gebhart/patrepeval huggingface dataset:
Functional effects of single amino acid substitutions in the region of Phe113 to Asp138 in the plasminogen activator inhibitor 1 molecule (1998)

Thirteen amino acid substitutions have been introduced within the stretch Phe113 to Asp138 in the plasminogen activator inhibitor 1 (PAI-1) molecule by site-directed mutagenesis. The different proteins and wild-type (wt) PAI-1 have been overexpressed in Escherichia coli and purified by chromatography on heparin-Sepharose and on anhydrotrypsin-agarose. The PAI-1 variants have been characterized by their reactivity with tissue plasminogen activator (tPA), interactions with vitronectin or heparin, and stability. Most PAI-1 variants, except for Asp125-->Lys, Phe126-->Ser and Arg133-->Asp, displayed a high spontaneous inhibitory activity towards tPA, which did not change greatly on reactivation with 4 M guanidinium chloride, followed by dialysis at pH 5.5. The variants Asp125-->Lys and Arg133-->Asp became much more active after reactivation and they were also more rapidly transformed to inactive forms (t12 22-31 min) at physiological pH and temperature than the other variants. However, in the presence of vitronectin they were both almost equally stable (t12 2.3 h) as wtPAI-1 (t12 3.0 h). The mutant Glu130-->Lys showed an increased stability, both in the absence and in the presence of vitronectin compared with wtPAI-1. Nevertheless a similar affinity between all the active PAI-1 variants and vitronectin was observed. Further, all mutants, including the three mutants with low activity, were to a large extent adsorbed on anhydrotrypsin-agarose and were eluted in a similar fashion. In accordance with these data, the three variants with a low activity were all to a large extent cleaved as a result of their reaction with tPA, suggesting that they occurred predominantly in the substrate conformation. Our results do not support the presence of a binding site for vitronectin in this part of the molecule, but rather that it might be involved in controlling the active PAI-1 to substrate transition. Partly, this region of the PAI-1 molecule (Arg115 to Arg118) seems also to be involved in the binding of heparin to PAI-1.
290 and 340 nm UV LED arrays for fluorescence detection from single airborne particles (2005)

We demonstrate a compact system, incorporating a 32-element linear array of ultraviolet (290 nm and 340 nm) light-emitting diodes (LEDs) and a multi-anode photomultiplier tube, to the in-flight fluorescence detection of aerosolized particles, here containing the biological molecules tryptophan and NADH. This system illustrates substantial advances in the growth and fabrication of new semiconductor UV light emitting devices and an evolution in packaging details for LEDs tailored to the bio-aerosol warning problem. Optical engineering strategies are employed which take advantage of the size and versatility of light-emitting diodes to develop a truly compact fluorescence detector.
Animal Models of Diabetic Retinopathy: Summary and Comparison (2013)

Diabetic retinopathy (DR) is a microvascular complication associated with chronic exposure to hyperglycemia and is a major cause of blindness worldwide. Although clinical assessment and retinal autopsy of diabetic patients provide information on the features and progression of DR, its underlying pathophysiological mechanism cannot be deduced. In order to have a better understanding of the development of DR at the molecular and cellular levels, a variety of animal models have been developed. They include pharmacological induction of hyperglycemia and spontaneous diabetic rodents as well as models of angiogenesis without diabetes (to compensate for the absence of proliferative DR symptoms). In this review, we summarize the existing protocols to induce diabetes using STZ. We also describe and compare the pathological presentations, in both morphological and functional aspects, of the currently available DR animal models. The advantages and disadvantages of using different animals, ranging from zebrafish, rodents to other higher-order mammals, are also discussed. Until now, there is no single model that displays all the clinical features of DR as seen in human. Yet, with the understanding of the pathological findings in these animal models, researchers can select the most suitable models for mechanistic studies or drug screening.
Parametric Amplification and Frequency Mixing in Propagating Circuits (1958)

