gebhart/patrepeval huggingface dataset:
BCL6, p53 and Molecular Targeted Therapy in B-Cell Lymphomas. (2005)

Abstract The BCL6 transcriptional repressor is an oncogene often constitutively expressed in diffuse large B-cell lymphomas (DLBCL). The oncogenic mechanism of action of BCL6 presumably involves repression of its direct target genes. We recently developed a targeted therapy agent (called BPI - BCL6 peptide inhibitor) that specifically blocks transcriptional repression by BCL6, and which causes apoptosis in lymphoma cells in vitro and in vivo. We present here potent and stable derivatives of BPI able to specifically eradicate lymphoma cells after a single dose in vitro. Expression array studies of BCL6 target genes reactivated by BPI revealed that one such gene is the p53 tumor suppressor. p53 was also recently shown to be BCL6 target gene by Phan et. al., Nature 2004. We find that BCL6 represses p53 in DLBCL cells through recruitment of the SMRT and N-CoR corepressors, which explains how BPI, which blocks recruitment of these corepressors, reactivates p53. We next wished to determine the contribution of BCL6-mediated repression of p53 to lymphomagenesis, and how p53 modulation might affect BCL6 targeted therapy strategies for DLBCL. We found that BPI could induce p53 target gene expression in DLBCL cells with wild-type p53 and that small molecules or peptides that block p53 rescue apoptosis induced by BPI. In contrast, although BPI also induces p53 in DLCBL cells with mutant p53, there was no activation of p53 target genes and no rescue by p53 blocking molecules. However BPI causes apoptosis of DLBCL cells regardless of p53 status indicating the BCL6 mediates its oncogenic actions through both p53 dependent and independent pathways. p53 is usually wild-type in DLBCL and our analysis of &amp;gt;100 patients show that p53 protein is, surprisingly, still expressed in these tumors. These data suggest that p53 is not fully active in DLBCL cells, consistent with the fact that we found that BCL6 also directly represses upstream activators of p53 such as Chk1 and ATR. BCL6 blockade thus can fully restore activity of p53, both by increasing its expression levels and by enhancing its activation by upstream mediators. Accordingly, sequential administration of p53 activating molecules that enhance p53 activity, potently synergizes with BPI in killing lymphoma cells. BPI also synergizes with chemotherapy drugs that act in part through p53, such as doxorubicin. From these studies we conclude that i) BCL6 mediates lymphomagenesis by direct repression of p53 and upstream target gene pathways; ii) BCL6 positive lymphomas are dependent on BCL6 for their survival regardless of whether p53 is wild type or mutated; iii) Sequential targeting of BCL6 and p53 with BPI and a p53 activating molecule or doxorubicin is likely to be a highly effective therapeutic regimen for patients with DLBCL, especially for the majority who have wild-type p53; iv) The new BPI derivatives are sufficiently potent and stable to be tested in the clinical setting.
<title>Infrared light-emitting diodes with lateral outcoupling taper for high extraction efficiency</title> (1999)

We present a non-resonant light emitting diode with a novel concept of light outcoupling. Light is generated in the center of a radially symmetric structure and propagates between two mirrors of a tapered region where outcoupling occurs. Principles of outcoupling are given using a simple ray tracing model. Different process routes are developed resulting in on-substrate as well as substratless devices. Not yet optimized devices show quantum efficiencies of 12% and 15%, respectively.
Anandamide injected into the lateral ventricle of the brain inhibits submandibular salivary secretion by attenuating parasympathetic neurotransmission (2009)

