gebhart/patrepeval huggingface dataset:
Binding parameters and idiotypic profile of the whole immunoglobulin and Fab' fragments of murine monoclonal antibody to distinct determinants of the human high molecular weight-melanoma associated antigen. (1992)

The nonspecific accumulation of radioactivity in bone marrow, liver, and spleen in patients with melanoma injected with radiolabeled whole IgG of anti-high molecular weight-melanoma associated antigen (HMW-MAA) monoclonal antibody (mAb) hampers the application of immunoscintigraphy to visualize melanoma lesions. This nonspecific background can be reduced by utilizing fragments which do not contain the Fc portion of anti-HMW-MAA mAb. Since the in vivo targeting to melanoma lesions of radiolabeled F(ab')2 and Fab' fragments of anti-HMW-MAA mAb is critically dependent on their binding parameters, we have analyzed the effect of fragmentation on the binding characteristics of the anti-HMW-MAA mAbs 225.28, 763.74, and TP41.2. The three mAbs recognize distinct and spatially distant determinants with a heterogeneous distribution on the pool of HMW-MAA molecules synthesized by melanoma cells. The determinant recognized by mAb TP41.2 is detectable on a markedly smaller population of HMW-MAA molecules than those recognized by mAbs 225.28 and 763.74. 125I-labeled F(ab')2 fragments of the three mAbs displayed an immunoreactive fraction similar to that of the whole IgG, while Fab' fragments displayed a lower one. Fragmentation of mAbs 225.28 and TP41.2 to F(ab')2 produced a 2- and 1.5-fold reduction in their association constants but did not cause a significant change in that of mAb 763.74. Cleavage of F(ab')2 fragments to Fab' fragments produced 2-, 40-, and 7-fold reductions in the association constants of mAbs 225.28, 763.74, and TP41.2, respectively. These changes qualitatively fit the predictions of theory for univalent and bivalent mAb binding, since mAbs 763.74 and TP41.2 appear to show bivalent binding to melanoma cells and mAb 225.28 to show univalent binding. The affinity constant of IgG, F(ab')2 and Fab' fragments of mAbs 225.28, 763.74, and TP41.2 displays an inverse relationship with the extent of their time-dependent release from the membrane of melanoma cells. Since no endocytosis of mAb could be detected, the latter results suggest that radioactivity remains bound to melanoma cells in vivo for a longer time following injection of F(ab')2 fragments than following that of Fab' fragments of each of the anti-HMW-MAA mAb tested. Radiolabeled Fab' fragments of mAbs 763.74 and TP41.2 displayed a marked reduction in their reactivity with some of the antiidiotypic mAb tested. The loss of some idiotopes is likely to be caused by changes in the conformation of the molecules associated with the fragmentation of IgG and by damage during the iodination procedure.
Complement activation by PEO‐grafted glass surfaces (1999)

Activation of the complement system is one way in which the human body reacts to foreign materials that come in contact with blood. Poly(ethylene oxide) (PEO) has been used quite frequently to modify biomaterial surfaces to prevent protein adsorption and cell adhesion. Despite extensive use of PEO, however, PEO-induced complement activation has not been examined before. We examined the complement activation by PEO chains grafted to glass surfaces. PEO was grafted to trichlorovinylsilane-treated glass (TCVS-glass) by γ-irradiation using PEO homopolymer, Pluronic® F108 (PF108), and PEO-polybutadiene-PEO triblock copolymer (COP5000). Complement activation was assessed by measuring the plasma C3a level. Of the three polymers grafted (PEO, PF108, and COP5000), only PF108 showed significant increases in complement activation over controls. Complement C3a production on PF108-grafted glass was linearly dependent on surface concentration of grafted PF108. The C3a concentration increased from 46 ng/mL to 316 ng/mL as the surface PF108 concentration increased from 0–0.25 μg/cm2. Kinetics of C3a generation by PF108-grafted surfaces show that 60% of the steady state C3a concentration was generated during the first hour of plasma exposure. When the same PF108-grafted glass surface was repeatedly exposed to fresh plasma, the amount of C3a generated decreased by 70% after the first exposure. This supports the “single-hit” mechanism in complement activation. PEO homopolymer did not activate complement in bulk solution, and, thus, it appears that C3a complement activation by PF108-grafted surfaces is due to the presence of poly(propylene oxide) units. Grafting of PEO using PEO-containing block copolymers requires examination of complement activating properties of the non-PEO segment. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 48: 640–647, 1999
Dynamic reassembly of peptide RADA16 nanofiber scaffold (2005)

