gebhart/patrepeval huggingface dataset:
Receptor binding and adenylate cyclase activities of glucagon analogs modified in the N-terminal region (1986)

In this study, we determined the ability of four N-terminally modified derivatives of glucagon, [3-Me-His1,Arg12]-, [Phe1,Arg12]-, [D-Ala4,Arg12]-, and [D-Phe4]glucagon, to compete with 125I-glucagon for binding sites specific for glucagon in hepatic plasma membranes and to activate the hepatic adenylate cyclase system, the second step involved in producing many of the physiological effects of glucagon. Relative to the native hormone, [3-Me-His1,Arg12]glucagon binds approximately twofold greater to hepatic plasma membranes but is fivefold less potent in the adenylate cyclase assay. [Phe1,Arg12]glucagon binds threefold weaker and is also approximately fivefold less potent in adenylate cyclase activity. In addition, both analogues are partial agonists with respect to adenylate cyclase. These results support the critical role of the N-terminal histidine residue in eliciting maximal transduction of the hormonal message. [D-Ala4,Arg12]glucagon and [D-Phe4]glucagon, analogues designed to examine the possible importance of a beta-bend conformation in the N-terminal region of glucagon for binding and biological activities, have binding potencies relative to glucagon of 31% and 69%, respectively. [D-Ala4,Arg12]glucagon is a partial agonist in the adenylate cyclase assay system having a fourfold reduction in potency, while the [D-Phe4] derivative is a full agonist essentially equipotent with the native hormone. These results do not necessarily support the role of an N-terminal beta-bend in glucagon receptor recognition. With respect to in vivo glycogenolysis activities, all of the analogues have previously been reported to be full agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
FLAPW: applications and implementations (2009)

Modern material design involves a close collaboration between experimental and computational materials scientists. To be useful, the theory must be able to accurately predict the stability and properties of new materials, describe the physics of the experiments, and be applicable to new and complex structures-the all-electron full-potential linearized augmented plane wave (FLAPW) is one such method that provides the requisite level of numerical accuracy, albeit at the cost of complexity. Technical aspects and modifications related to the choice of basis functions (energy parameters, core-valence orthogonality, extended local orbitals) that affect the applicability and accuracy of the method are described, as well as an approach for obtaining k-independent matrix elements. The inclusion of external electric fields is illustrated by results for the induced densities at the surfaces of both magnetic and non-magnetic metals, and the relationship to image planes and to nonlinear effects such as second harmonic generation. The magnetic coupling of core hole excitations in Fe, the calculation of intrinsic defect formation energies, the concentration-dependent chemical potentials, entropic contributions, and the relative phase stability of Zr-rich Zr-Al alloys are also discussed.
Relation between infarct size and ventricular arrhythmia. (1975)

In order to determine whether ventricular arrhythmia is quantitatively related to infarct size estimated enzymatically we studied 31 patients with acute myocardial infarction without cargiogenic shock. Infarct size index was estimated from hourly serum creatine kinase (CK) changes during periods of 48 to 72 hours. Ventricular arrhythmia was quantified by automated analysis of continuous electrocardiographic recordings over a period of 20 hours with the use of the Argus/H computer system. Patients were classified into three groups according to infarct size index. Patients in all groups had similar average heart rate, blood pressure, serum potassium, and arterial pH and PCO2 values during the first 10 hours after admission. The total number of ventricular ectopic beats (VEB), frequency of couplets, and ventricular tachycardia, and peak rate of ventricular ectopic beats during the first 10 hours after admission were all related to infarct size index. For example, patients with small, medium, and large estimated infarct size averaged 26, 104, and 405 ventricular ectopic beats, respectively. These results suggest that the severity of ventricular arrhythmia early after myocardial infarction is related to the extent of myocardial injury as estimated enzymatically. Thus the apparent efficacy and therefore the evaluation of antiarrhythmic agents early after myocardial infarction may be influenced by the magnitude of injury sustained by the heart.
Nuclear matrix proteins in normal and breast cancer cells. (1993)