Our objective was to determine the effect of arachidonylethanolamide (anandamide, AEA) injected intracerebroventricularly (icv) into the lateral ventricle of the rat brain on submandibular gland (SMG) salivary secretion. Parasympathetic decentralization (PSD) produced by cutting the chorda tympani nerve strongly inhibited methacholine (MC)-induced salivary secretion while sympathetic denervation (SD) produced by removing the superior cervical ganglia reduced it slightly. Also, AEA (50 ng/5 microL, icv) significantly decreased MC-induced salivary secretion in intact rats (MC 1 microg/kg: control (C), 5.3 +/- 0.6 vs AEA, 2.7 +/- 0.6 mg; MC 3 microg/kg: C, 17.6 +/- 1.0 vs AEA, 8.7 +/- 0.9 mg; MC 10 microg/kg: C, 37.4 +/- 1.2 vs AEA, 22.9 +/- 2.6 mg). However, AEA did not alter the significantly reduced salivary secretion in rats with PSD, but decreased the slightly reduced salivary secretion in rats with SD (MC 1 microg/kg: C, 3.8 +/- 0.8 vs AEA, 1.4 +/- 0.6 mg; MC 3 microg/kg: C, 14.7 +/- 2.4 vs AEA, 6.9 +/- 1.2 mg; P < 0.05; MC 10 microg/kg: C, 39.5 +/- 1.0 vs AEA, 22.3 +/- 0.5 mg; P < 0.001). We showed that the inhibitory effect of AEA is mediated by cannabinoid type 1 CB1 receptors and involves GABAergic neurotransmission, since it was blocked by previous injection of the CB1 receptor antagonist AM251 (500 ng/5 microL, icv) or of the GABA A receptor antagonist, bicuculline (25 ng/5 microL, icv). Our results suggest that parasympathetic neurotransmission from the central nervous system to the SMG can be inhibited by endocannabinoid and GABAergic systems.
Nox2-Derived Reactive Oxygen Species Mediate Neurovascular Dysregulation in the Aging Mouse Brain (2007)

Aging is associated with cerebrovascular dysregulation, which may underlie the increased susceptibility to ischemic stroke and vascular cognitive impairment occurring in the elder individuals. Although it has long been known that oxidative stress is responsible for the cerebrovascular dysfunction, the enzymatic system(s) generating the reactive oxygen species (ROS) have not been identified. In this study, we investigated whether the superoxide-producing enzyme NADPH oxidase is involved in alterations of neurovascular regulation induced by aging. Cerebral blood flow (CBF) was recorded by laser-Doppler flowmetry in anesthetized C57BL/6 mice equipped with a cranial window (age=3, 12, and 24 months). In 12-month-old mice, the CBF increases evoked by whisker stimulation or by the endothelium-dependent vasodilators acetylcholine and bradykinin were attenuated by 42, 36, and 53%, respectively (P<0.05). In contrast, responses to the nitric oxide donor S-nitroso-D-penicillamine or adenosine were not attenuated (P>0.05). These cerebrovascular effects were associated with increased production of ROS in neurons and cerebral blood vessels, assessed by hydroethidine microfluorography. The cerebrovascular impairment present in 12-month-old mice was reversed by the ROS scavenger Mn (III) tetrakis (4-benzoic acid) porphyrin chloride or by the NADPH oxidase peptide inhibitor gp91ds-tat, and was not observed in mice lacking the Nox2 subunit of NADPH oxidase. These findings establish Nox2 as a critical source of the neurovascular oxidative stress mediating the deleterious cerebrovascular effects associated with increasing age.
Role of α-Adrenergic Mechanism in Regulating Tonic Luteinizing Hormone Release in Conscious Ovariectomized Rats* (1981)

The role of brain catecholamines in controlling tonic LH secretion was studied in unanesthesized, freely moving, ovariectomized rats. Pretreatment with reserpine (10 mg/kg), given 24 h before the experiment, significantly suppressed pulsatile LH secretion in these rats. Intraperitoneal administration of clonidine (1 mg/kg), an alpha-adrenergic stimulating agent, significantly raised plasma LH levels in reserpine-treated rats. On the other hand, the administration of apomorphine (1.5 mg/kg), a dopamine receptor-stimulating agent, had no effect on the plasma LH levels. These findings suggest an excitatory role of noradrenaline, operating through alpha-adrenergic receptors, in pulsatile LH secretion in ovariectomized rats.
Concerted Activity of Tyrosine Phosphatase SHP-2 and Focal Adhesion Kinase in Regulation of Cell Motility (1999)

