gebhart/patrepeval huggingface dataset:
Boolean Logic Gates that Use Enzymes as Input Signals (2008)

Biochemical systems that demonstrate the Boolean logic operations AND, OR, XOR, and InhibA were developed by using soluble compounds, which represent the chemical "devices", and the enzymes glucose oxidase (GOx), glucose dehydrogenase (GDH), alcohol dehydrogenase (AlcDH), and microperoxidase-11 (MP-11), which operated as the input signals that activated the logic gates. The enzymes were used as soluble materials and as immobilized biocatalysts. The studied systems are proposed to be a step towards the construction of "smart" signal-responsive materials with built-in Boolean logic.
A Single-Dose Placebo-Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal Women (2004)

Forty-nine women were enrolled. A single subcutaneous dose of AMG 162 resulted in a dose-dependent, rapid (within 12 h), profound (up to 84%), and sustained (up to 6 months) decrease in urinary NTX. At 6 months, there was a mean change from baseline of -81% in the 3.0 mg/kg AMG 162 group compared with -10% in the placebo group; serum NTX changes were -56% and 2%, respectively. BALP levels did not decrease remarkably until after 1 month, indicating that the effect of AMG 162 is primarily antiresorptive. Intact parathyroid hormone (PTH) levels increased up to approximately 3-fold after 4 days in the 3.0 mg/kg dose group, but returned toward baseline with follow-up. Albumin-adjusted serum calcium did not decrease >10% on average in any group, and no subject had values below 2 mmol/liter. AMG 162 was well tolerated. No related serious adverse events occurred. No clinically meaningful laboratory changes, other than those described above, were observed. In summary, a single subcutaneous dose of AMG 162 resulted in a dose-dependent rapid and sustained decrease from baseline in bone turnover and could be an effective and convenient treatment for osteoporosis.
Extracellular TNFR1 Release Requires the Calcium-dependent Formation of a Nucleobindin 2-ARTS-1 Complex (2006)

Extracellular tumor necrosis factor (TNF) receptors function as TNF-binding proteins that modulate TNF activity. In human vascular endothelial cells (HUVEC), extracellular TNFR1 (type I TNF receptor, TNFRSF1A) is generated by two mechanisms, proteolytic cleavage of soluble TNFR1 ectodomains and the release of full-length 55-kDa TNFR1 in the membranes of exosome-like vesicles. TNFR1 release from HUVEC is known to involve the association between ARTS-1 (aminopeptidase regulator of TNFR1 shedding), an integral membrane aminopeptidase, and TNFR1. The goal of this study was to identify ARTS-1 binding partners that modulate TNFR1 release to the extracellular space. A yeast two-hybrid screen of a human placenta cDNA library showed that NUCB2 (nucleobindin 2), via its helix-loop-helix domains, binds the ARTS-1 extracellular domain. The association between endogenous ARTS-1 and NUCB2 in HUVEC was demonstrated by co-immunoprecipitation experiments, which showed the formation of a calcium-dependent NUCB2.ARTS-1 complex that associated with a subset of total cellular TNFR1. Confocal microscopy experiments demonstrated that this association involved a distinct population of NUCB2-containing intracytoplasmic vesicles. RNA interference was utilized to specifically knock down NUCB2 and ARTS-1 expression, which demonstrated that both are required for the constitutive release of a full-length 55-kDa TNFR1 within exosome-like vesicles as well as the inducible proteolytic cleavage of soluble TNFR1 ectodomains. We propose that calcium-dependent NUCB2.ARTS-1 complexes, which associate with TNFR1 prior to its commitment to pathways that result in either the constitutive release of TNFR1 exosome-like vesicles or the inducible proteolytic cleavage of TNFR1 ectodomains, play an important role in mediating TNFR1 release to the extracellular compartment.
Screening of Lactobacillus isolates from gastrointestinal tract of guinea fowl for probiotic qualities using in vitro tests to select species-specific probiotic candidates (2016)