The progression from normal breast epithelium to a malignant phenotype may depend on changes in genetic events as well as failure of host mechanisms. Intermediate biomarkers are needed to more effectively identify malignant progression as well as to develop the potential for more specific treatments and prevention strategies. The nuclear matrix is the RNA-protein network which forms the skeleton of the nucleus and participates in DNA organization as well as multiple cellular functions. Nuclear matrix proteins have been demonstrated to be tissue and cell type specific as well as to reflect the state of cell differentiation and/or transformation. We prepared nuclear matrices from normal and cancer breast tissue from 10 patients with infiltrating ductal carcinoma of the breast as well as the MCF-10 mortal, immortal, and transfected breast cell lines. Nuclear matrices derived from normal human breast tissue and tumor tissue share common nuclear matrix proteins as well as demonstrate specific changes which appear to occur with the acquisition of the cancer phenotype. The MCF-10 cell lines demonstrate a phenotype that is intermediate between the normal and cancer tissue. These data suggest that the nuclear matrix may be an important biomarker in the pathogenesis of breast cancer.
Morphological and phase characterizations of retrieved calcium phosphate cement implants (2001)

A self-hardening calcium phosphate cement (CPC), consisting of equimolar amounts of tetracalcium phosphate and dicalcium phosphate anhydrous, hardens when mixed with water and forms a resorbable hydroxyapatite (HA) as the end-product. The objective of this study was to investigate the changes of the phase and morphology of the CPC during hardening and aging under in vivo conditions. CPC samples retrieved 12 h after hardening in vivo had already contained carbonated HA (type B), even though the initial cement mixture did not contain carbonate as one of the solid components. The mass fraction of carbonate in the 12-h sample was about 1%. The results suggested that under in vivo conditions carbonate is readily available and this allows formation of carbonated HA in favor of carbonate-free HA. The carbonate content of the CPC samples retrieved 3 months after implantation was similar to that of the 12-h samples, and the exterior surfaces of the 3-month samples appeared less crystalline than that of the 12-h samples.
Activation of the NRF2 pathway and its impact on the prognosis of anaplastic glioma patients (2014)

The NRF2 activity is increased in a significant proportion of malignant gliomas in general but decreased in the majority of IDH1/2-mutant anaplastic gliomas. It is plausible that the NRF2 pathway plays an important role in tumor progression of anaplastic gliomas with IDH1/2 mutations.
Neuropilin-1 attenuates autoreactivity in experimental autoimmune encephalomyelitis (2011)

Neuropilin-1 (Nrp1) is a cell surface molecule originally identified for its role in neuronal development. Recently, Nrp1 has been implicated in several aspects of immune function including maintenance of the immune synapse and development of regulatory T (T(reg)) cells. In this study, we provide evidence for a central role of Nrp1 in the regulation of CD4 T-cell immune responses in experimental autoimmune encephalitis (EAE). EAE serves as an animal model for the central nervous system (CNS) inflammatory disorder multiple sclerosis (MS). EAE is mediated primarily by CD4(+) T cells that migrate to the CNS and mount an inflammatory attack against myelin components, resulting in CNS pathology. Using a tissue-specific deletion system, we observed that the lack of Nrp1 on CD4(+) T cells results in increased EAE severity. These conditional knockout mice exhibit preferential T(H)-17 lineage commitment and decreased T(reg)-cell functionality. Conversely, CD4(+) T cells expressing Nrp1 suppress effector T-cell proliferation and cytokine production both in vivo and in vitro independent of T(reg) cells. Nrp1-mediated suppression can be inhibited by TGF-β blockade but not by IL-10 blockade. These results suggest that Nrp1 is essential for proper maintenance of peripheral tolerance and its absence can result in unchecked autoreactive responses, leading to diseases like EAE and potentially MS.
Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes (2011)