The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time-dependent manner, suggesting that IGF-I triggers the activation of different integrins. On the other hand, IGF-I promotes the association of insulin receptor substrate 1 with the focal adhesion kinase (FAK), paxillin, and the tyrosine phosphatase SHP-2, resulting in FAK and paxillin dephosphorylation. Abrogation of SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I-stimulated chemotaxis compared with either mock- or SHP-2 wild-type-transfected cells. This impairment of cell migration is recovered by reintroduction of a catalytically active SHP-2. Interestingly, SHP-2-C>S cells show a larger number of focal adhesion contacts than wild-type cells, suggesting that SHP-2 activity participates in the integrin deactivation process. Although SHP-2 regulates mitogen-activated protein kinase activity, the mitogen-activated protein kinase kinase inhibitor PD-98059 has only a marginal effect on MCF-7 cell migration. The role of SHP-2 as a general regulator of cell chemotaxis induced by other chemotactic agents and integrins is discussed.
Development Of An Alignment System For The Three-Part COGNAC Platform Jacket (1979)

ABSTRACT This paper discusses the system incorporated into the three-part Cognac "A" Platform jacket to guide the sections into lateral alignment as they were positioned offshore. A brief description of the alignment appurtenances and data on the in-place misalignment are given. INTRODUCTION During the early phases of the Cognac design, the decision was made to fabricate the Cognac Platform in three separate sections (Reference 1 and 2), (Figures 1, 2, and 3=Available in full paper). The Base Section was launched from a barge in an upright position. It was then lowered to the seafloor and anchored by 24 large diameter skirt piling (Reference 3). This section was 178½ feet in height measured from the centerline of the bottom horizontal to the top of the upward looking mating flanges. The Mid Section was fabricated and launched in a horizontal position, ballasted to vertical, lowered and set on top of the Base Section. This brought the total height of the jacket to 498½ feet. The Top Section, which was 527½ feet in height, was fabricated and installed similar to the midsection and extended the platform so that the jacket :walkway was 14 feet above the waterline. The primary mating components were the ten jacket legs through which large diameter tubular connection pins were installed and grouted in place (Figure 4). These pins extended through all three jacket sections and terminate just above the mudline at the bottom of the Base Section. Two of the jacket legs (Rows XL and X4) terminate at approximately 400 feet below the waterline. The other eight legs extend above the waterline. At each mating interface, the jacket legs terminate with large mating flanges that contain a rubber seal for containment of the grout as it was pumped into the jacket leg/pin annulus. Other items which were fabricated as an integral part of each jacket section, and had to line-up after installation, included eleven pipeline pulltube risers, sixty straight conductor pipe guides and two curved conductor pipe sleeve guides. The proper alignment of these items was not necessary to insure the structural integrity of the platform; however, each of them could be utilized only if properly aligned. Precepts to be followed during the design and selection of the jacket alignment system were developed and alternate alignment systems were studied. Relative cost comparisons were made, taking into account the impact on the construction schedule that each system would have. The two most important functions of the alignment system were:To provide a guiding system that would allow the upper jacket section to be set down upon the landing supports of the lower section and released from the lowering lines without structural damage resulting from an underwater collision between the mating jacket sections.To provide a method of aligning the corresponding jacket legs of the mating sections to an accuracy that would allow installation of the leg connection pins.
Atypical Femoral Fractures: What Do We Know About Them? (2013)

