gebhart/patrepeval huggingface dataset:
A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19+tumor cells (2015)

To harness the potent tumor-killing capacity of T cells for the treatment of CD19(+) malignancies, we constructed AFM11, a humanized tetravalent bispecific CD19/CD3 tandem diabody (TandAb) consisting solely of Fv domains. The molecule exhibits good manufacturability and stability properties. AFM11 has 2 binding sites for CD3 and 2 for CD19, an antigen that is expressed from early B cell development through differentiation into plasma cells, and is an attractive alternative to CD20 as a target for the development of therapeutic antibodies to treat B cell malignancies. Comparison of the binding and cytotoxicity of AFM11 with those of a tandem scFv bispecific T cell engager (BiTE) molecule targeting the same antigens revealed that AFM11 elicited more potent in vitro B cell lysis. Though possessing high affinity to CD3, the TandAb mediates serial-killing of CD19(+) cells with little dependence of potency or efficacy upon effector:target ratio, unlike the BiTE. The advantage of the TandAb over the BiTE was most pronounced at lower effector:target ratios. AFM11 mediated strictly target-dependent T cell activation evidenced by CD25 and CD69 induction, proliferation, and cytokine release, notwithstanding bivalent CD3 engagement. In a NOD/scid xenograft model, AFM11 induced dose-dependent growth inhibition of Raji tumors in vivo, and radiolabeled TandAb exhibited excellent localization to tumor but not to normal tissue. After intravenous administration in mice, half-life ranged from 18.4 to 22.9 h. In a human ex vivo B-cell chronic lymphocytic leukemia study, AFM11 exhibited substantial cytotoxic activity in an autologous setting. Thus, AFM11 may represent a promising therapeutic for treatment of CD19(+) malignancies with an advantageous safety risk profile and anticipated dosing regimen.
Regulation of Mammary Stem/Progenitor Cells by PTEN/Akt/β-Catenin Signaling (2009)

Recent evidence suggests that many malignancies, including breast cancer, are driven by a cellular subcomponent that displays stem cell-like properties. The protein phosphatase and tensin homolog (PTEN) is inactivated in a wide range of human cancers, an alteration that is associated with a poor prognosis. Because PTEN has been reported to play a role in the maintenance of embryonic and tissue-specific stem cells, we investigated the role of the PTEN/Akt pathway in the regulation of normal and malignant mammary stem/progenitor cell populations. We demonstrate that activation of this pathway, via PTEN knockdown, enriches for normal and malignant human mammary stem/progenitor cells in vitro and in vivo. Knockdown of PTEN in normal human mammary epithelial cells enriches for the stem/progenitor cell compartment, generating atypical hyperplastic lesions in humanized NOD/SCID mice. Akt-driven stem/progenitor cell enrichment is mediated by activation of the Wnt/beta-catenin pathway through the phosphorylation of GSK3-beta. In contrast to chemotherapy, the Akt inhibitor perifosine is able to target the tumorigenic cell population in breast tumor xenografts. These studies demonstrate an important role for the PTEN/PI3-K/Akt/beta-catenin pathway in the regulation of normal and malignant stem/progenitor cell populations and suggest that agents that inhibit this pathway are able to effectively target tumorigenic breast cancer cells.
A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas (2002)

Natural killer (NK) T cells initiate potent antitumor responses when stimulated by exogenous factors such as interleukin (IL)-12 or alpha-galactosylceramide (alpha-GalCer), however, it is not clear whether this reflects a physiological role for these cells in tumor immunity. Through adoptive transfer of NK T cells from wild-type to NK T cell-deficient (T cell receptor [TCR] Jalpha281-/-) mice, we demonstrate a critical role for NK T cells in immunosurveillance of methylcholanthrene (MCA)-induced fibrosarcomas, in the absence of exogenous stimulatory factors. Using the same approach with gene-targeted and/or antibody-depleted donor or recipient mice, we have shown that this effect depends on CD1d recognition and requires the additional involvement of both NK and CD8+ T cells. Interferon-gamma production by both NK T cells and downstream, non-NK T cells, is essential for protection, and perforin production by effector cells, but not NK T cells, is also critical. The protective mechanisms in this more physiologically relevant system are distinct from those associated with alpha-GalCer-induced, NK T cell-mediated, tumor rejection. This study demonstrates that, in addition to their importance in tumor immunotherapy induced by IL-12 or alpha-GalCer, NK T cells can play a critical role in tumor immunosurveillance, at least against MCA-induced sarcomas, in the absence of exogenous stimulation.
Cytotoxic Constituents from Hyptis verticillata (1993)