A total of 32 Lactobacillus isolates, 8 each from the crop (LGFCP1-LGFCP8), proventriculus (LGFP9-LGFP16), ileum (LGFI17-LGFI24) and caeca (LGFCM25-LGFCM32) were isolated from 25 adult guinea fowl (Pearl variety), 22-28 weeks of age, and characterised morphologically, physiologically, biochemically and by molecular methods. Isolates were screened for their probiotic quality using range of in vitro tests: aggregation test, cell surface hydrophobicity, resistance to bile salts and acidic conditions, enzymatic tests and coaggregation and antagonistic test. Based on in vitro test results and a novel scoring method, the two best isolates were selected and partial 16S rRNA sequencing was done. BLAST (Basic Local Alignment Search Tool) analysis of sequence of isolate LGFCP4 showed 99% genetic identity with Lactobacillus plantarum and LGFP16 with Lactobacillus reuteri. The study shows that these two microbial agents may be suitable as potential probiotic candidates in guinea fowl, as well as in a feed supplement for other poultry species.
Notch3 Functions as a Tumor Suppressor by Controlling Cellular Senescence (2013)

Notch signaling regulates a broad spectrum of cell fate decisions and differentiation. Both oncogenic and tumor suppressor functions have been shown for Notch signaling. However, little is known about the underlying mechanisms of its tumor suppressor function. Here, we report that expression of Notch3, a member of Notch family transmembrane receptors, was elevated in human cells during senescence activated by various senescence-inducing stimuli. This upregulation of Notch3 was required for the induction of p21 expression in senescent cells. Downregulation of Notch3 led to a delayed onset of senescence and extended replicative lifespan, whereas adventitious expression of Notch3 was sufficient to activate senescence and p21 expression. The ability of Notch3 to induce senescence and p21 expression was dependent on the canonical Notch singling. Deletion of p21 in cells significantly attenuated Notch3-induced senescence. Furthermore, a significant decrease in Notch3 expression was observed in human tumor cell lines as well as primary human breast cancer and melanoma samples compared with normal tissues. Restoration of Notch3 expression in human tumor cells resulted in inhibition of cell proliferation and activation of senescence. Collectively, our results reveal a novel function of Notch3 in senescence regulation and tumor suppression.
Gastroretentive carbidopa/levodopa, DM‐1992, for the treatment of advanced Parkinson's disease (2015)

DM-1992 was associated with a reduction in %OFF time compared with CD/L-dopa IR despite a reduced dosing frequency. Although the open-label study design and the greater number of rescue doses during the DM-1992 arm call for caution in interpreting the results, the elevated predose plasma L-dopa concentration (12 h after DM-1992 administration) lends objective support to our findings, suggesting that phase 3 studies are warranted.
Purification of active human plasminogen activator inhibitor 1 from Escherichia coli (1989)

Plasminogen activator inhibitor 1 (PAI-1) inhibits both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) and, therefore, is an important regulator of plasminogen activation. We have developed eucaryotic and procaryotic expression systems for PAI-1 and characterized the recombinant glycosylated and non-glycosylated products, together with a non-recombinant natural control, produced in the histosarcoma cell line HT 1080. For eucaryotic expression, the PAI-1 cDNA was stably transfected into chinese hamster ovary cells (CHO cells), while procaryotic expression in Escherichia coli was examined after inserting the DNA sequence encoding the mature PAI-1 protein into an inducible expression vector. Recombinant PAI-1 from CHO cells was purified approximately 50-fold in two steps and was indistinguishable from natural PAI-1. Between 3% and 4% of total cellular protein in the procaryotic expression system consisted of PAI-1, from which it was purified approximately 30-fold, with yields of between 15% and 20%. This PAI-1 formed 1:1 complexes with uPA and also with the single- and two-chain forms of tPA. Kinetic analysis demonstrated that the procaryote-produced PAI-1 had an inhibitory activity towards all three forms of PA that resembled that of natural PAI-1 with association rate constants of approximately 10(7) M-1 s-1. In contrast to PAI-1 from eucaryotic cells, the PAI-1 from E. coli had an inherent activity equal to that of guanidine/HCl-activated natural PAI-1. The activity could not be increased by treatment with denaturants suggesting that the latent form of PAI-1 was absent. However, at 37 degrees C the procaryote-produced PAI-1 lost activity at the same rate as natural PAI-1, with approximately 50% of the activity remaining after 3 h. This activity could be partially restored by treatment with 4 M guanidine/HCl. E. coli-derived PAI-1, added to human plasma and fractionated by Sephacryl S-200 chromatography, eluted in two peaks that were similar to those obtained with guanidine-activated PAI-1 from eucaryotic cells, suggesting that it bound to the PAI-1-binding protein (vitronectin).
ChemInform Abstract: Cardiotonic Steroids. Part 8. Synthesis of 17β‐(3′‐Pyridyl)‐14β‐androst‐4‐ene‐3β,14‐diol from 17‐Oxandrostane Derivatives. (1985)

