gebhart/patrepeval huggingface dataset:
Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: Role of endoplasmic reticulum stress (2009)

1. Cisplatin is a potent chemotherapeutic agent with broad-spectrum antineoplastic activity against various types of tumours. However, a major factor limiting treatment with cisplatin is its acute and cumulative cardiotoxicity. The aim of the present study was to explore the effect of cisplatin on myocardial contractile function and the possible underlying cellular mechanisms. 2. C57 mice were treated with cisplatin (10 mg/kg per day, i.v.) or vehicle (0.9% NaCl) for 1 week and myocardial function was assessed using the Langendorff and cardiomyocyte edge-detection systems. Transmission electron microscopy, mitochondrial membrane potential, indices of endoplasmic reticulum (ER) stress and caspase 3 activity were evaluated. 3. Cisplatin-treated mice developed myocardial contractile dysfunction, as evidenced by a reduction in left ventricular developed pressure (LVDP) and the first derivative of LVDP (+/-dP/dt). Cisplatin treatment significantly prolonged time to 90% relengthening, depressed peak shortening, maximal velocity of shortening/relengthening (+/-dL/dt) and augmented the frequency-elicited depression in peak shortening. The JC-1 fluorescent assay demonstrated that cispatin-induced cardiac dysfunction was associated with mitochondrial membrane depolarization. Transmission electron microscopy revealed that cisplatin induces ultrastructural abnormalities of the mitochondria. Following cisplatin treatment, cardiomyocytes show activation of the ER stress response, increased caspase 3 activity and increased terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) staining. 4. The data indicate that cisplatin is cardiotoxic and may lead to left ventricular dysfunction and depressed cardiomyocyte contraction associated with mitochondrial abnormalities, enhanced ER stress and apoptosis. This work should shed some light on the management of cisplatin-induced cardiac injury.
Molecular Structure and Motion in Irradiated Polyethylene (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Structure and Motion in Irradiated PolyethyleneW. P. Slichter and Elaine R. MandellCite this: J. Phys. Chem. 1958, 62, 3, 334–340Publication Date (Print):March 1, 1958Publication History Published online1 May 2002Published inissue 1 March 1958https://doi.org/10.1021/j150561a022RIGHTS & PERMISSIONSArticle Views71Altmetric-Citations34LEARN 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 (948 KB) Get e-Alerts
Cylinder Alignment in Annular Structures of Microphase-Separated Polystyrene-b-Poly(methyl methacrylate) (2000)

We present a novel and simple method for generating micron-scale annular structures formed from polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) diblock copolymer on a silicon oxide substrate. This method is based on prewetting of the underlying substrate with a minor polar solvent before spin-casting of the diblock solution. When using this procedure, we also see, using atomic force microscopy, a unique alignment effect which occurs in the cylinder-forming microdomains of PS-b-PMMA annuli without the aid of an external alignment field. These aligned microdomains, with controlled nanometer-scale spacing and coherence on the order of microns, facilitate the ongoing exploration of self-organizing nanofabricated surfaces.
Genotypic and Phenotypic Characterization of Human Immunodeficiency Virus Type 1 Variants Isolated from AIDS Patients after Prolonged Adefovir Dipivoxil Therapy (1998)