A new cytotoxic (P-388 ED50 4 microgm/ml) arylnaphthalene lignan has been isolated from the Mexican medicinal plant Hyptis verticillata (Lamiaceae) and characterized as 5-methoxydehydropodophyllotoxin [1]. Eight additional lignans were also obtained by bioactivity-directed fractionation using the brine shrimp lethality test. Of these, the dehydro-beta-peltatin methyl ether 2 (P-388 ED50 1.8 microgm/ml) is reported for the first time as a natural product isolate. The other bioactive compounds were identified as dehydropodophyllotoxin [3], deoxydehydropodophyllotoxin [4]. (--)-yatein [5], 4'-demethyldeoxypodophyllotixin [6], isodeoxypodophyllotoxin [7], deoxypicropodophyllin [8], and beta-apopicropodophyllin [9]. Each of these compounds was evaluated against a panel of cell lines comprising a number of human cancer cell types [breast, colon, fibrosarcoma, lung, prostate, KB, and KB-VI (a multi-drug resistant cell line derived from KB)] and murine lymphocytic leukemia (P-388). Lignans 1-4 showed marginal cytotoxic activity against the human cell lines tested. In contrast, compounds 5-9 demonstrated a general nonspecific activity comparable to that of podophyllotoxin [12] (ED50 < 10-2 microgm/ml). In addition, the antimitotic potential of these compounds was determined in the astrocytoma (ASK) assay. Finally, the plant was also shown to contain the flavonoid sideritoflavone (KB ED50 1.6 microgm/ml) and the known pentacyclic triterpenoids ursolic, maslinic, 2 alpha-hydroxyursolic and oleanolic acids.
Heterogeneous calcium flux in peripheral T cell subsets revealed by five‐color flow cytometry using log‐ratio circuitry (1995)

Abstract Calcium flux measurements of different subpopulations of cells by flow cytometry are important in understanding complex interactions in the immune system. This paper discusses the use of the difference of Log signals as a preferred method for obtaining this information simultaneously with other immunofluorescence parameters. We describe simple modifications to a commercial instrument that enables the measurement of calcium flux in addition to three immunofluorescence paramein. Finally, we show an application of this technique to measuring calcium flux of T cell subsets in human blood. We show that different subsets of peripheral CD4 T cells have significantly different capabilities to flux calcium after CD3 stimulation. These differences are related to the functional capacities of the cells within these subsets. © 1995 Wiley‐Liss, Inc.
Synthetic mimetics of protein secondary structure domains (2010)

Proteins modulate the majority of all biological functions and are primarily composed of highly organized secondary structural elements such as helices, turns and sheets. Many of these functions are affected by a small number of key protein-protein contacts, often involving one or more of these well-defined structural elements. Given the ubiquitous nature of these protein recognition domains, their mimicry by peptidic and non-peptidic scaffolds has become a major focus of contemporary research. This review examines several key advances in secondary structure mimicry over the past several years, particularly focusing upon scaffolds that show not only promising projection of functional groups, but also a proven effect in biological systems.
Changes in ruminal bacterial community composition following feeding of alfalfa ensiled with a lactic acid bacterial inoculant (2011)

