gebhart/patrepeval huggingface dataset:
Direct preconditioning of cultured chick ventricular myocytes. Novel functions of cardiac adenosine A2a and A3 receptors. (1996)

Preconditioning with brief ischemia before a sustained period of ischemia reduces infarct size in the perfused heart. A cultured chick ventricular myocyte model was developed to investigate the role of adenosine receptor subtypes in cardiac preconditioning. Brief hypoxic exposure, termed preconditioning hypoxia, prior to prolonged hypoxia, protected myocytes against injury induced by the prolonged hypoxia. Activation of the adenosine A1 receptor with CCPA or the A3 receptor with C1-IB-MECA can replace preconditioning hypoxia and simulate preconditioning, with a maximal effect at 100 nM. While activation of the A2a receptor by 1 microM CGS21680 could not mimic preconditioning, its stimulation during preconditioning hypoxia, however, attenuated the protection against hypoxia-induced injury. Blockade of A2a receptors with the selective antagonist CSC (1 microM) during preconditioning hypoxia enhanced the protective effect of preconditioning. Nifedipine, which blocked the A2a receptor-mediated calcium entry, abolished the A2a agonist-induced attenuation of preconditioning. Isoproterenol, forskolin, and BayK 8644, which stimulated calcium entry, also attenuated preconditioning. Nifedipine blocked the increase in calcium uptake by these agents as well as their attenuating effect on preconditioning. The present study provides the first evidence that the adenosine A3 receptor is present on ventricular myocytes and can mediate simulation of preconditioning. The data demonstrate, for the first time, that activation of the A2a receptor antagonizes the preconditioning effect of adenosine, with increased calcium entry during the preconditioning stimuli as a novel mechanism.
AKT Activity Determines Sensitivity to Mammalian Target of Rapamycin (mTOR) Inhibitors by Regulating Cyclin D1 and c-myc Expression (2004)

Prior work demonstrates that AKT activity regulates sensitivity of cells to G(1) arrest induced by mammalian target of rapamycin (mTOR) inhibitors such as rapamycin and CCI-779. To investigate this, a novel high-throughput microarray polysome analysis was performed to identify genes whose mRNA translational efficiency was differentially affected following mTOR inhibition. The analysis also allowed the assessment of steady-state transcript levels. We identified two transcripts, cyclin D1 and c-myc, which exhibited differential expression in an AKT-dependent manner: High levels of activated AKT resulted in rapamycin-induced down-regulation of expression, whereas low levels resulted in up-regulation of expression. To ectopically express these proteins we exploited the finding that the p27(kip1) mRNA was efficiently translated in the face of mTOR inhibition irrespective of AKT activity. Thus, the p27(kip1) 5'-untranslated region was fused to the cyclin D1 and c-myc coding regions and these constructs were expressed in cells. In transfected cells, expression of cyclin D1 or c-myc was not decreased by rapamycin. Most importantly, this completely converted sensitive cells to a phenotype resistant to G(1) arrest. Furthermore, the AKT-dependent differential expression patterns of these two genes was also observed in a mouse xenograft model following in vivo treatment with CCI-779. These results identify two critical downstream molecular targets whose expression is regulated by AKT activity and whose down-regulation is required for rapamycin/CCI-779 sensitivity.
Synthesis and Biological Activity of Akt/PI3K Inhibitors (2006)

Phosphatidylinositol 3-kinase (PI3K) and serine/threonine protein kinase B (PKB or Akt) pathways regulate important cellular processes and are related to a number of human pathologies, such as cancer. The development of kinase inhibitors, with particular attention to small molecule analogues of natural phosphoinositides for pathway interruption and therapeutic applications will be reviewed.
Antioxidant and Antipromotional Effects of the Soybean Isoflavone Genistein (1995)

