gebhart/patrepeval huggingface dataset:
Activation and Inhibition of Phosphorylase Kinase by Monospecific Antibodies Raised against Peptides from the Regulatory Domain of the γ-Subunit (1996)

The C terminus of the catalytic gamma-subunit of phosphorylase kinase comprises a regulatory domain that contains regions important for subunit interactions and autoinhibitory functions. Monospecific antibodies raised against four synthetic peptides from this region, PhK1 (362-386), PhK5 (342-366), PhK9 (322-346), and PhK13 (302-326), were found to have significant effects on the catalytic activities of phosphorylase kinase holoenzyme and the gamma delta complex. Antibodies raised against the very C terminus of the gamma-subunit, anti-PhK1 and anti-PhK5, markedly activated both holoenzyme and the gamma delta complex, in the presence and absence of Ca2+. In the presence of Ca2+ at pH 8.2, anti-PhK1 activated the holoenzyme more than 11-fold and activated the gamma delta complex 2.5-fold. Activation of the holoenzyme and the gamma delta complex by anti-PhK5 was 50-70% of that observed with anti-PhK1. Prior phosphorylation of the holoenzyme by the cAMP-dependent protein kinase blocked activation by both anti-PhK1 and anti-PhK5. Antibodies raised against the peptides from the N terminus of the regulatory domain, anti-PhK9 and anti-PhK13, were inhibitory, with their greatest effects on the gamma delta complex. These data demonstrate that the binding of antibodies to specific regions within the regulatory domain of the gamma-subunit can augment or inhibit structural changes and subunit interactions important in regulating phosphorylase kinase activity.
The Universally Conserved GroE (Hsp60) Chaperonins (1991)

Microbiology began as a unified science using the principles of chemistry to understand living systems. The unified view quickly split into the subdisciplines of medical microbiology, molecular biology, and environmental microbiology. The advent of a ...Read More
High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome (2010)

Our experience suggests that paediatric patients with haemoglobinopaties have a high incidence of CSA related neurological events with no correlation between serum CSA levels and neurotoxicity. Prognosis is good following CSA removal. Specific prodromes such as arterial hypertension, headache or visual disturbances occurring in the early post-transplant period should be carefully evaluated with electrophysiological and MRI-based imaging in order to intervene promptly and avoid irreversible sequels.
Time reversal of wideband microwaves (2006)

In this letter, time reversal is applied to wideband electromagnetic waves in a reverberant room. To that end a multiantenna time reversal mirror (TRM) has been built. A 150MHz bandwidth pulse at a central frequency of 2.45GHz is radiated by a monopolar antenna, spread in time due to reverberation, recorded at the TRM, time reversed, and retransmitted. The time-reversed wave converges back to its source and focus in both time and space. The time compression is studied versus the number of antennas in the TRM and its bandwidth. The focal spot is also measured thanks to an eight-channel receiving array.
Combination Therapy with Multiple Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Preventive Strategy (1999)

The traditional "pyramid" or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti-inflammatory drug for months to years while seeking to avoid use of second-line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a "preventive" strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used "anchor drug" in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.
Microglial apolipoprotein E and astroglial apolipoprotein J expression in vitro: opposite effects of lipopolysaccharide (2003)

Apolipoprotein E (apoE) and apoJ are lipid carriers produced in the brain primarily by glial cells. A variety of glial-activating stimuli induce a parallel upregulation of both apolipoproteins expression in vivo and in vitro. To further characterize the cell type and mechanisms by which apoE and apoJ expression are upregulated in activated glia, mixed glial cultures from neonatal rat cortex were treated with the endotoxin lipopolysaccharide (LPS). LPS induced dose-dependent increases in apoJ and decreases in apoE expression and secretion with maximum effects at 1-10 ng/mL and 0.1-1 microg/mL, respectively. Experiments with enriched astroglial and microglial cultures demonstrated that apoE and apoJ expression are predominantly microglial and astroglial, respectively. Given the pivotal role that nuclear factor-kappa B (NF-kappa B) plays in glial activation, we assessed its possible role in mediating apoE and apoJ expression by activated glia. LPS robustly increased NF-kappa B activation in mixed glial cultures. Two NF-kappa B inhibitors, aspirin (10 mM) and MG-132 (0.1 microM), blocked basal apoE and apoJ secretion as well as LPS-induced apoJ secretion. These data demonstrate that glial apoE and apoJ expression are independently regulated by LPS in microglia and astroglia, respectively, and that activated microglia are the predominant source of apoE in mixed glial cultures. The transcription factor NF-kappa B appears to be a critical mediator of LPS-stimulated apoJ expression from astroglia.
microRNA‐124 Regulates Cardiomyocyte Differentiation of Bone Marrow‐Derived Mesenchymal Stem Cells Via Targeting STAT3 Signaling (2012)

