with locally advanced gastric cancer. This method may be useful for detection of circulating tumour cells in cancer patients.
Automated Percutaneous Discectomy (1991)

Automated percutaneous discectomy is a new, safe procedure for treating herniated lumbar discs still contained by the annulus or posterior longitudinal ligament. In 1985, one of the authors reported a percutaneous nucleus aspiration technique using a 2-mm aspiration probe. This small probe produced minimal tissue damage, allowing the procedure to be done on an outpatient. In this series, 518 patients were treated using this technique for an overall success rate of 85%. Compensation patients, elderly patients, and patients with previous surgery were treated successfully using percutaneous discectomy on an outpatient basis. No intraoperative or postoperative complications occurred.
Arzneimittelwirkungen – Lehrbuch der Pharmakologie und Toxikologie (2008)

Wissenschaftliche Verlagsgesellschaft mbH Stuttgart. 9. vollständig neu bearbeitete und erweiterte Auflage 2008 360 Abbildungen, 264 Tabellen und 1357 Strukturformeln. 68,50 EUR
HRG4 (UNC119) mutation found in cone-rod dystrophy causes retinal degeneration in a transgenic model. (2000)

HRG4, the only synaptic protein known to be highly enriched in photoreceptor ribbon synapses, is now shown to be pathogenic when mutated.
Redox‐Based Resistive Switching Memories – Nanoionic Mechanisms, Prospects, and Challenges (2009)

This review article introduces resistive switching processes that are being considered for nanoelectronic nonvolatile memories. The three main classes are based on an electrochemical metallization mechanism, a valence change mechanism, and a thermochemical mechanism, respectively. The current understanding of the microscopic mechanisms is discussed and the scaling potential is outlined..
Human-Human Monoclonal Antibody Directed Against Tumor Surface Antigen in the Treatment of Human Malignancy (1991)

Eighteen patients with a variety of refractory solid tumors received infusions of IgM class monoclonal antibody directed against tumor surface antigen and raised in a nonviral transformed human-human system. Three other patients with refractory hematologic or solid tumors had autologous marrow purged with antibody, regrown, and reinfused following high dose chemotherapy. A molecular weight of 200,000 was demonstrated for the whole antibody produced by the fusion line. Each antibody failed to react with nonspecific tumor tissue. No fetal antigen reactivity was noted. Antibody was cytotoxic. Complement dependence was not demonstrated. Chloroquine phosphate pretreatment was employed prior to each antibody infusion to block receptor recycling and host-antigen processing. Antibody dose was doubled with each treatment. Self-limiting chill and fever (with tachycardia) was noted in 12-hour infusions. Tumor biopsy following infusion demonstrated good binding for as long as 48 hours after dosing. Tumor regression was noted during infusions. Pulmonary metastases responded rapidly following infusion. Maximal shrinkage of skin metastases was noted at 4 days with some regrowth at 7 days. Reduction in size of liver metastases was the most durable response. Responses correlated with survival. There were no antibody-related deaths. Antibody used ex vivo to purge autologous bone marrow-cleared marrow of tumor. Marrow engraftment was noted between 7 and 21 days. Follow-up showed no antihuman antibody formation, alteration in renal or hepatic function, alteration in thyroid or adrenal function, or circulating antigen-antibody complexes. Natural killer cell activity and complement-activated clearing of immune complexes increased following infusion. The time for complete clearing of immune complexes from the circulation was 10 days. Mild anemia was seen after several courses of infusion. Reticulocytosis was unimpaired. Long-term follow-up showed no antihuman antibody formation or organ dysfunction.
The Intrinsic Threshold of the Fibrinolytic System Is Modulated by Basic Carboxypeptidases, but the Magnitude of the Antifibrinolytic Effect of Activated Thrombin-activable Fibrinolysis Inhibitor Is Masked by Its Instability (2004)

Activated thrombin-activable fibrinolysis inhibitor (TAFIa) is intrinsically unstable, a property that complicates the study of its role in regulating fibrinolysis. To investigate the effect of basic carboxypeptidases on fibrinolysis under conditions of constant carboxypeptidase activity, we employed pancreatic carboxypeptidase B (CPB), a homologous, stable basic carboxypeptidase, as a surrogate for TAFIa. Clots formed from TAFI-depleted plasma or from purified components were supplemented with tissue-type plasminogen activator and either CPB or TAFIa. The clot lysis data indicate that the down-regulation of fibrinolysis mediated by basic carboxypeptidases involves a threshold mechanism. At carboxypeptidase concentrations above the threshold, plasminogen activation is maintained in a fully down-regulated state; experiments in plasma showed that fibrinolysis is essentially halted by saturating concentrations of TAFIa and that fibrinolysis can be prolonged more than 45-fold by a stable carboxypeptidase. The threshold carboxypeptidase concentration was dependent on tissue-type plasminogen activator and antiplasmin concentrations, indicating that the threshold is determined by the steady-state plasmin concentration. Although obvious with CPB, the threshold was masked by the intrinsic instability of TAFIa and became apparent only when the effect of TAFIa was investigated over the picomolar concentration range. Because of the threshold effect and the instability of TAFIa, exponential increases in TAFIa concentration generate linear increases in lysis time. A model relating lysis time to TAFIa concentration, TAFIa half-life, and the threshold concentration of TAFIa is provided. The threshold effect has potentially important implications regarding the role of TAFIa and the regulation of clot lysis in vivo.
TGF-β3 in the Treatment of Pressure Ulcers: A Preliminary Report (2001)