Some silage inoculants help to improve silage quality and promote an increase in milk production, possibly through altering the rumen microflora. We hypothesized that rumen bacterial community composition (BCC) would be different in cows fed alfalfa ensiled with the inoculant Lactobacillus plantarum MTD/1 (LP) compared with those fed alfalfa ensiled without the inoculant (Ctrl). Eight ruminally cannulated Holstein cows were allotted to 2 diets (Ctrl or LP) in a double crossover design with four 28-d periods. Diets were formulated to contain (% dry matter basis) 28.0% neutral detergent fiber and 16.2% crude protein, and contained alfalfa silage, 50.9; corn silage, 20.6; high-moisture shelled corn, 21.4; soy hulls, 4.7; plus minerals and vitamins, 2.4. Ruminal digesta were collected just before feeding on 3 consecutive days near the end of each period, and were separated into solid and liquid phases. Microbial DNA was extracted from each phase, amplified by PCR using domain-level bacterial primers, and subjected to automated ribosomal intergenic spacer analysis. The pH was 4.56 and 4.86 and the lactate-to-acetate ratio 9.8 and 4.4, respectively, for the treated and untreated alfalfa silages. Dry matter intakes and milk production data were not influenced by diets but showed a cow effect. Total volatile fatty acids (mM) tended to be greater for LP compared with Ctrl. Individual volatile fatty acids were not influenced by diets but showed a significant cow effect. Ruminal acetate (mol/100 mol) and acetate-to-propionate ratio were lower and propionate (mol/100 mol) greater for the 2 milk fat-depressed (MFD; <3.2% fat content) cows compared with the other 6 cows. Correspondence analysis of the 265 peaks in the automated ribosomal intergenic spacer analysis profile across the 188 samples revealed that the first 2 components contributed 7.1 and 3.8% to the total variation in the profile. The ordination points representing the liquid and solid phases clustered separately, indicating that these phases differed in BCC. The analysis of similarity data showed differences between Ctrl and LP. The lactic acid bacterial counts (log(10) cfu/g of wet silage) were 3.94 and 4.53 for the untreated and treated silage, respectively, at ensiling. The relative population size (RPS) of L. plantarum, determined by real-time PCR of 16S rRNA gene copies, was greater in LP compared with Ctrl. The ordination points corresponding to certain individual cows clustered separately, and the most distinctive bacterial communities were those associated with MFD cows. The RPS of Megasphaera elsdenii was greater in 1 of the 2 MFD cows, although mean RPS of M. elsdenii did not differ between the treatments. In addition to the differences in rumen BCC between LP and Ctrl, MFD cows also displayed differences in BCC compared with cows with normal milk fat yield.
Enantioselective Reactions of Donor/Acceptor Carbenoids Derived from α-Aryl-α-Diazoketones (2009)

The reaction of a variety of alpha-aryl-alpha-diazo ketones with activated olefins, catalyzed by the adamantyl glycine-derived dirhodium complex Rh(2)(S-PTAD)(4), generates cyclopropyl ketones with high diastereoselectivity (up to >95:5 dr) and enantioselectivity (up to 98% ee). Intermolecular C-H functionalization of 1,4-cyclohexadiene by means of carbenoid-induced C-H insertion was also possible with this type of carbenoid.
Perspectives in Molecular Sieve Science (1988)

The characterization of catalysts before, during, and after their catalytic evaluation is essentiel. Nuclear magnetic resonance (NMR) is a well-suited technique to observe subtle changes in zeolite catalysts as their composition is made of several NMR-sensitive nuclei such as 27Al, 29Si, and 17O as well as others, i.e., 7Li, 23Na, etc... corresponding to exchange cations. In addition, the method can also be used to study the behavior of adsorbed molecules and of carbonaceous deposits during or after testing. In this review paper, we focus our attention on the characterization of the as-synthesized zeolites, the changes occurring during their pretreatment and/or subsequent modifications (calcination, steaming, dealumination, isomorphous substitution in their framework), and the conversion of adsorbed reactants.
Chunks in expert memory: Evidence for the magical number four … or is it two? (2004)

This study aims to test the divergent predictions of the chunking theory (Chase & Simon, 1973) and template theory (Gobet & Simon, 1996a, 2000) with respect to the number of chunks held in visual short-term memory and the size of chunks used by experts. We presented game and random chessboards in both a copy and a recall task. In a within-subject design, the stimuli were displayed using two presentation media: (a) physical board and pieces, as in Chase and Simon's (1973) study; and (b) a computer display, as in Gobet and Simon's (1998) study. Results show that, in most cases, no more than three chunks were replaced in the recall task, as predicted by template theory. In addition, with game positions in the computer condition, chess Masters replaced very large chunks (up to 15 pieces), again in line with template theory. Overall, the results suggest that the original chunking theory overestimated short-term memory capacity and underestimated the size of chunks used, in particular with Masters. They also suggest that Cowan's (2001) proposal that STM holds four chunks may be an overestimate.
Cytomegalovirus infection in infants:Report of 25 cases (2004)

