gebhart/patrepeval huggingface dataset:
Monoclonal Antibody Therapy for Cancer (2003)

Monoclonal antibody therapy has emerged as an important therapeutic modality for cancer. Unconjugated antibodies show significant efficacy in the treatment of breast cancer, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. Promising new targets for unconjugated antibody therapy include cellular growth factor receptors, receptors or mediators of tumor-driven angiogenesis, and B cell surface antigens other than CD20. Immunoconjugates composed of antibodies conjugated to radionuclides or toxins show efficacy in non-Hodgkin's lymphoma. One immunoconjugate containing an antibody and a chemotherapy agent exhibits clinically meaningful antitumor activity in acute myeloid leukemia. Numerous efforts to exploit the ability of antibodies to focus the activities of toxic payloads at tumor sites are under way and show early promise. The ability to create essentially human antibody structures has reduced the likelihood of host-protective immune responses that otherwise limit the duration of therapy. Antibody structures now can be readily manipulated to facilitate selective interaction with host immune effectors. Other structural manipulations that improve the selective targeting properties and rapid systemic clearance of immunoconjugates should lead to the design of effective new treatments, particularly for solid tumors.
Incremental Learning in SwiftFile (2000)

SwiftFile is an intelligent assistant that helps users organize their e-mail into folders. SwiftFile uses a text classifier to predict where each new message is likely to be filed by the user and provides shortcut buttons to quickly file messages into one of its predicted folders. One of the challenges faced by SwiftFile is that the user&amp;apos;s mail-ling habits are constantly changing -- users are frequently creating, deleting and rearranging folders to meet their current ling needs. In this paper, we discuss the importance of incremental learning in SwiftFile. We present several criteria for judging how well incremental learning algorithms adapt to quickly changing data and evaluate SwiftFile&amp;apos;s classifier using these criteria. We find that SwiftFile&amp;apos;s classifier is surprisingly responsive and does not require the extensive training that is often assumed in most learning systems.
Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper:glycylglycylhistidine complex. (1983)

Ascorbate in an aqueous solution is easily oxidized by molecular oxygen in the presence of cupric ion, thus producing reactive oxygen species and exhibiting cytotoxicity. In order to increase the antitumor activity of ascorbate, we used the innocuous form of cupric ion complexed with glycylglycylhistidine, a tripeptide designed to mimic the specific Cu(II) transport site of albumin molecule. Although this square planar copper:glycylglycylhistidine complex did not significantly oxidize ascorbate at pH 7.4, it killed Ehrlich ascites tumor cells in vitro in a high concentration of ascorbate. The injections of large doses of ascorbate together with copper: glycylglycylhistidine prolonged the life span of mice inoculated i.p. with Ehrlich tumor cells. The target specificity against tumor cells was primarily attributable to their high peptide-cleaving activity.
Hierarchical Grouping to Optimize an Objective Function (1963)

Abstract A procedure for forming hierarchical groups of mutually exclusive subsets, each of which has members that are maximally similar with respect to specified characteristics, is suggested for use in large-scale (n > 100) studies when a precise optimal solution for a specified number of groups is not practical. Given n sets, this procedure permits their reduction to n − 1 mutually exclusive sets by considering the union of all possible n(n − 1)/2 pairs and selecting a union having a maximal value for the functional relation, or objective function, that reflects the criterion chosen by the investigator. By repeating this process until only one group remains, the complete hierarchical structure and a quantitative estimate of the loss associated with each stage in the grouping can be obtained. A general flowchart helpful in computer programming and a numerical example are included.
Finite groups with Sylow 2-subgroups of class two. I (1975)

In this paper we classify finite simple groups whose Sylow <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="2"> <mml:semantics> <mml:mn>2</mml:mn> <mml:annotation encoding="application/x-tex">2</mml:annotation> </mml:semantics> </mml:math> </inline-formula>-subgroups have nilpotency class two.
In situ measurement of respiratory metabolism and nitrogen fluxes at the interface of oyster beds (1988)