Recent studies indicate that the DNA recognition domain of transcription activator-like (TAL) effectors can be combined with the nuclease domain of FokI restriction enzyme to produce TAL effector nucleases (TALENs) that, in pairs, bind adjacent DNA target sites and produce double-strand breaks between the target sequences, stimulating non-homologous end-joining and homologous recombination. Here, we exploit the four prevalent TAL repeats and their DNA recognition cipher to develop a 'modular assembly' method for rapid production of designer TALENs (dTALENs) that recognize unique DNA sequence up to 23 bases in any gene. We have used this approach to engineer 10 dTALENs to target specific loci in native yeast chromosomal genes. All dTALENs produced high rates of site-specific gene disruptions and created strains with expected mutant phenotypes. Moreover, dTALENs stimulated high rates (up to 34%) of gene replacement by homologous recombination. Finally, dTALENs caused no detectable cytotoxicity and minimal levels of undesired genetic mutations in the treated yeast strains. These studies expand the realm of verified TALEN activity from cultured human cells to an intact eukaryotic organism and suggest that low-cost, highly dependable dTALENs can assume a significant role for gene modifications of value in human and animal health, agriculture and industry.
99mTc-Pertechnetate Scintigraphy as an Aid in the Diagnosis of Breast Masses (1973)

99mTc-pertechnetate images of the breast were obtained in 6 patients, and the localization of the radionuclide in breast masses was correlated with the clinical examination, mammography, and pathological diagnosis of malignancy (when available). Digital image enhancement was useful in demonstrating the discrete area of uptake. This method may be of value as a supplemental approach in the diagnosis of breast disease.
Role of PCSK9 and IDOL in the pathogenesis of acquired LDL receptor deficiency and hypercholesterolemia in nephrotic syndrome (2013)

LDLR deficiency, hypercholesterolemia and elevated plasma LDL in NS are associated with upregulation of PCSK9 and IDOL. Interventions targeting these pathways may be effective in the management of hypercholesterolemia and the associated cardiovascular and other complications of NS.
Properties and use of botulinum toxin and other microbial neurotoxins in medicine (1992)

Crystalline botulinum toxin type A was licensed in December 1989 by the Food and Drug Administration for treatment of certain spasmodic muscle disorders following 10 or more years of experimental treatment on human volunteers. Botulinum toxin exerts its action on a muscle indirectly by blocking the release of the neurotransmitter acetylcholine at the nerve ending, resulting in reduced muscle activity or paralysis. The injection of only nanogram quantities (1 ng = 30 mouse 50% lethal doses [U]) of the toxin into a spastic muscle is required to bring about the desired muscle control. The type A toxin produced in anaerobic culture and purified in crystalline form has a specific toxicity in mice of 3 x 10(7) U/mg. The crystalline toxin is a high-molecular-weight protein of 900,000 Mr and is composed of two molecules of neurotoxin (ca. 150,000 Mr) noncovalently bound to nontoxic proteins that play an important role in the stability of the toxic unit and its effective toxicity. Because the toxin is administered by injection directly into neuromuscular tissue, the methods of culturing and purification are vital. Its chemical, physical, and biological properties as applied to its use in medicine are described. Dilution and drying of the toxin for dispensing causes some detoxification, and the mouse assay is the only means of evaluation for human treatment. Other microbial neurotoxins may have uses in medicine; these include serotypes of botulinum toxins and tetanus toxin. Certain neurotoxins produced by dinoflagellates, including saxitoxin and tetrodotoxin, cause muscle paralysis through their effect on the action potential at the voltage-gated sodium channel. Saxitoxin used with anaesthetics lengthens the effect of the anaesthetic and may enhance the effectiveness of other medical drugs. Combining toxins with drugs could increase their effectiveness in treatment of human disease.
Effects of insulin‐like growth factor‐I (IGF‐I), insulin and combined IGF‐I‐insulin infusions on protein metabolism in dogs (1994)