Antioxidant and antipromotional effects of the soybean isoflavone genistein have been studied in HL-60 cells and the mouse skin tumorigenesis model. Effects of structure-related flavone/isoflavones on hydrogen peroxide (H2O2) production by 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated HL-60 cells and superoxide anion (O2-) generation by xanthine/xanthine oxidase were compared. Of tested isoflavones, genistein is the most potent inhibitor among TPA-induced H2O2 formation by (dimethyl sulfoxide) DMSO-differentiated HL-60 cells, daidzein is second, and apigenin and biochanin A show little effect. In contrast, genistein, apigenin, and prunectin are equally potent in inhibiting O2- generation by xanthine/xanthine oxidase, with daidzein showing a moderate inhibitory effect and biochanin A exhibiting no effect. These results suggest that the antioxidant properties of isoflavones are structurally related and the hydroxy group at Position 4' is crucial in both systems. Dietary administration of 250 ppm genistein for 30 days significantly enhances the activities of antioxidant enzymes in the skin and small intestine of mice. Further studies show that genistein significantly inhibits TPA-induced proto-oncogene expression (c-fos) in mouse skin in a dose-dependent manner. In a two-stage skin carcinogenesis study, low levels of genistein (1 and 5 mumol) significantly prolong tumor latency and decrease tumor multiplicity by approximately 50%. We conclude that genistein's antioxidant properties and antiproliferative effects may be responsible for its anticarcinogenic effect. Its high content in soybeans and relatively high bioavailability favor genistein as a promising candidate for the prevention of human cancers.
Near-far resistance of multiuser detectors in asynchronous channels (1990)

Consideration is given to an asynchronous code-division multiple-access environment in which receiver has knowledge of the signature waveforms of all the users. Under the assumption of white Gaussian background noise, the authors compare detectors by their worst case bit error rate in a near-far environment with low background noise, where the received energies of the users are unknown to the receiver and are not necessarily similar. Conventional single-user detection in a multiuser channel is not near-far resistant, and the substantially higher performance of the optimum multiuser detector requires exponential complexity in the number of users. The authors explore suboptimal demodulation schemes which exhibit a low order of complexity while not exhibiting the impairment of the conventional single-user detector. It is shown that there exists a linear detector whose bit-error-rate is independent of the energy of the interfering users. It is also shown that the near-far resistance of optimum multiuser detection can be achieved by a linear detector. The optimum linear detector for worst-case energies is found, along with existence conditions, which are always satisfied in the models of practical interest.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A phorbol ester receptor/protein kinase, nPKC eta, a new member of the protein kinase C family predominantly expressed in lung and skin. (1990)

Protein kinase C (PKC)-related cDNA clones isolated from mouse epidermis cDNA library encoded a 78-kDa protein, nPKC eta. nPKC eta contains a characteristic cysteine-rich repeat sequence (C1 region) and a protein kinase domain sequence (C3 region), both of which are conserved among PKC family members. However, nPKC eta lacks a putative Ca2+ binding region (C2 region) that is seen in conventional PKCs (alpha, beta I, beta II, gamma), but not in novel PKCs (nPKC delta, -epsilon, -zeta). nPKC eta shows the highest sequence similarity to nPKC epsilon (59.4% identity). The similarity extends to the NH2-terminal sequence (E region) which corresponds to one of the divergent regions (D1 region). Northern blot analysis showed that the mRNA for nPKC eta is highly expressed in the lung and skin but, in contrast to other members of the PKC family, only slightly expressed in the brain. nPKC eta expressed in COS cells shows phorbol ester binding activity with a similar affinity to nPKC epsilon. Antiserum raised against a COOH-terminal peptide of nPKC eta identified an 82-kDa protein in mouse lung extract as well as in an extract from COS cells transfected with the nPKC eta-cDNA expression plasmid. Autophosphorylation of nPKC eta immunoprecipitated with the specific antiserum was observed, indicating that nPKC eta is a protein kinase. These results clearly demonstrate the existence and the possible importance of nPKC eta as a member of the phorbol ester receptor/protein kinase, PKC, family.
Small and decentralized wastewater management systems (1998)

1 Decentralized Wastewater Management Systems and Management 2 Constituents in Wastewater 3 Fate of Wastewater Constituents in the Environment 4 Introduction to Process Analysis and Design 5 Wastewater Pretreatment Operations and Processes 6 Alternative Wastewater Collection Systems 7 Biological Treatment and Nutrient Removal 8 Pond Treatment Systems 9 Wetlands and Aquatic Treatment Systems 10 Land Treatment Systems 11 Intermittent and Recalculating Medium Filters 12 Effluent Repurification and Reuse 13 Effluent Reuse and Disposal for Decentralized Systems 14 Biosolids and Septage Management 15 Management of Decentralized Wastewater Systems Appendixes
Binding of HIV‐1 gp120 to the nicotinic receptor (1992)