Objective:To explore the clinical features of infants infected with cytomegalovirus(CMV) and investigate the detection methods and treatment.Methods:The clinical data of 25 infants with CMV infection confirmed by detection of serum CMV-IgM using enzyme immunodot technic were analyzed.Results:Of the 25 patients,bronchopneumonia accounted for 11 cases(44%),central nervous system damage 11 cases(44%)and hyperbilirubinemia 8 cases(32%).All the patients were treated with ganciclovir.Bronchopneumonia was cured in 8 cases and improved in 3 cases.Central nervous system damage was cured in 1 case,improved in (9 cases) and uncured in 1 case.Hyperbilirubinemia was cured in 2 cases and improved in 6 cases.Conclusions:The most common manifestations of CMV infection in infants include bronchopneumonia,central nerves system damage and hyperbilirubinemia.The presence of serum CMV-IgM antibody is a laboratory diagnostic evidence.Ganciclovir is the choice of treatment for CMV infection.
Tracking from multiple view points: Self-calibration of space and time (2003)

This paper tackles the problem of self-calibration of multiple cameras which are very far apart. Given a set of feature correspondences one can determine the camera geometry. The key problem we address is finding such correspondences. Since the camera geometry (location and orientation) and photometric characteristics vary considerably between images one cannot use brightness and/or proximity constraints. Instead we propose a three step approach: first we use moving objects in the scene to determine a rough planar alignment, next we use static features to improve the alignment, finally we compute the epipolar geometry from the the homography matrix of the planar alignment. We do not assume synchronized cameras and we show that enforcing geometric constraints enables us to align the tracking data in time. We present results on challenging outdoor scenes using real time tracking data.
Semiclassical molecular dynamics computation of spontaneous light emission in the condensed phase: Resonance Raman spectra (2001)

The three-time correlation function that describes resonance Raman (RR) spectra is computed directly using the Herman–Kluk semiclassical propagator. The trace expression for this correlation function {C(t1,t2,t3)=Tr[e−βĤe−iĤg(t1+t2)e−iĤet3e+iĤg(t2+t3)e+iĤet1]} allows forward–backward time propagation of trajectories over closed time-circuits, leading to efficient convergence in multidimensional systems. A local harmonic approximation is used to derive an expression for the density operator in the coherent state representation (〈p1 q1|e−βĤ|p2 q2〉). This allows efficient sampling of phase space as well as simulations at arbitrary temperatures and in arbitrary coordinates. The resulting method is first analyzed for a one-dimensional problem, where the results are shown to be in excellent agreement with exact quantum calculations. The method is then applied to the problem of RR scattering of iodine in the condensed phase. The RR spectrum of an I2 molecule in a xenon fluid at 230 K is calculated and also found to be in excellent agreement with experiment.
The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. (1990)

Staphylococcal enterotoxin B (SEB) has been shown in the past to be a potent T cell stimulant in mouse or man. The toxin acts as a superantigen that is, it binds to class II MHC proteins and, as such a complex, stimulates T cells bearing particular V beta s as part of their receptors. The toxin also has several pathological effects, causing, in mice, rapid weight loss, thymus atrophy, immunosuppression, and, at high doses, death. The data in this paper show that at least one of these effects, weight loss, is T cell mediated. Staphylococcal enterotoxin-mediated weight loss is MHC dependent, and is almost absent in animals expressing MHC class II molecules, which, complexed with SEB, are poor T cell stimulants. Also, mice that lack T cell function, genetically or because of cyclosporin A treatment, lose no or less weight than controls in response to SEB. Finally, animals bred such that they express few T cells bearing V beta s with which SEB can interact lose much less weight in response to the toxin than littermate controls that have higher numbers of reactive T cells. It is therefore suggested that the pathological effects of the staphylococcal, T cell-stimulating toxins in mouse and man may be partially or wholly the consequence of massive T cell stimulation.
Phytochrome D Acts in the Shade-Avoidance Syndrome in Arabidopsis by Controlling Elongation Growth and Flowering Time1 (1999)