The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol min-1 kg-1), insulin (3.4, 10.3 or 68.8 pmol min-1 kg-1) or combined infusions (34 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin or 103 pmol IGF-I + 3.4 pmol min-1 kg-1 insulin) on protein metabolism, using an infusion of [1-14C]leucine was investigated in anaesthetized fasted dogs. Leucine concentration, production rate (measure of protein degradation), oxidation rate and non-oxidative disappearance rate (measure of protein synthesis) were decreased in a similar dose dependent manner by the IGF-I and insulin infusions (P < 0.01). The decrease in these measurements of leucine metabolism were greater following 34 pmol IGF-I + 3.4 pmol insulin than with either component infused alone (P < 0.05). Free fatty acid concentrations were decreased by all insulin doses (P < 0.01) but only by 103 and 688 pmol min-1 kg-1 insulin-like growth factor (P < 0.05, P < 0.01). These data demonstrate that IGF-I, like insulin, has a dose dependent effect on protein metabolism and that combined insulin and IGF-I infusions have additive effects on protein metabolism.
Implementing neural nets with programmable logic (1988)

Networks of Boolean programmable logic modules are presented as one purely digital class of artificial neural nets. The approach contrasts with the continuous analog framework usually suggested. Programmable logic networks are capable of handling many neural net applications. They avoid some of the limitations of threshold logic networks and present distinct opportunities. The network nodes are called dynamically programmable logic modules. They can be implemented with digitally controlled demultiplexers. Each node performs a Boolean function of its inputs which can be dynamically assigned. The overall network is therefore a combinational circuit and its outputs are Boolean global functions of the network's input variables. The approach offers definite advantages for VLSI implementation, namely, a regular architecture with limited connectivity, simplicity of the control machinery, natural modularity, and the support of a mature technology.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Androgens Down-Regulate bcl-2 Protooncogene Expression in ZR-75-1 Human Breast Cancer Cells**This work was supported by a grant from the Canadian Breast Cancer Research Initiative (to C.L.), scholarships from the Fonds de la Recherche en Sante du Quebec (to C.L. and J.L.). Additional financial support was provided by Endorecherche. (1999)

Although a large proportion of primary human breast cancers express the androgen receptor, and treatment with androgens exerts beneficial effects in women with breast cancer, the role and especially the mechanism of action of androgens in breast cancer development and growth are not well understood. The potential effect of androgens on bcl-2 protooncogene expression was investigated in a human breast cancer cell line whose proliferation is known to be inhibited by androgens. The estrogen-responsive ZR-75-1 cells were grown in the presence or absence of 5alpha-dihydrotestosterone (DHT), alone or in combination with 17beta-estradiol. DHT caused a marked down-regulation of Bcl-2 protein and messenger RNA levels in both the presence and absence of 17beta-estradiol. The inhibitory effect of DHT was completely prevented by coincubation with the pure antiandrogen hydroxyflutamide. The present data indicate that androgens can down-regulate bcl-2 protooncogene levels via an androgen receptor-mediated mechanism, thus providing a novel mechanism for their known inhibitory effect on breast cancer cell growth.
The Roles of Therapy-Induced Autophagy and Necrosis in Cancer Treatment (2007)

Metabolic and therapeutic stresses activate several signal transduction pathways that regulate cell death and cell survival in cancer cells. Although decades of research unraveled the pathways that regulate apoptosis and allowed the development of novel diagnostic and therapeutic modalities in cancer treatment, only recently has the regulation and significance of tumor cell autophagy and necrosis become the focus of investigations. Necrosis is an irreversible inflammatory form of cell death. In contrast, autophagy is a reversible process that can contribute both to tumor cell death and survival. This review describes recent advances in understanding the regulation of autophagy and necrosis and their implications for cancer therapy. Currently available methods to measure autophagy and necrosis are highlighted. The effect of tumor cell autophagy and necrosis on host immunity is explored. Finally, therapeutic approaches that target autophagy and necrosis in cancer are described.
Purification and characterization of a novel β‐agarase from Vibrio sp. AP‐2 (1990)

beta-Agarase was purified from the culture fluid of a porphyran-decomposing marine bacterium (strain AP-2) by ammonium sulfate precipitation, successive column chromatography and DNase and RNase treatment. The final enzyme preparation appeared to be homogeneous on polyacrylamide gel electrophoresis. The enzyme had a molecular mass of 20 kDa, a pH optimum of 5.5, and was stable in the pH region 4.0-9.0 and at temperatures below 45 degrees C. The beta-agarase was a novel endo-type enzyme which hydrolyzed neoagarotetraose, larger neoagarooligosaccharides and agar to give neoagarobiose [3,6-anhydro-alpha-L-galactopyranosyl-(1----3)-D-galactose] as the predominant product. The enzyme did not act on kappa-carrageenan. According to the criteria of Bergey's Manual of Systematic Bacteriology, the strain was assigned to the genus Vibrio.
Multiple Independent Inputs Are Required for Activation of the p70 S6 Kinase (1995)