Accumulating evidence demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) may transdifferentiate into cardiomyocytes and replace apoptotic myocardium so as to improve functions of damaged hearts. However, little information is known about molecular mechanisms underlying myogenic conversion of BMSCs. microRNAs as endogenous noncoding small molecules function to inhibit protein translation post-transcriptionally by binding to complementary sequences of targeted mRNAs. Here, we reported that miR-124 was remarkably downregulated during cardiomyocyte differentiation of BMSCs induced by coculture with cardiomyocytes. Forced expression of miR-124 led to a significant downregulation of cardiac-specific markers-ANP, TNT, and α-MHC proteins as well as reduction of cardiac potassium channel currents in cocultured BMSCs. On the contrary, the inhibition of endogenous miR-124 with its antisense oligonucleotide AMO-124 obviously reversed the changes of ANP, TNT, and α-MHC proteins and increased cardiac potassium channel currents. Further study revealed that miR-124 targeted the 3'UTR of STAT3 gene so as to suppress the expression of STAT3 protein but did not affect its mRNA level. STAT3 inhibitors AG490, WP1066, and S3I-201 were shown to attenuate the augmented expression of ANP, TNT, α-MHC, GATA-4 proteins, and mRNAs in cocultured BMSCs with AMO-124 transfection. Moreover, GATA-4 siRNA reduced the expression of ANP, TNT, α-MHC, and GATA-4 proteins but did not impact STAT3 protein in cocultured BMSCs, indicating GATA-4 serves as an effector of STAT3. In summary, we found that miR-124 regulated myogenic differentiation of BMSCs via targeting STAT3 mRNA, which provides new insights into molecular mechanisms of cardiomyogenesis of BMSCs.
Use of Encapsulated Single Chain Antibodies for Induction of Anti-Idiotypic Humoral and Cellular Immune Responses (1998)

The use of biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses has been investigated using a single chain antibody scFv-pDL10, which recognizes the human ovarian cancer antigen CA125. Immunization of mice with scFv-pDL10 encapsulated in PLGA microspheres resulted in enhanced humoral and cellular immune responses when compared to scFv-pDL10 alone. Induced anti-idiotypic antibodies (Ab2) which mimic the original antigen CA125 compete with CA125 for the epitope. A cellular response (T2 induction) was also observed. These results raise the possibility of anti-idiotypic antibody induction by a single chain antibody, encapsulated in biodegradeble microspheres, as a potential vaccine for ovarian carcinoma.
Effect of pressure on echocardiographic videodensity from sonicated albumin: an in vitro model. (1995)

The effect of different pressures (0, 10, 30, 60, 80, 100, 120, or 180 mm Hg) on the ultrasound contrast effect obtained from sonicated albumin was evaluated by videodensity decay curves in an in vitro model immersed in a water tank. Decay rates and half-times were calculated from the videodensity decay curves at each pressure. A significant (P < 0.0001) relation was found between contrast disappearance and pressure: the higher the pressure the more rapid the contrast disappearance. Release of pressure did not result in contrast reappearance. Contrast decrease with pressure may result from microbubble destruction or alteration in acoustic properties by pressure. These findings may help explain the limited success of sonicated albumin for systemic ultrasonographic arteriography and myocardial perfusion imaging after intravenous injection. An ideal contrast agent for contrast echo studies should be stable at physiologic pressures.
Possibility of optical bistability due to resonant intersubband excitation in stepped modulation-doped quantum wells (1987)

We propose the use of a novel doped, stepped semiconductor quantum well structure as an optical nonlinear element. The large nonlinearity results from the change of many-body effects on resonant excitation of electrons from the ground to the first excited subband. Self-consistent calculations showed that the intersubband energy separation can be increased by up to 7 meV on intense illumination, compared to 1 meV for a conventional, square quantum well. We estimate that optical switching at powers below 1 W are feasible in an optimized structure, with switching times of about 1 ps.
Rapidly Deployable Video Analysis Sensor units for wide area surveillance (2010)

This paper presents an overview of self-contained automated video analytics units that are man-portable and constitute nodes of a large-scale distributed sensor network. The paper highlights issues with traditional video surveillance systems in volatile environments such as a battle field and provides solutions to them in the form of Rapidly Deployable Video Analysis sensors. We discuss scientific and engineering aspects of the system and present the outcome of a field deployment in an exercise conducted by the Office of Naval Research.
Reversibility of Ischemic Brain Damage (1973)