When two circuits such as filters or transmission lines are coupled together by means of distributed reactances which can vary sinusoidally in time and space, energy can be converted between waves of different frequencies in a variety of ways. If the waves on the two transmission lines are characterized by frequencies ω1 and ω2 and phase constants β1 and β2, while the coupling reactances vary as ω=ω1−ω2 and β=β1−β2+Δβ, power P1 at ω1 is converted into power P2 at ω2 and vice versa in a manner reminiscent of waves on coupled passive circuits, except that a relationship (P2/ω2)=(P1/ω1) is obeyed. If the group velocities on both transmission lines are in the same direction, the direction of power transfer reverses periodically with distance. If they are not in the same direction, the power transfer increases monotonically with distance for small Δβ but reverses periodically for Δβ larger than a certain limit. When the coupling reactance varies as given by ω=ω1+ω2 and β=β1+β2, parametric amplification is possible in the form of exponentially growing waves at frequencies ω1 and ω2 if the group velocities are in the same direction, and in a form reminiscent of the backward wave amplifier when the group velocities are not in the same direction. In both cases the excess energy is supplied by the variable coupling reactance and can be indefinitely large. Possible applications of new principles of these coupled circuits to broad-band frequency converters, frequency-channel selectors, wide-band amplifiers, tunable narrow-band amplifiers, and oscillators are described. Noise performances of the circuits are also discussed.
High-level production of human .BETA.-endorphin in escherichia coli. (1987)

A human opioid peptide hormone, β-endorphin, was expressed in Escherichia coli as the C-terminal portion of a fused protein. The fused protein consisting of the N-terminal 62% of E. coli anthranilate synthetase (323 amino acids), a peptide corresponding to the linker DNA (7 amino acids), and the precursor form of β-endorphin (47 amino acids), was highly expressed under the control of a tryptophan promoter. The level of expression of β-endorphin was estimated to be 17mg/liter broth by radioimmunoassay, and 51 mg/liter broth by SDS polyacrylamide gel electrophoresis followed by a densitometric analysis, β-Endorphin was cleaved from the fused protein and purified by HPLC, and is presumed to be identical with human β-endorphin because of its amino acid composition and amino acid sequence.
Molybdenum (1999)

Molybdenum does not exist naturally in the pure metallic form and of the 5 oxidation states (2-6) the predominant species are Mo(IV) and Mo(VI). Molybdenum rapidly polymerizes to a wide variety of complex polymolybdate compounds in solution. The vast majority of molybdenum is used in metallurgical applications (stainless steel, cast-iron alloys). Ammonium tetrathiomolybdate is an experimental chelating agent for Wilson's disease. For the general population, the diet is the most important source of molybdenum and concentrations in water and air usually are negligible. The average daily dietary intake is about 0.1-0.5 mg m.o. Molybdenum is an essential element with relatively low toxicity. Enzymes containing molybdenum catalyze basic metabolic reactions in the carbon, sulfur, and nitrogen cycles. Elimination of molybdenum occurs via the kidney and usually is complete within several weeks. Molybdenosis (teart) is a form of molybdenum toxicity that produces a disease in ruminants similar to copper-deficiency. Little data are available on the human toxicity of molybdenum. A gout-like syndrome and pneumoconiosis have been associated with excessive concentrations of molybdenum, but the inadequate design of the studies prevents an adequate determination of the etiology of these effects.
Leptin Counteracts Sodium Butyrate-induced Apoptosis in Human Colon Cancer HT-29 Cells via NF-κB Signaling (2004)

This study shows that leptin induced a rapid phosphorylation of p42/44 mitogen-activated protein kinase, an enhancement of both NF-kappaB DNA binding and transcriptional activities, and a concentration-dependent increase of HT-29 cell proliferation. These effects are consistent with the presence of leptin receptors on cell membranes. The leptin induction of cell growth was associated with an increase of cell population in S and G2/M phase compared with control cells found in G0/G1 phase of the cell cycle. Moreover, cyclin D1 immunoreactivity was enhanced in leptin-treated HT-29 cells and this increase was essentially associated with cell population in G0/G1 phase. On the other hand, we observed that sodium butyrate inhibited cell proliferation by blocking HT-29 cells in G0/G1 phase of the cell cycle. Interestingly, at physiological concentration, leptin prevented sodium butyrate-induced morphological nucleus changes, DNA laddering and suppressed butyrate-induced cell cycle arrest. This anti-apoptotic effect of leptin was associated with HT-29 cell proliferation and activation NF-kappaB pathways. However, the phosphorylation of p42/44 MAP kinase in response to leptin was reduced in butyrate-treated cells. These data demonstrated that leptin is a potent mitogenic factor for intestinal epithelial cells through the MAP kinase and NF-kappaB pathways. They also showed, for the first time, that leptin promotes colon cancer HT-29 cell survival upon butyrate challenge by counteracting the apoptotic programs initiated by this short chain fatty acid probably through the NF-kappaB pathways. Although further studies are required to unravel the precise mechanism, these data may have significance in the pathogenesis of colorectal cancer and ulcerative colitis diseases.
Improvement of φ29 DNA polymerase amplification performance by fusion of DNA binding motifs (2010)