Shade avoidance in higher plants is regulated by the action of multiple phytochrome (phy) species that detect changes in the red/far-red ratio (R/FR) of incident light and initiate a redirection of growth and an acceleration of flowering. The phyB mutant of Arabidopsis is constitutively elongated and early flowering and displays attenuated responses to both reduced R/FR and end-of-day far-red light, conditions that induce strong shade-avoidance reactions in wild-type plants. This indicates that phyB plays an important role in the control of shade avoidance. In Arabidopsis phyB and phyD are the products of a recently duplicated gene and share approximately 80% identity. We investigated the role played by phyD in shade avoidance by analyzing the responses of phyD-deficient mutants. Compared with the monogenic phyB mutant, the phyB-phyD double mutant flowers early and has a smaller leaf area, phenotypes that are characteristic of shade avoidance. Furthermore, compared with the monogenic phyB mutant, the phyB-phyD double mutant shows a more attenuated response to a reduced R/FR for these responses. Compared with the phyA-phyB double mutant, the phyA-phyB-phyD triple mutant has elongated petioles and displays an enhanced elongation of internodes in response to end-of-day far-red light. These characteristics indicate that phyD acts in the shade-avoidance syndrome by controlling flowering time and leaf area and that phyC and/or phyE also play a role.
Hydrogen-Bonding-Induced Phenomena in Bifunctional Heteroazaaromatics (2003)

Ground and excited state processes induced by hydrogen bond formation are discussed for a family of heterocyclic compounds which possess both a proton donor (pyrrole NH group) and an acceptor (pyridine-type nitrogen). Excited state double proton transfer and rapid S(0) <-- S(1) internal conversion are observed only for molecules capable of forming cyclic, multiply hydrogen-bonded complexes. If the 1:1 cyclic, doubly hydrogen-bonded solvate is present in the ground state, the phototautomerization occurs even in rigid solvents at low temperatures. Internal conversion process requires solvent rearrangement and, therefore, does not proceed in a rigid environment. Another type of fluorescence quenching was also detected, involving photoinduced electron transfer from an excited chromophore to an aromatic hydrogen-bonded acceptor, such as pyridine. In molecules consisting of proton donor and acceptor units linked by a single bond, syn-anti rotamerization caused by hydrogen bonding is observed.
Concentration dependence of transcriptional transactivation in inducible E1A-containing human cells. (1988)

The adenovirus E1A proteins are essential for the normal temporal activation of transcription from every other adenoviral early promoter. High-level E1A expression in the absence of viral infection would facilitate biochemical studies of E1A-mediated transactivation. Toward this end, we introduced the adenovirus type 2 E1A gene under the control of the murine mammary tumor virus promoter into HeLa cells. Uninduced cells expressed little or no detectable E1A mRNA. Upon induction, mRNA levels accumulated to about 50% of the level observed in 293 cells. The level of E1A expression in these cells could be controlled by varying the concentration of the inducing glucocorticoid. Under these conditions of varying E1A concentrations, it was observed that activation of the E2, E3, and E4 promoters of H5dl312 initiated at the same E1A concentration and that transcription from each promoter increased as the E1A concentration increased. These results indicate that E1A-mediated transactivation is proportional to the concentration of E1A protein. E1A-dependent transcriptional stimulation of the E4 promoter was reproduced in an in vitro transcription system, demonstrating that expression of only the E1A proteins was sufficient to increase the transcriptional activity of nuclear extracts.
SYNTHESIS OF METALLOPHTHALOCYANINES FROM PHTHALONITRILE WITH STRONG ORGANIC BASES (1983)

Abstract Several metallophthalocyanines (MPc: M=Ni(II), Co(II), Zn(II), Pb(II), Fe(II), Sn(II), Cd(II), Mg(II), and Mn(III)) were obtained by heating phthalonitrile with metal salts in alcohols in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene. Metal acetylacetonates as well as metal halides were available as metal sources for preparation of metallophthalocyanines by this method.
Structure-activity relationship of calcitonin gene-related peptide and its receptor (2000)

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Nano Wheat Fields Prepared by Plasma-Etching Gold Nanowire-Containing Membranes (2003)

The template method is a general approach for preparing nanomaterials, in particular nanowires and nanotubes. The ability to control the dimensions of the nanowires and tubes obtained is an important feature of the template method. Diameter can be controlled at will by varying the diameter of the pores in the template membrane. The lengths of the nanostructures can be controlled by varying the thickness of the template membrane. We report here a new approach for effectively controlling the lengths of template-synthesized nanostructures. This method is illustrated with gold nanowires deposited within the pores of a polycarbonate template membrane. When these nanowire-containing membranes are exposed to an O2 plasma, the polymer at the membrane surface is selectively removed, thus exposing the ends of the Au nanowires. The length of the exposed nanowire can be controlled at will by varying the plasma etch time. The protruding ends of the Au nanowires resemble wheat fields.