Nanofiber structures of some peptides and proteins as biological materials have been studied extensively, but their molecular mechanism of self-assembly and reassembly still remains unclear. We report here the reassembly of an ionic self-complementary peptide RADARADARADARADA (RADA16-I) that forms a well defined nanofiber scaffold. The 16-residue peptide forms stable beta-sheet structure and undergoes molecular self-assembly into nanofibers and eventually a scaffold hydrogel consisting of >99.5% water. In this study, the nanofiber scaffold was sonicated into smaller fragments. Circular dichroism, atomic force microscopy, and rheology were used to follow the kinetics of the reassembly. These sonicated fragments not only quickly reassemble into nanofibers that were indistinguishable from the original material, but their reassembly also correlated with the rheological analyses showing an increase of scaffold rigidity as a function of nanofiber length. The disassembly and reassembly processes were repeated four times and, each time, the reassembly reached the original length. We proposed a plausible sliding diffusion model to interpret the reassembly involving complementary nanofiber cohesive ends. This reassembly process is important for fabrication of new scaffolds for 3D cell culture, tissue repair, and regenerative medicine.
Whole-body cooling after perinatal asphyxia: a pilot study in term neonates (2002)

In order to test the practicability and safety of whole-body cooling in term neonates with moderate-to-severe hypoxic-ischaemic encephalopathy (HIE) and to report outcomes, a prospective pilot study was carried out in 25 term infants (median postmenstrual age 38 weeks, range 36 to 41 weeks; 20 males, five females). Whole-body cooling, to a target core temperature of 33 to 34 degrees C, started within 6 hours of birth and was maintained for 72 hours. Of the 25 newborn infants (19 Sarnat II and six Sarnat III, 18 outborn), 18 survived, including 13 (72%) with normal cerebral signal by MRI. Temperature instability occurred during cooling in 15 infants, but neither severe haemodynamic instability nor renal failure was seen. Thrombocytopenia developed in 12 infants, including seven with biological disseminated intravascular coagulation. One patient had hypoxaemia with right-to-left shunting through the ductus arteriosus, and seven had limited meningeal or subdural bleeding. Whole-body cooling is feasible in term neonates, with no life-threatening adverse events. Improvements are needed to obtain stable hypothermia for 72 hours.
Kinetic and Mechanistic Studies on the Hydrolysis of Ubiquitin C-Terminal 7-Amido-4-Methylcoumarin by Deubiquitinating Enzymes (1998)

Deubiquitinating enzymes constitute a family of cysteine hydrolases that specifically cleave ubiquitin-derived substrates of general structure Ub-X, where X can be any number of leaving groups ranging from small thiols and amines to Ub and other proteins (Ub, ubiquitin). We have developed a general assay for deubiquitinating enzymes based on the substrate ubiquitin C-terminal 7-amido-4-methylcoumarin (Ub-AMC). Ub-AMC is efficiently hydrolyzed with liberation of highly fluorescent AMC by two rabbit reticulocyte deubiquitinating enzymes: isopeptidase T (IPaseT), a member of the gene family of ubiquitin-specific processing enzymes, and UCH-L3, a member of the family of ubiquitin C-terminal hydrolases. We used this new assay to probe kinetic and mechanistic aspects of catalysis by IPaseT and UCH-L3. Results from four series of experiments are discussed: (1) For UCH-L3, we determined steady-state kinetic parameters that suggest a diffusion-limited reaction of UCH-L3 with Ub-AMC. To probe this, we determined the viscosity dependence of kc/Km, as well as kc. We found complex viscosity dependencies and interpreted these in the context of a model in which association and acylation are viscosity-dependent but deacylation is viscosity-independent. (2) The kinetics of inhibition of UCH-L3 by ubiquitin C-terminal aldehyde (Ub-H) were determined and reveal a Ki that is less than 10(-14) M. Several mechanisms are considered to account for the extreme inhibition. (3) The IPaseT-catalyzed hydrolysis of Ub-AMC is modulated by Ub with activation at low [Ub] and inhibition at high [Ub]. (4) Finally, we compare kc/Km values for deubiquitinating enzyme-catalyzed hydrolysis of Ub-AMC and Z-Leu-Arg-Gly-Gly-AMC. For IPaseT, the ratio of rate constants is 10(4), while for UCH-L3 this ratio is > 10(7). These results suggest the following: (i) Deubiquitinating enzymes are able to utilize the free energy that is released from remote interactions with Ub-containing substrates for stabilization of catalytic transition states, and (ii) UCHs are more efficient at utilizing the energy from these interactions, presumably because they do not possess a binding domain for a Ub "leaving group".
Concentration-Time Profiles of Ethanol in Arterial and Venous Blood and End-Expired Breath During and After Intravenous Infusion (1997)