The findings of this study indicate that the topical application of TGF-beta3 is safe and useful in the treatment of pressure ulcers and is most effective at the earliest stages of therapy.
Euthanasia in Western Australia 2010: Background and Analysis (2010)

In September 2010, Western Australia's Legislative Council, the Upper House of that State's Parliament, voted down a Private Member's Bill to introduce voluntary euthanasia by a margin of 24 votes to 11. This article reviews the general context and content of the Bill and the public debate on euthanasia before offering more focused analysis.
Porphyries with Aromatic 26π‐Electron Systems (1993)

Remarkably aromatic are the diaza[26]annulenes of type 1, which are stabilized by pyrrole rings positioned at the corners. This has been proven by 1H NMR spectroscopy, crystal structure analysis, and by electrophilic substitution reactions. In contrast, for the simple annulenes (CH)n, the aromaticity “stops” at the 22π electron system.
Detection of beta 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET) (2000)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Recent progress in 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-HSD1) inhibitor development (2006)

Glucocorticoids regulate a plethora of processes via stimulation of nuclear glucocorticoid receptors. Exaggerated effects of glucocorticoids can give rise to multiple clinical features typified by Cushing's disease, a metabolic syndrome comprising hyperglycemia, insulin-resistant diabetes, obesity, dyslipidemia and hypertension. Since the enzyme 11-β-hydroxysteroid dehydrogenase type 1 (11-β-HSD1) locally regenerates active glucocorticoids, tissue-specific inhibitors of 11-β-HSD1 have potential for ameliorating the above conditions. This review describes the racent efforts to identify potent and selective 11-β-HSD1 inhibitors, aimed at correcting abnormalities associated with the metabolic syndrome. The primary focus is on aspects of the metabolic syndrome, but a is recognized that inactivation of 11-β-HSD1 may also be beneficial in other diseases.
Capillary Fluid Exchange: Regulation, Functions, and Pathology (2010)

Abstract The partition of fluid between the vascular and interstitial compartments is regulated by forces (hydrostatic and oncotic) operating across the microvascular walls and the surface areas of permeable structures comprising the endothelial barrier to fluid and solute exchange, as well as within the extracellular matrix and lymphatics. In addition to its role in the regulation of vascular volume, transcapillary fluid filtration also allows for continuous turnover of water bathing tissue cells, providing the medium for diffusional flux of oxygen and nutrients required for cellular metabolism and removal of metabolic byproducts. Transendothelial volume flow has also been shown to influence vascular smooth muscle tone in arterioles, hydraulic conductivity in capillaries, and neutrophil transmigration across postcapillary venules, while the flow of this filtrate through the interstitial spaces functions to modify the activities of parenchymal, resident tissue, and metastasizing tumor cells. Likewise, the...
Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report (2010)

This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed to evaluate the efficacy of restricted ketogenic diets, administered alone or together with standard treatment, as a therapy for GBM and possibly other malignant brain tumors.
Introduction to Data Mining (2004)

Chapter One begins by defining data mining, investigating why it is needed and how widespread data mining is. One of the strong themes of DKD is the need for human direction and supervision of data mining at all levels. The CRISP-DM standard process is described, so that data miners within a corporate or research enterprise do not suffer from isolation. The six phases of the standard process are described in detail, including (1) the business or research understanding phase, (2) the data understanding phase, (3) the data preparation phase, (4) the modeling phase, (5) the evaluation phase, and (6) the deployment phase. A case study from Daimler-Chrysler illustrating these phases is provided. Common fallacies of data mining are debunked. The primary tasks of data mining are described in detail, including description, estimation, prediction, classification, clustering, and association. Finally four case studies are examined, in relation to the phases of the standard process, and the set of data mining tasks.
Cyclic and Acyclic Amides of cis-β-(p-Bromobenzoyl)-β-methylacrylic Acid (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic and Acyclic Amides of cis-β-(p-Bromobenzoyl)-β-methylacrylic AcidROBERT E. LUTZ, CARROLL T. CLARK, and JOSEPH P. FEIFERCite this: J. Org. Chem. 1960, 25, 3, 346–352Publication Date (Print):March 1, 1960Publication History Published online1 May 2002Published inissue 1 March 1960https://doi.org/10.1021/jo01073a009RIGHTS & PERMISSIONSArticle Views74Altmetric-Citations5LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (800 KB) Get e-Alertsclose Get e-Alerts
A Stochastic Approximation Method (1951)

Let $M(x)$ denote the expected value at level $x$ of the response to a certain experiment. $M(x)$ is assumed to be a monotone function of $x$ but is unknown to the experimenter, and it is desired to find the solution $x = \theta$ of the equation $M(x) = \alpha$, where $\alpha$ is a given constant. We give a method for making successive experiments at levels $x_1,x_2,\cdots$ in such a way that $x_n$ will tend to $\theta$ in probability.