gebhart/patrepeval huggingface dataset:
Quantitative Analysis of Molecular Interaction in a Microfluidic Channel:  The T-Sensor (1999)

The T-sensor is a recently developed microfluidic chemical measurement device that exploits the low Reynolds number flow conditions in microfabricated channels. The interdiffusion and resulting chemical interaction of components from two or more input fluid streams can be monitored optically, allowing measurement of analyte concentrations on a continuous basis. In a simple form of T-sensor, the concentration of a target analyte is determined by measuring fluorescence intensity in a region where the analyte and a fluorescent indicator have interdiffused. An analytical model has been developed that predicts device behavior from the diffusion coefficients of the analyte, indicator, and analyte--indicator complex and from the kinetics of the complex formation. Diffusion coefficients depend on the local viscosity which, in turn, depends on local concentrations of all analytes. These relationships, as well as reaction equilibria, are often unknown. A rapid method for determining these unknown parameters by interpreting T-sensor experiments through the model is presented.
Intraseptal Flumazenil Enhances, while Diazepam Binding Inhibitor Impairs, Performance in a Working Memory Task (1996)

GABAA/benzodiazepine receptors in the medial septum modulate the activity of cholinergic neurons that innervate the hippocampus. Injection of benzodiazepine (BDZ) agonists into the medial septum impairs working memory performance and decreases high-affinity choline transport (HAChT) in the hippocampus. In contrast, intraseptal injection of the BDZ antagonist flumazenil increases HAChT and prevents the memory deficits induced by systemic BDZs. The present studies attempted to further characterize the behavioral effects of medial septal injections of flumazenil to an endogenous negative modulator of the GABAA/BDZ receptor complex, diazepam binding inhibitor (DBI). Male Sprague-Dawley rats were cannulated to study the effects of intraseptal injections of these BDZ ligands on spatial working memory, anxiety-related behaviors in the elevated plus maze, and on general locomotor activity. Intraseptal flumazenil (10 nmol/0.5 microliter) produced a delay-dependent enhancement of DNMTS performance after an 8-h, but not a 4-h, delay interval. This promnestic dose of flumazenil had no effect on locomotor activity and did not produce changes in measures of anxiety on the plus maze. Intraseptal injection of DBI had no effect (8 nmol/0.5 microliter) or slightly impaired (4 nmol/0.5 microliter) DNMTS radial maze performance following an 8-h delay, without producing changes in locomotion or plus maze behavior. These data demonstrate that flumazenil has a unique profile of activity in enhancing working memory following intraseptal injection.
Preclinical Science Regarding Cannabinoids as Analgesics: An Overview (2005)

Modern pharmacology of cannabinoids began in 1964 with the isolation and partial synthesis of delta-9-tetrahydrocannabinol, the main psycho-active agent in herbal cannabis. Since then, potent antinociceptive and antihyperalgesic effects of cannabinoid agonists in animal models of acute and chronic pain; the presence of cannabinoid receptors in pain-processing areas of the brain, spinal cord and periphery; and evidence supporting endogenous modulation of pain systems by cannabinoids has provided support that cannabinoids exhibit significant potential as analgesics. The present article presents an overview of the preclinical science.
A model of Neisseria meningitidis vaccine based on LPS micelles detoxified by synthetic antiendotoxin peptides (1997)