We previously described a significant sequence homology between HIV-1 gp120 and the functional sites responsible for the specific binding of snake curare-mimetic neurotoxins and rabies virus glycoprotein to the nicotinic acetylcholine receptor. Here we report findings about the existence of a mechanism of functional molecular mimicry which could enable the binding of HIV-1 gp120 to nicotinic acetylcholine receptors in muscle cells and neurons.
The Saccharomyces cerevisiae Srb8-Srb11 Complex Functions with the SAGA Complex during Gal4-Activated Transcription (2004)

The Saccharomyces cerevisiae SAGA (Spt-Ada-Gcn5-acetyltransferase) complex functions as a coactivator during Gal4-activated transcription. A functional interaction between the SAGA component Spt3 and TATA-binding protein (TBP) is important for TBP binding at Gal4-activated promoters. To better understand the role of SAGA and other factors in Gal4-activated transcription, we selected for suppressors that bypass the requirement for SAGA. We obtained eight complementation groups and identified the genes corresponding to three of the groups as NHP10, HDA1, and SRB9. In contrast to the srb9 suppressor mutation that we identified, an srb9Delta mutation causes a strong defect in Gal4-activated transcription. Our studies have focused on this requirement for Srb9. Srb9 is part of the Srb8-Srb11 complex, associated with the Mediator coactivator. Srb8-Srb11 contains the Srb10 kinase, whose activity is important for GAL1 transcription. Our data suggest that Srb8-Srb11, including Srb10 kinase activity, is directly involved in Gal4 activation. By chromatin immunoprecipitation studies, Srb9 is present at the GAL1 promoter upon induction and facilitates the recruitment or stable association of TBP. Furthermore, the association of Srb9 with the GAL1 upstream activation sequence requires SAGA and specifically Spt3. Finally, Srb9 association also requires TBP. These results suggest that Srb8-Srb11 associates with the GAL1 promoter subsequent to SAGA binding, and that the binding of TBP and Srb8-Srb11 is interdependent.
Direct In Vivo Gene Transfer to Airway Epithelium Employing Adenovirus–Polylysine–DNA Complexes (1993)

Adenovirus-polylysine-DNA complexes were evaluated for their capacity to accomplish direct in vivo gene transfer to airway epithelium employing a rodent model. Binary complexes containing transferrin or adenovirus, or combination complexes containing both transferrin and adenovirus, were evaluated. The highest in vitro gene transfer efficiency in primary cultures of airway epithelial cells was accomplished by the combination complexes. This result was paralleled in vivo. Transient gene expression of up to 1 week was observed with localization of the transduced cells to the region of the small airways. These results establish the feasibility of this type of approach for gene therapy applications.
Synthesis and Immunological Characterization of Toll-Like Receptor 7 Agonistic Conjugates (2009)

Activation of toll-like receptors (TLRs) on cells of the innate immune system initiates, amplifies, and directs the antigen-specific acquired immune response. Ligands that stimulate TLRs, therefore, represent potential immune adjuvants. In this study, a potent TLR7 agonist was conjugated to phospholipids, poly(ethylene glycol) (PEG), or phospholipid-PEG via a versatile benzoic acid functional group. Compared to the unmodified TLR7 agonist, each conjugate displayed a distinctive immunological profile in vitro and in vivo. In mouse macrophages and human peripheral blood mononuclear cells, the phospholipid TLR7 agonist conjugate was at least 100-fold more potent than the free TLR7 ligands, while the potency of PEG-phospholipid conjugate was similar to that of the unmodified TLR7 agonist. When administered systemically in mice, the phospholipid and phospholipid-PEG TLR7 conjugates induced prolonged increases in the levels of proinflammatory cytokines in serum, compared to the unmodified TLR7 activator. When the conjugates were used as adjuvants during vaccination, only the phospholipid TLR7 agonist conjugates induced both Th1 and Th2 antigen-specific immune responses. These data show that the immunostimulatory activity of a TLR7 ligand can be amplified and focused by conjugation, thus broadening the potential therapeutic application of these agents.
Design and testing of an interpolating mixing architecture for electrowetting-based droplet-on-chip chemical dilution (2004)