Adefovir dipivoxil [bis(pivaloyloxymethyl)-ester prodrug], an orally bioavailable prodrug of adefovir [9-(2-phosphonylmethoxyethyl)adenine], is currently in phase III clinical trials for the treatment of human immunodeficiency virus (HIV). In vitro experiments demonstrated that either a K65R or a K70E mutation in HIV reverse transcriptase (RT) was selected in the presence of adefovir, conferring a 16- or 9-fold decrease in susceptibility to adefovir, respectively. Previous data demonstrated that patients receiving adefovir dipivoxil monotherapy (125 mg daily) for 12 weeks experienced a median decrease in HIV RNA levels of 0.5 log10 copies/ml and that resistance to adefovir dipivoxil did not arise during that period. In the present investigation, a further study was undertaken to investigate whether RT mutations developed among viruses from patients who completed the 12-week study and who opted to enroll in a maintenance phase of prolonged (6- to 12-month) adefovir dipivoxil therapy (120 mg daily). Concomitant treatment with antiretroviral agents was permitted during the maintenance phase. The median decreases in HIV RNA levels for patients who completed 6 or 12 months of maintenance-phase dosing were 0.6 and 1.14 log10 copies/ml, respectively. The reductions in the HIV RNA levels were similar among patients who received adefovir dipivoxil with or without concomitant treatment with antiretroviral agents. Viruses from 8 of 29 patients dosed for up to 12 months developed RT mutations that were not present at baseline; these mutations may have been related to adefovir dipivoxil therapy. Viruses from two of the eight patients developed the K70E mutation while the patients were on therapy, but none of the viruses from patients developed the K65R RT substitution. Despite the development of RT mutations, sustained reductions (6 to 12 months) in viral load (> or = 0.7 log10 copies/ml decrease from baseline) were observed in all eight patients.
[Bone marrow mesenchymal stem cells: progress in bone/cartilage defect repair]. (2002)

Mesenchymal stem cells (MSC) are thought to be multi-potent cells that have the potential to differentiate into lineages of mesenchymal tissues, including bone, cartilage, tendon, fat, muscle, and marrow stroma during embryo morphogenesis. In recent years, cells that have the characteristics of mesenchymal stem cells were isolated from marrow aspirates of human and a few animals. It was found that these cells retain the characteristics of stem cells in vitro and could be induced to differentiate exclusively into the osteocytic, chondrocytic, myoblastic and adipocytic lineages. It was demonstrated that MSC could heal clinically significant bone and cartilage defects in animal models. The role of MSC in repairing tendon defect was also testified. In addition, for its multi-potential to differentiate into lineages of mesenchymal tissues, MSC could be used as gene vehicle for gene therapy of trauma care.
Induction, Selection and Expansion of Acute Myeloid Leukemia Reactive Autologous T Cells for Adoptive Immunotherapy. (2005)

Abstract To generate highly AML reactive autologous CTL, the optimal protocol of growth factor combination and sequence of administration were screened and compared in an AML-DC culture system aimed to induce AML cell DC differentiation, activate and expand naïve T cells against AML; and simultaneously activate and expand possible rare existing AML reactive memory T cells. Primary AML peripheral blood or marrow cells containing more than 90% AML blasts were cultured in 96 well plates. Every single well was regarded and treated as an independent culture. Various growth factor combinations of GM-CSF, IL2, IL-3, IL-4, IL7, IL12, CD40L, TNF-α, anti-CTLA-4 mAb were compared for efficiency of AML cell DC differentiation induction and autologous T cell activation in 7 day culture. Significantly enhanced CD80/CD86 expression and total cell number (include both AML-DC and T cells, see attached figure) in the culture was observed when GM-CSF/IL-4 combined with IL-12. The T cells in each well were than expanded with high dose IL-2 (6000 u/ml) and CTL activity against autologous AML were examined by both 51Cr release assay and culture supernatant IFN-γ concentration assay. Multiple wells of AML cell culture from the same patient with the same cell number and culture condition exhibited substantial functional variation demonstrated by MHC-restricted autologous AML cell killing (3 - 70% specific lysis) and IFN-γ secretion (25 - 2994 pg/ml), indicating that the T cells randomly put in the independent wells vary greatly in efficiency of AML antigen recognition and activation. IL-12 alone exerted significant enhanced IFN-γ secretion in 4 of 5 patients. IL-12 combined with GM-CSF/IL-2/IL-4/IL-7 enhanced IFN-γ secretion compared with IL-12 alone in 3 of 5 patients. CTLA-4 blockade further significantly enhanced T cell activity in 5 of 5 patients. Highly active CTL lines were selected from high IFN-γ secretion wells and rapidly expanded using OKT-3/CD28 coated, mitomycin-c treated autologous AML cells. After expansion, the highly active lines still maintained high autologous AML cell killing compared to the low active lines. A therapeutic quantity of AML reactive autologous T cells (20.2±30.1)x109, (n=5) can be obtained after 6 weeks of culture from (6.4±2.9)x107 AML PBMC. This study demonstrated AML cells cultured in IL-12 or IL-12 combined with GM-CSF/IL-2/IL-4/IL-7/anti-CTLA4 mAb activated the potential of the patient immune system and may maximize the possibility of AML reactive CTL generation for adoptive immunotherapy. Figure Figure
Exome sequencing identifies MXRA5 as a novel cancer gene frequently mutated in non–small cell lung carcinoma from Chinese patients (2012)