We describe a model of vaccine based on detoxified endotoxin (LPS) conserving the supramolecular structure of micelles. Detoxification of LPS from Neisseria meningitidis group A, strain A1 (LPS A1), has been achieved by complex formation with a synthetic anti-endotoxin peptide (SAEP 2) binding to the lipid A moiety of LPS A1 with high affinity. Following subcutaneous injection in SW mice, LPS A1/SAEP 2 complex induced high titers of boostable IgG antibodies against the immunotype determinants of LPS A1, cross-reactive with group B LPS in either purified or cell-associated form. These antibodies were able to functionally fix and activate homologous and heterologous species of complement after binding to LPS A1-coated sheep erythrocytes. None of the IgG antibodies induced were specific for lipid A or SAEP 2 and none of the IgG antibodies cross-reacted with heterologous LPS. The purified IgG polyclonal antibodies significantly inhibited serum TNF production in CD1 mice intravenously challenged by homologous but not heterologous LPS. The immunogenic properties of LPS A1/SAEP 2 complex, investigated by the kinetic, magnitude and sub-isotype composition of the polyclonal antibodies induced, were comparable to those of a glycoconjugate obtained by covalent binding of LPS A1, detoxified by SAEP 2, to BSA working as a T-cell dependent carrier protein. The results obtained suggest that LPS behaves in vivo as a T-cell dependent antigen. The strategy of properly delivering to the immune system of mammalians, non-toxic LPS fully expressing its supramolecular antigenic structure, represents a novel approach for development of a new generation of R- and S-LPS/SAEP complex-based vaccines for prophylaxis of specific Gram-negative infections leading to sepsis and endotoxemia.
CpG-oligodeoxynucleotides inhibit RSV-enhanced allergic sensitisation in guinea pigs (2005)

Experimental respiratory syncytial virus (RSV) infection of guinea pigs is associated with enhanced allergic sensitisation to inhaled ovalbumin (OA) and low-level viral persistence in the lungs. Based on the T-helper (Th)1/Th2 paradigm, in which a Th2 shift is characteristic of an allergic response and less effective anti-viral immunity, the effects of immunotherapy with synthetic cytosine phosphate-guanine-oligodeoxynucleotides (CpG-ODN), which are potent Th1 stimuli, on OA sensitisation with and without RSV infection were evaluated. Measurements included quantitative histology for airway inflammation by T-cells and eosinophils, semiquantitative RT-PCR for lung Th1/Th2 balance (interferon (IFN)-γ/interleukin (IL)-5 mRNA ratios), and serology for circulating titres of OA-specific immunoglobulin (Ig)G 1 antibodies. RSV antigens were identified in lung tissue sections by immunohistochemistry. CpG-ODN immunotherapy did not prevent OA sensitisation of guinea pigs; however, in RSV-infected, OA-sensitised animals, CpG-ODN administration was associated with significant reductions of airway T-cells and eosinophils, increased lung IFN-γ/IL-5 ratios, and decreased OA-specific IgG 1 antibody titres to levels observed in uninfected, OA-sensitised animals. Viral antigens were identified in a similar proportion of the lungs of RSV-infected animals, irrespective of CpG-ODN immunisation status. In conclusion, cytosine phosphate-guanine-oligodeoxynucleotides immunotherapy protects guinea pigs against respiratory syncytial virus-enhanced ovalbumin sensitisation and might be a relevant intervention in the context of post-bronchiolitis allergic sensitisation in children.
High-resolution in-vivo intra-arterial imaging with optical coherence tomography (1999)

High resolution imaging of intraarterial structure is necessary for the identification of high risk coronary plaque. Optical coherence tomography (OCT), a recently developed technology, is a compact, fiber optic based imaging modality with resolutions between 2-20 μm and real time image acquisition rate. Previous in vitro studies have demonstrated the capability of OCT to identify plaque morphology and distinguish plaques with high lipid content. This work demonstrates the feasibility for OCT imaging of in-vivo intraarterial structures. We demonstrate the detection of microstructural detail and the effects of blood on imaging. Saline injections were required during imaging to reduce the signal attenuation of blood. An axial resolution of 10 μm was achieved. Microstructure within the arterial wall was sharply defined and correlated with histology. OCT shows potential to assist in the risk stratification of plaques and the guidance of interventional procedures, such as stent deployment.
Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution. (1975)

After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection. These observations contribute to understanding of some of the persisting immunodeficiencies that are observed in man after fatal irradiation and bone marrow transplantation. These results should suggest better approaches to more effective cellular engineering for correction of immunodeficiency diseases and for treatment of immunodeficiency diseases and of leukemias and malignancies of man.
Inhibition of thrombosis and intimal thickening by in situ photopolymerization of thin hydrogel barriers. (1994)

