gebhart/patrepeval huggingface dataset:
Matrix metalloproteinase 9 and the epidermal growth factor signal pathway in operable non-small cell lung cancer. (2000)

Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen. Enhanced expression has been related to tumor progression both in vitro and in vivo. The control of MMP transcription is complex, but recently, epidermal growth factor receptor (EGFR) expression has been implicated in up-regulation of MMP-9 in tumor cells in vitro. Our objective was to evaluate the relationship between MMP-9 and EGFR expression in non-small cell lung cancer (NSCLC) and to assess the impact of expression on clinicopathological parameters and survival. This is a retrospective study of 169 patients who underwent resection for stage I-IIIa NSCLC with a postoperative survival >60 days. Minimum follow-up was 2 years. Standard avidin-biotin complex immunohistochemistry was performed on 4-microm paraffin-embedded sections from the tumor periphery using monoclonal antibodies to EGFR and MMP-9. MMP-9 was expressed in the tumor cells of 88 of 169 (52%) cases. EGFR expression was found in 94 of 169 (56%) cases [membranous, 55 of 169 (33%); cytoplasmic, 39 of 169 (23%)]. MMP-9 expression was associated with poor outcome in univariate (P = 0.0023) and multivariate (P = 0.027) analysis. Membranous, cytoplasmic, and overall EGFR expression were not associated with outcome (P = 0.13, 0.99, and 0.17, respectively). MMP-9 expression showed a strong correlation with EGFR expression (P < 0.0001) and EGFR membranous expression (P = 0.002) but not with cytoplasmic EGFR expression (P = 0.18). Co-expression of MMP-9 and EGFR (37%) conferred a worse prognosis (P = 0.0001). Subset analysis revealed only MMP-9 and membranous EGFR co-expression (22%) was associated with poor outcome (P = 0.0019). Our results show that a significant proportion of NSCLC tumors co-express MMP-9 and EGFR. The co-expression of these markers confers a poor prognosis. This finding suggests that EGFR signaling pathway may play an important role in the invasive behavior of NSCLC via specific up-regulation of MMP-9.
Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial (2007)

Serum sodium improvements during hospitalization for heart failure were associated with improved survival at 60 days.
Unifying synchronous/asynchronous state machine synthesis (1993)

We present a design style and synthesis algorithm that encompasses both asynchronous and synchronous state machines. Our proposed design style not only supports generalized multiple-input change asynchronous designs, but also allows the automatic synthesis of any synchronous Moore machine using only basic gates (and not state-holding elements). Moreover, the synthesis method covers many circuit styles in the range between burst-mode and fully synchronous. We can easily specify and synthesize sequential circuits which change state on both rising and falling clock edges, have multiple-phase clocks, etc., and mixed synchronous/asynchronous designs, subject only to setup and hold-time constraints. To demonstrate the effectiveness of the design style and the synthesis tool, we present a modified version of a previously published large practical controller design - the SCSI data transfer controller redesigned to improve performance and to eliminate preprocessing circuit for converting level-sensitive signals to edge-sensitive signals, often a cumbersome manual design process, by interfacing directly with level-sensitive signals.
Synthesis and in Vitro Evaluation of Novel Morpholinyl- and Methylpiperazinylacyloxyalkyl Prodrugs of 2-(6-Methoxy-2-naphthyl)propionic Acid (Naproxen) for Topical Drug Delivery (2000)

Various novel morpholinyl- (3a,b) and methylpiperazinylacyloxyalkyl (3c-f) esters of 2-(6-methoxy-2-naphthyl)propionic acid were synthesized and evaluated in vitro for topical drug delivery as potential prodrugs of naproxen (1). Compounds 3a-f were prepared by coupling the corresponding naproxen hydroxyalkyl ester with the morpholinyl- or (4-methyl-1-piperazinyl)acyl acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP) and quantitatively hydrolyzed (t(1/2) = 1-26 min) to naproxen in human serum. Compounds 3c-f showed higher aqueous solubility and similar lipophilicity, determined by their octanol-buffer partition coefficients (log P(app)), at pH 5.0 when compared to naproxen. At pH 7.4 they were significantly more lipophilic than naproxen. The best prodrug 3c led to a 4- and 1.5-fold enhancement of skin permeation when compared to naproxen at pH 7.4 and 5.0, respectively. The present study indicates using a methylpiperazinyl group yields prodrugs that are partially un-ionized under neutral and slightly acidic conditions, and thus, a desirable combination is achieved in terms of aqueous solubility and lipophilicity. Moreover, the resulting combination of biphasic solubility and fast enzymatic hydrolysis of the methylpiperazinylacyloxyalkyl derivatives gave improved topical delivery of naproxen.
Issues in the development of gene therapy: preclinical experiments in E1A gene delivery. (1999)