Abstract Die Titelverbindung (XIa) wird ausgehend von der Reaktion zwischen dem Dienon (I) und dem Bromid (II) synthetisiert und zusammen mit den Vorstufen (VIII)‐(X) pharmakologisch getestet.
The Peptidyl-Prolyl Isomerase Motif Is Lacking in PmpA, the PrsA-Like Protein Involved in the Secretion Machinery of Lactococcus lactis (2002)

The prsA-like gene from Lactococcus lactis encoding its single homologue to PrsA, an essential protein triggering the folding of secreted proteins in Bacillus subtilis, was characterized. This gene, annotated pmpA, encodes a lipoprotein of 309 residues whose expression is increased 7- to 10-fold when the source of nitrogen is limited. A slight increase in the expression of the PrsA-like protein (PLP) in L. lactis removed the degradation products previously observed with the Staphylococcus hyicus lipase used as a model secreted protein. This shows that PmpA either triggers the folding of the secreted lipase or activates its degradation by the cell surface protease HtrA. Unlike the case for B. subtilis, the inactivation of the gene encoding PmpA reduced only slightly the growth rate of L. lactis in standard conditions. However, it almost stopped its growth when the lipase was overexpressed in the presence of salt in the medium. Like PrsA of B. subtilis and PrtM of L. lactis, the L. lactis PmpA protein could thus have a foldase activity that facilitates protein secretion. These proteins belong to the third family of peptidyl-prolyl cis/trans-isomerases (PPIases) for which parvulin is the prototype. Almost all PLP from gram-positive bacteria contain a domain with the PPIase signature. An exception to this situation was found only in Streptococcaceae, the family to which L. lactis belongs. PLP from Streptococcus pneumoniae and Enterococcus faecalis possess this signature, but those of L. lactis, Streptococcus pyogenes, and Streptococcus mutans do not. However, secondary structure predictions suggest that the folding of PLP is conserved over the entire length of the proteins, including the unconserved signature region. The activity associated with the expression of PmpA in L. lactis and these genomic data show that either the PPIase motif is not necessary for PPIase activity or, more likely, PmpA foldase activity does not necessarily require PPIase activity.
Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. (1996)

Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.
Functional Analysis of Transmembrane Domain 2 of the M1 Muscarinic Acetylcholine Receptor (2007)

Ala substitution scanning mutagenesis has been used to probe the functional role of amino acids in transmembrane (TM) domain 2 of the M1 muscarinic acetylcholine receptor, and of the highly conserved Asn43 in TM1. The mutation of Asn43, Asn61, and Leu64 caused an enhanced ACh affinity phenotype. Interpreted using a rhodopsin-based homology model, these results suggest the presence of a network of specific contacts between this group of residues and Pro415 and Tyr418 in the highly conserved NPXXY motif in TM7 that exhibit a similar mutagenic phenotype. These contacts may be rearranged or broken when ACh binds. D71A, like N414A, was devoid of signaling activity. We suggest that formation of a direct hydrogen bond between the highly conserved side chains of Asp71 and Asn414 may be a critical feature stabilizing the activated state of the M1 receptor. Mutation of Leu67, Ala70, and Ile74 also reduced the signaling efficacy of the ACh-receptor complex. The side chains of these residues are modeled as an extended surface that may help to orient and insulate the proposed hydrogen bond between Asp71 and Asn414. Mutation of Leu72, Gly75, and Met79 in the outer half of TM2 primarily reduced the expression of functional receptor binding sites. These residues may mediate contacts with TM1 and TM7 that are preserved throughout the receptor activation cycle. Thermal inactivation measurements confirmed that a reduction in structural stability followed the mutation of Met79 as well as Asp71.
The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase (1993)

