gebhart/patrepeval huggingface dataset:
Indolo[2,3-b]-Quinolizinium Bromide: An Efficient Intercalator with DNA-Photodamaging Properties (2002)

The associative interactions of indolo[2,3-b]-quinolizinium bromide with DNA and its DNA photocleavage properties were studied in detail. Absorption and emission spectroscopy, linear dichroism, and energy-transfer measurements indicate that the indoloquinolizinium binds to DNA primarily by intercalation, with a preference for GC base pairs. In agreement with this data, the results of primer extension analysis indicate that photocleavage occurrs prevalently at the GC nucleotides. Molecular modeling studies confirm that intercalative stacking between adjacent base pairs is energetically favorable. However, it is also observed that the location of the dye in the minor groove of the DNA is energetically even more favorable. Upon UVA irradiation, the indoloquinolizinium causes single-strand cleavage with an efficiency that varies with the dye-DNA ratio. This observation is rationalized in terms of more efficient photocleavage by the externally bound dye compared with the intercalated one. The kinetics of strand degradation under aerobic and anaerobic conditions suggest that a Type I reaction occurs, that is, radical-mediated DNA damage.
Mammalian MagT1 and TUSC3 are required for cellular magnesium uptake and vertebrate embryonic development (2009)

Magnesium (Mg(2+)) is the second most abundant cation in cells, yet relatively few mechanisms have been identified that regulate cellular levels of this ion. The most clearly identified Mg(2+) transporters are in bacteria and yeast. Here, we use a yeast complementary screen to identify two mammalian genes, MagT1 and TUSC3, as major mechanisms of Mg(2+) influx. MagT1 is universally expressed in all human tissues and its expression level is up-regulated in low extracellular Mg(2+). Knockdown of either MagT1 or TUSC3 protein significantly lowers the total and free intracellular Mg(2+) concentrations in mammalian cell lines. Morpholino knockdown of MagT1 and TUSC3 protein expression in zebrafish embryos results in early developmental arrest; excess Mg(2+) or supplementation with mammalian mRNAs can rescue the effects. We conclude that MagT1 and TUSC3 are indispensable members of the vertebrate plasma membrane Mg(2+) transport system.
The phosphatidylinositol 3‐kinases (PI3K) inhibitor GS‐1101 synergistically potentiates histone deacetylase inhibitor‐induced proliferation inhibition and apoptosis through the inactivation of PI3K and extracellular signal‐regulated kinase pathways (2013)

Previously, we showed that inhibition of the protein kinase C β (PKCβ)/AKT pathway augments engagement of the histone deacetylase inhibitor (HDI)-induced apoptosis in lymphoma cells. In the present study, we investigated the cytotoxicity and mechanisms of cell death induced by the delta isoform-specific phosphatidylinositide 3-kinase (PI3K) inhibitor, GS-1101, in combination with the HDI, panobinostat (LBH589) and suberoylanilide hydroxamic acid (SAHA). Lymphoma cell lines, primary non-Hodgkin Lymphoma (NHL) and chronic lymphocytic leukaemia (CLL) cells were simultaneously treated with the HDI, LBH589 and GS-1101. An interaction of the LBH589/GS-1101 combination was formally examined by using various concentrations of LBH589 and GS-1101. Combined treatment resulted in a synergistic inhibition of proliferation and showed synergistic effect on apoptotic induction in all tested cell lines and primary NHL and CLL cells. This study indicates that interference with PI3K signalling dramatically increases HDI-mediated apoptosis in malignant haematopoietic cells, possibly through both AKT-dependent or AKT- independent mechanisms. Moreover, the increase in HDI-related apoptosis observed in PI3K inhibitor-treated cells appears to be related to the disruption of the extracellular signal-regulated kinase (ERK) signalling pathway. This study provides a strong rational for testing the combination of PI3K inhibitors and HDI in the clinic.
A Review of the Foreign-body Response to Subcutaneously-implanted Devices: The Role of Macrophages and Cytokines in Biofouling and Fibrosis (2008)

