gebhart/patrepeval huggingface dataset:
New options for the treatment of advanced ovarian cancer. (1997)

Over the last decade, platinum-based combination chemotherapy regimens have led to higher response rates and longer survival for advanced ovarian cancer patients than previous regimens based on alkylating agents. The advent of paclitaxel for salvage therapy and, more recently, as a component of first-line treatment in advanced disease has further improved response rates and prolonged survival. Nonetheless, even with current treatments, relapse rates remain high and most women with advanced ovarian cancer ultimately will die of their disease. For this reason, the development of new, effective second-line treatments, as well as better first-line agents, for advanced disease remains a high priority. To maximize the efficacy of second- or third-line drugs, new agents should be non-cross-resistant with platinum or paclitaxel. Chemotherapy drugs for advanced ovarian cancer with novel mechanisms of action include topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a topoisomerase I inhibitor. Topotecan was recently shown to be effective in platinum-refractory or -resistant patients, with response rates ranging from 14% to 23%. Results from a phase III clinical study indicate that topotecan compares favorably with paclitaxel as a second-line treatment for stage III and IV patients who have failed platinum-based regimens. Moreover, a phase II study demonstrated clinical responses with topotecan in patients who had failed both paclitaxel- and platinum-based therapies. Other agents for advanced ovarian cancer are also under investigation, including docetaxel, oral etoposide, liposome encapsulated doxorubicin, gemcitabine, ifosfamide, and hexymethylmelamine.
Cyclooxygenase in biology and disease (1998)

Cyclooxygenase (COX), the key enzyme required for the conversion of arachidonic acid to prostaglandins was first identified over 20 years ago. Drugs, like aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in biology and disease than at any other time in history. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Here, we summarize the current understanding of the role of cyclooxygenase-1 and -2 in different physiological situations and disease processes ranging from inflammation to cancer. We have attempted to include all of the most relevant material in the field, but due to the rapid progress in this area of research we apologize that certain recent findings may have been left out.
Pressure Cycling to Enhance an Immobilized Enzymic Reaction by Enzyme Entrapment in a Pressure‐Sensitive Gel (1996)

The enzyme β-galactosidase was entrapped in poly(N-isopropylacrylamide) gel. The gel swelled or collapsed sharply upon the rise or fall of environmental pressure. The gel beads, prepared by reverse suspension polymerization, were placed in a stirred batch reactor filled with a solution of the substrateo-nitrophenol β-D-galactopyranoside. Operations under constant or cycling pressure were performed. A considerable increase in conversion rate was observed under pressure cycling operation, compared with isobaric operations at either atmospheric or high pressure. This result could be explained by the enhancement of mass transfer inside the gel beads during the pressure cycling operation.
Nitrofurantoin and older women (2015)

We read with interest the article by Singh and collegues suggesting that nitrofurantoin is effective for treating urinary tract infections (UTIs) in older women with lower glomerular filtration rates (GFRs).[1][1] The prevalence of asymptomatic bacteriuria is very high in older people. However,
Conformational stability and warfarin-binding properties of human serum albumin studied by recombinant mutants (2001)

Correctly folded recombinant wild-type human serum albumin and the single-residue mutants K199A, W214A, R218H and H242Q were produced with the use of a yeast expression system. The changes in R218H resulted in a pronounced decrease in intrinsic fluorescence. Thermodynamic parameters for thermal denaturation of the present mutants and of five additional mutants have been determined, showing small increases in stability for two mutants (R218H and H242Q) and a larger decrease in stability for one (W214A). In the last of these, denaturation was a heterogeneous process starting at physiological temperature. The high-affinity binding constant for warfarin at pH7.4 was determined by fluorescence spectroscopy: there was a significant increase in affinity for binding of warfarin to H242Q and K199A and a smaller decrease in affinity for W214A and R218H. The findings show that Trp-214 is not as essential for the high-affinity binding of warfarin as has previously been thought.
Analysis of polyethylene glycol esters (1957)

Summary The products obtained by esterification of polyethylene glycols with fatty acid, or by means of the reaction of ethylene oxide with fatty acids, can be analyzed for their content of monoester, diester, and unreacted polyethylene glycol by taking advantage of the extractability of the polyethylene glycol with water. A hot salt solution is used to insure selective extraction. Saponification and hydroxyl numbers are used to calculate the composition of the mixture; the molecular weights of the acid and glycol are presumed to be known.
Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age (2003)