Background: The use of cementless acetabular components in total hip arthroplasty has gained popularity over the past decade. Most total hip arthroplasties being performed in North America currently use cementless acetabular components. The objective of this systematic review and meta-analysis was to compare the survivorship and revision rate of cemented and cementless acetabular components utilized in total hip arthroplasty. Methods: A primary literature search in PubMed identified 3488 articles, of which 3407 did not meet the inclusion criteria and were excluded. Only English-language articles on either the survivorship or revision rate of primary total hip arthroplasty at a minimum of ten years of follow-up were included. The present study analyzed forty-five articles reporting the long-term outcome of cementless acetabular components, twenty-nine reporting the outcome of cemented acetabular components, and seven comparing cemented and cementless acetabular components. Meta-analysis (with a random-effects model) was performed on the data from the seven comparative studies, and study-level logistic regression analysis (with a quasibinomial model) was performed on the pooled data on the eighty-one included articles to determine a consensus. The studies were weighted according to the number of total hip arthroplasties performed. Results: The meta-analysis did not reveal any effect of the type of acetabular component fixation on either survivorship or revision rate. The regression analysis revealed the estimated odds ratio for survivorship of a cemented acetabular component to be 1.60 (95% confidence interval, 1.32 to 2.40; p = 0.002) when adjustments for factors including age, sex, and mean duration of follow-up were made. Conclusions: The preference for cementless acetabular components on the basis of improved survivorship is not supported by the published evidence. Although concerns regarding aseptic loosening of cemented acetabular components may have led North American surgeons toward the nearly exclusive use of cementless acetabular components, the available literature suggests that the fixation of cemented acetabular components is more reliable than that of cementless components beyond the first postoperative decade.
μ-(2,6-Bis{[3-(dimethylamino)propyl]iminomethyl}-4-methylphenolato)-μ-hydroxido-bis[(thiocyanato-κN)copper(II)] (2013)

In the title compound, [Cu2(C19H31N4O)(OH)(NCS)2], the mol-ecular structure of the dinuclear complex reveals two penta-coordinated Cu(II) ions, which are bridged by the phenolate O atom of the ligand and by an exogenous hydroxide ion. The bridging atoms occupy equatorial positions in the coordination sphere of the metal atoms and complete the equatorial coordination planes with two ligand N atoms, the apical positions being occupied by thio-cyanate N atoms. The crystal structure also features π-π stacking inter-actions involving the benzene rings with a centroid-centroid distance of 3.764 (4)Å. The crystal studied was a non-merohedral twin, with a refined BASF value of 0.203 (2).
Data Mining and Machine Learning (2020)

The fundamental algorithms in data mining and machine learning form the basis of data science, utilizing automated methods to analyze patterns and models for all kinds of data in applications ranging from scientific discovery to business analytics. This textbook for senior undergraduate and graduate courses provides a comprehensive, in-depth overview of data mining, machine learning and statistics, offering solid guidance for students, researchers, and practitioners. The book lays the foundations of data analysis, pattern mining, clustering, classification and regression, with a focus on the algorithms and the underlying algebraic, geometric, and probabilistic concepts. New to this second edition is an entire part devoted to regression methods, including neural networks and deep learning.
Prognostic Significance of Adenocarcinoma In Situ, Minimally Invasive Adenocarcinoma, and Nonmucinous Lepidic Predominant Invasive Adenocarcinoma of the Lung in Patients With Stage I Disease (2014)

According to the IASLC/ATS/ERS classification, the lepidic predominant pattern consists of 3 subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and nonmucinous lepidic predominant invasive adenocarcinoma. We reviewed tumor slides from 1038 patients with stage I lung adenocarcinoma, recording the percentage of each histologic pattern and measuring the invasive tumor size. Tumors were classified according to the IASLC/ATS/ERS classification: 2 were AIS, 34 MIA, and 103 lepidic predominant invasive. Cumulative incidence of recurrence (CIR) was used to estimate the probability of recurrence. Patients with AIS and MIA experienced no recurrences. Patients with lepidic predominant invasive tumors had a lower risk for recurrence (5-y CIR, 8%) than nonlepidic predominant tumors (n=899; 19%; P=0.003). Patients with >50% lepidic pattern tumors experienced no recurrences (n=84), those with >10% to 50% lepidic pattern tumors had an intermediate risk for recurrence (n=344; 5-y CIR, 12%), and those with ≤10% lepidic pattern tumors had the highest risk (n=610; 22%; P<0.001). CIR was lower for patients with ≤2 cm tumors than for those with >2 to 3 cm tumors (for both total and invasive tumor size), with the difference more pronounced for invasive tumor size (5-y CIR, 13% vs. 21% [total size; P=0.022] and 12% vs. 27% [invasive size; P<0.001]). Most patients with lepidic predominant adenocarcinoma who experienced a recurrence had potential risk factors, including sublobar resection with close margins (≤0.5 cm; n=2), 20% to 30% micropapillary component (n=2), and lymphatic or vascular invasion (n=2). It therefore may be possible to identify lepidic predominant adenocarcinomas that carry a low or high risk for recurrence.
Immobilization of Hydrophilic Low Molecular-Weight Molecules in Nanoparticles of Chitosan/Poly(sodium 4-styrenesulfonate) Assisted by Aromatic–Aromatic Interactions (2014)