The biological response to implanted biomaterials in mammals is a complex series of events that involves many biochemical pathways. Shortly after implantation, fibrinogen and other proteins bind to the device surface, a process known as biofouling. Macrophages then bind to receptors on the proteins, join into multinucleated giant cells, and release transforming growth factor beta and other inflammatory cytokines. In response to these signals, quiescent fibroblasts are transformed into myofibroblasts, which synthesize procollagen via activation of Smad mediators. The procollagen becomes crosslinked after secretion into the extracellular space. Mature crosslinked collagen and other extracellular matrix proteins gradually contribute to formation of a hypocellular dense fibrous capsule that becomes impermeable or hypopermeable to many compounds. Porous substrates and angiogenic growth factors can stimulate formation of microvessels, which to some extent can maintain analyte delivery to implanted sensors. However, stimulation by vascular endothelial growth factor alone may lead to formation of leaky, thin-walled, immature vessels. Other growth factors are most probably needed to act upon these immature structures to create more robust vessels.During implantation of foreign bodies, the foreign-body response is difficult to overcome, and thousands of biomaterials have been tested. Biomimicry (i.e., creating membranes whose chemical structure mimics natural cellular compounds) may diminish the response, but as of this writing, it has not been possible to create a stealth material that circumvents the ability of the mammalian surveillance systems to distinguish foreign from self.
Targeting of T lymphocytes against egf‐receptor+ tumor cells by bispecific monoclonal antibodies: Requirement of CD3 molecule cross‐linking for t‐cell activation (1993)

Targeting of T lymphocytes against epidermal growth-factor-receptor (EGF-R)+ tumor cells was achieved by constructing a hybrid hybridoma which secretes an anti-EGF-R/anti-CD3 bispecific monoclonal antibody (biMAb) of hybrid isotype (IgG1/IgG2a). Purification of biMAb molecules from parental anti-EGF-R and anti-CD3 MAbs was performed by protein-A chromatography. The purified biMAb was able to trigger the lysis of EGF-R+ tumor cell lines (A431, IGROV-1, MDA-468 and U-87) and of NIH-3T3 transfectants expressing human EGF-R by cytolytic T lymphocytes, but it was ineffective in the case of EGF-R-negative tumor targets. Normal EGF-R+ cells (keratinocytes and endometrial cells) were also susceptible to biMAb-targeted cytolysis. However, the amount of biMAb required to induce half-maximal cytolysis of tumor cells over-expressing the EGF-R molecule (A431) was considerably lower than that required to induce lysis of EGF-R+ tumor or normal cells which express EGF-R at considerably lower density. The ability of such biMAbs to deliver activation signals to T cells was evaluated by Ca++ mobilization and lymphokine production experiments. The soluble anti-EGF-R/anti-CD3 biMAb failed to induce intracellular Ca++ increases, which occurred only after cross-linking induced by an anti-mouse IgG antibody. Secretion of lymphokines (IFN-gamma, TNF-alpha and GM-CSF) was induced by contact of the biMAb-coated effector cells with the relevant tumor target, whereas the soluble biMAb was virtually ineffective. In addition, biMAb-coated effector cells retained the ability to recognize and to lyse EGF-R+ tumor cells for a prolonged period of time. Our data indicate that activation of effector cells targeted by biMAbs can only occur at the tumor site, where cross-linking of surface CD3 molecules is induced by contact with the tumor cells.
Photochemical and Electrochemical Reduction of Carbon Dioxide to Carbon Monoxide Mediated by (2,2′‐Bipyridine)tricarbonylchlororhenium(I) and Related Complexes as Homogeneous Catalysts (1986)

Abstract [ fac ‐Re(bpy) (CO) 3 Cl] (bpy = 2,2′‐bipyridine) is an efficient homogeneous catalyst for the selective and sustained photochemical or electrochemical reduction of CO 2 to CO. A quantum yield of 14% and a faradic efficiency of 98% were measured in the presence of excess Cl − ions. The photochemical process took place under visible‐light irradiation and consumed a tertiary amine as electron donor. A formato‐rhenium complex was isolated in the absence of excess Cl − ions. Substitution by Cl − ion generated free formate, but no CO was detected. Luminescence measurements showed that the tertiary amine quenches the metal‐to‐ligand charge‐transfer excited state of the rhenium complex via a reductive mechanism, with a rate constant of 3.4 × 10 7 M −1 S −1 . The 19e‐complex [Re(bpy) (CO) 3 X] − produced either photochemically or electrochemically appears to be the active precursor in the CO‐generation process. Detailed spectroscopic studies on 13 C‐enriched carbonyl‐rhenium and formato‐rhenium complexes derived from 13 C‐enriched CO 2 were performed in order to confirm the origin of the products and to study the exchange of the ligands. A mechanism for the present CO 2 photoreduction process is presented; it involves separate pathways for CO and formate generation, in which the [Re(bpy) (CO) 3 X] complex plays the role of both the photoactive and the catalytic center .
Immunological Cross-Reactivity Between a Heat-Labile Enterotoxin(s) of Escherichia coli and Subunits of Vibrio cholerae Enterotoxin (1978)

Heat-labile enterotoxin from Escherichia coli is immunologically related to both subunits, A and B, of cholera enterotoxin as demonstrated by neutralization and immunodiffusion.
Immune Responses and Disease Enhancement during Respiratory Syncytial Virus Infection (2005)

Respiratory syncytial virus (RSV) is one of the commonest and most troublesome viruses of infancy. It causes most cases of bronchiolitis, which is associated with wheezing in later childhood. In primary infection, the peak of disease typically coincides with the development of specific T- and B-cell responses, which seem, in large part, to be responsible for disease. Animal models clearly show that a range of immune responses can enhance disease severity, particularly after vaccination with formalin-inactivated RSV. Prior immune sensitization leads to exuberant chemokine production, an excessive cellular influx, and an overabundance of cytokines during RSV challenge. Under different circumstances, specific mediators and T-cell subsets and antibody-antigen immune complex deposition are incriminated as major factors in disease. Animal models of immune enhancement permit a deep understanding of the role of specific immune responses in RSV disease, assist in vaccine design, and indicate which immunomodulatory therapy might be beneficial to children with bronchiolitis.
Vagus Nerve Stimulation for Treatment of Partial Seizures: 3. Long‐Term Follow‐Up on First 67 Patients Exiting a Controlled Study (1994)

Vagus nerve stimulation (VNS) has demonstrated a significant anticonvulsant effect in preclinical studies, in pilot studies in humans, and in the acute phase of a multicenter, double-blinded, randomized study. After completion of a 14-week, blinded, randomized study, with 31 receiving high (therapeutic) VNS and 36 receiving low (less or noneffective) VNS, 67 patients elected to continue in an open extension phase. During the extension phase, all 67 patients received high VNS. Seizure frequency during the 3-month treatment blocks was compared with a 12-week baseline. For both groups, all periods of high VNS demonstrated a significant decrease in seizure frequency (p < 0.01 level) as compared with baseline. For the 16-18-month period of VNS, data were available for 26 of the 31 patients randomized to high VNS. This group achieved a 52.0% mean seizure frequency percentage reduction as compared with baseline. For those converted from low to high VNS, data were available for 24 of the 36 patients at the 16-18-month time period. This group reported a mean seizure frequency percentage reduction of 38.1% as compared with baseline. No significant change in the safety/side effect profile was reported during long-term follow-up. The previously reported side effects of hoarseness/voice change, coughing, and paresthesia (sensation in neck and jaw) continued to occur during VNS. These side effects were well tolerated. During the follow-up period, 1 patient died of thrombotic thrombocytopenic purpura (TTP) and 5 patients discontinued treatment because of unsatisfactory efficacy.
Synthesis of Some New Heterocycles Derived from Arylmethylenemalononitriles (1998)

Abstract Arylmethylenemalononitriles 1 were treated with halo compounds under phase transfer catalysis (PTC) conditions to yield α-polyfunctional arylmethylene-malononitrile derivatives 2–4. The treatment of compounds 2–4 with hydrazine hydrate gave pyridinones 5,6 and pyridine 7, respectively. Triazines, triazepines, tetrazines, and triazoles 8–15 fused with pyridinone were synthesized by treating pyridinones 5 with a suitable reagent.
Anti-Siglec-F Antibody Reduces Allergen-Induced Eosinophilic Inflammation and Airway Remodeling (2009)