Bacteriophage ϕ29 DNA polymerase is a unique enzyme endowed with two distinctive properties, high processivity and faithful polymerization coupled to strand displacement, that have led to the development of protocols to achieve isothermal amplification of limiting amounts of both circular plasmids and genomic DNA. To enhance the amplification efficiency of ϕ29 DNA polymerase, we have constructed chimerical DNA polymerases by fusing DNA binding domains to the C terminus of the polymerase. The results show that the addition of Helix-hairpin-Helix [(HhH)(2)] domains increases DNA binding of the hybrid polymerases without hindering their replication rate. In addition, the chimerical DNA polymerases display an improved and faithful multiply primed DNA amplification proficiency on both circular plasmids and genomic DNA and are unique ϕ29 DNA polymerase variants with enhanced amplification performance. The reported chimerical DNA polymerases will contribute to make ϕ29 DNA polymerase-based amplification technologies one of the most powerful tools for genomics.
Plasma Endothelinlike Immunoreactivity Levels in IDDM Patients with Microalbuminuria (1992)

The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.
Antitumor Therapeutic Effect of Neurotropin on Transplanted Tumors in Rats (1984)

The antitumor therapeutic effect of neurotropin (NSP) was examined using the moderately immunogenic KMT-17 tumor in WKA rats and the lower immunogenic 9098 tumor in ACI rats. Treatment with NSP was effective in causing tumor regression and of prolonging the mean survival time of animals which were inoculated with the KMT-17 tumor whereas it is ineffective with the 9098 tumor. Mitogen studies with 9098 tumor-bearing animals, which were treated with NSP, showed that the PHA-P mitogenic reactivity of spleen cells from NSP treated tumor bearing rats (TBR) was higher than that from NSP untreated TBR. When 9098 tumor bearing animals were given combination therapy with NSP and adriamycin (ADR), a beneficial therapeutic effect of NSP was observed. No adverse effect of NSP treatment was observed when it was given before, intermediate or after ADR treatment. These experiments demonstrate that immunomodulation by NSP may possibly have a beneficial therapeutic effect on tumor growth but the conditions to demonstrate this may be highly variable.
Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites (1997)

Two different responses to the therapy were observed in a group of patients receiving the protease inhibitor indinavir. In one, suppression of virus replication occurred and has persisted for 90 weeks (bDNA, < 500 human immunodeficiency virus type 1 [HIV-1] RNA copies/ml). In the second group, a rebound in virus levels in plasma followed the initial sharp decline observed at the start of therapy. This was associated with the emergence of drug-resistant variants. Sequence analysis of the protease gene during the course of therapy revealed that in this second group there was a sequential acquisition of protease mutations at amino acids 46, 82, 54, 71, 89, and 90. In the six patients in this group, there was also an identical mutation in the gag p7/p1 gag protease cleavage site. In three of the patients, this change was seen as early as 6 to 10 weeks after the start of therapy. In one patient, a second mutation occurred at the gag p1/p6 cleavage site, but it appeared 18 weeks after the time of appearance of the p7/p1 mutation. Recombinant HIV-1 variants containing two or three mutations in the protease gene were constructed either with mutations at the p7/p1 cleavage site or with wild-type (WT) gag sequences. When recombinant HIV-1-containing protease mutations at 46 and 82 was grown in MT2 cells, there was a 68% reduction in its rate of replication compared to the WT virus. Introduction of an additional mutation at the gag p7/p1 protease cleavage site compensated for the partially defective protease gene. Similarly, rates of replication of viruses with mutations M46L/I, I54V, and V82A in protease were enhanced both in the presence and in the absence of Indinavir when combined with mutations in the gag p7/p1 and the gag p1/p6 cleavage sites. Optimal rates of virus replication require protease cleavage of precursor polyproteins. A mutation in the cleavage site that enhanced the availability of a protein that was rate limiting for virus maturation would confer on that virus a significant growth advantage and may explain the uniform emergence of viruses with alterations at the p7/p1 cleavage site. This is the first report of the emergence of mutations in the gag p7/p1 protease cleavage sites in patients receiving protease therapy and identifies this change as an important determinant of HIV-1 resistance to protease inhibitors in patient populations.
Peptide Alpha-Amidation (1988)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
[Relationship between phenotype and genotype of ABCB11 deficiency in siblings and literature review]. (2018)