Thin hydrogel barriers formed on the inner surface of injured arteries by interfacial photopolymerization dramatically reduced thrombosis and intimal thickening in rat and rabbit models of vascular injury. This polymerization technique allowed the synthesis of a thin hydrogel barrier that conformed to the vessel wall, directly blocking contact between blood and the damaged vessel. The illumination conditions could be varied to control the thickness of the barrier from 10 microns to > 50 microns. The hydrogel was designed to degrade by nonenzymatic hydrolysis. In rats in which the carotid artery had been severely injured by crushing, treatment with the hydrogel barrier completely eliminated thrombosis (P < 0.01) and preserved long-term patency (P < 0.01). Treatment in a rabbit model of balloon injury inhibited thrombosis (P < 0.02) and reduced long-term intimal thickening by approximately 80% (P < 0.003). These results suggest that blood-borne signals acting in the early phases of healing play an important role in stimulating thickening of the intima.
The Lactate Issue Revisited: Novel Feeding Protocols To Examine Inhibition of Cell Proliferation and Glucose Metabolism in Hematopoietic Cell Cultures (2000)

It is well established that cell proliferation in batch (unfed) hematopoietic cell cultures is greatly inhibited relative to that in cultures with feeding. What is not known, however, is the nature of this inhibition. On the basis of our observations in hematopoietic cultures that cell proliferation ceases when the lactate concentration ([lactate]) exceeds 20 mM (accompanied by a decrease in culture pH), we investigated the effect of lactate accumulation on cell proliferation, metabolism, and differentiation. We differ in our approach from previous efforts in that we have tried to more accurately recreate the manner in which lactate accumulates in culture by employing a daily feeding protocol in which [lactate] and/or pH in the fresh medium was adjusted to match the conditions prior to feeding. We conclude that the decrease in pH associated with lactate accumulation significantly inhibits both cell proliferation and metabolism. Although inhibition in cultures with high [lactate] and low pH is similar to that in unfed cultures, pH control in unfed cultures does not alleviate the inhibition, indicating that other inhibitory factors are also present. Thus, pH control is necessary, but not sufficient, to eliminate inhibition of cell growth and metabolism in unfed hematopoietic cell cultures. We also conclude that high [lactate] and low pH have little effect on cell differentiation in fed cultures, although there is evidence to suggest that low pH may play a role in monocyte differentiation in unfed cultures.
Angiotensin II Receptor Blocker: Possibility of Antitumor Agent for Prostate Cancer (2006)

It is known that the renin-angiotensin system (RAS) plays a fundamental role not only as a vasoconstrictor in controlling blood pressure and electrolyte/fluid homeostasis, but also as a mitogenic factor through the Ang-II type-1 (AT1) receptor in smooth muscle cells and cardiac myocytes. Angiotensin II (Ang-II) is indeed thought to be a growth factor, and Ang-II receptor blockers (ARBs), a class of antihypertensive agent, suppress signal transduction pathways mediated by several growth factors or cytokines, through the AT1 receptor. There is increasing evidence that the RAS is implicated in the development of various cancers. We previously demonstrated that ARBs have the potential to inhibit the growth of prostate cancer cells and tumors through the AT1 receptor. This review highlights the possibility of ARBs as novel agents for prostate cancer as well as other cancers, and reviews the literature on this area.
Stable atrial sensing on long-term follow up of VDD pacemakers. (2006)

Implantation of a single lead VDD pacemaker is possible in all patients with symptomatic AV block and intact sinus node function without any technical complications. P wave sensing is reliable and consistent with floating atrial lead at an average follow up of 15.8 months, providing an excellent alternative to DDD pacemaker implantation.
A 1 V 5 mA Multimode IEEE 802.15.6/Bluetooth Low-Energy WBAN Transceiver for Biotelemetry Applications (2012)