Siglec-F is a sialic acid-binding Ig superfamily receptor that is highly expressed on eosinophils. We have investigated whether administration of an anti-Siglec-F Ab to OVA-challenged wild-type mice would reduce levels of eosinophilic inflammation and levels of airway remodeling. Mice sensitized to OVA and challenged repetitively with OVA for 1 mo who were administered an anti-Siglec-F Ab had significantly reduced levels of peribronchial eosinophilic inflammation and significantly reduced levels of subepithelial fibrosis as assessed by either trichrome staining or lung collagen levels. The anti-Siglec-F Ab reduced the number of bone marrow, blood, and tissue eosinophils, suggesting that the anti-Siglec-F Ab was reducing the production of eosinophils. Administration of a F(ab')(2) fragment of an anti-Siglec-F Ab also significantly reduced levels of eosinophilic inflammation in the lung and blood. FACS analysis demonstrated increased numbers of apoptotic cells (annexin V(+)/CCR3(+) bronchoalveolar lavage and bone marrow cells) in anti-Siglec-F Ab-treated mice challenged with OVA. The anti-Siglec-F Ab significantly reduced the number of peribronchial major basic protein(+)/TGF-beta(+) cells, suggesting that reduced levels of eosinophil-derived TGF-beta in anti-Siglec-F Ab-treated mice contributed to reduced levels of peribronchial fibrosis. Administration of the anti-Siglec-F Ab modestly reduced levels of periodic acid-Schiff-positive mucus cells and the thickness of the smooth muscle layer. Overall, these studies suggest that administration of an anti-Siglec-F Ab can significantly reduce levels of allergen-induced eosinophilic airway inflammation and features of airway remodeling, in particular subepithelial fibrosis, by reducing the production of eosinophils and increasing the number of apoptotic eosinophils in lung and bone marrow.
Inverse relationship between heart rate and blood pressure variabilities in rats. (1987)

The interplay of heart rate variability, baroreceptor control of heart rate, and blood pressure (BP) variability was examined in chronically instrumented, unanesthetized, freely moving rats in which the efferent neural influences on heart rate were pharmacologically altered. In each rat, BP was recorded continuously for 90 minutes in the control condition and in one or more of the following conditions: 1) beta-adrenergic receptor blockade by propranolol, 1 mg/kg; 2) cholinergic blockade by atropine, 0.75 mg/kg, and 3) combined blockade by propranolol plus atropine. Each BP recording was analyzed beat-to-beat by a computer that calculated heart rate and BP variabilities, both expressed as variation coefficients. In addition, under each condition the sensitivity of the arterial baroreceptor control of heart rate was assessed by measuring the reflex changes in pulse interval in response to BP changes induced by bolus i.v. injections of phenylephrine and nitroprusside. As compared with the control condition, 1) propranolol (n = 10) reduced heart rate variability by 23 +/- 4% (p less than 0.01), only slightly impaired baroreceptor reflex sensitivity, and did not significantly modify BP variability (+11 +/- 7%); 2) atropine (n = 11) reduced heart rate variability by 30 +/- 7% (p less than 0.01), drastically impaired baroreceptor reflex sensitivity, and increased BP variability (+40 +/- 8%, p less than 0.01); 3) combined blockade (n = 10) caused variability and baroreceptor reflex changes similar to those induced by atropine alone. Thus, heart rate variability depends on both vagal and sympathetic influences. However, only the former component affects BP variability, that is, it plays an antioscillatory role.(ABSTRACT TRUNCATED AT 250 WORDS)
The lung inflammatory response to thermal injury: relationship between physiologic and histologic changes. (1989)

We studied the effect of a body burn on lung physiologic, biochemical, and histologic changes in a 2-day postburn period. A 15% of total-body-surface third-degree burn was produced in 24 adult sheep with lung and burn lymph fistulas. Eight sheep were killed at 12 hours and eight at 48 hours. At 12 hours we noted increased lung tissue lipid peroxidation, lung congestion, and neutrophil sequestration, in addition to a 30% decrease in lung compliance. Lung permeability and water content were not increased. Increased release of lipid peroxides and prostanoids were noted from burn tissue, as evidenced by increased plasma levels of malondialdehyde and conjugated dienes that remained elevated for about 8 hours and were decreased with wound removal. The lung inflammatory response was still present at 48 hours, the cells being primarily neutrophils. Nevertheless, the lipid peroxidation process, as measured by lung tissue malondialdehyde, had resolved. There was no evidence of burn tissue infection, measured by quantitative culture, to explain the persistent increase in lung inflammatory cells. Excision and closure of the burn wound at 3 hours postburn in eight sheep attenuated the lipid peroxidation and compliance changes but did not decrease the neutrophil sequestration. We conclude that burn injury results in a local wound oxidant release that leads to lipid peroxidation, both in wounds and in lung, as well as lung inflammation. The lipid peroxidation process may be attenuated by removal of the wound. The neutrophil sequestration is not altered, however, indicating this response occurs very early after injury, probably as a result of oxidant-initiated complement activation.
Application of Fenton’s Reagent to Remediate Diesel Contaminated Soils (2005)