<b>Objective:</b> To explore the relationship between genotype and phenotype of ABCB11 deficiency. <b>Methods:</b> Clinical data of two siblings with ABCB11 deficiency were retrospectively analyzed. Related literature from PubMed, CNKI and Wangfang databases was reviewed to date (up to August 2017) with 'ABCB11 gene' or 'bile salt export pump', 'cholestasis' and 'child' as key words. <b>Results:</b> The patients were siblings. Both of them presented as jaundice, pruritus and hepatosplenomegaly since 3 days after birth. Significant laboratory findings on admission of the older sister included high total bilirubin, 170 µmol/L;conjugated bilirubin, 115.8 µmol/L;alanine aminotransferase, 168 U/L;total bile acid 186.3 µmol/L and normal gamma-glutamyl transpeptidase. While routine laboratory data of the younger brother were as follows: total bilirubin, 148.8 µmol/L;conjugated bilirubin, 96.3 µmol/L;alanine aminotransferase, 232.8 U/L;total bile acid 226 µmol/L, and normal gamma-glutamyl transpeptidase.Both received ursodeoxycholic acid and fat-soluble vitamins. Liver pathology of the younger brother showed giant hepatocytes with ballooning degeneration, focal necrosis and intrahepatic cholestasis. Both the patients harbor the same compound heterozygous mutations in ABCB11 gene, c.145C>T (p.Q49X) and c.1510G>A (p.E504K). The sister is 9 years old now, with normal liver function. Jaundice faded around 3 months after birth, pruritus relieved at age 5, and medications was stopped since then. The brother progressed to liver failure after an operation on perianal abscess when he was 8-month-old, and received living-related liver transplantation when he was 9 month and 20 days old (from his mother). Now he is 1 year and 5 months old, with normal liver function. Both are under our follow-up. Literature review revealed 18 ABCB11 deficiency patients from 7 families who had apparent different prognoses, within each family the siblings had the same ABCB11 gene mutation. Seven cases relieved after ursodeoxycholic acid therapy and/or partial external biliary diversion, 5 received orthotopic liver transplantation, 2 developed hepatocellular carcinoma and 4 cases died in childhood. <b>Conclusions:</b> The clinical manifestations of ABCB11 deficiency may vary greatly in patients carrying the same genotype, even in siblings. Patients should be managed in individualized maner.
An 86-106 GHz quasi-integrated low noise Schottky receiver (1993)

An integrated planar receiver has been developed and tested over the 82-112 GHz bandwidth. The quasi-integrated antenna used in the receiver has a high gain, a high Gaussian coupling efficiency and a wide bandwidth. The mixer design consists of a planar GaAs Schottky diode placed at the feed of a dipole probe suspended inside an integrated horn antenna. The diode uses an etched surface channel and a planar air bridge for reduced parasitic capacitance. At 92 GHz, the room temperature antenna-mixer exhibits a double sideband (DBS) conversion loss and noise temperature of 5.5+or-0.5 Db and 770 K+or-50 K, respectively. The measured DSB conversion loss, and noise temperature over a 20-GHz bandwidth (86-106 GHz) remain less than 6.2+or-0.5 dB and 1000 K+or-50 K, respectively. The low cost of fabrication and simplicity of the design makes it ideal for millimeter- and submillimeter-wave receivers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
User Datagram Protocol (1980)

