gebhart/patrepeval huggingface dataset:
Norepinephrine Increases Glucose Transport in Brown Adipocytes via β3-Adrenoceptors through a cAMP, PKA, and PI3-Kinase-Dependent Pathway Stimulating Conventional and Novel PKCs (2003)

To identify the signaling pathways that mediate the adrenergic stimulation of glucose uptake in brown adipose tissue, we used mouse brown adipocytes in culture. The endogenous adrenergic neurotransmitter norepinephrine (NE) induced 2-deoxy-D-glucose uptake 3-fold in a concentration-dependent manner (pEC50 approximately 6.5). The uptake was abolished by high doses of propranolol. The NE effect was mimicked by isoprenaline (pEC50 approximately 6.9), BRL 37344 (pEC50 approximately 8.6), CL 316243 (pEC50 approximately 9.7) and CGP 12177 (pEC50 approximately 7.3) and was thus mediated by beta3-adrenergic receptors. The NE-induced effect on 2-deoxy-D-glucose uptake was mediated by adenylyl cyclase and cAMP because responses were inhibited by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine and the protein kinase A inhibitor 4-cyano-3-methylisoquinoline. Cholera toxin and 8-bromoadenosine cAMP were both able to increase 2-deoxy-D-glucose uptake. Involvement of other adrenergic signaling pathways (alpha1-and alpha2-adrenergic receptors) were excluded. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, abolished beta-adrenergic- or 8-bromoadenosine cAMP-stimulated 2-deoxy-D-glucose uptake, demonstrating that a cAMP-dependent PI3K-mediated pathway is positively connected to glucose uptake. Inhibition of the beta-adrenergically stimulated response with protein kinase C (PKC) inhibitors (Gö 6983, which inhibits (alpha, beta, gamma), (delta), and (zeta) isoforms and Ro-31-8220, which inhibits (alpha, beta1, beta2, gamma) and (epsilon) but not atypical isoforms) indicated that cAMP-mediated glucose uptake is stimulated via conventional and novel PKCs. These results demonstrate that adrenergic stimulation, through beta3-adrenergic receptors/cAMP/protein kinase A, recruits a PI3K pathway stimulating conventional and novel PKCs, which mediate glucose uptake in brown adipocytes.
Non-invasive assessment of coronary flow and coronary flow reserve by transthoracic Doppler echocardiography: a magic tool for the real world (2008)

Transthoracic Doppler echocardiography, introduced in the echo-lab in recent last years, to measure coronary flow and coronary flow reserve, is a very attractive tool, totally non-invasive, and easily available at bedside. This review summarizes the actual possibilities of this tool, its multiple potential clinical applications and diagnostic insights, and its arising prognosis value, in coronary artery disease as in various settings affecting the coronary microcirculation.
Proportional rate reduction for TCP (2011)

Packet losses increase latency for Web users. Fast recovery is a key mechanism for TCP to recover from packet losses. In this paper, we explore some of the weaknesses of the standard algorithm described in RFC 3517 and the non-standard algorithms implemented in Linux. We find that these algorithms deviate from their intended behavior in the real world due to the combined effect of short flows, application stalls, burst losses, acknowledgment (ACK) loss and reordering, and stretch ACKs. Linux suffers from excessive congestion window reductions while RFC 3517 transmits large bursts under high losses, both of which harm the rest of the flow and increase Web latency.
Biosynthetic analysis of the human interferon-γ receptor (1989)