This paper presents a 1 V multi-mode RF transceiver for wireless body area network (WBAN) applications. Operating in the 2.36 GHz Medical Body Area Networks (MBANs) and the 2.4 GHz Industrial, Scientific & Medical (ISM) frequency bands, the transceiver implements rotated differential-phase shift keying (DPSK) and Gaussian filtered frequency shift keying (GFSK) modulation for both IEEE 802.15.6 Narrow Band (NB) and Bluetooth Low-Energy (LE) PHY standards. Also included is a proprietary 900 MHz ISM band transmitter utilizing FSK modulation. The wireless transceiver operates half-duplex, and for IEEE 802.15.6 achieves -104/-96.5 dBm receiver input sensitivity (for 10% packet error rate) at data rates of 121.4/971.4 kbps and -94 dBm for Bluetooth LE (for 0.1% bit error rate) at 1 Mbps. Transmit power up to +3/+5 dBm is achievable for IEEE 802.15.6 and Bluetooth LE respectively. The transceiver consumes 4.8 mA during IEEE 802.15.6 & Bluetooth LE receive, and 4.6 mA during Bluetooth LE transmit at -10 dBm output power, from a 1.0 V supply. For IEE802.15.6 transmission at -10 dBm output power, 5.9 mW is consumed, dropping to 1.7 mW for proprietary 900 MHz transmission. This performance surpasses state-of-the-art power consumption and represents the first published transceiver for the IEEE 802.15.6 NB PHY standard. It is fabricated in a 0.13 μm CMOS technology and occupies approximately 5.9 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
Bordetella pertussis filamentous hemagglutinin interacts with a leukocyte signal transduction complex and stimulates bacterial adherence to monocyte CR3 (CD11b/CD18). (1994)

Bordetella pertussis, the causative agent of whooping cough, adheres to human monocytes/macrophages by means of a bacterial surface-associated protein, filamentous hemagglutinin (FHA) and the leukocyte integrin, complement receptor 3 (CR3, alpha M beta 2, CD11b/CD18). We show that an FHA Arg-Gly-Asp site induces enhanced B. pertussis binding to monocytes, and that this enhancement is blocked by antibodies directed against CR3. Enhancement requires a monocyte signal transduction complex, composed of leukocyte response integrin (alpha? beta 3) and integrin-associated protein (CD47). This complex is known to upregulate CR3 binding activity. Thus, a bacterial pathogen enhances its own attachment to host cells by coopting a host cell signaling pathway.
Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer (2013)

Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (~10% of all EGFR mutations) are generally associated with insensitivity to available TKIs (gefitinib, erlotinib, and afatinib). The basis of this primary resistance is poorly understood. We studied a broad subset of exon 20 insertion mutations, comparing in vitro TKI sensitivity with responses to gefitinib and erlotinib in NSCLC patients, and found that most are resistant to EGFR TKIs. The crystal structure of a representative TKI-insensitive mutant (D770_N771insNPG) reveals an unaltered adenosine triphosphate-binding pocket, and the inserted residues form a wedge at the end of the C helix that promotes the active kinase conformation. Unlike EGFR-L858R, D770_N771insNPG activates EGFR without increasing its affinity for EGFR TKIs. Unexpectedly, we find that EGFR-A763_Y764insFQEA is highly sensitive to EGFR TKIs in vitro, and patients whose NSCLCs harbor this mutation respond to erlotinib. Analysis of the A763_Y764insFQEA mutant indicates that the inserted residues shift the register of the C helix in the N-terminal direction, altering the structure in the region that is also affected by the TKI-sensitive EGFR-L858R. Our studies reveal intricate differences between EGFR mutations, their biology, and their response to EGFR TKIs.
Lipoxins: endogenous regulators of inflammation (2004)

