gebhart/patrepeval huggingface dataset:
Targeting of an activated T-cell subset using a bispecific antibody- toxin conjugate directed against CD4 and CD26 (1993)

We have developed a bispecific antibody that recognizes the CD4 and CD26 antigens simultaneously and that was examined for its ability to target CD4+CD26+T cells. These latter cells constitute the activated component of the CD4+ CD29highCD45RO+ memory T-cell subset that provides help for B-cell Ig synthesis and help for responses against recall antigens. The purified bispecific antibody exhibited an estimated dissociation constant (kd) of 2.4 x 10(-9) mol/L, on comparison with 1.1 x 10(-9) mol/L for anti-CD26, and 1.6 x 10(-10) mol/L for anti-CD4. Surface plasmon resonance was used to show the bifunctional capacity of the antibody. On binding 125I-bispecific antibody to phytohemagglutinin (PHA)-activated T cells, 54.4% of the bound antibody was internalized. This was the result of bispecific binding, because monovalent fragments of anti-CD4 and anti-CD26 were not able to modulate antigen or induce internalization using both a fluorescent assay and an 125I-internalization assay. The ability of the bispecific antibody to be internalized was used to deliver a toxin, blocked ricin, specifically to cells that are CD4+CD26+. The inability of monovalent fragments to be internalized formed the basis for our hypothesis that monovalent binding by the bispecific immunotoxin would not result in internalization. Against resting E+ T cells, the bispecific immunotoxin developed a minimal effect. On preactivating the same cells, using phorbol myristate acetate (PMA)/ionomycin on concanavalin A (ConA) or especially PHA, levels of CD26 were upregulated and the immunotoxin effectively inhibited the ability to provide help for B-cell Ig synthesis while leaving intact the CD4-CD26+ and CD4+CD26- populations; an effect observed both functionally and by phenotype. The bispecific antibody proved to be most effective at inhibiting a heterologous mixed leukocyte reaction. We propose that this reagent may form the basis for the rational design of toxins designed to modulate activated T cells from, or directed against, tissue grafts.
Staphylococcus aureus IsdB Is a Hemoglobin Receptor Required for Heme Iron Utilization (2006)

The pathogenesis of human infections caused by the gram-positive microbe Staphylococcus aureus has been previously shown to be reliant on the acquisition of iron from host hemoproteins. The iron-regulated surface determinant system (Isd) encodes a heme transport apparatus containing three cell wall-anchored proteins (IsdA, IsdB, and IsdH) that are exposed on the staphylococcal surface and hence have the potential to interact with human hemoproteins. Here we report that S. aureus can utilize the host hemoproteins hemoglobin and myoglobin, but not hemopexin, as iron sources for bacterial growth. We demonstrate that staphylococci capture hemoglobin on the bacterial surface via IsdB and that inactivation of isdB, but not isdA or isdH, significantly decreases hemoglobin binding to the staphylococcal cell wall and impairs the ability of S. aureus to utilize hemoglobin as an iron source. Stable-isotope-tracking experiments revealed removal of heme iron from hemoglobin and transport of this compound into staphylococci. Importantly, mutants lacking isdB, but not isdH, display a reduction in virulence in a murine model of abscess formation. Thus, IsdB-mediated scavenging of iron from hemoglobin represents an important virulence strategy for S. aureus replication in host tissues and for the establishment of persistent staphylococcal infections.
Prediction of pre‐eclampsia by uterine artery Doppler imaging: relationship to gestational age at delivery and small‐for‐gestational age (2008)

Pre-eclampsia requiring early delivery is more likely to be associated with SGA than less severe pre-eclampsia in women who deliver at term. Doppler ultrasound assessment of the uterine arteries is more effective in identifying pre-eclampsia requiring preterm than term delivery.
A 6-ns 1-Mb CMOS SRAM with latched sense amplifier (1993)

A 1-Mb (256 K*4) CMOS SRAM with 6-ns access time is described. The SRAM, having a cell size of 3.8 mu m*7.2 mu m and a die size of 6.09 mm*12.94 mm, is fabricated by using 0.5- mu m triple-polysilicon and double-metal process technology. The fast access time and low power dissipation of 52 mA at 100-MHz operation are achieved by using a new NMOS source-controlled latched sense amplifier and a data-output prereset circuit. In addition, an equalizing technique at the end of the write operation is used to avoid lengthening of access time in a read cycle following a write cycle.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Along the Way to a Neurofibrillary Tangle: A Look at the Structure of Tau (1989)