Lung cancer has become the top killer among malignant tumors in China and is significantly associated with somatic genetic alterations. We performed exome sequencing of 14 non-small cell lung carcinomas (NSCLCs) with matched adjacent normal lung tissues extracted from Chinese patients. In addition to the lung cancer-related genes (TP53, EGFR, KRAS, PIK3CA, and ROS1), this study revealed "novel" genes not previously implicated in NSCLC. Especially, matrix-remodeling associated 5 was the second most frequently mutated gene in NSCLC (first is TP53). Subsequent Sanger sequencing of matrix-remodeling associated 5 in an additional sample set consisting of 52 paired tumor-normal DNA samples revealed that 15% of Chinese NSCLCs contained somatic mutations in matrix-remodeling associated 5. These findings, together with the results from pathway analysis, strongly indicate that altered extracellular matrix-remodeling may be involved in the etiology of NSCLC.
Spatial/spectral analysis of hyperspectral image data (2004)

The integration of spatial and spectral responses in hyperspectral image data analysis has been identified as a desirable objective by the remote sensing community. However, most available attempts are based on the consideration of spectral information separately from spatial information, and thus the two types of information are not treated simultaneously. In this paper, we describe our background in applying joint spatial/spectral techniques for full (pure)- and mixed-pixel classification of hyperspectral image data. Most of the techniques described in this work are based on classic mathematical morphology theory, which provides a remarkable framework to achieve the desired integration. The performance of the proposed methodologies is demonstrated by comparing them to other well-known pure- and mixed-pixel classifiers, using both simulated and real hyperspectral data collected by the NASA/JPL-AVIRIS and DLR-DAIS 7915 imaging spectrometers.
Platelets and coronary heart disease: potential psychophysiologic mechanisms. (1991)

Although there has been extensive research attempting to identify psychophysiologic mechanisms linking psychological events and behavior patterns with risk for coronary heart disease, these are important potential mechanisms that remain largely unexplored. One of these mechanisms is thrombosis, which is widely recognized as the precipitant of acute coronary events (myocardial infarction and sudden ischemic death). A major element in arterial thrombosis is the platelet, and platelet inhibition has been shown to be effective in preventing coronary events. In the present paper, platelet physiology and pathophysiology are reviewed. Platelet function testing and the clinical role of platelet activation in atherosclerosis and acute coronary events are also discussed. Because epinephrine and possibly shear stress are clinically important activators of platelets, it is proposed that platelet reactivity to psychological stress may be a major mechanism in coronary events. The literature to date supports the hypothesis that platelet activity is increased by emotional stress. Suggestions are made for future research in this area.
The Future of Antifungal Therapy (1996)

In the late 1970s the options for systemic antifungal therapy doubled with the addition of intravenous miconazole and oral ketoconazole to the two previously available agents, amphotericin B and flucytosine. The 1980s ushered in the next generation of triazole antifungals, fluconazole and itraconazole. These are the present-day mainstays of treatment for some of the most serious systemic fungal infections. However, the increase in the numbers and types of fungal pathogens, and especially the emergence of azole-resistant fungi, have prompted a continuing search for new therapeutic options. This search has yielded more-potent triazole antifungals, new vehicles for both polyenes and triazoles, and entirely new classes of agents such as the echinocandin derivatives; in addition, it has prompted the evaluation of new combinations of present-day antifungals and exploration of the use of immunomodulators for treatment of fungal infections. Rapid developments in molecular mycology are permitting a concentrated search for more targets for antifungals. We are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases but will have greatly expanded options for treatment.
Regulation of peripheral blood and synovial fluid lymphocyte apoptosis in juvenile idiopathic arthritis (2004)

