gebhart/patrepeval huggingface dataset:
Coexpression of the T-cell receptor constant α domain triggers tumor reactivity of single-chain TCR-transduced human T cells (2010)

Transfer of tumor antigen-specific T-cell receptors (TCRs) into human T cells aims at redirecting their cytotoxicity toward tumors. Efficacy and safety may be affected by pairing of natural and introduced TCRalpha/beta chains potentially leading to autoimmunity. We hypothesized that a novel single-chain (sc)TCR framework relying on the coexpression of the TCRalpha constant alpha (Calpha) domain would prevent undesired pairing while preserving structural and functional similarity to a fully assembled double-chain (dc)TCR/CD3 complex. We confirmed this hypothesis for a murine p53-specific scTCR. Substantial effector function was observed only in the presence of a murine Calpha domain preceded by a TCRalpha signal peptide for shuttling to the cell membrane. The generalization to a human gp100-specific TCR required the murinization of both C domains. Structural and functional T-cell avidities of an accessory disulfide-linked scTCR gp100/Calpha were higher than those of a dcTCR. Antigen-dependent phosphorylation of the proximal effector zeta-chain-associated protein kinase 70 at tyrosine 319 was not impaired, reflecting its molecular integrity in signaling. In melanoma-engrafted nonobese diabetic/severe combined immunodeficient mice, adoptive transfer of scTCR gp100/Calpha transduced T cells conferred superior delay in tumor growth among primary and long-term secondary tumor challenges. We conclude that the novel scTCR constitutes a reliable means to immunotherapeutically target hematologic malignancies.
The Shape of Things to Come: Importance of Design in Nanotechnology for Drug Delivery (2012)

The design of nanoparticle (NP) size, shape and surface chemistry has a significant impact on their performance. While the influences of the particle size and surface chemistry on drug delivery have been studied extensively, little is known about the effect of particle shapes on nanomedicine. In this perspective article, we discuss recent progress on the design and fabrication of NPs of various shapes and their unique delivery properties. The shapes of these drug carriers play an important role in therapeutic delivery processes, such as particle adhesion, distribution and cell internalization. We envision that stimuli-responsive NPs, which actively change their shapes and other properties, might pave way to the next generation of nanomedicine.
Integrated grating demultiplexer and pin array for high-density wavelength division multiplexed detection at 1.5 μm (1993)

An integrated wavelength demultiplexer and pin detector array is reported for high density WDM detection at 1.5 μm. Signals spaced at 1 nm over the 1.48–1.55 μm wavelength range are separated and detected; channel passbands are 0.6–0.8 nm. Grown on a semi-insulating substrate, and providing a pseudoplanar device surface, the HD-WDM detector array is suitable for monolithic integration with high-speed multichannel receiver circuitry.
Acute Otitis Media Caused by Branhamella catarrhalis: Biology and Therapy (1987)

Since 1980, we have observed an epidemic of otitis media caused by Branhamella catarrhalis. This event was characterized by studying the nasopharyngeal colonization of infants and children with B. catarrhalis and the clinical presentation and therapeutic outcome of acute otitis media caused by this organism. Pharyngeal colonization with B. catarrhalis was commoner in winter than summer. B. catarrhalis was present in middle-ear fluid (MEF) of 17% of children with otitis media, and was commoner in fall and winter (20%) than in spring and summer (11%, P less than .05). Seventy-five percent of isolates produced beta-lactamase (Ravasio type). In five of 20 patients, treatment with beta-lactamase-susceptible agents failed to sterilize B. catarrhalis-infected MEF. All of these five patients were infected with beta-lactamase-producing strains. The increasing prominence of antibiotic-resistant B. catarrhalis in acute otitis media may lead to a reevaluation of initial antibiotic therapy for acute otitis media, particularly in winter or in areas where colonization with such strains is prevalent.
Functionalized Bis(thiosemicarbazonato) Complexes of Zinc and Copper:  Synthetic Platforms Toward Site-Specific Radiopharmaceuticals (2006)

Two new types of unsymmetrical bis(thiosemicarbazone) proligands and their neutral zinc(II) and copper(II) complexes have been synthesized. These bifunctional ligands both chelate the metal ions and provide pendent amino groups that can be readily functionalized with biologically active molecules. Functionalization has been demonstrated by the synthesis of three water-soluble glucose conjugates of the new zinc(II) bis(thiosemicarbazonato) complexes, and their copper(II) analogues have been prepared in aqueous solution via transmetalation. A range of techniques including NMR, electron paramagnetic resonance, cyclic voltammetry, high-performance liquid chromatography (HPLC), UV/vis, and fluorescence emission spectroscopy have been used to characterize the complexes. Four compounds, including two zinc(II) complexes, have been characterized by X-ray crystallography. The connectivity and conformation of the glucose conjugates have been assigned by NMR spectroscopy. Time-dependent density functional theory calculations have been used to assign the electronic transitions of the copper(II) bis(thiosemicarbazonato) chromophore. Two copper-64-radiolabeled complexes, including one glucose conjugate, have been prepared and characterized using radio-HPLC, and transmetalation is shown to be a viable method for radiolabeling compounds with copper radionuclides. Preliminary cell washout studies have been performed under normoxic conditions, and the uptake and intracellular distribution have been studied using confocal fluorescence microscopy.
Contact Adhesion of Thin Gold Films on Elastomeric Supports: Cold Welding Under Ambient Conditions (1991)

Thin gold films placed in contact on compliant elastomeric poly(dimethylsiloxane) supports weld together. This ;;cold welding'' is remarkable both for the low loads required and for the fact that it occurs under ambient laboratory conditions, conditions in which the gold surfaces are covered with films of weakly adsorbed organic impurities. These impurities are probably displaced laterally during the welding. Welding can be prevented by the presence of a self-assembled gold(I) alkylthiolate monolayer on the gold surfaces. The welded contacts have low electrical resistivity and can be made thin enough to transmit light. This system is a promising one with which to study interaction between interfaces.
Recording monophasic action potentials using a platinum-electrode ablation catheter (2000)

(1) Platinum electrodes can be used for timely recording of MAPs in patients. (2) It is feasible to record MAPs and deliver radiofrequency currents via the same platinum-tip electrode. These findings suggest that MAP-guided catheter ablation is technically possible.
N-terminal pro-atrial natriuretic peptide (N-ANP) and N-terminal pro-B-type natriuretic peptide (N-BNP) in the prediction of death and heart failure in unselected patients following acute myocardial infarction (2004)

Elevated plasma natriuretic peptide levels after AMI (acute myocardial infarction) are associated with adverse outcome. The aim of the present study was to examine the relationship of plasma N-ANP (N-terminal pro-atrial natriuretic peptide) and N-BNP (N-terminal pro-B-type natriuretic peptide) with mortality and heart failure following AMI. We studied 403 patients with AMI. Blood was sampled for measurement of N-ANP and N-BNP on a single occasion between 72 and 96 h after symptom onset. Natriuretic peptide levels were related to all-cause mortality and heart failure episodes. During follow up (median, 462 days; range 5-764), 43 (10.7%), 25 (6.2%) and 49 (12.2%) patients suffered death, heart failure hospitalization and outpatient heart failure respectively. Only N-BNP (P < 0.0005), N-ANP (P = 0.005) and previous AMI (P = 0.016) were independently predictive of death. N-BNP, but not N-ANP, predicted 30-day mortality. N-ANP, but not N-BNP, predicted mortality after 30 days. N-BNP was the better predictor of heart failure. N-ANP and N-BNP were above the median in 35 and 38 respectively, of 43 patients who later died. N-ANP, N-BNP, or both were above the median in 41 out of 43 patients. Of 25 patients hospitalized with heart failure, N-ANP and N-BNP was above the median in 20 and 24 respectively, and one or other was elevated in all cases. Above-median N-ANP predicted 36 and N-BNP predicted 41 out of 49 episodes of outpatient heart failure. One or other peptide was above the median in 45 out of 49 patients. Our results indicate that N-BNP predicts 30-day and N-ANP >30-day mortality. We conclude that consideration of both N-ANP and N-BNP identifies a greater number of patients at risk of death or heart failure than either peptide alone.
Interleukin-6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte–dendritic cell cross-talk (2006)

Anti-tumour T cell response requires antigen presentation via efficient immunological synapse between antigen presenting cells, e.g. dendritic cells (DC), and specific T cells in an adapted Th1 cytokine context. Nine renal cell carcinoma (RCC) primary culture cells were used as sources of tumour antigens which were loaded on DC (DC-Tu) for autologous T cell activation assays. Cytotoxic activity of lymphocytes stimulated with DC-Tu was evaluated against autologous tumour cells. Assays were performed with 75 grays irradiated tumour cells (Tu irr) and with hydrogen peroxide +/- heat shock (Tu H(2)O(2) +/- HS) treated cells. DC-Tu irr failed to enhance cytotoxic activity of autologous lymphocytes in seven of 13 assays. In all these defective assays, irradiated tumour cells displayed high interleukin (IL)-6 and vascular endothelial growth factor (VEGF) release. Conversely, when tumour cells released low IL-6 levels (n = 4), DC-Tu irr efficiently enhanced CTL activity. When assays were performed with the same RCC cells treated with H(2)O(2) + HS, DC-Tu stimulation resulted in improved CTL activity. H(2)O(2) + HS treatment induced post-apoptotic cell necrosis of tumour cells, totally abrogated their cytokine release [IL-6, VEGF, transforming growth factor (TGF)-beta1] and induced HSP70 expression. Taken together, data show that reduction in IL-6 and VEGF release in the environment of the tumour concomitantly to tumour cell HSP expression favours induction of a stronger anti-tumour CTL response.
Temperature-insensitive arrayed waveguide gratings on InP substrates (2002)

The temperature dependence of wavelength in optical devices is a serious issue in building high-density WDM optical networks. The lasing wavelength of semiconductor lasers and the central wavelength in the semiconductor optical filters have a typical temperature dependence of 1 /spl Aring///spl deg/C or higher. This is too high for these lasers to be used without temperature control units in WDM systems, which typically have a few hundreds of GHz spacing and temperature variation up to a few tens of degrees centigrade. Recently, we fabricated temperature-insensitive optical filters (TIOF) with the InGaAsP/InP material system. Although the operation principle of the TIOF was clearly verified in that work, the filtering characteristics of the device were relatively unsuitable for multiplexing or demultiplexing devices. In this presentation, by extending the principle of the TIOF to arrayed waveguide grating, we propose a novel temperature-insensitive arrayed waveguide grating and show its highly feasible filtering characteristics for practical applications.
Thermodynamics of Ligand Binding to the Starch‐Binding Domain of Glucoamylase from Aspergillus Niger (1994)

The thermodynamics of ligand binding to the starch-binding domain (SBD) of glucoamylase from Aspergillus niger has been studied using titration calorimetry. The ligand binding was studied both with the SBD fragment as well as glucoamylase G1 which contains both a catalytic domain and SBD. The ligands were beta-cyclodextrin and three thiopanose analogues [panose = alpha-D-Glcp-(1-->6)-alpha-D-Glcp-(1-->4)-D-Glcp] each including an alpha-(1-->6) thioglycosidic linkage at the non-reducing end. beta-Cyclodextrin binds more strongly than the thiopanose analogues and these have a slightly increasing binding constant with chain length. The reactions are enthalpy-driven with unfavourable contributions from entropy and the variations in enthalpy and entropy compensate each other linearly. SBD was shown to have two binding sites that appear to bind identically and independently in the isolated binding domain, whereas they interact with each other in a negatively cooperative fashion when the catalytic domain of glucoamylase is present (glucoamylase G1). In glucoamylase G1 one site of SBD has an increased binding constant compared to the SBD fragment, whereas the other has the same association constant. The change in binding constant and induced cooperativity were not due to interactions with the catalytic binding site, since binding of beta-cyclodextrin was the same both when the catalytic site was occupied by the strong inhibitor acarbose and when the catalytic site was free.
Reagent or myeloperoxidase-generated hypochlorite affects discrete regions in lipid-free and lipid-associated human apolipoprotein A-I (2000)

We have previously shown that the modification of high-density lipoprotein subclass 3 (HDL(3)) by HOCl transformed an anti-atherogenic lipoprotein into a high-uptake form for macrophages and caused a significant impairment of cholesterol efflux capacity [Panzenboeck, Raitmayer, Reicher, Lindner, Glatter, Malle and Sattler (1997) J. Biol. Chem. 272, 29711-29720]. To elucidate the consequences of treatment with OCl(-) on distinct regions in apolipoprotein A-I (apo A-I), lipid-free and lipid-associated apo A-I were modified with increasing molar ratios of NaOCl or HOCl generated by the myeloperoxidase/H(2)O(2)/Cl(-) system. CD analysis revealed a pronounced decrease in alpha-helicity for lipid-free apo A-I modified by NaOCl, whereas lipid-associated apo A-I was less affected. The modification of apo A-I by NaOCl (molar oxidant-to-lipoprotein ratio 6:1) resulted in the formation of two distinct oxidized forms of apo A-I with molecular masses 32 or 48 atomic mass units (a.m.u.) higher than that of native apo A-I, indicating the addition of two or three oxygen atoms to the native protein. HPLC analysis of tryptic digests obtained from lipid-free and lipid-associated apo A-I modified with increasing oxidant-to-apolipoprotein molar ratios revealed a concentration-dependent modification of apo A-I: at a low molar oxidant-to-lipoprotein ratio (5:1) the peaks corresponding to the methionine-containing tryptic peptides T11 (residues 84-88), T16 (residues 108-116) and T22 (residues 141-149), located in the central region of apo A-I, disappeared. Their loss was accompanied by the formation of three oxidation products with a molecular mass 16 a.m.u. higher than that of the native peptides. This indicates the addition of oxygen, most probably caused by the oxidation of Met(86), Met(112) and Met(148) to the corresponding methionine sulphoxides. At a molar NaOCl-to-apo A-I ratio of 10:1 the disappearance of peptides T1 (residues 1-10), T7 (residues 46-59) and T9 (residues 62-77) was accompanied by the occurrence of new peaks 33.5 and 33.1 a.m.u. higher than those of the native peptides. Amino acid analyses of peptides T7 and T9 after modification with NaOCl confirmed that Phe(57) and Phe(71) were primary targets for oxidation by HOCl. GLC-MS analysis of hydrolysates obtained from OCl(-)-modified T7, T9, apo A-I and HDL(3) confirmed that Phe residues are an early target for OCl(-) modification. At molar NaOCl-to-apo A-I ratios of 25:1, the peak areas of peptides T31 (residues 189-195) and T32 (residues 196-206) decreased markedly. Most importantly, incubation of apo A-I with the myeloperoxidase/H(2)O(2)/Cl(-) system (the source of HOCl in vivo) resulted in almost identical modification patterns to those observed with reagent NaOCl.
Induction of vascular permeability enhancement by human tryptase: dependence on activation of prekallikrein and direct release of bradykinin from kininogens. (1996)

Tryptase is a trypsin-type serine protease that is released from mast cells. Bradykinin (BK) is released directly from kininogens or through activation of either Hageman factor or subsequent plasma prekallikrein. Its nasal administration or inhalation induces allergy-like symptoms. Although elevated levels of tryptase and BK in allergic fluids have been detected, the role of this proteinase and the mechanism of BK production at allergic reaction sites are still unknown. To investigate the pathologic functions of tryptase, the enzyme, purified from human lung, was incubated with normal human plasma, deficient plasmas, kininogens, or prekallikrein. High molecular weight kininogen was then added, and the mixtures were examined for vascular permeability enhancement (VPE) activity, a representative function of bradykinin, using guinea pig skin. Tryptase-treated plasma induced VPE in a dose-dependent manner; activity was lost in the absence of a kininase inhibitor but not an antihistamine drug. Tryptase produced VPE activity from normal or Hageman factor-deficient plasma, but only 30% of this activity was produced from prekallikrein-deficient plasma. Significantly, no activity was obtained from kininogen-deficient plasma. Deficient plasma that were reconstituted with each missing factor resulted in VPE-inducing capacity by tryptase, equivalent to that found with normal plasma. Incubation of tryptase with high or low molecular weight kininogen induced VPE activity in a dose- and incubation time-dependent manner. Prekallikrein incubated with tryptase also generated a soybean trypsin inhibitor-sensitive VPE-inducing activity from high molecular weight kininogen. The loss of tryptase VPE-producing activity as a function of incubation time was found to be a result of spontaneous inactivation of the enzyme and not of the degradation of high molecular weight kininogen by the enzyme. We conclude that tryptase induces VPE by releasing BK, primarily through prekallikrein activation, but also through direct release from kininogens. This indicates that this mast cell-derived proteinase contributes to kinin production in allergic diseases.
Identification of the factors that interact with NCBP, an 80 kDa nuclear cap binding protein (1995)

It has been shown that the monomethylated cap structure plays important roles in pre-mRNA splicing and nuclear export of RNA. As a candidate for the factor involved in these nuclear events we have previously purified an 80 kDa nuclear cap binding protein (NCBP) from a HeLa cell nuclear extract and isolated its full-length cDNA. In this report, in order to obtain a clue to the cellular functions of NCBP, we attempted to identify a factor(s) that interacts with NCBP. Using the yeast two-hybrid system we isolated three clones from a HeLa cell cDNA library. We designated the proteins encoded by these clones NIPs (NCBP interacting proteins). NIP1 and NIP2 have an RNP consensus-type RNA binding domain, whereas NIP3 contains a unique domain of Arg-Glu or Lys-Glu dipeptide repeats. We also show that NCBP requires NIP1 for binding to the cap structure. Possible roles of NIPs in cap-dependent nuclear processes are discussed.
The influence of plaque composition on underlying arterial wall stress during stent expansion: The case for lesion-specific stents (2009)