This paper presents the results of an experimental investigation into usage of Fenton’s reagent (a mixture of ferrous salts and hydrogen peroxide) to remediate diesel-impacted soils. A number of process variables such as the presence of iron salts, comparison between ferrous and ferric salts, amount of diesel washed out and mineralized and the use of surfactant to augment the treatment were investigated. Additionally, studies were conducted to evaluate the in-situ injection technique for remediation of diesel-impacted soil using H2O2 and also its effect on the hydraulic conductivity of the soil. The results indicate that external amendment of iron is not necessary in soils containing iron, and that concentration and volume of H2O2 were important process variables in modified Fenton’s reaction. The hydraulic conductivity of the soil for H2O2 was significantly lower than that of water due to generation of gas and other reaction products, which blocked the pores. In some experiments, injection of H2O2 into the soil matrix met with resistance due to gas generation and the H2O2 moved up along the sides of the injector.
Radiosensitivity in Ataxia-telangiectasia: Anomalies in Radiation-induced Cell Cycle Delay (1994)

A number of anomalies have been described in the progression of ataxia-telangiectasia (AT) cells through the cell cycle post-irradiation. Some uncertainty still exists as to whether AT cells show increased or reduced division delay after exposure to ionizing radiation. We have attempted to resolve the apparent inconsistencies that exist by investigating the effects of radiation on AT cells at various stages of the cell cycle. Specific labelling of S phase cells with 5-bromodeoxyuridine (BrdU) followed by irradiation caused a prolonged accumulation of these cells in G2/M phase with only 2-7% of AT cells progressing through to G1 24h post-irradiation. In contrast, 23-28% of control cells irradiated in S phase reached G1 by 24 h after irradiation. As observed previously with AT fibroblasts, AT lymphoblastoid cells irradiated in G1 phase did not experience a delay in entering S phase. After progressing through S phase these cells also were delayed in G2/M, but not to the same extent as irradiated S phase cells. On the other hand, when AT cells were irradiated in G2 phase they showed less delay initially in entry to mitosis and the subsequent G1 phase than did irradiated control cells. The overall results demonstrate that AT cells fail to show an initial delay in transitions between the G1/S and G2/M phases of the cell cycle and in progression through these phases post-irradiation, but in the long-term, after passage through S phase, they experience a prolonged delay in G2/M. Since several AT complementation groups are represented in this study, the cell cycle anomalies appear to be universal in AT. These results implicate deficiencies in control of cell cycle progression in the increased radiosensitivity and cancer predisposition in AT.
Error Recovery using FEC and Retransmission for Interactive Video Transmission (1998)

This paper proposes a new error recovery technique for interactive video transmission over error-prone, slow, and bandwidth constrained networks. The technique effectively combines forward error correction (FEC) and retransmission to solve the error propagation problem which is inherent in any motion-based video codecs. Prior work has mainly taken an approach that prevents display errors from occurring from the first place. This approach is not effective for interactive video transmission over the target network environments because data losses inevitably occur in such networks and repairing them tends to introduce the delays in video playout. Our approach is to focus on eliminating error propagation and isolating errors when they occur. This approach allows more time for packet repairs and can effectively mask out delays in repairing lost packets. A simulation study shows that the proposed techniques can be effectively used to transmit high-frame-rate interactive video over slow, erro...
Genetic recombination of human immunodeficiency virus (1989)

We investigated genetic recombination of the human immunodeficiency virus (HIV) in a tissue culture system. A clonal cell line expressing a single integrated HIV provirus with a termination codon affecting pol gene expression was transfected with different defective mutants derived from an infectious molecular clone of HIV. Replication-competent viral particles were recovered, passaged, and plaque purified. Restriction analyses of the proviral DNA corresponding to several of these viruses indicated that their emergence was the result of genetic recombination.
Visual Functioning and General Health Status in Patients With Uveitis (2001)

Patients with uveitis reported markedly poorer visual functioning and general health status than normal subjects. Patients with more severe uveitis have poorer visual functioning and general health status than patients with milder disease. Visual functioning and general health status measurement contribute complementary information and should both be performed in patients with uveitis to measure the effect of disease and its therapy on their quality of life.