The results suggest that a higher incidence of apoptosis of PB lymphocytes observed in JIA may be associated with down-regulation of Bcl-2, rather than with changes in expression of Bax and p53. In contrast, the low p53 expression and elevated IL-15 appear to provide mechanisms responsible for suppression of apoptosis in SF cells from JIA patients.
Potential Mechanism for the Effects of Dexamethasone on Growth of Androgen-Independent Prostate Cancer (2001)

Dexamethasone inhibited the growth of GR-positive cancers, possibly through the disruption of the NF-kappaB-IL-6 pathway.
Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume (2015)

Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation. We conclude that the addition of stromal cell-derived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.
Optimal multipath congestion control and request forwarding in Information-Centric Networks (2013)

The evolution of the Internet into a distributed Information access system calls for a paradigm shift to enable an evolvable future network architecture. Information-Centric Networking (ICN) proposals rethink the communication model around named data, in contrast with the host-centric transport view of TCP/IP. Information retrieval is natively pull-based, driven by user requests, point-to-multipoint and intrinsically coupled with in-network caching. In this paper, we tackle the problem of joint multipath congestion control and request forwarding in ICN for the first time. We formulate it as a global optimization problem with the twofold objective of maximizing user throughput and minimizing overall network cost. We solve it via decomposition and derive a family of optimal congestion control strategies at the receiver and of distributed algorithms for dynamic request forwarding at network nodes. An experimental evaluation of our proposal is carried out in different network scenarios to assess the performance of our design and to highlight the benefits of an ICN approach.
Optical lenses for atomic beams (2009)

Superpositions of paraxial laser beam modes to generate atom-optical lenses based on the optical dipole force are investigated theoretically. Thin, wide, parabolic, cylindrical, and circular atom lenses with numerical apertures much greater than those reported in the literature to date can be synthesized. This superposition approach promises to make high-quality atom beam imaging and nanodeposition feasible.
Expression of Membrane Type 1 Matrix Metalloproteinase Is Associated with Cervical Carcinoma Progression and Invasion (2005)

Membrane type 1 matrix metalloproteinase (MT1-MMP) is frequently expressed by cancer cells and is believed to play an important role in cancer cell invasion and metastasis. However, little is known about the role of MT1-MMP in mediating invasiveness of cervical cancer cells. In this study, we examined MT1-MMP expression in 58 primary human cervical tissue specimens, including normal cervix, low-grade squamous intraepithelial lesions (LSIL), high-grade SILs (HSIL), and invasive carcinomas. We also evaluated MT1-MMP, MMP-2, and tissue inhibitor of metalloproteinase-2 expression in several cervical cancer-derived cell lines, human papillomavirus (HPV)-immortalized keratinocytes, and keratinocytes derived from a LSIL. Using in situ hybridization techniques to study the cervical tissue specimens, we found that MT1-MMP expression increases with cervical tumor progression (Spearman correlation coefficient = 0.66; P < 0.0001, exact test). Specifically, MT1-MMP expression is very low or absent in normal cervix and LSILs, is readily detectable in HSILs, and is very strongly expressed in nearly all invasive carcinomas. Most but not all cervical cancer-derived cell lines also expressed significant levels of MT1-MMP and MMP-2. Constitutive expression of exogenous MT1-MMP in cervical carcinoma-derived cells and HPV-immortalized keratinocytes with low endogenous levels of MT1-MMP induced invasiveness in collagen I, but this effect was not observed in LSIL-derived keratinocytes. Our results show that MT1-MMP is a key enzyme mediating cervical cancer progression. However, MT1-MMP alone is not always sufficient for inducing keratinocyte invasiveness at least in the collagen I invasion assay used in this study. Further studies of gene expression in preinvasive and invasive cervical cancers should assist with identification of additional critical factors mediating cervical cancer progression.
First Synthesis of 2′‐Deoxyfluoropuromycin Analogues: Experimental Insight into the Mechanism of the Staudinger Reaction (2007)