An on-chip dilution scheme for an electrowetting based microfluidic system is presented in this paper. The dilution scheme uses the mixing and splitting of two droplets of different concentrations to result in an intermediate concentration, as the fundamental operation. A range of dilution factors can be obtained repeating the simple two-droplet mixing and splitting cycles, in various combinations. The accuracy of the dilution scheme primarily depends on two factors-variation in droplet volume during dispensing and splitting, and homogenous mixing. The proposed on-chip dilution architecture was tested for the dilution factors of 2, 4 and 8, using a red food dye as the sample solution and 0.1M KCl solution as the buffer. The concentrations were measured using an optical absorbance measurement system, consisting of an LED and photodiode. The error in the dilution factor was found to be /spl sim/15% for a dilution factor of 4 and /spl sim/25% for a dilution factor of 8. Droplet volume variations in dispensing and splitting contribute to /spl sim/80% of this error.
Safety and Efficacy of Subretinal Readministration of a Viral Vector in Large Animals to Treat Congenital Blindness (2010)

Leber's congenital amaurosis (LCA) is a group of severe inherited retinal degenerations that are symptomatic in infancy and lead to total blindness in adulthood. Recent clinical trials using recombinant adeno-associated virus serotype 2 (rAAV2) successfully reversed blindness in patients with LCA caused by RPE65 mutations after one subretinal injection. However, it was unclear whether treatment of the second eye in the same manner would be safe and efficacious, given the potential for a complicating immune response after the first injection. Here, we evaluated the immunological and functional consequences of readministration of rAAV2-hRPE65v2 to the contralateral eye using large animal models. Neither RPE65-mutant (affected; RPE65(-/-)) nor unaffected animals developed antibodies against the transgene product, but all developed neutralizing antibodies against the AAV2 capsid in sera and intraocular fluid after subretinal injection. Cell-mediated immune responses were benign, with only 1 of 10 animals in the study developing a persistent T cell immune response to AAV2, a response that was mediated by CD4(+) T cells. Sequential bilateral injection caused minimal inflammation and improved visual function in affected animals. Thus, subretinal readministration of rAAV2 in animals is safe and effective, even in the setting of preexisting immunity to the vector, a parameter that has been used to exclude patients from gene therapy trials.
Pluripotency: Toward a gold standard for human ES and iPS cells (2009)

With the advent of technologies for the derivation of embryonic stem cells and reprogrammed stem cells, use of the term "pluripotent" has become widespread. Despite its increased scientific and political importance, there are ambiguities with this designation and a common standard for experimental approaches that precisely define this state in human cells remains elusive. Recent studies have revealed that reprogramming may occur via many pathways which do not always lead to pluripotency. In addition, the pluripotent state itself appears to be highly dynamic, leading to significant variability in the results of molecular studies. Establishment of a stringent set of criteria for defining pluripotency will be vital for biological studies and potential clinical applications in this rapidly evolving field. In this review, we explore the various definitions of pluripotency, examine the current status of pluripotency testing in the field and provide an analysis of how these assays have been used to establish pluripotency in the scientific literature.
Human B-cell immune response to the polymorphic epithelial mucin. (1993)

Human antibodies generated by Epstein-Barr virus immortalized B-cells from tumor-draining lymph nodes of an ovarian cancer patient were screened for reactivity in enzyme-linked immunosorbent assay with a synthetic peptide corresponding to the protein core of the polymorphic epithelial mucin. Epitopes within this region are in fact considered tumor specific since they are selectively exposed in tumor cells due to aberrant glycosylation. Human antibody BB5, thus selected, reacts in enzyme-linked immunosorbent assay and immunohistochemistry with polymorphic epithelial mucin-expressing tumor cells. This is the first demonstration of the existence of a B-cell immune response to selected epitopes of polymorphic epithelial mucin and, together with the cytotoxic T-cell response already demonstrated, constitutes the basis for the use of synthetic peptides as a vaccine in cancer patients.
Receptor-Ligand Interaction Between CD44 and Osteopontin (Eta-1) (1996)