Biosynthesis of the human IFN gamma receptor was studied using metabolic labeling techniques and immunoprecipitation with receptor-specific monoclonal antibodies. Colo-205 and HepG2 cells labeled with [35S]methionine gave rise to two components with molecular mass 75 and 90 kDa following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No bands were detected when immunoprecipitation was performed using irrelevant monoclonal IgG or in the presence of excess ligand, a condition known to block antibody-receptor interaction. When Colo-205 were labeled for increasing periods of time, the 75-kDa form was detected after 5 min, whereas the 90-kDa form appeared only after 60 min. Pulse-chase analysis established that the 75-kDa form was the precursor of the 90-kDa component. Only the 90-kDa form was detected on extrinsically radioiodinated Colo-205 cell surfaces. This observation was confirmed by Western blot analysis of isolated Colo-205 membranes. Digestion of labeled precipitates with peptide:N-glycosidase F caused a 22% reduction in the apparent molecular weight of the IFN gamma receptor. Receptor derived from tunicamycin-treated Colo-205 labeled for 5 min displayed a single molecular mass of 65 kDa and expressed ligand binding activity. Longer labeling periods in the presence of tunicamycin revealed the appearance of a second ligand-binding form of 70 kDa. Thus, Colo-205 IFN gamma receptors carry asparagine (N)-linked oligosaccharides and possibly some other form of post-translational modification.
The Role of Myb Proteins in Normal and Neoplastic Cell Proliferation (1994)

The c-myb protooncogene is the prototype of a gene family that contains two other recently described members, A-myb and B-myb. The c-myb gene encodes a transcription regulatory protein, c-Myb, that has distinct DNA-binding domain structure and binding specificity compared with unrelated transcription factors. All three members of the myb protein family, however, display a high degree of homology within their DNA-binding domain, suggesting that they may regulate transcription of a similar set of target genes. We examine here whether, by implication, the individual members of the myb gene family play analogous roles within the cell, in particular focusing on their potential functions in the control of cell proliferation. Expression of both c-myb and B-myb is subject to regulation in the cell cycle, transcripts of these genes being induced within the G1 phase of the cell cycle and persisting at maximal levels through S phase. Consistent with this timing of expression, inhibition of c-Myb and B-Myb synthesis by treatment of cells with anti-sense oligonucleotides indicates that both proteins are required for transition from the G1 to S phase of the cell cycle. The c-Myb and B-Myb proteins cannot be considered as analogs, however, as they show certain differences in trans-activation activity of their target genes. Moreover, while superficially similar, expression of c-myb and B-myb is not coordinated, and it is conceivable that their products have quite distinct functions in the regulation of cell proliferation. The ubiquitous expression of B-myb in cycling cells and its strict regulation during late G1 suggest a universal function for B-Myb in G1 to S phase transition. Consistent with this conclusion, B-myb transcription is controlled by the transcription factor E2F, which has been implicated in cell cycle regulation of a number of genes involved in DNA synthesis. The restricted tissue tropism of c-myb expression and its regulation by certain growth factors such as IL-2 suggest a specific function in transduction of extrinsic proliferation (and differentiation) signals. The role of A-myb in the cell remains to be determined; however, its expression shows no correlation with cell cycling, implying that it has no direct role in cell proliferation. Recent data show that the necessity for c-myb function in proliferation of a number of cell types provides a promising opportunity for intervention in the treatment of certain tumors.
Lipid-modified proteins as biomarkers for cardiovascular disease: a review (2005)

Lipid-modified proteins are classified based on the identity of the attached lipid, a post- or co-translational modification required for their biological function. At least five different lipid modifications of cysteines, glycines and other residues on the COOH- and NH(2)-terminal domains have been described. Cysteine residues may be modified by the addition of a 16-carbon saturated fatty acyl group by a labile thioester bond (palmitoylation) or by prenylation processes that catalyze the formation of thioether bond with mevalonate derived isoprenoids, farnesol and geranylgeraniol. The NH(2)-terminal glycine residues may undergo a quite distinct process involving the formation of an amide bond with a 14-carbon saturated acyl group (myristoylation), while glycine residues in the COOH-terminal may be covalently attached with a cholesterol moiety by an ester bond. Finally, cell surface proteins can be anchored to the membrane through the addition of glycosylphosphatidylinositol moiety. Several lines of evidence suggest that lipid-modified proteins are directly involved in different steps of the development of lesions of atherosclerosis, from leukocyte recruitment to plaque rupture, and their expression or lipid modification are likely altered during atherogenesis. This review will briefly summarize the different enzymatic pathways of lipid modification and propose a series of lipid-modified proteins that can be used as biomarkers for cardiovascular disease.
Monoclonal antibodies as probes for functional domains in cAMP-dependent protein kinase II. (1985)