Nitrogen and oxygen fluxes were measured in situ during monthly dark enclosure experiments on oyster beds. The incubations were performed on undisturbed sediment with its endofauna, on 10 oysters Crassostrea gigas isolated from the substratum, and on 10 oysters associated with the sediment, to assess the impact of oyster farming on the environment. Ammonia was released by the sediment following a seasonal pattern, &splaying low winter (51 pm01 m-' h-') and hlgh spring (237 pm01 m-' h-') and autumn (264 to 369 pm01 m-' h-') rates, in accordance with changes in temperature and oxygen consumption (22 and 163 mg O2 m-2 h-' in winter and spring respectively). Nitrate was mainly absorbed into the sediment, up to 120 pm01 m-2 h-' in winter, when the water column concentration was high. Organic nitrogen (urea and primary amines) contributed significantly to increase the rate of nitrogen release during summer and autumn. In spite of a summer deficit of ammonia exchange and of inorganic and organic nitrogen accumulation into the sediment, the coupling between oxygen uptake and nitrogen release was still significant. A similar seasonal pattern governs the metabolic rates of oysters; ammonia excretion increased in spring (3.21 pm01 g-' h-') and autumn (2.5 to 6.7 pm01 g-' h-'), compared to low winter values (0.28 pm01 g-' h-'), in accordance with changes in temperature and oxygen consumption (0.14 and 1.3 mg O2 g-' h-' in winter and summer respectively). Some nitrate production was observed, suggesting occasional nitrification. Primary amine exchanges were rather erratic, whereas urea seems to play an important role seasonally as a nitrogenous end-product, in relation to a lower condition index at the end of the winter A sirnp!e budge? sf sediment-water exchanges, calculated on a m-' basis (e. g. 2 kg oysters m-'), indicates that over the year the oysters' contribution to the fluxes averages 37 and 40 % for ammonia and urea release respectively, and 26 O/ O for oxygen uptake. However, the actual contribution of oysters to the exchanges at the water-sediment interface rarely fits the expected values from potential estimates. Oxygen consumption, ammonia release and nitrate absorption of the association of oysters with sediment are mainly depressed, except durlng winter and early spring when respiration is stimulated.
The Influence of Glycosaminoglycans on the Formation of Fibers from Monomeric Tropocollagen in vitro (1973)

Well‐characterized, monomeric, lathyritic tropocollagen and a variety of well‐characterized glycosaminoglycan preparations have been used in turbidimetric studies on collagen fiber formation in vitro. The experiments have been performed under physiological ionic conditions and at 37°C. It has been shown by others that the fibrillogenetic process consists of two stages, a nucleation phase and a fiber growth phase. By addition of polysaccharides before and after the nucleation phase it was possible to differentiate between the effects of the polysaccharides on the nucleation and on the fiber‐growth, respectively. Chondroitin sulphate, dermatan sulphate, heparan sulphate, heparin and proteoglycans of chondroitin sulphate and dermatan sulphate, which at 4°C form complexes with tropocollagen, in most cases accelerated the fiber formation, when they were added before the nucleation phase. This phenomenon was ascribed to an effect on the nucleation process. When added after the nucleation phase chondroitin sulphate, a heparan sulphate fraction and especially the proteoglycans delayed the fiber formation. This observation was ascribed to an inhibition of fiber growth from the nuclei. Hyaluronic acid, which increases the activity of the tropocollagen molecules by steric exclusion, accelerated both the nucleation and the fiber growth processes. Keratan sulphate, which does not form complexes with collagen, had no or a slightly decelerating effect, either when added before or after the nucleation. It could be demonstrated by light‐scattering technique that certain glycosaminoglycans influenced the properties of the collagen fibrils formed during the early fiber formation process. The observation that certain polysaccharides had different effects on collagen fiber formation, when added before or after the nucleation, shows that the state of aggregation (nucleation) of collagen is of prime importance in determining the effects exerted by the polysaccharides. This finding may explain some of the contradictory data in the literature. Chemical and physical heterogeneity of the glycosaminoglycans also influenced their mode of interaction with collagen during fiber formation.
Pig Liver Xenotransplantation as a Bridge to Allotransplantation: Which Patients Might Benefit? (2009)