This User Datagram Protocol (UDP) is defined to make available a datagram mode of packet-switched computer communication in the environment of an interconnected set of computer networks. This
Automated docking with grid‐based energy evaluation (1992)

Abstract The ability to generate feasible binding orientations of a small molecule within a site of known structure is important for ligand design. We present a method that combines a rapid, geometric docking algorithm with the evaluation of molecular mechanics interaction energies. The computational costs of evaluation are minimal because we precalculate the receptor‐dependent terms in the potential function at points on a three‐dimensional grid. In four test cases where the components of crystallographically determined complexes are redocked, the “force field” score correctly identifies the family of orientations closest to the experimental binding geometry. Scoring functions that consider only steric factors or only electrostatic factors are less successful. The force field function will play an important role in our efforts to search databases for potential lead compounds.
A New Pteridine-requiring Enzyme System for the Oxidation of Glyceryl Ethers (1964)

Recent work has directed attention to the occurrence throughout nature of lipids in which long chain alkyl residues are linked to glycerol by ether bonds, rather than by the more common ester linkages.
Prostaglandins E1 and E2 antagonize indomethacin-induced decrease in survival rate of haemorrhagically shocked rats. (1980)

Indomethacin treatment (15 mg/kg) reduced bleeding volume and diminished the survival rate in haemorrhagically shocked rats. These effects of indomethacin were prevented by a continuous infusion of prostaglandin E1 or E2 (0,1 microgram x min--1). Without indomethacin treatment, prostaglandin E1 in this concentration had no effect on bleeding volume or survival rate. The results are consistent with the possibility that indomethacin decreases the survival rate in haemorrhagically shocked rats by inhibiting prostaglandin synthesis, and that endogenous prostaglandins might counteract the development of irreversible haemorrhagic shock.
Kinetics and Growth Mechanism of Electrodeposited Palladium Nanocrystallites (2003)

Palladium particles have been electrodeposited on AISI 316 stainless steel substrate from aqueous solution of palladium chloride. The kinetics of the electrodeposition process and growth mechanism of such three-dimensionally grown palladium particles have been studied. It has been found that the kinetics of electrodeposition of palladium follows parabolic law, which indicates involvement of instantaneous nucleation and subsequent three-dimensional growth. It was also observed that the nucleation density of palladium electrodeposits was a function of the nature of the electrode substrate. The structure, morphology, texture, chemical state, and composition of the electrodeposited palladium particles have been characterized using SEM, TEM, XPS, EDS, EBSD, and OIM. The growth of the palladium nuclei situated at the grain interior was found to be more than that at the grain boundaries on steel substrate. The micron-size electrodeposited palladium particles consisted of a number of nanocrytallites. The surface morphology of the electrodeposited palladium particles was uneven due to the preferential growth of such nanocrystallites in certain crystallographic directions. The results of the present investigation indicate that the growth of the palladium electrodeposits was limited by the diffusivity of bulky palladium tetrachloro square-planar complex from bulk solution to near the electrode surface.
Hypochlorous acid as a potential wound care agent: part I. Stabilized hypochlorous acid: a component of the inorganic armamentarium of innate immunity. (2007)

On the basis of the antimicrobial activity and the lack of animal toxicity, it is predicted that stabilized HOCl has potential pharmaceutical applications in the control of soft tissue infection.
Model of the interactions of calichemicin gamma 1 with a DNA fragment from pBR322. (1989)

An analysis of the binding interactions of several DNA-drug complexes that utilize carbohydrates for DNA recognition has been undertaken. It is proposed that the carbohydrate residues function as general minor groove binding elements, and the stereochemistry of aglycone attachment sites is generally disposed to promote a right-handed helical geometry that is complementary to right-handed DNA. The constitution and stereochemistry of the DNA double-strand cleaving agent calichemicin gamma 1 is consistent with this analysis. Docking experiments with computer-generated models of this drug and a dodecamer duplex that was found to serve as a calichemicin cleavage site were performed to gain insight into the origin of the drug's sequence-selective binding and cutting properties. A model is presented that provides a molecular level understanding of the double-strand cleavage patterns that result from the action of calichemicin gamma 1 on DNA.