The susceptibility of the brain to anoxia is considered to be the limiting factor for resuscitation after transient circulatory arrest, both in clinical and experimental conditions.<sup>1,2</sup>In the classic experiments of Weinberger et al,<sup>3</sup>Kabat et al,<sup>4</sup>Grenell,<sup>5</sup>Hirsch et al,<sup>6</sup>and others, the upper limit for full recovery was found to be three to four minutes of cardiocirculatory arrest, and eight to ten minutes of isolated cerebrovascular arrest. The high sensitivity of the central nervous tissue to ischemia has been attributed to low reserves in substrates suitable for anaerobic energy metabolism, because a close correlation was found between the depletion of energy-rich phosphates and the irreversibility of brain damage.<sup>7</sup>This concept, however, is difficult to reconcile with more recent demonstrations of the recovery of various neuronal functions after time intervals which by far exceed the limit of energy depletion. Examples are the return
Network Tomography of Binary Network Performance Characteristics (2006)

In network performance tomography, characteristics of the network interior, such as link loss and packet latency, are inferred from correlated end-to-end measurements. Most work to date is based on exploiting packet level correlations, e.g., of multicast packets or unicast emulations of them. However, these methods are often limited in scope-multicast is not widely deployed-or require deployment of additional hardware or software infrastructure. Some recent work has been successful in reaching a less detailed goal: identifying the lossiest network links using only uncorrelated end-to-end measurements. In this paper, we abstract the properties of network performance that allow this to be done and exploit them with a quick and simple inference algorithm that, with high likelihood, identifies the worst performing links. We give several examples of real network performance measures that exhibit the required properties. Moreover, the algorithm is sufficiently simple that we can analyze its performance explicitly
Multidrug resistance in Yoshida rat ascites hepatoma cell lines. (1992)

Rat ascites hepatoma (AH) cell lines that were induced by dimethylaminoazobenzene and established as transplantable tumors had different sensitivities to vinblastine (VBL). The most VBL-resistant cells, AH66, showed more cross-resistance to vincristine and anthracyclines than AH66F cells. The resistance of AH66 cells was significantly decreased by verapamil. VBL-resistance of AH66 cells was inhibited by other drugs reported as overcoming acquired multidrug resistance, while the sensitivity of AH66F cells was hardly influenced by these drugs. The lowered uptake and enhanced extrusion of the antitumor drug in AH66 cells were suppressed by verapamil. M(r) 160,000 protein in the plasma membrane from AH66 was labeled with a photoactive VBL analog and was immunopositive to a monoclonal antibody against P-glycoprotein, C219. The sensitive cells had barely detectable levels of the surface membrane components. Specific photo-labeling with a VBL analog of P-glycoprotein of AH66 cell membrane was inhibited by reserpine and verapamil which restored the VBL resistance. These results indicate that AH66 cells are a naturally acquired multidrug-resistant cell line overexpressing a P-glycoprotein, and AH cell lines are useful to study multidrug resistance of hepatic carcinomas and development of counteracting drugs.
Multi‐channel magnetocardiography for detecting beat morphology variations in fetal arrhythmias (2003)

The beat morphology and the beat-to-beat variations allow new insights into the electrophysiology of the fetal heart.
Simple diffusion-constrained immunoassay for p24 protein with the sensitivity of nucleic acid amplification for detecting acute HIV infection (2012)

Nucleic acid amplification techniques have become the mainstay for ultimate sensitivity for detecting low levels of virus, including human immunodeficiency virus (HIV). As a sophisticated technology with relative expensive reagents and instrumentation, adoption of nucleic acid testing (NAT) can be cost inhibited in settings in which access to extreme sensitivity could be clinically advantageous for detection of acute infection. A simple low cost digital immunoassay was developed for the p24 capsid protein of HIV based on trapping enzyme-labeled immunocomplexes in high-density arrays of femtoliter microwells and constraining the diffusion of the enzyme-substrate reaction. The digital immunoassay was evaluated for analytical sensitivity for HIV capsid protein p24, and compared with commercially available NAT methods and immunoassays for p24, including 4th-generation antibody/antigen combo assays, for early detection of HIV in infected individuals. The digital immunoassay was found to exhibit 2000-3000-fold greater analytical sensitivity than conventional immunoassays reactive for p24, and comparable sensitivity to NAT methods. Assaying serial samples from 10 HIV-infected individuals, the digital immunoassay detected acute HIV infection as early as NAT methods, and 7-10 days earlier than conventional immunoassays. Comparison of assay results between the digital immunoassay and a quantitative NAT method from HIV infected serum exhibited a linear correlation R(2)>0.99. The data indicate that by constraining diffusion of the signal generation step of a simple sandwich immunoassay and enabling the digital counting of immunocomplexes, dramatic improvements in sensitivity to virus can be obtained to match the sensitivity of NAT at a fraction of the cost.
Implementing Synaptic Plasticity in a VLSI Spiking Neural Network Model (2006)