Ethanol (0.40 g/kg) was administered to 13 healthy men by intravenous (i.v.) infusion at a constant rate for 30 min. The concentrations of ethanol in arterial blood (ABAC), venous blood (VBAC), and end-expired breath (BrAC) were measured at 17 exactly timed intervals. Blood-ethanol was determined by headspace gas chromatography and breath-ethanol was measured with a quantitative infrared analyzer (DataMaster). BrAC was multiplied by 2300 to estimate the concentrations of alcohol in blood. During the infusion of ethanol, ABAC exceeded VBAC by about 10 mg/dL on the average and ABAC was also higher than BrAC x 2300 by about 4 mg/dL on average. When infusion of alcohol ended, ABAC, VBAC, and BrAC were 94.8 +/- 2.06 (+/- SE), 84.7 +/- 1.54, and 89.3 +/- 2.10 mg/dL, respectively. The concentrations of alcohol in blood (ABAC and VBAC) and breath decreased abruptly after the administration of alcohol stopped and by 5 min postinfusion, the A-V differences in concentration of ethanol were small or negligible. The mean apparent half-life of the distribution plunge was 7 to 8 min, being about the same for ABAC, VBAC, and BrAC. The disappearance rate of ethanol was 15.5 +/- 0.55 mg/ dL/h (mean +/- SE) for arterial blood, 15.2 +/- 0.49 mg/dL/h for venous blood, and 16.3 +/- 0.73 mg/230 L/h for breath; no significant differences were noted (p > 0.05). We conclude that A-V differences in the concentration of ethanol exist during the loading phase but are rapidly abolished when the administration of ethanol terminates. In the post-absorptive phase of ethanol kinetics, when alcohol has mixed with the total body water, VBAC exceeds ABAC by about 1-2 mg/100 mL on average.
A Human Multi-Epitope Recombinant Vaccinia Virus as a Universal T Cell Vaccine Candidate against Influenza Virus (2011)

There is a need to develop a universal vaccine against influenza virus infection to avoid developing new formulations of a seasonal vaccine each year. Many of the vaccine strategies for a universal vaccine target strain-conserved influenza virus proteins, such as the matrix, polymerase, and nucleoproteins, rather than the surface hemagglutinin and neuraminidase proteins. In addition, non-disease-causing viral vectors are a popular choice as a delivery system for the influenza virus antigens. As a proof-of-concept, we have designed a novel influenza virus immunogen based on the NP backbone containing human T cell epitopes for M1, NS1, NP, PB1 and PA proteins (referred as NPmix) as well as a construct containing the conserved regions of influenza virus neuraminidase (N-terminal) and hemagglutinin (C-terminal) (referred as NA-HA). DNA vectors and vaccinia virus recombinants expressing NPmix (WR-NP) or both NPmix plus NA-HA (WR-flu) in the cytosol were tested in a heterologous DNA-prime/vaccinia virus-boost vaccine regimen in mice. We observed an increase in the number of influenza virus-specific IFNγ-secreting splenocytes, composed of populations marked by CD4(+) and CD8(+) T cells producing IFNγ or TNFα. Upon challenge with influenza virus, the vaccinated mice exhibited decreased viral load in the lungs and a delay in mortality. These findings suggest that DNA prime/poxvirus boost with human multi-epitope recombinant influenza virus proteins is a valid approach for a general T-cell vaccine to protect against influenza virus infection.
Lymphokine-activated killer cell induction in tumor-infiltrating leukocytes from colon cancer patients (1989)

Lymphokine-activated killer (LAK) cell induction was evaluated in the peripheral blood mononuclear cells (PBMC) from 28 colon cancer patients and in the tumor-infiltrating leukocytes (TIL) from 20 of the patients' colon cancer specimens. Modulation of LAK cell induction in TIL and PBMC by inhibitors of arachidonic acid metabolism also was examined. LAK cells were induced in vitro in isolated TIL and PBMC by culturing with 500 U/ml of recombinant interleukin-2 (IL-2) for 3 to 5 days, and this was followed by the assessment of cytolytic activity against natural killer (NK)-resistant Chang hepatoma cells. LAK cell induction in the TIL was depressed significantly, compared with LAK cell induction in the PBMC of colon cancer patients (P less than 0.01). In the majority of cases, indomethacin augmented LAK cell induction in the TIL (P = 0.073 for the entire group, compared with cultures not treated with indomethacin) and nordihydroguaiaretic acid (NDGA) depressed LAK cell induction (P less than 0.05 for the entire group, compared with cultures not treated with NDGA). Further characterization of the mechanisms responsible for modulating LAK cell induction in the TIL of cancer patients may identify ways to optimize their use in adoptive cellular immunotherapy.
Debonding of photoresists by organic solvents (1996)

Chlorofluorocarbons (CFCs) have been widely used in the printed circuit board industry for many decades. However, the growing concern regarding their ozone depleting properties has demanded a ban on these solvents and consequently brought forth the search for environmentally friendly alternatives. In printed circuit board technology, methyl chloroform and methylene chloride have been widely utilized as solvents for developing and stripping, respectively, radiation sensitive materials useful in creating fine line circuitry patterns. The solubility of unexposed and exposed T168 resist in selected solvents or solvent mixtures at various temperatures is described here. Results addressing the ease of removal of such solvent based resists using environmentally friendly alternatives are presented. Debonding of the polymer layer from the underlying substrate was observed by monitoring the deflection of the composite strip immersed in the solvent using a Fotonic Sensor accessory. Debonding time, identified as the necessary time to remove the photoresist from such surfaces, can vary with temperature, solvent, photoresist type or thickness, and exposure energy. © 1996 John Wiley & Sons, Inc.
Temperature dependent electron-hole recombination in polymer light-emitting diodes (1997)

The current density–voltage characteristics of poly(dialkoxy p-phenylene vinylene) based polymer are investigated as a function of temperature. Model calculations show that the differences between single and double carrier devices can be well understood by taking into account a bimolecular recombination process. It is found that the bimolecular recombination is thermally activated with an identical activation energy as measured for the charge carrier mobility. This demonstrates that the recombination process is of the Langevin type, and explains why the conversion efficiency (photon/carrier) of a polymer light-emitting diode is temperature independent.
Identification of an immunodominant epitope within the capsid protein of hepatitis C virus. (1991)

We have isolated cDNA clones from the 5' end of the Hutchinson strain of hepatitis C virus. Sequences encoding various segments of the HCV structural region were fused to the gene for glutathione S-transferase and analyzed for the expression of hepatitis C virus-capsid fusion proteins. With a set of these fusion proteins, both human and chimpanzee immune responses to capsid were studied. An immunodominant epitope was located within the amino-terminal portion of capsid that is preferentially recognized by antibodies in both human and chimpanzee hepatitis C virus-positive sera. In addition, analyses of sequential serum samples taken from humans and chimpanzees with either chronic or apparently self-limited infections revealed that a strong anti-capsid response develops rapidly after onset of infection.
Synthesis of pyridazino(4,5-e)(1,3,4)thiadiazines and the ring contraction to pyrazolo(3,4-d)pyridazines through extrusion of sulfur. (1984)

Cyclization of 2-substituted 5-[(α-bromobenzylidene) hydrazino)]-4-chloro-3 (2H)-pyridazinones (2) with potassium thioacetate, followed by deacetylation, provided new ring system derivatives, 7-substituted 2-phenyl-4H-pyridazino [4, 5-e] [1, 3, 4] thiadiazin-8 (7H)-ones (4). 8-Chloro and 8-amino derivatives (10) of the pyridazinothiadiazine ring were readily derived from 4-acetyl-2-phenyl-4H-pyridazino [4, 5-e] [1, 3, 4] thiadiazin-8 (7H)-one (3d) by chlorination and subsequent amination. Ring contraction of the 8-oxo derivatives (4) to 5-substituted 3-phenyl-1H-pyrazolo [3, 4-d] pyridazin-4 (5H)-ones (6), through extrusion of sulfur under basic or thermal conditions, was observed. A similar reaction occurred in the case of the 8-chloro and 8-amino derivatives (10). Probable mechanisms for these reactions and differences of reactivity between 4 and 10 are discussed.
Interventricular and intraventricular dyssynchrony are common in heart failure patients, regardless of QRS duration (2004)