The antigenic regions of the type II regulatory subunit of cAMP-dependent kinase from bovine heart have been correlated with the previously established domain structure of the molecule. Immunoblotting with both serum and monoclonal antibodies of fragments generated by limited proteolysis or chemical cleavage of the R-subunit established that the major antigenic sites were confined to the amino-terminal portion of the polypeptide chain (residues 1-145). Radioimmunoassays using two different antisera suggested that one or more of the high affinity serum antibody recognition sites were further restricted to residues 91-145. This amino-terminal portion of the R-subunit includes the hinge region which is particularly sensitive to proteolysis, allowing the R-subunit to be cleaved readily into a COOH-terminal domain which retains the cAMP-binding sites and an NH2-terminal fragment which appears to be the major site for interaction of the R-subunits in the native dimer. Monoclonal antibodies that recognized determinants on both sides of this hinge region were characterized and their specific recognition sites localized. Accessibility of antigenic sites in the holoenzyme in contrast to free R2 was compared. Although cAMP did tend to slightly increase the affinity of the holoenzyme for one of the monoclonal antibodies, all of the antigenic sites clearly were exposed and accessible in the holoenzyme. Furthermore, despite the presumed close proximity of antigenic sites to interaction sites between the R- and C-subunits, in no case did binding of antibody to the holoenzyme promote dissociation of the complex. The fact that the monoclonal antibodies would precipitate holoenzyme as well as free R2 was used to ascertain the importance of specific amino acid residues in the interaction of the R- and C-subunits. cAMP-binding domains were isolated following limited proteolysis with chymotrypsin and thermolysin. These fragments differed by only three amino acid residues at the NH2-terminal end. U of these fragments in conjunction with immunoadsorption established that the chymotryptic fragment, which contained the Asp-Arg-Arg preceding the site of autophosphorylation, was capable of forming a stable complex with the C-subunit. In contrast, the thermolytic fragment which differed by only those three residues no longer complexed with the C-subunit, indicating that the arginine residues not only contribute to the specificity of the phosphorylation site but also are an essential component for energetically stabilizing the holoenzyme complex.
Effect of different tryptophan sources on amino acids availability to the brain and mood in healthy volunteers (2008)

The use of a tryptophan-rich hydrolyzed protein source may be more adequate to increase brain tryptophan and 5-HT function compared with intact alpha-lactalbumin protein or pure tryptophan.
Dominant-Negative Mutants of a Toxin Subunit: An Approach to Therapy of Anthrax (2001)

The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.
Sialoadhesin and CD163 join forces during entry of the porcine reproductive and respiratory syndrome virus (2008)

The porcine reproductive and respiratory syndrome virus (PRRSV) shows a restricted tropism for subsets of porcine macrophages in vivo. To date, two PRRSV receptors have been identified on primary macrophages, heparan sulphate for binding and sialoadhesin for binding and internalization. However, additional factors are needed because the expression of both receptors in non-permissive cells results in virus internalization but not in virus uncoating and productive infection. Recently, CD163 was described as a PRRSV receptor on Marc-145 cells that renders non-permissive cells susceptible to PRRSV. Therefore, the potential role of CD163 in PRRSV entry in macrophages and its potential interplay with sialoadhesin were studied. Incubation of macrophages at 37 degrees C with either sialoadhesin- or CD163-specific antibodies reduced PRRSV infection by up to 75 %, while infection was completely blocked by a combination of both antibodies. When incubated at 4 degrees C, only sialoadhesin- and not CD163-specific antibodies reduced PRRSV infection. In addition, confocal analysis of PRRSV entry in non-permissive cells expressing only sialoadhesin showed PRRSV internalization but no uncoating. In contrast, when both sialoadhesin and CD163 were expressed, PRRSV was uncoated upon internalization, resulting in productive infection. Virus internalization was not observed when only CD163 was expressed; although, cells became productively infected. Thus, sialoadhesin is confirmed as a PRRSV internalization receptor and CD163 is shown to be involved in PRRSV entry, probably during uncoating. Co-expression of recombinant sialoadhesin and CD163 in non-permissive cells increased virus production 10-100 times compared with cells expressing only CD163, sustaining the requirement of both for efficient PRRSV infection.
Introduction of Purified Genes Into Mammalian Cell (1984)