This paper describes an area-efficient mixed-signal implementation of synapse-based long term plasticity realized in a VLSI model of a spiking neural network. The artificial synapses are based on an implementation of spike time dependent plasticity (STDP). In the biological specimen, STDP is a mechanism acting locally in each synapse. The presented electronic implementation succeeds in maintaining this high level of parallelism and simultaneously achieves a synapse density of more than 9k synapses per mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> in a 180 nm technology. This allows the construction of neural micro-circuits close to the biological specimen while maintaining a speed several orders of magnitude faster than biological real time. The large acceleration factor enhances the possibilities to investigate key aspects of plasticity, e.g. by performing extensive parameter searches.
Bonding of microfluidic devices fabricated in polycarbonate (2010)

A simple method for bonding polycarbonate, based on controlled exposure of the pieces to vapours of solvents, yields a tight seal and unmodified geometry of the channels.
Photodetectors based on treated CdSe quantum-dot films (2005)

We demonstrate photodetectors of sandwich geometry active in the visible spectrum in which the active layer is a 200 nm thick film of CdSe quantum dots (QDs). The solution-phase treatment of the QD film with n-butylamine after casting greatly increases the exciton dissociation efficiency and charge-transport properties of the film. Under 110mW∕cm2 illumination with light at λ=514nm, the photocurrent to dark current ratio, Iphoto∕Idark, is 103 at V=0V, and the 3 dB frequency is ∼50kHz. At room temperature, we observe zero-bias external quantum efficiencies (EQE) from 0.08% to 0.23% in the wavelength range λ=350nm to λ=575nm, corresponding to an internal quantum efficiency (IQE) of 0.6±0.1% across the tested spectrum. At V=−6V, EQE ranges from 15% to 24%, corresponding to an IQE of 70±10%.
Isolation of two isoforms of a novel 15-kDa protein from rabbit polymorphonuclear leukocytes that modulate the antibacterial actions of other leukocyte proteins. (1990)

We have recently reported the use of the highly selective and reversible binding of the potent bactericidal/permeability-increasing protein (BPI) to target Gram-negative bacteria (Escherichia coli) for its isolation from crude extracts of human polymorphonuclear leukocytes (PMN). We now report the use of the same procedure for the purification from rabbit PMN of BPI and also of a novel 15-kDa species that consists of two nearly identical isoforms. These 15-kDa proteins have no demonstrable antibacterial activities by themselves. However, one isoform (p15A) potentiates strongly and the other (p15B) weakly the early antibacterial effects of both rabbit and human BPI. Both isoforms inhibit the late lethal action of BPI. Whereas the potentiating effect is specific for BPI the inhibitory effect is seen also with another antibacterial protein of PMN granules, azurocidin. Thus, we have identified in rabbit PMN a previously unrecognized 15-kDa protein species that may modulate during phagocytosis the antimicrobial effects of BPI (and other granule proteins).
Most viral peptides displayed by class I MHC on infected cells are immunogenic (2019)

CD8<sup>+</sup> T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immunogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8<sup>+</sup> T cell responses.
Potential triple helix-mediated inhibition of IGF-I gene expression significantly reduces tumorigenicity of glioblastoma in an animal model. (1997)

Oligonucleotide-directed triple helix formation is a powerful approach to block transcription of specific genes. Although the oligonucleotide triplex approach is efficient for inhibiting gene expression in cultured cells, suppression is transient. We developed an approach which inhibits insulin-like growth factor-I (IGF-I) expression following stable transfection of C6 rat glioblastoma cells with a plasmid from which an RNA is transcribed that codes for the third strand of a potential triple helix. We tested the ability of this expression vector to inhibit IGF-I gene expression in vitro as well as tumorigenesis in an animal. A dramatic reduction of IGF-I RNA and protein levels in cultured cells occurred following transfection of rat C6 cells with a eukaryotic expression plasmid encoding the oligopurine variant of the triple helix but not the oligopyrimidine or a control sequence. The cells transfected with the oligopurine variant displayed morphological changes, upregulation of major histocompatibility complex I, and increased expression of protease nexin I. Dramatic inhibition of tumor growth occurred in nude mice following injection of transfected C6 cells. To our knowledge, this is the first example of tumor growth inhibition in an animal model employing a triple helix approach.