We report our ongoing work to characterize the molecular nature of neurofibrillary tangles (NFT). An epitope map of tau protein using monoclonal antibodies that crossreact with NFT reveals the presence of epitopes that span the entire tau molecule from the amino terminus to the carboxy terminus. Several antibodies that recognize tau protein including Alz50 do not recognize primary amino acid sequence but are directed either against a post-translational modification or a complex higher order structure. The importance of tau protein in the development of the pathology is underscored by the extent of the tau-reactive neuritic lesions. These dystrophic neurites or "curly fibers" extend well beyond the classical distributions of the senile plaques and NFT. Furthermore, the neuropil lesion is considerably more extensive than either the senile plaques or neurofibrillary tangles. One of the features of the dystrophy in Alzheimer's disease is widespread neuronal sprouting characteristic of dystrophic neurites and tangle-bearing cells.
Requirement for a Functional int Product in Temperature Inductions of Prophage P22 ts mnt (1970)

Prophage P22 ts mnt was found to be inducible by high temperatures. This property was maintained when the ts mnt allele was recombined into a phage that cannot synthesize phage deoxyribonucleic acid at high temperature. Prophage P22 int ts mnt, on the other hand, was not inducible at high temperature. This result leads to the suggestion that the int enzyme, which is involved in excision, is regulated by the product of gene mnt.
Liposomes That Can Be Disintegrated by Photo-Irradiation (1989)

Abstract Photo-labile phosphatidylcholine (PLPC) was synthesized which contains 2-nitrobenzyl esters at the terminals of both alkyl chains. Photolysis of the esters generates carboxylate ions in the hydrophobic region of the PLPC membrane, leading to instant disintegration of PLPC liposomes as observed by the phase contrast microscopy. Upon UV irradiation, entrapped macromolecules (45-kdalton ovalbumin) were released from PLPC liposomes.
Preliminary results of non-surgical intra-uterine insemination of sheep with thawed frozen semen. (1985)

Non-surgical intra-uterine insemination was achieved in 70 of 97 ewes (72%). Of the 70 ewes in which intra-uterine thawed semen was deposited, a total of 50 ewes (71%) conceived. Routine use of this technique is not at present foreseen due to the complicated and time consuming nature of the procedure.
Comparison of rural remote site production of digital images employing a film digitizer or a computed radiography (CR) system (2002)

This project describes two digital image acquisition methods for transmission from two rural sites to a remote site for primary interpretation of images. Practical considerations or implementation of rural teleradiology links are discussed. Digital image production occurred by either employing a film digitizer or a computed radiography (CR) system. Adequate image resolution was possible for most clinical applications for both methods (minimum array size of 2048/spl times/2048/spl times/10-12 bits for digital transmission). Benefits of CR included reduction in the image production cycle time and improved image handling. The technical sophistication and the cost of the link are directly proportional. Film digitizer technology was two to three times less expensive than CR. CR, on the other hand, offered significant operative expense reductions in the long run. Both CR and digitizer approaches are clinically useful methods for teleradiology. The type of equipment depends on the requirements of the applications needed and financial resources available.
Structural junctions in DNA: the influence of flanking sequence on nuclease digestion specificities (1985)

When a protein binds to DNA, the affinity of this protein for its primary site of interaction may be influenced by the nature of flanking sequences. This is thought to be a consequence of local cooperativity in the DNA molecule, where the conformation at one point along the helix can influence the conformation at another, and thereby modulate the free energy of protein-DNA recognition. In order to learn more about this process, we have carried out experiments of two sorts. First, we have constructed sequences of the type (dA)11 (dG)8, where the conformational preferences of the DNA molecule switch from one extreme to another over just a single base pair, and subjected them to digestion by DNAase I and DNAase II. This is to learn whether the structure changes abruptly at the junction point, or more gradually with an influence extending into residues on either side. Secondly, we have subjected long plasmid DNA to digestion by restriction enzymes Fnu DII, Hae III, Hha I and Msp I, to look for correlations between cutting rate and the identity of nucleotides on either side of the restriction site. The influence of flanking sequence on nuclease digestion specificities is clearly evident in both kinds of experiment, but the rules governing this seem complex and not easily formulated. The best that can be done at present is to divide the problem into two parts, "analogue" and "digital", representing sugar-phosphate and base components of recognition.
PP.12.06 (2015)