There are a number of methods to introduce genes into mammalian cells. These include cell hybridization, chromosome-mediated and DNA-mediated gene transfer. DNA-mediated transfer can be achieved by direct microinjection methods or by indirect methods. The DNA enters the nucleus and is expressed in a high proportion of cells transiently. The DNA then becomes integrated into host cell DNA at random sites resulting in more stably expressing transformants. A number of genes for which selection systems exist can be introduced into mammalian cells. Nonselectable genes can also be introduced into cells by either ligating them to a selectable gene or by mixing them with carrier DNA and a selectable gene. If an amplifiable gene sequence is introduced into cells, it and other genes in its proximity can be coamplified. Amplification of the genes can also be achieved by the use of appropriate viral vectors and recipient cells. The foreign genes are expressed in the recipient cells if they contain the appropriate recognition signals for initiation and termination of transcription. Transfection systems are thus permitting identification of DNA sequences which have a regulatory role in gene expression. The identification of transcriptional signal sequences has formed the basis for construction of appropriate molecules which would permit expression of genes which cannot normally be expressed in mammalian cells (e.g., bacterial genes). The foreign genes are not only expressed in the recipient cells but they can also be subject to regulation in the appropriate environment. This observation is paving the way for identification of regulatory sequences. The foreign DNA sequences integrated into the host genome can be recovered by a variety of methods. Such methods permit isolation of genes which code for a selectable gene product.
<title>VBR MPEG-2-encoded video over broadband networks</title> (1997)

The end-to-end quality of service (QoS) of a variable bit rate (VBR) MPEG-2 compressed video transported over an interconnected ATM satellite-cable-terrestrial network incorporates the impact of the characteristics of these three media as well as the specificity of the video encoding/decoding processes. In this paper, we present the impact of a selected set of the QoS parameters on a number of VBR MPEG-2 encoded video clips on each segment of such internetworking. The QoS parameters used in our simulation include cell transmission delay, cell delay variance, cell misinsertion rate, and cell error rate. Also, we discuss and compare the quantified impact of bit error characteristics of satellite and fiber optics ATM systems. Objective and subjective results of our simulation show that the impact of the satellite segment on the MPEG-2 encoded video quality is comparable to that of the fiber optics system and to that generated from the VBR MPEG-2 vide encoding/decoding process.
Gene product of region E4 of adenovirus type 5 modulates accumulation of certain viral polypeptides (1988)

An adenovirus type 5 mutant, designated H5ilE4I, was constructed in which region E4 was replaced by a cloned cDNA. The cDNA was a copy of an mRNA which exclusively contains open translational reading frames 6 and 7. The phenotype of the mutant was compared with that of the previously characterized E4 mutant H2dl808 and wild-type adenovirus 5. Although the H5ilE4I mutant lacked at least five E4 genes, it was nondefective for growth in HeLa cells. The defects in viral DNA replication, late protein synthesis, and shutoff of host cell protein synthesis associated with the phenotype of the H2dl808 mutant were not observed in HeLa cells infected with the H5ilE4I mutant. However, differences were observed regarding the time of onset of viral DNA replication and the accumulation of the hexon polypeptide as well as the 72-kilodalton adenovirus-specific DNA-binding protein. The results thus indicate that open reading frame 6 or 7 or both contain all genetic information required for viral replication in tissue culture cells, whereas another E4 gene modulates the accumulation of certain viral polypeptides. The early onset of viral DNA replication in H5ilE4I-infected cells may be an indirect effect of the enhanced expression of the 72-kilodalton DNA-binding protein.
Asymmetric Synthesis of Both Antipodes of β-Hydroxy Nitriles and β-Hydroxy Carboxylic Acids via Enzymatic Reduction or Sequential Reduction/Hydrolysis (2009)