Intracoronary stent implantation is a mechanical procedure, the success of which depends to a large degree on the mechanical properties of each vessel component involved and the pressure applied to the balloon. Little is known about the influence of plaque composition on arterial overstretching and the subsequent injury to the vessel wall following stenting. An idealised finite element model was developed to investigate the influence of both plaque types (hypercellular, hypocellular and calcified) and stent inflation pressures (9, 12 and 15 atm) on vessel and plaque stresses during the implantation of a balloon expandable coronary stent into an idealised stenosed artery. The plaque type was found to have a significant influence on the stresses induced within the artery during stenting. Higher stresses were predicted in the artery wall for cellular plaques, while the stiffer calcified plaque appeared to play a protective role by reducing the levels of stress within the arterial tissue for a given inflation pressure. Higher pressures can be applied to calcified plaques with a lower risk of arterial vascular injury which may reduce the stimulus for in-stent restenosis. Results also suggest that the risk of plaque rupture, and any subsequent thrombosis due to platelet deposition at the fissure, is greater for calcified plaques with low fracture stresses.
Cyclic AMP-induced conformational change of cyclic AMP receptor protein (CRP): intragenic suppressors of cyclic AMP-independent CRP mutations (1988)

We isolated and characterized crp mutations in Escherichia coli that allow cyclic AMP (cAMP) receptor protein to function without cAMP. These mutants defined a region involved in the cAMP-induced allosteric change of cAMP receptor protein that is necessary for activation of the protein. Currently, we have isolated intragenic suppressors of the crp mutations. These crp (Sup) mutants require cAMP for activity. The crp (Sup) mutations map in regions which define new sites of changes involved in cAMP receptor protein activation. From these results, we suggest that to activate cAMP receptor protein cAMP brings about (i) a hinge reorientation to eject the DNA-binding F alpha-helices, (ii) proper alignment between the two subunits, and (iii) an adjustment between the position of the two domains. Cyclic GMP fails to effect the last step.
Light-stable rhodopsin. II. An opsin mutant (TRP-265—-Phe) and a retinal analog with a nonisomerizable 11-cis configuration form a photostable chromophore. (1992)

In order to prepare a completely light-stable rhodopsin, we have synthesized an analog, II, of 11-cis retinal in which isomerization at the C11-C12 cis-double bond is blocked by formation of a cyclohexene ring from the C10 to C13-methyl. We used this analog to generate a rhodopsin-like pigment from opsin expressed in COS-1 cells and opsin from rod outer segments (Bhattacharya, S., Ridge, K.D., Knox, B.E., and Khorana, H. G. (1992) J. Biol. Chem. 267, 6763-6769). The pigment (lambda max, 512 nm) formed from opsin and analog II (rhodospin-II) showed ground state properties very similar to those of rhodopsin, but was not entirely stable to light. In the present work, 12 opsin mutants (Ala-117----Phe, Glu-122----Gln(Ala, Asp), Trp-126----Phe(Leu, Ala), Trp-265----Ala(Tyr, Phe), Tyr-268----Phe, and Ala-292----Asp), where the mutations were presumed to be in the retinal binding pocket, were reconstituted with analog II. While all mutants formed rhodopsin-like pigments with II, blue-shifted (12-30 nm) chromophores were obtained with Ala-117----Phe, Glu-122----Gln(Ala), Trp-126----Leu(Ala), and Trp-265----Ala(Tyr, Phe) opsins. The extent of chromophore formation was markedly reduced in the mutants Ala-117----Phe and Trp-126----Ala. Upon illumination, the reconstituted pigments showed varying degrees of light sensitivity; the mutants Trp-126----Phe(Leu) showed light sensitivity similar to wild-type. Continuous illumination of the mutants Glu-122----Asp, Trp-265----Ala, Tyr-268----Phe, and Ala-292----Asp resulted in hydrolysis of the retinyl Schiff base. Markedly reduced light sensitivity was observed with the mutant Trp-265----Tyr, while the mutant Trp-265----Phe was light-insensitive. Consistent with this result, the mutant Trp-265----Phe showed no detectable light-dependent activation of transducin or phosphorylation by rhodopsin kinase.