The immobilization of the hydrophilic low molecular-weight cationic molecules rhodamine 6G, methylene blue, and citidine in nanoparticles composed of two opposite charged polyelectrolytes, poly(sodium 4-styrenesulfonate) and chitosan, is studied, and the results correlated with their physicochemical properties. Nanoparticles containing both polyelectrolytes have been synthesized showing hydrodynamic diameters of around 200 nm and tunable zeta potential. It was found that the strength of binding of the cationic molecules to the polyanion bearing charged aromatic groups poly(sodium 4-styrenesulfonate) by means of short-range aromatic-aromatic interactions increases with their hydrophobicity and polarizability, as seen by (1)H NMR and UV-vis spectroscopies, and diafiltration. Consequently, association efficiencies of 45, 21, and 12% have been found for the three molecules, respectively, revealing the different ability of the molecules to be immobilized in the nanoparticles. These results provide a proof of concept on a new strategy of immobilization of hydrophilic low molecular-weight molecules based on aromatic-aromatic interactions between polyelectrolytes and their aromatic counterions.
Physiology of the Airway (2007)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
An Introduction to the Organic Chemistry of High Polymers (Marvel, Carl S.) (1960)

ADVERTISEMENT RETURN TO ISSUEPREVBook and Media Revie...Book and Media ReviewAn Introduction to the Organic Chemistry of High Polymers (Marvel, Carl S.)Richard H. Wiley Cite this: J. Chem. Educ. 1960, 37, 12, A830Publication Date (Print):December 1, 1960Publication History Received3 August 2009Published online1 December 1960Published inissue 1 December 1960https://doi.org/10.1021/ed037pA830RIGHTS & PERMISSIONSArticle Views127Altmetric-Citations-LEARN 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 (457 KB) Get e-Alerts Get e-Alerts
Oxaliplatin: mechanism of action and antineoplastic activity. (1998)

Oxaliplatin, a platinum-based chemotherapeutic agent with a 1,2-diaminocyclohexane (DACH) carrier ligand, has shown in vitro and in vivo efficacy against many tumor cell lines, including some that are resistant to cisplatin and carboplatin. The retention of the bulky DACH ring by activated oxaliplatin is thought to result in the formation of platinum-DNA adducts, which appear to be more effective at blocking DNA replication and are more cytotoxic than adducts formed from cisplatin. Studies by the National Cancer Institute (NCI) have suggested that oxaliplatin has a spectrum of activity different from that of either cisplatin or carboplatin, suggesting that it has different molecular targets and/or mechanisms of resistance. Oxaliplatin has been demonstrated to differ in some mechanisms associated with the development of cisplatin resistance. Compared with cisplatin-conditioned cells, deficiencies in mismatch repair (MMR) and increases in replicative bypass, which appear to contribute to cisplatin resistance, have not been shown to induce a similar resistance to oxaliplatin. A decreased likelihood of resistance development makes oxaliplatin a good candidate for first-line therapy. Studies also demonstrate additive and/or synergistic activity with a number of other compounds, however, suggesting the possible use of oxaliplatin in combination therapies.