Objective: Recently anterograde influences of left ventricular contractility over arterial stiffness have been evidenced in young men in population studies. However, is possible that different patterns of cardiovascular adjustment could be recognized through beat-to-beat measurements. a- To describe beat-to-beat relationships between left ventricular function and aortic stiffness (anterograde (AI) and retrograde (RI) interactions), in normotensive and hypertensive patients. b- Correlate these profiles with the autonomic modulation. Design and method: Of 130 patients evaluated, and after exclusion criteria (female, age < 18 > 60 years, secondary hypertension, diabetes, kidney disease, cardiovascular event, and sympatholytics) 22 males were included: 11normotensives (40.8 ± 9.8 years,126.1 ± 8.6/81.1 ± 8.0 mm Hg) and 11mild hypertensive patients (42.1 ± 10.2 years, 137.2 ± 15.1/89.3 ± 9.0 mm Hg) treated with RAAS-blockers. BP (ESH), HR, ejection time (ET) and dZ/dT(a dV/dT estimator) were determined by impedance cardiography, together with tonometric carotid-femoral PWV; all the measurements were performed beat-to-beat, for 3 minutes at rest. Both sets of determinations were coordinated through R-R intervals. Spectral analysis of parasympathetic (HF, ms2)/sympathetic (LF/HF) and overall autonomic modulation (total power, TP, ms2) were performed through heart rate variability during 3 minutes/lying. Aortic augmentation index at 75bpm (AIX75) was measured. Beat-to-beat correlations between dZ/dT and ET with PWV were performed, identifying positive/negative signs of the interactions (AI/RI, respectively),(Pearson). We assessed differences between autonomic modulation and AIX75 according to AI/RI (T-test). Results: Significant beat-to-beat correlations between dZ/dT and PWV were evident: Type-AI in 59% (n = 13; r = from 0.22 to 0.71, p < 0.05) and Type-RI in the remaining 41% (n = 9; r = -0.22 to -0.72, p < 0.05). ET was not significantly associated with PWV (p > 0.05). AI/RI prevalence were similar between normotensive and hypertensive patients (chi2, p = 0.96). LF/HF was similar between AI/RI (p = 0.87). HF and TP were higher in AI subjects (409 vs. 112 ms2 and 1007 vs. 418 ms2, respectively; p < 0.05). AIX75 was higher in RI subjects (20.8 vs.7.3%, p < 0.002).Conclusions: Two beat-to-beat ventricular-arterial interaction types in young men were noted. The anterograde interaction pattern appears to be more physiological, presenting greater parasympathetic and overall autonomic modulations, and less aortic reflections, which could have a lesser impact on target organ damage development.
Sandwiched Graphene−Membrane Superstructures (2009)

We demonstrate by molecular dynamics simulations that graphene sheets could be hosted in the hydrophobic interior of biological membranes formed by amphiphilic phospholipid molecules. Our simulation shows that these hybrid graphene--membrane superstructures might be prepared by forming hydrated micelles of individual graphene flakes covered by phospholipids, which can be then fused with the membrane. Since the phospholipid layers of the membrane electrically isolate the embedded graphene from the external solution, the composite system might be used in the development of biosensors and bioelectronic materials.
Compatible solutes improve cryopreservation of human endothelial cells. (2013)

Dimethyl sulfoxide (DMSO) is till now a widely used cryoprotective agent for cryopreservation of cells. Since high concentrations of DMSO have detrimental effects on cell functioning the aim of this study is to reduce the DMSO concentration by using compatible solutes (CS). These are small organic osmolytes that microorganisms synthesize and accumulate to counteract stress factors. Three CS, hydroxyectoine, ectoine and L-proline were investigated as cryoprotective agents for the cryopreservation of the human endothelial cell line HPMEC-ST1.6R. They were either supplemented to freezing or to cell culture medium. L-proline was the most effective CS, the efficiency of recultivation was improved by more than 100 percent. A combination of L-proline and ectoine in the cell culture medium resulted in an improvement by 63 percent. Our results show that L-proline and ectoine could be used as additional CPAs to improve the cryopreservation of human endothelial cells in the presence of low DMSO concentration.
Complex Sequence Dependence by Excess‐Electron Transfer through DNA with Different Strength Electron Acceptors (2005)