Deletions in mitochondrial DNA (mtDNA) accumulate with age in humans without overt mitochondriopathies, but relatively limited attention has been devoted to the measurement of the total number of mtDNA molecules per cell during ageing. We have developed a precise assay that determines mtDNA levels relative to nuclear DNA using a PCR-based procedure. Quantification was performed by reference to a single recombinant plasmid standard containing a copy of each target DNA sequence (mitochondrial and nuclear). Copy number of mtDNA was determined by amplifying a short region of the cytochrome b gene (although other regions of mtDNA were demonstrably useful). Nuclear DNA content was determined by amplification of a segment of the single copy beta-globin gene. The copy number of mtDNA per diploid nuclear genome in myocardium was 6970 +/- 920, significantly higher than that in skeletal muscle, 3650 +/- 620 (P = 0.006). In both human skeletal muscle and myocardium, there was no significant change in mtDNA copy number with age (from neonates to subjects older than 80 years). This PCR-based assay not only enables accurate determination of mtDNA relative to nuclear DNA but also has the potential to quantify accurately any DNA sequence in relation to any other.
Cardiac Pacemakers From the Patient’s Perspective (2002)

here are about 3 million people worldwide with pacemakers, and each year 600 000 pacemakers are implanted. With rare exception, implantation of a pacemaker does not change the recipient's activities or lifestyle. Although most people who receive pacemakers are aged 60 years or older, people of any age, even children, may need pacemakers.
Cationic Hyperbranched Poly(amino ester):  A Novel Class of DNA Condensing Molecule with Cationic Surface, Biodegradable Three-Dimensional Structure, and Tertiary Amine Groups in the Interior (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCationic Hyperbranched Poly(amino ester): A Novel Class of DNA Condensing Molecule with Cationic Surface, Biodegradable Three-Dimensional Structure, and Tertiary Amine Groups in the InteriorYong-beom Lim, Seon-Mi Kim, Yan Lee, Woo-kyoung Lee, Tae-gyun Yang, Min-jae Lee, Hearan Suh, and Jong-sang ParkView Author Information School of Chemistry & Molecular Engineering Seoul National University, Seoul 151-742, Korea Cite this: J. Am. Chem. Soc. 2001, 123, 10, 2460–2461Publication Date (Web):February 16, 2001Publication History Received20 October 2000Published online16 February 2001Published inissue 1 March 2001https://pubs.acs.org/doi/10.1021/ja005715ghttps://doi.org/10.1021/ja005715grapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1672Altmetric-Citations132LEARN 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 SUBJECTS:Amines,Dendrons,Gene delivery,Organic compounds,Polymers Get e-Alerts
Bend and twist sensing in a multi-core optical fiber (2008)

We present a method for sensing both bending and twisting in an optical fiber which is compatible with extensive multiplexing. The technique employs a multi-core fiber design, high-performance static strain sensing, and robust reconstruction algorithms.
Cyclization of isothiosemicarbazones. Part 10. A novel route to 2-amino[1,2,4]triazolo[1,5-a]pyridine derivatives (1994)

2-Alkylamino[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile and 8-carboxylate derivatives 3 are obtained directly in moderate yields by the reaction of ketone isothiosemicarbazones 1, carrying a bulky alkyl group on the terminal nitrogen and at least one α-methylene group, with an active ethoxymethylene compound with elimination of a thiol. Butanone isothiosemicarbazone 1e gives an isomeric pair of 5-ethyl- and 5,6-dimethyl-triazolopyridines 3e and 3f depending upon which of the α-carbons is incorporated into the ring system, with the 5,6-dimethyl compound being the major product. When the substituent on the terminal nitrogen is less bulky, the reaction gives both [1,2,4]triazolo[1,5-a]pyridines 3 and penta-substituted 2-triazolines 4 or the latter compounds only. A plausible reaction mechanism is proposed.
Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: a proof-of-concept study in the preoperative window period (ImPACCT) (2017)

ClinicalTrials.gov: NCT02685046 . Registration date: February 9, 2016.
Membrane Anomalies in Huntington's Disease Fibroblasts (1984)

Plasma membranes, microsomes, and mitochondria were isolated from paired, passage number matched, cultured human fibroblasts. The cells were obtained from skin biopsies of Huntington's disease (HD) subjects and from sex and age matched controls. All fibroblasts were cultured in identical media for three to seven passages. Enrichment of surface marker enzymes such as Na+,K+-ATPase indicated a 10-fold purification of the isolated plasma membrane. The specific activity of Na+,K+-ATPase was 62 and 82% greater in the crude homogenate and isolated plasma membrane, respectively, of HD fibroblasts than in control fibroblasts. The specific activity of plasma membrane Na+,K+-ATPase was correlated with lipid composition and with membrane structure as determined by measurement of the rotational relaxation time and limiting anisotropy of fluorescence probe molecules. Major alterations in the structure of the plasma membranes in HD fibroblasts were not noted. The rotational relaxation time and limiting anisotropy of 1,6-diphenyl-1,3,5-hexatriene and of trans-parinaric acid were not significantly different between the plasma membrane, microsomes, or mitochondria of HD versus those of control fibroblasts. trans-Parinaric acid demonstrated the coexistence of fluid and solid domains in all three subcellular membrane fractions of the normal and HD skin fibroblasts. Lastly, both trans-parinaric acid and 1,6-diphenyl-1,3,5-hexatriene displayed characteristic breakpoints in Arrhenius plots of absorbance corrected fluorescence in plasma membranes, microsomes, and mitochondria. In all cases, similar breakpoint temperatures, indicative of phase alterations, were noted near 20 degrees and 30 degrees C. These breakpoints were unaltered in HD. In summary, the data do not support the concept of major membrane structural defects in HD.
An experimental model of affinity cell separation (1994)