Lipoprotein lipase (LPL) causes a marked increase in the cellular binding of beta-migrating very low density lipoprotein (beta-VLDL) to a large receptor compatible with the alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) (Beisiegel, U., Weber, W., and Bengtsson-Olivecrona, G. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 8342-8346). Here we demonstrate that LPL binds to the alpha-chain of purified alpha 2MR/LRP immobilized on microtiter plates. The binding, apparently to multiple sites, was blocked by heparin and inhibited by the alpha 2MR-associated protein (alpha 2MRAP) and by EDTA. Immobilized LPL bound alpha 2MR/LRP in solution as well as beta-VLDL prepared from cholesterol-fed rabbits. Both binding reactions were dependent on an intact carboxyl-terminal folding domain of LPL, but were independent of its dimeric structure and intact catalytical function. Dimeric LPL could mediate binding of beta-VLDL to immobilized alpha 2MR/LRP and to cells, e.g. monocytes. In contrast, LPL monomers were not able to mediate binding to immobilized alpha 2MR/LRP, presumably because of cross-inhibition due to close relation between the binding regions for the lipoprotein and for the receptor in the carboxyl-terminal domain of the LPL monomer. Heparin, but not alpha 2MRAP, inhibited cellular binding of 125I-LPL or 125I-beta-VLDL supplemented with LPL. However, alpha 2MRAP inhibited degradation of the two ligands by about 90% and 40-50%, respectively. The results show that LPL is a ligand for alpha 2MR/LRP and, because of its affinity for lipoprotein particles, dimeric LPL can mediate or strengthen binding of beta-VLDL to this receptor. It is proposed that LPL binds primarily to cell surface heparan sulfate in monocytes and is presented for endocytosis and degradation by alpha 2MR/LRP. Moreover, beta-VLDL may be further supplemented with LPL at the cell surface and achieve affinity for alpha 2MR/LRP.
A New Mechanism for DNA Alterations Induced by Alpha Particles Such as Those Emitted by Radon and Radon Progeny (1997)

Bruce E. Lehnert, Edwin H. Goodwin, A New Mechanism for DNA Alterations Induced by Alpha Particles Such as Those Emitted by Radon and Radon Progeny, Environmental Health Perspectives, Vol. 105, Supplement 5: Particle Toxicity (Sep., 1997), pp. 1095-1101
A practical approach to the clinical diagnosis of Ewing’s sarcoma/primitive neuroectodermal tumour and other small round cell tumours sharing EWS rearrangement using new fluorescence in situ hybridisation probes for EWSR1 on formalin fixed, paraffin wax embedded tissue (2005)

Interphase FISH using this newly developed probe is sensitive and specific for detecting the EWS gene on FFPE tissues and is of value in the routine clinical diagnosis of ES/PNET, DSRCT, and CCS.
Parvovirus replication (1990)

The members of the family Parvoviridae are among the smallest of the DNA viruses, with a linear single-stranded genome of about 5 kilobases. Currently the family is divided into three genera, two of which contain viruses of vertebrates and a third containing insect viruses. This review concentrates on the vertebrate viruses, with emphasis on recent advances in our insights into the molecular biology of viral replication. Traditionally the vertebrate viruses have been distinguished by the presence or absence of a requirement for a coinfection with a helper virus before productive infection can occur, hence the notion that the dependoviruses (adeno-associated viruses [AAV]) are defective. Recent data would suggest that not only is there a great deal of structural and genetic organizational similarity between the two types of vertebrate viruses, but also there is significant similarity in the molecular biology of productive replication. What differs is the physiological condition of the host cell that renders it permissive. Healthy dividing cells are permissive for productive replication by autonomous parvoviruses; such cells result in latent infection by dependoviruses. For a cell to become permissive for productive AAV replication, it must have been exposed to toxic conditions which activate a latent AAV genome. Such conditions can be caused by helper-virus infection or exposure to physical (UV light) or chemical (some carcinogens) agents. In this paper the molecular biology of replication is reviewed, with special emphasis on the role of the host and the consequences of viral infection for the host.
Recent advances in drug-antibody immunoconjugates for the treatment of cancer (2003)