The N(6),N(6)-dedimethyl-2'-deoxyfluoro analogue of puromycin (= 3'-deoxy-N(6),N(6)-dimethyl-3'-[O-methyltyrosylamido]adenosine), its 2',3'-regioisomer and a 3'-cytidyl-5'-(2'-deoxyfluoro)puromycyl dinucleotide analogue were synthesized following an approach involving i) the diastereospecific nitrite-assisted formation of a lyxo nucleosidic 2',3'-epoxide from an adenosine-2',3'-ditriflate derivative in a biphasic solvent mixture; ii) the regio- and stereoselective epoxide ring opening with sodium azide under mildly acidic aqueous conditions, iii) the stereospecific introduction of the fluor atom using DAST and iv) the reaction between the nucleosidyl or dinucleotidyl azide and an active ester of the N-protected amino acid using highly efficient solution conditions for the Staudinger-Vilarrasa coupling, to obtain the corresponding carboxamide directly from the in situ formed iminophosphorane. This coupling reaction furnished sterically quite demanding amides in 94 % isolated yields under very mild conditions and should therefore be of a more general value. Under certain reaction conditions we isolated (amino)acyltriazene derivatives from which dinitrogen was not eliminated. These secondary products are trapped and stabilized witnesses of the first intermediate of the Staudinger reaction, the phosphatriazenes (phosphazides, triazaphosphadienes) which usually eliminate dinitrogen in situ and rapidly rearrange into iminophosphoranes, unless they are derived from conjugated or sterically bulky azides and phosphines. The acyltriazenes could either be thermally decomposed or converted to the corresponding N-alkyl carboxamides through proton-assisted elimination of dinitrogen. All compounds were carefully characterized through MS spectrometry, (1)H, (19)F, (31)P and (13)C NMR spectroscopy.
Regeneration of Sensory Hair Cells After Acoustic Trauma (1988)

Any loss of cochlear hair cells has been presumed to result in a permanent hearing deficit because the production of these cells normally ceases before birth. However, after acoustic trauma, injured sensory cells in the mature cochlea of the chicken are replaced. New cells appear to be produced by mitosis of supporting cells that survive at the lesion site and do not divide in the absence of trauma. This trauma-induced division of normally postmitotic cells may lead to recovery from profound hearing loss.
Solution-Phase Synthesis of a Diverse Isocoumarin Library (2009)

The solution-phase synthesis of a 167-member library of isocoumarins is described. The key intermediates for library generation, 4-iodoisocoumarins, are easily prepared by iodocyclization of the corresponding 2-(1-alkynyl)arenecarboxylate esters. The 4-iodoisocoumarins undergo palladium-catalyzed Sonogashira, Suzuki-Miyura, and Heck reactions to yield a diverse set of isocoumarins. Alternatively, isocoumarins, bearing hydroxyl or bromine functionalities, have been prepared by ZnCl(2)- and Pd(PPh(3))(4)-mediated cyclization of the corresponding o-iodobenzoic acid and appropriate terminal alkynes. The resulting isocoumarins were further diversified by derivatization of the hydroxyl or bromine groups. A small set of isoquinolinones were also prepared from the corresponding isocoumarins.
Rotational Viscometry of a Zinc Phosphate and a Zinc Polyacrylate Cement (1977)

The rheological properties of a zinc phosphate and a zinc polyacrylate cement were investigated using a rotational viscometer. The effects of time, temperature, shear rate, and spindle geometry on the measured viscosities were evaluated. Results indicated that both cements exhibited Newtonian behavior.