Cell affinity separations are based on the selective attachment of cell phenotype using antibody or lectins specific for cell surface markers. The major physicochemical factors which influence ligand-mediated cell adhesion dynamics and the efficiency of cell affinity separation have been examined. Uniform cell detachment forces were generated with a parallel-plate flow cell (plate separation 100 microns, surface area 3 cm2). Hydrodynamic shear stress was used to measure cell adhesion strength and to separate cells on the basis of surface affinity. Human cell lines grown in tissue culture were separated on a flat derivatised glass immunoadsorbent which formed the floor of the flow chamber. Flow-cell residence time, detachment shear stress, temperature, and ligand density were shown to influence cell attachment probability. An understanding of the physical basis of ligand-mediated cell adhesion provided a rationale for optimisation of affinity cell separation. At room temperature attachment of positive cells was rapid (< 2 min) and adhesion strength was directly related to immunoadsorbent ligand density. Purity and recovery of enriched fractions were dependent on the separation shear stress and could be optimised using this parameter. Enrichment factors were greater than 100-fold, with at least 90% of positive cells recovered in enriched fractions. Enrichment purity and yields did not decline at higher loading densities (10(5) cells/cm2). Selective immunoadsorbent surface chemistry is a prerequisite for efficient affinity cell separation. Purity and recovery may be optimised by fractionating enriched and depleted cell populations with uniform fluid shear stress.
B7-H4 Pathway in Islet Transplantation andβ-Cell Replacement Therapies (2011)

Type 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency. β-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D. The two main obstacles after islet transplantation are alloreactive T-cell-mediated graft rejection and recurrence of autoimmune diabetes mellitus in recipients. T cells play a central role in determining the outcome of both autoimmune responses and allograft survival. B7-H4, a newly identified B7 homolog, plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. The relationship between B7-H4 and allograft survival/autoimmunity has been investigated recently in both islet transplantation and the nonobese diabetic (NOD) mouse models. B7-H4 protects allograft survival and generates donor-specific tolerance. It also prevents the development of autoimmune diabetes. More importantly, B7-H4 plays an indispensable role in alloimmunity in the absence of the classic CD28/CTLA-4 : B7 pathway, suggesting a synergistic/additive effect with other agents such as CTLA-4 on inhibition of unwanted immune responses.
Molecular architecture of intermediate filaments (2003)

Together with microtubules and actin microfilaments, approximately 11 nm wide intermediate filaments (IFs) constitute the integrated, dynamic filament network present in the cytoplasm of metazoan cells. This network is critically involved in division, motility and other cellular processes. While the structures of microtubules and microfilaments are known in atomic detail, IF architecture is presently much less understood. The elementary 'building block' of IFs is a highly elongated, rod-like dimer based on an alpha-helical coiled-coil structure. Assembly of cytoplasmic IF proteins, such as vimentin, begins with a lateral association of dimers into tetramers and gradually into the so-called unit-length filaments (ULFs). Subsequently ULFs start to anneal longitudinally, ultimately yielding mature IFs after a compaction step. For nuclear lamins, however, assembly starts with a head-to-tail association of dimers. Recently, X-ray crystallographic data were obtained for several fragments of the vimentin dimer. Based on the dimer structure, molecular models of the tetramer and the entire filament are now a possibility.
A Novel Lipase Belonging to the Hormone-sensitive Lipase Family Induced under Starvation to Utilize Stored Triacylglycerol in Mycobacterium tuberculosis (2005)

Twenty-four putative lipase/esterase genes of Mycobacterium tuberculosis H37Rv were expressed in Escherichia coli and assayed for long-chain triacylglycerol (TG) hydrolase activity. We show here that the product of Rv3097c (LIPY) hydrolyzed long-chain TG with high specific activity. LIPY was purified after solubilization from inclusion bodies; the enzyme displayed a K(m) of 7.57 mM and V(max) of 653.3 nmol/mg/min for triolein with optimal activity between pH 8.0 and pH 9.0. LIPY was inhibited by active serine-directed reagents and was inactivated at temperatures above 37 degrees C. Detergents above their critical micellar concentrations and divalent cations inhibited the activity of LIPY. The N-terminal half of LIPY showed sequence homology with the proline glutamic acid-polymorphic GC-rich repetitive sequences protein family of M. tuberculosis. The C-terminal half of LIPY possesses amino acid domains homologous with the hormone-sensitive lipase family and the conserved active-site motif GDSAG. LIPY shows low sequence identity with the annotated lipases of M. tuberculosis and with other bacterial lipases. We demonstrate that hypoxic cultures of M. tuberculosis, which had accumulated TG, hydrolyzed the stored TG when subjected to nutrient starvation. Under such conditions, lipY was induced more than all lipases, suggesting a central role for it in the utilization of stored TG. We also show that in the lipY-deficient mutant, TG utilization was drastically decreased under nutrient-deprived condition. Thus, LIPY may be responsible for the utilization of stored TG during dormancy and reactivation of the pathogen.
A Laser Technology Test Facility for Laser Inertial Fusion Energy (LIFE) (2010)

A LIFE laser driver needs to be designed and operated which meets the rigorous requirements of the NIF laser system while operating at high average power, and operate for a lifetime of >30 years. Ignition on NIF will serve to demonstrate laser driver functionality, operation of the Mercury laser system at LLNL demonstrates the ability of a diode-pumped solid-state laser to run at high average power, but the operational lifetime >30 yrs remains to be proven. A Laser Technology test Facility (LTF) has been designed to specifically address this issue. The LTF is a 100-Hz diode-pumped solid-state laser system intended for accelerated testing of the diodes, gain media, optics, frequency converters and final optics, providing system statistics for billion shot class tests. These statistics will be utilized for material and technology development as well as economic and reliability models for LIFE laser drivers.
Dose‐dependent expression of neuronopathy after experimental pyridoxine intoxication (1989)

We examined the sequence of nervous system abnormalities that resulted when rats were given excess amounts of vitamin B6 (pyridoxine). High doses of pyridoxine (1,200 or 600 mg/kg/d) for 6 to 10 days caused a neuronopathy with necrosis of dorsal root ganglion (DRG) sensory neurons, accompanied by centrifugal axonal atrophy and breakdown of peripheral and central sensory axons. Large diameter neurons with long processes and large cytoplasmic volumes were especially affected. Smaller doses (300 to 150 mg/kg/d) for up to 12 weeks had minor effects on DRG neurons, but produced a neuropathy with axonal atrophy and degeneration. Guinea pigs given 1,800 mg/kg/d developed sensory neuronopathy, whereas mice given similar or higher doses did not have neuropathologic abnormalities. Multiple factors including rate of administration, differential neuronal vulnerability, and species susceptibility have bearing on the final expression of pyridoxine neurotoxicity.
High-resolution liquid chromatography of DNA fragments on non-porous poly(styrene-divinylbenzene) particles (1993)

DNA restriction fragments and PCR products were separated by means of ion-pair reversed-phase high-performance liquid chromatography on alkylated non-porous poly(styrene-divinylbenzene) particles with a mean diameter of 2.1 microns. Optimum resolution was obtained by using an acetonitrile gradient in 100 mM of triethylammonium acetate and a column temperature of 50 degrees C. This allowed the separation of DNA fragments differing in chain length by 1-5% up to a size of 500 base pairs. PCR products could be analyzed directly in less than two minutes with a concentration sensitivity of at least 300 ng/ml. Compared with anion-exchange chromatography or gel electrophoresis no desaltation of the purified DNA molecules is required because the volatile buffer system can be readily evaporated. Subsequently, the method was used for the semiquantitative evaluation of the expression of multidrug resistance genes in mononuclear white blood cells.
Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers. (1998)

c-erbB-2 protein overexpression may have a predictive value with regard to adjuvant therapy in node-positive patients, for whom adjuvant tamoxifen with radiotherapy appears insufficient in the presence of c-erbB-2 overexpression. Combination of conventional and newer tumor markers may identify patients with a worse prognosis within groups with a generally favorable prognosis.
Cellular responses to cisplatin. The roles of DNA-binding proteins and DNA repair. (1994)

The anticancer drug cisplatin provokes a complex response in the cell. A lethal dose of the drug kills cells primarily by forming DNA adducts, causing G2 arrest in the cell cycle, and then triggering apoptosis. A sublethal dose induces drug resistance by several mechanisms, including changes in drug uptake and efflux, glutathione and metallothionein levels, and DNA repair. Cisplatin-DNA adducts bind several cellular proteins, including some that enhance survival of the cell by mediating DNA repair and others that hasten its death by conferring sensitivity to the drug.
A simple method for human peripheral blood monocyte Isolation (2000)

We describe a simple method using percoll gradient for isolation of highly enriched human monocytes. High numbers of fully functional cells are obtained from whole blood or buffy coat cells. The use of simple laboratory equipment and a relatively cheap reagent makes the described method a convenient approach to obtaining human monocytes.