Over the past decade, compelling in vivo and in vitro studies have highlighted lipoxins (LXs) and aspirin-triggered LXs (ATLs) as endogenously produced anti-inflammatory eicosanoids. LXs and ATLs elicit distinct anti-inflammatory and proresolution bioactions that include inhibition of leukocyte-mediated injury, stimulation of macrophage clearance of apoptotic neutrophils, repression of proinflammatory cytokine production, modulation of cytokine-stimulated metalloproteinase activity, and inhibition of cell proliferation and migration. An overview of recent advances in LX physiology is provided, with particular emphasis on the cellular and molecular processes involved. These data coupled with in vivo models of inflammatory diseases suggest that LX bioactions may be amenable to pharmacological mimicry for therapeutic gain.
bcl-2 transgene expression can protect neurons against developmental and induced cell death. (1995)

The bcl-2 protooncogene, which protects various cell types from apoptotic cell death, is expressed in the developing and adult nervous system. To explore its role in regulation of neuronal cell death, we generated transgenic mice expressing Bcl-2 under the control of the neuron-specific enolase promoter, which forced expression uniquely in neurons. Sensory neurons isolated from dorsal root ganglia of newborn mice normally require nerve growth factor for their survival in culture, but those from the bcl-2 transgenic mice showed enhanced survival in its absence. Furthermore, apoptotic death of motor neurons after axotomy of the sciatic nerve was inhibited in these mice. The number of neurons in two neuronal populations from the central and peripheral nervous system was increased by 30%, indicating that Bcl-2 expression can protect neurons from cell death during development. The generation of these transgenic mice suggests that Bcl-2 may play an important role in survival of neurons both during development and throughout adult life.
Characterization of mucins and proteoglycans synthesized by a mucin-secreting HT-29 cell subpopulation (1995)

HT-29 cells selected by adaptation to 10(-5) M methotrexate (HT-29 MTX) are a homogeneous cell population producing high amounts of mucin. Intracellular mucins and proteoglycans were isolated from these cells by ultracentrifugation of cell lysates on a cesium bromide gradient and further separated by anion-exchange high performance liquid chromatography. The major mucin fraction isolated was characterized by a high hydroxy amino acid content (40%), a Thr/Ser ratio of 1.52, a high sialic acid content, and a low sulfate content. When the same procedure was applied to undifferentiated HT-29 cells, a minor mucin fraction was isolated which appeared less sialylated and more sulfated. The major proteoglycan species identified in HT-29 MTX cells showed less acidic behavior than the proteoglycan isolated from HT-29 cells. The effect of brefeldin A and the sugar analog GalNAc-alpha-O-benzyl on the synthesis and biochemical properties of mucins synthesized by HT-29 MTX cells was examined. Brefeldin A induced the synthesis of more-sulfated mucins. GalNAc-alpha-O-benzyl treatment resulted in mucins with an increased content of T antigen and a 13-fold lower sialic acid content. We show that GalNAc-alpha-O-benzyl was metabolized by the cells to Gal beta 1-3GalNAc-alpha-O-benzyl, which, in turn, was a potent competitive inhibitor of the O-glycan alpha-2,3-sialyltransferase. These results illustrate the suitability of HT-29 MTX cells as a model to analyse mucin synthesis and sialylation.
A highly reliable interconnection for a BF+ 2-implanted junction utilizing a TiN/Ti barrier metal system (1987)

A submicrometer-rule interconnection structure of the Al-Si layer to the BF <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -implanted Si region is described. The contact resistance of Al-Si to BF <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -implanted Si increases more than those to B <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> - or As <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -implanted Si, as contact hole size is scaled down to around 1 µ2. Through SEM and TEM analyses, it is found that solid phase epitaxial growth of Si takes place on the contact interfaces, where crystalline defects induced by BF <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> implantation act as seeds. Thus, the effective metal contact area to Si is reduced very much. In order to realize a stable metallization system, a TiN/Ti barrier metal structure is introduced. The TiN/Ti structure is optimized in terms of contact resistance and contact barriers, and its feasibility for submicrometer-rule CMOS VLSI's is clarified.