An independent jump: Excess electrons move through DNA by using a hopping-type mechanism in which the pyrimidine bases dT and dC act as ‘stepping stones’. It was shown that GC base pairs, in contrast to AT base pairs, lower the efficiency of the excess-electron transfer through the duplex. Through the use of the shown DNA hairpins, three different electron acceptors ( ) were investigated with the electron donor, reduced flavin ( ).
Localization of Granzyme B in the Nucleus (1996)

One mechanism used by cytotoxic T cells and natural killer cells to kill target cells involves synergy between the pore-forming protein, perforin, and a serine protease termed granzyme B, both constituents of the cytoplasmic granules of cytolytic lymphocytes. Exposing susceptible cells to perforin and granzyme B results in apoptosis, the morphological consequences of which are most clearly seen in the nucleus. It is conventionally accepted that perforin acts by perforating the target cell membrane; however, the site and mode of action of granzyme B are unknown. We have addressed this issue using Western blotting, proteolytic assays, and confocal laser scanning microscopy to demonstrate that purified human granzyme B can be taken up in large amounts and bound within nuclei. By contrast, perforin and nongranzyme serine proteases did not undergo nuclear uptake. Both unglycosylated human granzyme B (26 kDa) and that bearing high mannose glycosylation (32 kDa) were internalized and bound within nuclei, but forms greater than 32 kDa with complex carbohydrate addition were excluded. The uptake of granzymes was not dependent on net charge, as nuclei absorbed similar quantities of granzyme B at neutral pH and through a range of basic pHs but did not take up other very basic serine proteases such as the mouse mast cell protease 5. Confocal laser scanning microscopy indicated nuclear and nucleolar accumulation of fluoresceinated granzyme B by isolated nuclei. Measurement of the kinetics of nuclear import using an in vitro nuclear transport assay indicated maximal levels of nuclear accumulation of granzyme about 2.5-fold above those in the cytoplasm and nucleolar accumulation a further 3-4-fold higher. Nuclear and nucleolar accumulation were exceedingly rapid, reaching half-maximal levels within 3.3 and 7.5 min, respectively, implying that nuclear accumulation probably occurs prior to transport to the nucleolus. Our observations may provide a mechanism explaining how aspartate-specific cell death proteases access the nuclear substrate poly(ADP-ribose) polymerase, the cleavage of which is an early event in apoptosis.
Antichymotrypsin interaction with chymotrypsin. Partitioning of the complex. (1993)

The interactions of bovine pancreatic chymotrypsin (Chtr) and recombinant alpha 1-antichymotrypsin (rACT) and rACT variants were studied by kinetic and gel electrophoretic analyses, leading to the formulation of a general kinetic scheme that accounts for all known results concerning this serpin-protease pair, as well as for results obtained with other such pairs. Incubation of rACT and Chtr leads rapidly to the formation of an inhibited complex, Chtr.rACT*, that is stable toward sodium dodecyl sulfate denaturation and boiling. The extent of release of active Chtr from this complex increases markedly as ionic strength, mu, is raised. The kinetic scheme quantitatively accounts for this effect on the basis of a partitioning of Chtr.rACT* between dissociation of the complex to yield active enzyme and cleaved rACT, and Chtr-catalyzed conversion of the complex to a form that is much more resistant to release of active enzyme. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses of reaction mixtures of rACT and Chtr are consistent with the scheme. Also consistent are the results of experiments measuring the effects of 1) Chtr.rACT* concentration, 2) uncomplexed Chtr, and 3) added alpha 2-macroglobulin on active Chtr release from Chtr.rACT*. Proteolysis of Chtr.rACT* to give a resistant complex is also catalyzed by human neutrophil elastase, a process with potential physiological relevance. Comparison of the rates of Chtr dissociation from the complexes formed with rACT and with rACT variants mutated at the P1 site suggests that such rates are more sensitive to P1 substitution at low mu than at high mu. Several equivalents of the L358R-rACT variant are required for full inhibition of Chtr. This observation is also quantitatively accounted for by the proposed kinetic scheme, on the basis of another partitioning step between L358R-rACT acting as a substrate or as an inhibitor toward Chtr.
A low-friction passive fluid transmission and fluid-tendon soft actuator (2014)