We recently completed a phase I trial of E1A gene therapy for patients with advanced breast or ovarian cancers. The trial's rationale was that E1A gene would downregulate HER-2/neu expression by repressing the gene's transcription, thus reversing the malignant phenotype. Our preclinical studies showed that i) transfection capabilities were not reduced in preparing E1A/cationic liposome complexes, ii) samples after ex vivo transfection, and iii) HER-2/neu gene expression could be quantified by quantitative imaging analysis. These results facilitated the translation of our basic research findings into a clinical trial and to obtain final approval from the National Institutes of Health Recombinant DNA Advisory Committee.
T cell homeostasis (2008)

The pool of mature T cells comprises a heterogeneous mixture of naive and memory CD4(+) and CD8(+) cells. These cells are long lived at a population level but differ markedly in their relative rates of turnover and survival. Here, we review how contact with exogenous stimuli, notably self MHC ligands and various gamma(c) cytokines, plays a decisive role in controlling normal T cell homeostasis.
Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling (2001)

The adventitial layer surrounding the blood vessels has long been exclusively considered a supporting tissue the main function of which is to provide adequate nourishment to the muscle layers of tunica media. Although functionally interconnected, the adventitial and medial layers are structurally interfaced at the external elastic lamina level, clearly distinguishable at the maturational phase of vascular morphogenesis. Over the last few years the "passive" role that the adventitia seemed to play in experimental and spontaneous vascular pathologies involving proliferation, migration, differentiation, and apoptosis of vascular smooth muscle cells (VSMCs) has been questioned. It has been demonstrated that fibroblasts from the adventitia display an important partnership with the resident medial VSMCs in terms of phenotypic conversion, proliferation, apoptotic, and migratory properties the result of which is neointima formation and vascular remodeling. This article is an attempt at reviewing the major themes and more recent findings dealing with the phenotypic conversion process that leads adventitial "passive" (static) fibroblasts to become "activated" (mobile) myofibroblasts. This event shows some facets in common with vascular morphogenesis, ie, the process of recruitment, incorporation, and phenotypic conversion of cells surrounding the primitive endothelial tube in the definitive vessel wall. We hypothesize that during the response to vascular injuries in the adult, "activation" of adventitial fibroblasts is, at least in part, reminiscent of a developmental program that also invests, although with distinct spatiotemporal features, medial VSMCs.
Profile of Cerebrospinal Fluid and Serum Cytokines in Patients with Relapsing-Remitting Multiple Sclerosis. A Correlation with Clinical Activity (1998)

Levels of tumor necrosis factor (TNF)-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-10 and transforming growth factor (TGF)-beta in cerebrospinal fluid (CSF) and serum of 29 patients with multiple sclerosis (MS) of the relapsing-remitting type and of 20 controls with other non inflammatory neurological diseases were studied. Sixteen patients were in the active phase of disease and 13 in remission. In CSF, higher IL-10 and TGF-beta concentrations were found in patients with a stable phase of MS, while in the active phase there were elevated levels of TNF-alpha and GM-CSF. These results suggest that a different cytokine pattern could be probably involved in the pathogenesis of relapsing-remitting MS.
Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation (2002)

There are many sources of systematic variation in cDNA microarray experiments which affect the measured gene expression levels (e.g. differences in labeling efficiency between the two fluorescent dyes). The term normalization refers to the process of removing such variation. A constant adjustment is often used to force the distribution of the intensity log ratios to have a median of zero for each slide. However, such global normalization approaches are not adequate in situations where dye biases can depend on spot overall intensity and/or spatial location within the array. This article proposes normalization methods that are based on robust local regression and account for intensity and spatial dependence in dye biases for different types of cDNA microarray experiments. The selection of appropriate controls for normalization is discussed and a novel set of controls (microarray sample pool, MSP) is introduced to aid in intensity-dependent normalization. Lastly, to allow for comparisons of expression levels across slides, a robust method based on maximum likelihood estimation is proposed to adjust for scale differences among slides.
Pulmonary arterial hypertension associated to connective tissue diseases (2005)