Previous studies have shown that the noncatalytic carboxy-terminal tail of the p70 S6 kinase (amino acids 422 to 525) contains an autoinhibitory pseudosubstrate domain that is phosphorylated in situ during activation and in vitro by mitogen-activated protein kinases. The present study shows that a recombinant p70 deleted of the carboxy-terminal tail (p70 delta CT104) nevertheless exhibits a basal and serum-stimulated 40S kinase activity and susceptibility to inhibition by wortmannin very similar to those of the parent, full-length p70 kinase. Carboxy-terminal deletion reduces the extent of maximal inhibition produced by rapamycin, from > 95% in the full-length p70 to 60 to 80% in p70 delta CT104, without altering the sensitivity to rapamycin inhibition (50% inhibitory concentration of 2 nM). Serum activation of p70 delta CT104, as with the parent, full-length p70, is accompanied by an increase in 32P content (about twofold) in situ and a slowing in electrophoretic mobility; both modifications are inhibited by pretreatment with wortmannin or rapamycin. 32P-peptide maps of p70 delta CT104 show multisite phosphorylation, and wortmannin and rapamycin appear to cause preferential dephosphorylation of the same subset of sites. Thus, it is likely that activation of the kinase requires phosphorylation of p70 at sites in addition to those previously identified in the carboxy-terminal tail. Evidence that the carboxy-terminal tail actually functions as a potent intramolecular inhibitor of kinase activity in situ is uncovered by deletion of a short acidic segment (amino acids 29 to 46) from the p70 amino-terminal noncatalytic region. Deletion of amino acids 29 to 46 causes a >95% inhibition of p70 activity despite continue phosphorylation of the carboxy-terminal tail in situ; additional deletion of the carboxy-terminal tail (yielding p70 delta 29-46/ delta CT104) increases activity 10-fold, to a level approaching that of p70 delta CT104. Deletion of residues 29 to 46 also abolishes completely the sensitivity of p70 to inhibition by rapamycin but does not alter the susceptibility to activation by serum of inhibition by wortmannin. Although the mechanisms underlying the effects of the delta 29-46 deletion are not known, they are not attributable to loss of the major in situ p70 phosphorylation site at Ser-40. Thus, activation of the p70 S6 kinase involves multiple, independent inputs directed at different domains of the p70 polypeptide. Disinhibition from the carboxy-terminal tail requires, in addition to its multisite phosphorylation, an activating input dependent on the presence of amino acids 29 to 46; this p70-activating input may be the same as that inhibited by rapamycin but is distinct from that arising from the wortmannin-inhibitable phosphatidylinositol 3-kinase. In addition, as exemplified by the rapamycin-resistant but mitogen- and wortmannin-sensitive p70 delta 29-46/ delta CT104 mutant, a further activating input, which probably involves site-specific phosphorylation in the segment between amino acids 46 to 421, is necessary.
Microwave-activated conditional-phase gate for superconducting qubits (2013)

We introduce a new entangling gate between two fixed-frequency qubits statically coupled via a microwave resonator bus which combines the following desirable qualities: all-microwave control, appreciable qubit separation for reduction of crosstalk and leakage errors and the ability to function as a two-qubit conditional-phase gate. A fixed, always-on interaction is explicitly designed between higher energy (non-computational) states of two transmon qubits, and then a conditional-phase gate is ‘activated’ on the otherwise unperturbed qubit subspace via a microwave drive. We implement this microwave-activated conditional-phase gate with a fidelity from quantum process tomography of ∼ 87%.