Acute liver failure is a potentially devastating clinical syndrome that, without liver transplantation (Tx), is associated with high mortality. Rapid deterioration in clinical status and a shortage of deceased human organs prohibits liver Tx in many patients. Bridging to liver Tx has been attempted by various approaches, for example, bioartificial liver support, extracorporeal pig liver perfusion, and hepatocyte Tx, but none of these approaches has convincingly improved patient survival. The orthotopic Tx of a genetically engineered pig liver could theoretically provide successful bridging. Immediate availability, perfect metabolic condition, adequate size-match and hepatocyte mass, and freedom from potentially pathogenic microorganisms could be assured. The advantages and disadvantages of bridging by pig liver Tx compared with other approaches are discussed. The selection of patients for an initial clinical trial of pig liver Tx would be similar to that of various prior trials in patients experiencing rapid and severe deterioration in liver function. The ability to give truly informed consent for a pig bridging procedure at the time of listing for liver Tx renders the patient with acute-on-chronic liver failure or primary allograft failure is a preferable candidate for this procedure than a patient who is admitted urgently with acute (fulminant) liver failure in whom consent may not be possible. Although several barriers to successful pig organ xenoTx remain, for example, coagulation dysfunction between pig and primate, if these can be resolved by further genetic engineering of the organ-source pigs, a pig liver may prove life saving to patients dying rapidly of liver failure.
Longitudinal Analysis of CD8+T Cells Specific for Structural and Nonstructural Hepatitis B Virus Proteins in Patients with Chronic Hepatitis B: Implications for Immunotherapy (2004)

The cytotoxic T-cell response in chronic hepatitis B virus (HBV) infection has been described as weak and mono- or oligospecific in comparison to the more robust virus-specific T-cell response present in resolved infection. However, chronic hepatitis B is a heterogeneous disease with markedly variable levels of virus replication and liver disease activity. Here we analyzed (both directly ex vivo and after in vitro stimulation) the HBV-specific CD8 T-cell responses against structural and nonstructural HBV proteins longitudinally in patients with different patterns of chronic infections. We found that the profiles of virus-specific CD8(+)-T-cell responses during chronic infections are highly heterogeneous and influenced more by the level of HBV replication than by the activity of liver disease. An HBV DNA load of <10(7) copies/ml appears to be the threshold below which circulating multispecific HBV-specific CD8(+) T cells are consistently detected. Furthermore, CD8(+) T cells with different specificities are differentially regulated during chronic infections. HBV core-specific CD8(+) T cells are associated with viral control, while CD8(+) T cells specific for envelope and polymerase epitopes can occasionally be found in the setting of high levels (>10(7) copies) of HBV replication. These findings have implications for the design of immunotherapy for chronic HBV infections.
Functional LCK Is Required for Optimal CD28-mediated Activation of the TEC Family Tyrosine Kinase EMT/ITK (1996)

Activation of CD28 on T lymphocytes initiates a cascade of intracellular events, which in concert with activation of the T cell receptor, culminates in production of cytokines and a functional immune response. One of the earliest biochemical changes observed following stimulation of CD28 is tyrosine phosphorylation. We have demonstrated that both the LCK and the EMT/ITK/TSK (EMT) intracellular tyrosine kinases are activated following cross-linking of CD28. Utilizing somatic cell mutants lacking LCK, we demonstrate that functional LCK is required for CD28-induced activation of EMT as evidenced by increased tyrosine phosphorylation and kinase activity. In support of a role for LCK in EMT activation, reconstitution of a LCK-negative Jurkat T cell line by transfection with normal LCK recreates CD28-mediated EMT activation. Furthermore, co-transfection of LCK and EMT into COS-7 cells showed that EMT becomes phosphorylated in the presence of LCK. In addition, increases in EMT association with CD28 were eliminated in a LCK-negative Jurkat cell line, but were restored following transfection of wild type LCK. The data are most compatible with a model in which LCK, either directly or indirectly, initiates EMT activation and association with CD28 following ligation of CD28.
Bacillus thuringiensiscrystal proteins that target nematodes (2003)

Bacillus thuringiensis (Bt) crystal proteins are pore-forming toxins used as insecticides around the world. Previously, the extent to which these proteins might also target the invertebrate phylum Nematoda has been mostly ignored. We have expressed seven different crystal toxin proteins from two largely unstudied Bt crystal protein subfamilies. By assaying their toxicity on diverse free-living nematode species, we demonstrate that four of these crystal proteins are active against multiple nematode species and that each nematode species tested is susceptible to at least one toxin. We also demonstrate that a rat intestinal nematode is susceptible to some of the nematicidal crystal proteins, indicating these may hold promise in controlling vertebrate-parasitic nematodes. Toxicity in nematodes correlates with damage to the intestine, consistent with the mechanism of crystal toxin action in insects. Structure-function analyses indicate that one novel nematicidal crystal protein can be engineered to a small 43-kDa active core. These data demonstrate that at least two Bt crystal protein subfamilies contain nematicidal toxins.
Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes (2009)

Surfactant protein (SP)-D plays an important role in host defense and pulmonary surfactant homeostasis. In SP-D-deficient (Sftpd(-/-)) mice, the abnormal large surfactant forms seen at the ultrastructural level are taken up inefficiently by type II cells, resulting in an over threefold increase in the surfactant pool size. The mechanisms by which SP-D influences surfactant ultrastructure are unknown. We hypothesized that SP-D binds to surfactant immediately after being secreted and influences surfactant ultrastructure conversion. In newborn and adult sheep lungs, immunogold-labeled SP-D was associated with both lamellated membranous lipid structures of newly secreted surfactant and with small aggregate surfactant but not with tubular myelin. Since SP-D preferentially binds to phosphatidylinositol (PI) in vitro, the postnatal changes in PI were assessed. PI content in the bronchoalveolar lavage fluid increased after birth and peaked at 2-5 days of age, a time of rapid conversion of surfactant forms that is associated with the peak of surfactant lipid pool size. SP-D selectively interacted with PI-rich liposomes in vitro, causing their lysis. Similarly, the abnormal surfactant ultrastructure in Sftpd(-/-) mice was corrected by the addition of SP-D or melittin, and both peptides caused lysis of lipid vesicles. The normal conversion of surfactant ultrastructure requires SP-D that preferentially interacts with PI-rich, newly secreted surfactant, causing lysis of surfactant lipid membranes, converting the lipid forms into smaller surfactant lamellated structures that are critical for surfactant uptake by type II cells and normal surfactant homeostasis. SP-D regulates the dramatic decreases in the surfactant pool size that occurs in the newborn period.
Biosynthesis and intracellular transport of a bile canalicular plasma membrane protein: Studies in vivo and in the perfused rat liver (1994)

B10 is an integral glycoprotein of the plasma membrane that is exclusively localized to the canalicular (apical) domain in normal rat hepatocytes but may be expressed on the basolateral (sinusoidal and lateral) membrane in pathophysiological situations. To understand how B10 may be localized to the basolateral surface, we studied the biosynthesis and transport of this apical protein. In vivo pulse-chase experiments, followed by subcellular fractionation of the liver and immunoprecipitation, showed that B10 is first synthesized as a high-mannose form of 123 kD and then matured to a complex glycosylated form of 130 kD, which peaks in the Golgi apparatus after 15 min of chase and reaches the plasma membrane with a half-time of 30 to 45 min. Analysis of the protein in plasma membrane domain fractions showed that most of the newly synthesized molecule was localized in basolateral fractions after 30 min of chase and subsequently appeared in apical fractions. After 90 min of chase, most of the radiolabeled protein had reached its steady-state apical distribution. The same experiments performed in the perfused rat liver, in which the chase can be improved, gave similar results, except that the apical distribution of the radioactive molecule was attained more quickly. Thus B10, like all apical plasma membrane proteins studied so far in hepatocytes, is first transported to the basolateral surface and then reaches the membrane of the bile canaliculi. Alterations of the transcytotic step from the basolateral to the apical surfaces may result in abnormal basolateral localization.
Inaccessible Pore Volume of Associative Polymer Floods (2010)

Abstract Approximately half of current oil production is from waterfloods where a major concern is mobility control of the injected phase. Addition of polymer to the injection water decreases the mobility ratio leading to greater flood efficiency, especially for recovery of viscous oil. Of the various EOR polymer formulations, newly developed associative, water-soluble polymers show special promise. We investigate, experimentally and numerically, the inaccessible pore volume (IPV), permeability reduction (Rk), and interfacial tension characteristics of 3 different molecular weight associative polymers and, for reference, a conventional hydrolyzed polyacrylimide. Previous studies of these same associative polymers revealed good secondary and tertiary oil recovery efficiency for displacement of a viscous 140 cP oil. To our knowledge, this is the first study to observe and report IPV – Rk properties of these associative polymer solutions. New experiments were conducted by injecting polymer solutions through a roughly 12 Darcy sandpack and measuring the separation between effluent concentration profiles of the polymer and the salt used as the tracer. Results are interpreted from the effluent profiles using an analytical superposition model as well as a conventional finite difference formulation. The associative polymers yield moderate to large IPV (20 to 40%) and mild Rk (1.1 to 1.5) that increases with molecular weight. Brine salinity reduces both IPV and permeability reduction. Differences between the classical interpretation, the analytical interpretation, and the numerical implementation of IPV are discussed as is the adequacy of the conventional IPV-Rk description of the mobility control of polymer.
Why Does Cisplatin Reach Guanine-N7 with Competing S-Donor Ligands Available in the Cell? (1999)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTWhy Does Cisplatin Reach Guanine-N7 with Competing S-Donor Ligands Available in the Cell?Jan ReedijkView Author Information Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands Cite this: Chem. Rev. 1999, 99, 9, 2499–2510Publication Date (Web):August 21, 1999Publication History Received16 February 1999Revised25 May 1999Published online21 August 1999Published inissue 8 September 1999https://pubs.acs.org/doi/10.1021/cr980422fhttps://doi.org/10.1021/cr980422fresearch-articleACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views3207Altmetric-Citations690LEARN 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-Alertsclose SUBJECTS:Antineoplastic agents,Genetics,Ligands,Peptides and proteins,Platinum Get e-Alerts
Fleet Management Trials in Western Canada (1991)

&lt;div class="htmlview paragraph"&gt;THE PURPOSE of this paper is to describe the components of a fleet management system and the preliminary findings of two demonstration projects. Being Canadian based, the paper opens with an overview of the Canadian road-vehicle system. Statistics are given for the road network and the estimated numbers of various types of vehicles. The Canadian Vision 2000 initiative, which is being spear headed by Communications Canada, and consists of approximately 50 communications related companies working in various consortiums, is briefly described. A Western Canadian consortia, consisting of a communications manufacturer, a systems integrator and two carriers, are carrying out various demonstration projects over the next three years. The first project discussed is an assessment of current Canadian digital mapping data for the application of vehicle navigation systems and the second is a test with the Calgary Police Department using Pulsearch's NavTrax™ fleet management system in five vehicles. Some conclusions based on experience to date conclude the paper.&lt;/div&gt;