Pulmonary arterial hypertension is a well-known complication of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, mixed connective tissue diseases, and to a lesser extent, rheumatoid arthritis, dermatopolymyositis and primary Sjögren's syndrome. In these patients, pulmonary hypertension may occur in association with left heart disease, interstitial fibrosis or as a result of a isolated pulmonary arteriopathy. The incidence of pulmonary arterial hypertension in the limited form of systemic sclerosis is about 10%. The pathophysiologic mechanisms leading to pulmonary arterial hypertension remain unknown. Symptoms and clinical presentation are very similar to idiopathic pulmonary arterial hypertension but mortality was confirmed to be higher. Echocardiography is the reference investigation for the detection of pulmonary arterial hypertension but the results should be confirmed by right heart catheterization. Treatment appears more complex as compared to idiopathic pulmonary arterial hypertension. Intravenous epoprostenol therapy has been shown to be effective in a special trail. Also, the endothelin receptor antagonists bosentan and sitaxentan, the phosphodyesterase-type-5 sildenafil and subcutaneous treprostinil have shown favourable results.
Synthesis of (optically active) sulfur-containing trifunctional amino acids by radical addition to (optically active) unsaturated amino acids (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of (optically active) sulfur-containing trifunctional amino acids by radical addition to (optically active) unsaturated amino acidsQuirinus B. Broxterman, Bernard Kaptein, Johan Kamphuis, and Hans E. SchoemakerCite this: J. Org. Chem. 1992, 57, 23, 6286–6294Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November 1992https://pubs.acs.org/doi/10.1021/jo00049a041https://doi.org/10.1021/jo00049a041research-articleACS PublicationsRequest reuse permissionsArticle Views911Altmetric-Citations52LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Body Shaping under Water Stress: Osmosensing and Osmoregulation of Solute Transport in Bacteria (2002)

Fluctuation of external osmolarity is one of the most common types of environmental stress factors for all kind of cells, both of prokaryotic and of eukaryotic origin. Cells try to keep their volume and/or turgor pressure constant; consequently, both a decrease (hypoosmotic stress) and an increase (hyperosmotic stress) of the solute concentration (correctly: increase or decrease in water activity) in the surrounding area, respectively, are challenges for cellular metabolism and survival. A common example from the prokaryotic world is the fate of a soil bacterium that, after a sunny day has dried out the soil (hyperosmotic stress), is suddenly exposed to a drop of distilled water from a rain cloud (hypoosmotic stress). The immediate and inevitable passive response to the sudden osmotic shift in the surroundings is fast water efflux out of the cell in the former situation and water influx in the latter. In the worst case, these responses may lead to either loss of cell turgor and plasmolysis or to cell burst. In order to overcome such drastic consequences cells have developed effective mechanisms, namely osmoadaptation, to cope with the two different types of osmotic stress. For a graded reaction to osmotic shifts, cells must be able (1) to sense stimuli related to osmotic stress, (2) to transduce corresponding signals to those systems that properly respond (3) by activating transport or enzymatic functions or (4) by changing gene expression profiles. In this review, membrane proteins involved in the cell's active response to osmotic stress are described. Molecular details of structure, function, and regulation of mechanosensitive efflux channels from various organisms, as well as of osmoregulated uptake systems are discussed.
The Vascular Endothelial Growth Factor (VEGF) Signaling Pathway: A Therapeutic Target in Patients with Hematologic Malignancies (2001)

Angiogenesis is an important component in the progression and metastasis of solid tumors. We now appreciate that angiogenesis is also critically involved in the pathogenesis of hematologic malignancies. Current data suggest important prognostic and therapeutic implications of angiogenesis in a variety of malignancies of the hematopoietic system, including acute and chronic leukemias, myeloproliferative diseases, multiple myeloma, non-Hodgkin's lymphomas, and Hodgkin's disease. Vascular endothelial growth factor (VEGF) is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies.
Geomechanical Modeling of Wellbore Stability in Salt Formations (2013)

Abstract Exploration drilling is venturing out into deeper regions of water. While exploring these deeper water depths, large hydrocarbon deposits have been found below salt formations. These reservoirs are located in formations called "pre-salts," which are located below the salt formations. Pre-salt reservoirs have been found in offshore Brazil, the Gulf of Mexico, West Africa, and the North Sea. Completions in salt formations can be difficult owing to the creep behavior that the salt formations exhibit. Creep behavior results from the instability of the salt formation, which causes a slow flow and permanent deformations. Creep deformation occurs over time and is initiated once the salt formation has been penetrated. Completion of the wellbore does not stop formation creep. The constant creep of the salt formation causes excess stress on the wellbore casing, which may eventually cause the casing to collapse. In this study, a 3D geomechanical model is developed, using data such as wellbore pressure and temperature, formation stress and temperature, rock, cement, and casing properties, to predict the effects of salt creep behavior on stress loading in the wellbore casing, which helps to assess the life expectancy of wells in pre-salt reservoirs. The simulation results of this model can provide quantitative results of casing stress and deformation as a function of time under various temperature, in-situ stress and operation conditions, that can be used as useful information for subsequent wellbore casing design and wellbore integrity analysis. In addition, possible methods that can mitigate the severity of salt mobility and reduce the risks of casing collapse are discussed.
Sequence Effect of Irinotecan and Fluorouracil Treatment on Pharmacokinetics and Toxicity in Chemotherapy-Naive Metastatic Colorectal Cancer Patients (2001)

The sequence of treatment with irinotecan and infusional 5-FU affects the tolerability of this combination. This can be explained in part by a reduced SN-38 AUC when irinotecan preceded infusional 5-FU. Well-defined 5-FU/irinotecan regimens are needed because the administration sequence or the interval between the agents might affect treatment tolerance and perhaps also activity.
Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model (2015)

Inhibition of immune checkpoints, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and its ligand PD-L1, has demonstrated exciting and durable remissions across a spectrum of malignancies. Combinatorial regimens blocking complementary immune checkpoints further enhance the therapeutic benefit. The activity of these agents for patients with glioblastoma, a generally lethal primary brain tumor associated with significant systemic and microenvironmental immunosuppression, is not known. We therefore systematically evaluated the antitumor efficacy of murine antibodies targeting a broad panel of immune checkpoint molecules, including CTLA-4, PD-1, PD-L1, and PD-L2 when administered as single-agent therapy and in combinatorial regimens against an orthotopic, immunocompetent murine glioblastoma model. In these experiments, we observed long-term tumor-free survival following single-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy in 50%, 20%, and 15% of treated animals, respectively. Combination therapy of anti-CTLA-4 plus anti-PD-1 cured 75% of the animals, even against advanced, later-stage tumors. In long-term survivors, tumor growth was not seen upon intracranial tumor rechallenge, suggesting that tumor-specific immune memory responses were generated. Inhibitory immune checkpoint blockade quantitatively increased activated CD8(+) and natural killer cells and decreased suppressive immune cells in the tumor microenvironment and draining cervical lymph nodes. Our results support prioritizing the clinical evaluation of PD-1, PD-L1, and CTLA-4 single-agent targeted therapy as well as combination therapy of CTLA-4 plus PD-1 blockade for patients with glioblastoma.
Hunting or waiting? Discovering passenger-finding strategies from a large-scale real-world taxi dataset (2011)

In modern cities, more and more vehicles, such as taxis, have been equipped with GPS devices for localization and navigation. Gathering and analyzing these large-scale real-world digital traces have provided us an unprecedented opportunity to understand the city dynamics and reveal the hidden social and economic &#x201C;realities&#x201D;. One innovative pervasive application is to provide correct driving strategies to taxi drivers according to time and location. In this paper, we aim to discover both efficient and inefficient passenger-finding strategies from a large-scale taxi GPS dataset, which was collected from 5350 taxis for one year in a large city of China. By representing the passenger-finding strategies in a Time-Location-Strategy feature triplet and constructing a train/test dataset containing both top- and ordinary-performance taxi features, we adopt a powerful feature selection tool, L1-Norm SVM, to select the most salient feature patterns determining the taxi performance. We find that the selected patterns can well interpret the empirical study results derived from raw data analysis and even reveal interesting hidden &#x201C;facts&#x201D;. Moreover, the taxi performance predictor built on the selected features can achieve a prediction accuracy of 85.3% on a new test dataset, and it also outperforms the one based on all the features, which implies that the selected features are indeed the right indicators of the passenger-finding strategies.
Isolation and characterization of mutants of firefly luciferase which produce different colors of light (1991)

The luciferase cDNA from the 'Genji' firefly, Luciola cruciata, was mutated with hydroxylamine to isolate mutant luciferases. Some of the isolated mutant enzymes produced different colors of light, ranging from green to red. Five such mutants, producing green (lambda max = 558 nm), yellow-orange (lambda max = 595 nm), orange (lambda max = 607 nm) and red light (lambda max = 609 and 612 nm), were analyzed. The mutations were found to be single amino acid changes, from Val239 to Ile, Pro452 to Ser, Ser286 to Asn, Gly326 to Ser and His433 to Tyr respectively.
Bitocast: a hybrid BitTorrent and IP Multicast content distribution solution (2009)

Dissertacao apresentada para obtencao do Grau de Mestre em Informatica, pela Universidade Nova de Lisboa, Faculdade de Ciencias e Tecnologia
Accidental Deaths, Saved Lives, and Improved Quality (2005)

The authors argue that despite the success of the patient-safety movement in attracting the attention of the public and the medical profession, the Institute of Medicine's goal of reducing deaths from medical errors by 50 percent has not been achieved. They believe the greatest promise will come not from a focus on preventing accidental deaths but from dedication to evidence-based interventions to deliver more effective medical care.