Use of isolated carbonyl reductases in the reduction of aromatic beta-ketonitriles have completely eliminated the competing alpha-ethylation, which is often observed with whole cell biocatalysts. By choosing suitable recombinant carbonyl reductase, the reduction of beta-ketonitriles afforded (R)- or (S)-beta-hydroxy nitriles with excellent optical purity and yield. Subsequently, nitrilase-catalyzed hydrolysis of the obtained optically pure beta-hydroxy nitriles led to the corresponding beta-hydroxy carboxylic acids in high yields. More importantly, the sequential enzymatic reduction and hydrolysis could be carried out in "two-step-one-pot" fashion without the isolation of intermediates beta-hydroxy nitriles, lowering the cost and minimizing the environmental impact. This allows ready access to both antipodes of chiral beta-hydroxy nitriles and beta-hydroxy carboxylic acids of pharmaceutical importance with excellent optical purity.
B-Lymphocyte Alloantigens Associated with Systemic Lupus Erythematosus (1978)

We examined B-lymphocyte alloantigens in 41 patients with systemic lupus erythematosus and 184 controls, using a panel of 47 pregnancy serums, and compared reaction frequencies of individual serums. One serum, la-715, reacted with B lymphocytes from 75.6 per cent of patients and 14.1 per cent of controls (Pc less than 0.005, relative risk 18.8). Twenty-eight of the patients were also typed with a panel of HLA-D-related serums from the Seventh International Histocompatibility Workshop, HLA-DRw types assigned, and compared to 490 Workshop controls. Both HLA-DRw2 (57.1 per cent vs. 26.4 per cent, Pc less than 0.004) and HLA-DRw3 (46.4 per cent vs. 22.2 per cent, Pc less than 0.03) were increased in systemic lupus erythematosus. This study demonstrates that select B-lymphocyte alloantigens, which are controlled by genes in the major histocompatibility complex, are present in increased frequency in systemic lupus erythematosus.
Incidence Proportions of Brain Metastases in Patients Diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System (2004)

Total IP% of brain metastases was lower than previously reported, and it varied by primary site, race, sex, age at diagnosis of primary cancer, and SEER stage of primary cancer.
Evolution of medical treatment for endometriosis: back to the roots? (2007)

Experimental evidence is accumulating to suggest that medicinal botanicals have anti-inflammatory and pain-alleviating properties and hold promise for treatment of endometriosis. Herein, we present a systematic review of clinical and experimental data on the use of medicinal herbs in the treatment of endometriosis. Although there is a general lack of evidence from clinical studies on the potential efficacy of medicinal herbs for the treatment of endometriosis-associated symptoms, our review highlights the anti-inflammatory and pain-alleviating mechanisms of action of herbal remedies. Medicinal herbs and their active components exhibit cytokine-suppressive, COX-2-inhibiting, antioxidant, sedative and pain-alleviating properties. Each of these mechanisms of action would be predicted to have salutary effects in endometriosis. Better understanding of the mechanisms of action, toxicity and herb-herb and herb-drug interactions permits the optimization of design and execution of complementary alternative medicine trials for endometriosis-associated pain. A potential benefit of herbal therapy is the likelihood of synergistic interactions within individual or combinations of plants. In this sense, phytotherapies may be analogous to nutraceuticals or whole food nutrition. We encourage the development of herbal analogues and establishment of special, simplified registration procedures for certain medicinal products, particularly herbal derivates with a long tradition of safe use.
Radioprotection of Normal Tissues in Tumor-bearing Mice by Troxerutin (2004)

The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of gamma-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from gamma-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by ip one hour prior to 4 Gy whole-body gamma-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in gamma-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals.