gebhart/patrepeval huggingface dataset:
Identification of chymotrypsin inhibitors from a second-generation template assisted combinatorial peptide library (2000)

In an earlier study (McBride JD, Freeman N, Domingo GJ, Leatherbarrow RJ. Selection of chymotrypsin inhibitors from a conformationally-constrained combinatorial peptide library. J. Mol. Biol. 1996; 259: 819-827) we described a resin-bound cyclic peptide library, constructed based on the sequence of the anti-tryptic reactive site loop of Bowman Birk Inhibitor (BBI), a proteinase inhibitor protein. This library was used to identify re-directed chymotrypsin inhibitors with Ki values as low as 17 nM. We have now extended this work by constructing an enhanced library in which a further position, at the P4 site of the inhibitor, has been randomized. This new library has variation at three target locations (P4, P1 and P2) within the inhibitory loop region, producing 8,000 variants. Screening this library allowed selection of new inhibitor sequences with Ki values as low as 3.4 nM. The success of this approach is reflected by the fact that the inhibition constant given by the selected peptide sequence is slightly lower than that reported against chymotrypsin for the most studied full length BBI protein, Soybean BBI 2-IV.
The Activation of Human Type IV Collagenase Proenzyme (1989)

Type IV collagenase is a metalloproteinase which cleaves type IV collagen in a pepsin-resistant domain. Organomercurial activation of the latent 70-kDa type IV collagenase (type IV procollagenase) results in the autocatalytic removal of an amino-terminal domain resulting in the conversion to a 62-kDa activated form of the enzyme. Synthetic peptides corresponding to domains from the amino terminus (residues 1-17) and an internal domain near the carboxyl terminus (residues 472-490) were used as antigens to generate affinity-purified polyclonal antibodies which recognized their respective domains on the native type IV procollagenase. Western immunoblotting studies of the time course of the organomercurial activation process demonstrate a direct loss of the amino-terminal domain during the conversion to the lower molecular weight form. The amino-terminal sequence of the purified type IV procollagenase before and after activation reveals cleavage at a single locus with removal of residues 1-80, generating a new amino terminus YNFFPRKPKWDKNQ. This results in the removal of three distal cysteine residues located at positions 31, 36, and 73. The type IV collagenase site of autocatalytic cleavage corresponds exactly to the homologous sites of type I collagenase and stromelysin cleavage during their respective organomercurial activation. This site is adjacent to the carboxyl end of a highly conserved region consisting of the sequence PRCGVPDV, which contains an unpaired cysteine residue.
Deep and Highly Sensitive Proteome Coverage by LC-MS/MS Without Prefractionation (2011)

In-depth MS-based proteomics has necessitated fractionation of either proteins or peptides or both, often requiring considerable analysis time. Here we employ long liquid chromatography runs with high resolution coupled to an instrument with fast sequencing speed to investigate how much of the proteome is directly accessible to liquid chromatography-tandem MS characterization without any prefractionation steps. Triplicate single-run analyses identified 2990 yeast proteins, 68% of the total measured in a comprehensive yeast proteome. Among them, we covered the enzymes of the glycolysis and gluconeogenesis pathway targeted in a recent multiple reaction monitoring study. In a mammalian cell line, we identified 5376 proteins in a triplicate run, including representatives of 173 out of 200 KEGG metabolic and signaling pathways. Remarkably, the majority of proteins could be detected in the samples at sub-femtomole amounts and many in the low attomole range, in agreement with absolute abundance estimation done in previous works (Picotti et al. Cell, 138, 795-806, 2009). Our results imply an unexpectedly large dynamic range of the MS signal and sensitivity for liquid chromatography-tandem MS alone. With further development, single-run analysis has the potential to radically simplify many proteomic studies while maintaining a systems-wide view of the proteome.
Inhibition of food stimulated acid secretion by misoprostol, an orally active synthetic E1 analogue prostaglandin. (1985)

The effect of 200 micrograms misoprostol (a synthetic prostaglandin E1 analogue) on food stimulated intragastric acidity has been monitored over a 9 h period in 16 normal volunteers. Misoprostol caused a significant inhibition of intragastric acidity for 2 h post-dosing, but no significant effect was seen thereafter on either basal or food stimulated acidity.
Successful treatment of simulated Clostridium difficile infection in a human gut model by fidaxomicin first line and after vancomycin or metronidazole failure (2013)

Fidaxomicin successfully treated simulated primary and recurrent CDI. Fidaxomicin was superior to metronidazole in reducing CD TVC and SP, and superior to vancomycin in reducing SP without recurrence of vegetative cell growth. Fidaxomicin, but not vancomycin or metronidazole, persisted in the gut model for >20 days after instillation.
Low-Dose Immunosuppression Reduces the Incidence of Post-transplant Lymphoproliferative Disease in Pediatric Liver Graft Recipients (2004)

The authors conclude that low-dose immunosuppressive protocols significantly reduce the incidence of PTLD. In patients treated with that regimen, the monitoring of EBV viral load seems not to be helpful. It can be assumed that low-dose immunosuppression does not suppress EBV-specific cytotoxic CD8+ T cells, thus allowing the host to control EBV infection without the risk of PTLD. Our low-dose immunosuppression protocol did not increase the risk of chronic rejection.
Interindividual Heterogeneity in the Hypoxic Regulation of VEGF (1999)