Standard chemotherapy in the treatment of cancer often has a low therapeutic index due to the lack of specificity. Antibody-directed cancer chemotherapy can improve therapeutic indices, with the potential to enhance efficacy and decrease systemic toxicity. Several drug-antibody conjugates have shown impressive antitumor activity in preclinical models arid are currently being evaluated in clinical trials. Drug-antibody conjugates may play a substantial role in the future as a single regimen or combination therapy in the treatment of cancer.
Nucleotide sequence of the bacterial transposon Tn1681 encoding a heat-stable (ST) toxin and its identification in enterotoxigenic Escherichia coli strains. (1980)

the Escherichia coli heat-stable toxin (ST I) is encoded within a transposon (Tn1681) flanked by inverted repeats of insertion sequence 1 (IS1) [So, M., Heffron, F. & McCarthy, B. J. (1979) Nature (London) 277, 453-456]. By subcloning restriction fragments and by insertion mutagenesis, we located precisely the gene for ST I within the transposon. We determined the complete nucleotide sequence of the central portion of Tn1681 (i.e., that part flanked by IS1) and identified the coding sequence of the toxin. From the nucleotide sequence, we deduced a probable amino acid sequence for ST I. The NH2-terminal portion of the amino acid sequence is extremely hydrophobic and bears a striking resemblance to the signal sequence of the fd phage minor coat protein. By using a subcloned restriction fragment containing the gene for ST I but no IS1 sequences, we determined (i) that the ST toxin with activity assayable in suckling mice (ST I) is genetically distinct from the St toxin assayable in ligated ileal loops (ST II) and (ii) that ST I can be responsible for diarrheal disease in different animals.
An Introduction to Cosmology (1995)

MICROPAEDIA: Part I. MACROPAEDIA: Part II. 1. Expanding Universe -Phenomenology. 2. Expanding Universe - Theory. 3. Ages. 4. Equilibrium. 5. Elementary Particles. 6. Helium Production. 7. Massive Neutrinos. 8. Horizons. 9. Beyond the Standard Model.
The Rhodococcus sp. Cocaine Esterase: A Bacterial Candidate for Novel Pharmacokinetic‐based Therapies for Cocaine Abuse (2003)

Cocaine is a powerful central nervous stimulant and among the most abused of drugs. Despite decades of efforts, however, no effective pharmacological treatments are available against cocaine addiction or toxic effects. Classical receptor-antagonist therapeutic approaches have not yielded significant effects, although cocaine targets are well known, thus fostering development of alternative therapeutic strategies. Recent evidence indicates that a sensible approach for treatment of cocaine abuse could be to interfere with cocaine pharmacokinetics, i.e. by preventing the drug from reaching the receptors responsible for its biological effects. Administration of cocaine binding antibodies as well as catalytic antibodies and enzymes that hydrolyze cocaine represent potential alternative therapeutic approach(es). The discovery of the cocaine esterase from the strain MBI of the bacterium Rhodococcus sp. (cocE) could be a major breakthrough in this field; cocE hydrolyzes cocaine faster than any known cocaine esterase and catalytic antibody.
A fuzzy commitment scheme (1999)

We combine well-known techniques from the areas of error-correcting codes and cryptography to achieve a new type of cryptographic primitive that we refer to as a fuzzy commitment scheme. Like a conventional cryptographic commitment scheme, our fuzzy commitment scheme is both concealing and binding: it is infeasible for an attacker to learn the committed value, and also for the committer to decommit a value in more than one way. In a conventional scheme, a commitment must be opened using a unique witness, which acts, essentially, as a decryption key. By contrast, our scheme is fuzzy in the sense that it accepts a witness that is close to the original encrypting witness in a suitable metric, but not necessarily identical.