A substantial proportion of heart failure patients with a slightly prolonged QRS or even with normal conduction may exhibit ventricular dyssynchrony. Both standard echocardiography and TDI are necessary to describe the entire spectrum of mechanical abnormalities due to dyssynchrony.
Surgical treatment of myelopathy with cervical spondylosis (1973)

The results of treatment over a period of 10 years of 102 cases of cervical spondylosis with myelopathy are presented, with a complete follow-up in all cases to two years after the end of that period. Results similar to those previously recorded were obtained with treatment by a light Minerva plaster collar, or laminectomy, but the best results, 73% sustained improvement, were obtained in 65 cases treated from an anterior approach, by Cloward's operation. Of 48 patients showing sustained improvement, 38 returned to, and remained at work. Cloward's operation was first undertaken at the beginning of the 10 year period, and was increasingly adopted as a primary procedure. It became evident that benefit from any treatment in cases with symptoms of long duration was likely to be limited, and the best results were in cases with less than a year's history who had Cloward's operation (86% sustained improvement). The necessity for careful clinical and radiological diagnosis, and operative technique, is emphasized, also the desirability of careful scrutiny of assessments in series of this disorder.
3-D model-based tracking of humans in action: a multi-view approach (1996)

We present a vision system for the 3-D model-based tracking of unconstrained human movement. Using image sequences acquired simultaneously from multiple views, we recover the 3-D body pose at each time instant without the use of markers. The pose-recovery problem is formulated as a search problem and entails finding the pose parameters of a graphical human model whose synthesized appearance is most similar to the actual appearance of the real human in the multi-view images. The models used for this purpose are acquired from the images. We use a decomposition approach and a best-first technique to search through the high dimensional pose parameter space. A robust variant of chamfer matching is used as a fast similarity measure between synthesized and real edge images. We present initial tracking results from a large new Humans-in-Action (HIA) database containing more than 2500 frames in each of four orthogonal views. They contain subjects involved in a variety of activities, of various degrees of complexity, ranging from the more simple one-person hand waving to the challenging two-person close interaction in the Argentine Tango.
Brain imaging in awake infants by near-infrared optical topography (2003)

Studies of young infants are critical to understand perceptual, motor, and cognitive processing in humans. However, brain mechanisms involved are poorly understood, because the use of brain-imaging methods such as functional magnetic resonance imaging in awake infants is difficult. In the present study we show functional brain imaging of awake infants viewing visual stimuli by means of multichannel near-infrared spectroscopy, a technique that permits a measurement of cerebral hemoglobin oxygenation in response to brain activation through the intact skull without subject constraint. We found that event-related increases in oxyhemoglobin were evident in localized areas of the occipital cortex of infants aged 2-4 months in response to a brief presentation of a checkerboard pattern reversal while they maintained fixation to attention-grabbing stimuli. The dynamic change in cerebral blood oxygenation was qualitatively similar to that observed in the adult brain. This result introduces near-infrared optical topography as a method for investigating the functional development of the brain in early infancy.
Isolation and expression of a cDNA encoding Renilla reniformis luciferase. (1991)

Renilla reniformis is an anthozoan coelenterate capable of exhibiting bioluminescence. Bioluminescence in Renilla results from the oxidation of coelenterate luciferin (coelenterazine) by luciferase [Renilla-luciferin:oxygen 2-oxidoreductase (decarboxylating), EC 1.13.12.5]. In vivo, the excited state luciferin-luciferase complex undergoes the process of nonradiative energy transfer to an accessory protein, green fluorescent protein, which results in green bioluminescence. In vitro, Renilla luciferase emits blue light in the absence of any green fluorescent protein. A Renilla cDNA library has been constructed in lambda gt11 and screened by plaque hybridization with two oligonucleotide probes. We report here the isolation and characterization of a luciferase cDNA and its gene product. The recombinant luciferase expressed in Escherichia coli is identical to native luciferase as determined by SDS/PAGE, immunoblot analysis, and bioluminescence emission characteristics.