The CD44 family of surface receptors regulates adhesion, movement, and activation of normal and neoplastic cells. The cytokine osteopontin (Eta-1), which regulates similar cellular functions, was found to be a protein ligand of CD44. Osteopontin induces cellular chemotaxis but not homotypic aggregation, whereas the inverse is true for the interaction between CD44 and a carbohydrate ligand, hyaluronate. The different responses of cells after CD44 ligation by either osteopontin or hyaluronate may account for the independent effects of CD44 on cell migration and growth. This mechanism may also be exploited by tumor cells to promote metastasis formation.
Effects of the β-adrenoceptor Antagonists Atenolol and Propranolol on Human Parotid and Submandibular-Sublingual Salivary Secretion (1994)

The aim of the study was to evaluate the effects of a beta 1-selective (atenolol 50 mg q.d.) and a non-selective (propranolol 80 mg b.i.d.) beta-adrenoceptor antagonists on human stimulated parotid and submandibular-sublingual (SM-SL) gland secretion. A randomized double-blind, placebo-controlled cross-over ("Latin square") design was used in 19 healthy male volunteers. Stimulated parotid and SM-SL saliva were sampled immediately before and 7 days after the start of each treatment period. Stimulation of salivary secretion was achieved by use of a 3% citric acid solution. Plasma concentrations of propranolol and atenolol were determined from blood samples. The salivary secretion of both glands was assessed for flow rate, amylase, lysozyme, and salivary peroxidase activity and for concentrations of total protein, hexosamine, sialic acid, Ca2+, Cl-, K+, Mg2+, Na+, and PO4(3-). In both parotid and SM-SL secretions, the total protein and phosphate concentrations and amylase activity were significantly decreased during the two active treatment periods. In SM-SL gland secretion, there were significant changes in potassium and calcium concentrations during active treatment as compared with baseline, with potassium showing a decreased and calcium an increased concentration. During atenolol treatment, salivary peroxidase activity decreased significantly in SM-SL secretion. In parotid secretion, the hexosamine/total protein ratio decreased and the sialic acid/hexosamine ratio increased during atenolol treatment, which may indicate an effect on protein synthesis. No significant effects on salivary secretion rates were disclosed.
The distribution of tetraphenylporphinesulfonate in the tumor-bearing rat. (1962)

Summary The distribution of tetraphenylporphinesulfonate, following its parenteral administration to rats bearing the Walker carcinosarcoma, has been studied. It was found that the concentration in the tumor was greater than that in any of the other tissues studied, but several of these tissues also had appreciable concentrations. The concentration was found to be dependent upon dose, and the distribution was affected by time following administration. Tetraphenylporphinesulfonate was found to be transported in the blood bound to the serum proteins. The concentration of this material found in the tumor was far greater than that obtained with hematoporphyrin in other studies.
Molecular Cloning and Characterization of Human Keratan Sulfate Gal-6-Sulfotransferase (1997)

We have previously cloned chondroitin 6-sulfotransferase (C6ST) cDNA from chick embryo chondrocytes. C6ST catalyzes sulfation of chondroitin, keratan sulfate, and sialyl N-acetyllactosamine oligosaccharides. In this study, we report the cloning and characterization of a novel sulfotransferase that catalyzes sulfation of keratan sulfate. This new sulfotransferase cDNA clone was obtained from a human fetal brain library by cross-hybridization with chick C6ST cDNA. The cDNA clone obtained contains a single open reading frame that predicts a type II transmembrane protein composed of 411 amino acid residues. When the cDNA was introduced into a eukaryotic expression vector and transfected in COS-7 cells, keratan sulfate sulfotransferase activity was overexpressed, but C6ST activity was not increased over that of the control. Structural analysis of 35S-labeled glycosaminoglycan, which was formed from keratan sulfate by the reaction with 35S-labeled 3'-phosphoadenosine 5'-phosphosulfate and the recombinant sulfotransferase, showed that keratan sulfate was sulfated at position 6 of Gal residues. On the basis of the acceptor substrate specificity, we propose keratan sulfate Gal-6-sulfotransferase (KSGal6ST) for the name of the newly cloned sulfotransferase. KSGal6ST was assigned to chromosome 11p11. 1-11.2 by fluorescence in situ hybridization. Among various human adult tissues, a 2.8-kilobase message of KSGal6ST was expressed mainly in the brain. When poly(A)+ RNAs from the chick embryo cornea and brain were probed with the human KSGal6ST cDNA in Northern hybridization, a clear band with about 2.8 kilobases was detected. These observations suggest that KSGal6ST may participate in the biosynthesis of keratan sulfate in the brain and cornea.