We present a passive fluid transmission based on antagonist pairs of rolling diaphragm cylinders. The transmission fluid working volume is completely sealed, forming a closed, passive system, ensuring input-output symmetry and complete backdrivability. Rolling diaphragm-sealed cylinders provide leak-free operation without the stiction of a traditional sliding seal. Fluid pressure preloading allows for bidirectional operation and also serves to preload the gears or belts in the linear-to-rotary output coupler, eliminating system backlash end-to-end. A prototype transmission is built and tested for stiffness, bandwidth, and frictional properties using either air or water as working fluids. Torque transmission is smooth over the entire stroke and stiction is measured to be one percent of full-range torque or less. We also present a tendon-coupled design where the rolling diaphragm is inverted from its normal orientation; this design does not require shaft support bushings, tolerates misalignment, and can be made out of substantially soft materials. Actuator units and a passive transmission are demonstrated using this new soft cylinder design.
SPP1 polymorphisms associated with HBV clearance and HCC occurrence (2007)

Our findings suggest that SPP1 polymorphisms might be among the genetic factors for HBV clearance and/or HCC occurrence.
From micrograms to picograms: quantitative PCR reduces the material demands of high-throughput sequencing (2007)

Current efforts to recover the Neandertal and mammoth genomes by 454 DNA sequencing demonstrate the sensitivity of this technology. However, routine 454 sequencing applications still require microgram quantities of initial material. This is due to a lack of effective methods for quantifying 454 sequencing libraries, necessitating expensive and labour-intensive procedures when sequencing ancient DNA and other poor DNA samples. Here we report a 454 sequencing library quantification method based on quantitative PCR that effectively eliminates these limitations. We estimated both the molecule numbers and the fragment size distributions in sequencing libraries derived from Neandertal DNA extracts, SAGE ditags and bonobo genomic DNA, obtaining optimal sequencing yields without performing any titration runs. Using this method, 454 sequencing can routinely be performed from as little as 50 pg of initial material without titration runs, thereby drastically reducing costs while increasing the scope of sample throughput and protocol development on the 454 platform. The method should also apply to Illumina/Solexa and ABI/SOLiD sequencing, and should therefore help to widen the accessibility of all three platforms.
Ratiometric dosing of anticancer drug combinations: Controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice (2006)

Anticancer drug combinations can act synergistically or antagonistically against tumor cells in vitro depending on the ratios of the individual agents comprising the combination. The importance of drug ratios in vivo, however, has heretofore not been investigated, and combination chemotherapy treatment regimens continue to be developed based on the maximum tolerated dose of the individual agents. We systematically examined three different drug combinations representing a range of anticancer drug classes with distinct molecular mechanisms (irinotecan/floxuridine, cytarabine/daunorubicin, and cisplatin/daunorubicin) for drug ratio-dependent synergy. In each case, synergistic interactions were observed in vitro at certain drug/drug molar ratio ranges (1:1, 5:1, and 10:1, respectively), whereas other ratios were additive or antagonistic. We were able to maintain fixed drug ratios in plasma of mice for 24 hours after i.v. injection for all three combinations by controlling and overcoming the inherent dissimilar pharmacokinetics of individual drugs through encapsulation in liposomal carrier systems. The liposomes not only maintained drug ratios in the plasma after injection, but also delivered the formulated drug ratio directly to tumor tissue. In vivo maintenance of drug ratios shown to be synergistic in vitro provided increased efficacy in preclinical tumor models, whereas attenuated antitumor activity was observed when antagonistic drug ratios were maintained. Fixing synergistic drug ratios in pharmaceutical carriers provides an avenue by which anticancer drug combinations can be optimized prospectively for maximum therapeutic activity during preclinical development and differs from current practice in which dosing regimens are developed empirically in late-stage clinical trials based on tolerability.