This study provides evidence in support of the hypothesis that the ability to respond to progressive coronary artery stenosis is strongly associated with the ability to induce VEGF in response to hypoxia. The observed interindividual heterogeneity in this response may be due to environmental, epigenetic, or genetic causes. This interindividual heterogeneity may also help to explain the variable angiogenic responses seen in other conditions such as diabetic retinopathy and solid tumors.
Effect of Molecular Characteristics on Cellular Uptake, Subcellular Localization, and Phototoxicity of Zn(II) N-Alkylpyridylporphyrins (2013)

Tetra-cationic Zn(II) meso-tetrakis(N-alkylpyridinium-2 (or -3 or -4)-yl)porphyrins (ZnPs) with progressively increased lipophilicity were synthesized to investigate how the tri-dimensional shape and lipophilicity of the photosensitizer (PS) affect cellular uptake, subcellular distribution, and photodynamic efficacy. The effect of the tri-dimensional shape of the molecule was studied by shifting the N-alkyl substituent attached to the pyridyl nitrogen from ortho to meta and para positions. Progressive increase of lipophilicity from shorter hydrophilic (methyl) to longer amphiphilic (hexyl) alkyl chains increased the phototoxicity of the ZnP PSs. PS efficacy was also increased for all derivatives when the alkyl substituents were shifted from ortho to meta, and from meta to para positions. Both cellular uptake and subcellular distribution of the PSs were affected by the lipophilicity and the position of the alkyl chains on the periphery of the porphyrin ring. Whereas the hydrophilic ZnPs demonstrated mostly lysosomal distribution, the amphiphilic hexyl derivatives were associated with mitochondria, endoplasmic reticulum, and plasma membrane. A comparison of hexyl isomers revealed that cellular uptake and partition into membranes followed the order para > meta > ortho. Varying the position and length of the alkyl substituents affects (i) the exposure of cationic charges for electrostatic interactions with anionic biomolecules and (ii) the lipophilicity of the molecule. The charge, lipophilicity, and the tri-dimensional shape of the PS are the major factors that determine cellular uptake, subcellular distribution, and as a consequence, the phototoxicity of the PSs.
Stability studies on derivatives of the bovine pancreatic trypsin inhibitor (1987)

Gibbs energy, enthalpy, and entropy data were determined for two selectively modified analogues of bovine pancreatic trypsin inhibitor (BPTI) to provide a model free set of thermodynamic parameters that characterize (a) the energetic and entropic contributions of the 14-38 disulfide bridge and (b) the variation of the overall stability resulting from the introduction of two negative charges into the positions 14 and 38. The two BPTI analogues studied were BPTI having Cys-14 and Cys-38 carboxymethylated (BPTI-RCOM) and BPTI having Cys-14 and Cys-38 carboxamidomethylated (BPTI-RCAM). They were obtained from native BPTI by reduction, followed by modification of the sulfhydryl groups with iodoacetic acid or iodoacetamide, respectively. The temperature dependence of all thermodynamic parameters of BPTI is drastically altered in the absence of the third disulfide bridge. Even the apparently minute difference of two dissociable carboxyl groups instead of uncharged amide groups in positions 14 and 38 has surprisingly large effects on the temperature dependence of the stabilization enthalpy. The Gibbs energy of BPTI at pH 2, 25 degrees C, decreases by approximately 70% when the 14-38 disulfide bond is cleaved. BPTI-RCOM is more stable than BPTI-RCAM in the whole pH range studied. The difference of -4 kJ/mol at pH 2, 25 degrees C, is reduced to -2.7 kJ/mol at pH 5, 25 degrees C. This finding demonstrates that the presence of two negative charges reduces the higher stability of BPTI-RCOM slightly; however, the overall effect of the two charges is still a stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)
Purification and biochemical characterization of human liver-derived inhibitory protein (LIP). (1983)

The liver-derived inhibitory protein (LIP), described by us in 1974 (1), has now been purified and biochemically characterized. LIP was purified 166-fold from liver extract (LE) by a combination of gel filtration and ion exchange chromatography, using AcA 44, DEAE-cellulose, hydroxylapatite and Sephadex G-150 superfine. The m.w. of purified LIP was determined by gel filtration to be 67,000 daltons and by SDS-PAGE to be 37,000 daltons. The pI was in the range of 8.83 to 8.96. The protein is temperature labile (60 to 70 degrees C) and acid labile (pH 4). The specific lymphocyte inhibitory activity of the purified protein is 0.15 microgram/culture. LIP is distinct from other liver-derived inhibitory proteins.
P2‐122: ULTRASENSITIVE DETECTION OF NEURODEGENERATIVE BIOMARKERS IN BLOOD WITH THE FULLY AUTOMATED SIMOA ANALYZER: CLINICAL APPLICATIONS (2014)

There is increasing interest for the assessment of neurodegenerative biomarkers in blood, which have previously been restricted to cerebrospinal fluid (CSF). For example, m ethods for measuring total tau in serum and plasma have, until recently, been unavailable. We employed a new technology (Single molecule arrays, Simoa) capable of ultrasensitive protein measurements to measure changes of Abeta1-42 and total tau in different clinical applications, sports-related concussion and Alzheimer's disease. Reagents for bead-based sandwich immunoassays were developed for a fully automated version of Simoa technology (Simoa HD-1). For Abeta 1-42 in blood, the limit of detection was 0.03 pg/ml with inter-day precision of less than 5 % overall. The limit of detection of the total tau assay in blood is 0.02 pg/ml, which is represent 1000 fold improvement in sensitivity over current assays. These assays were used to measure the concentrations of these biomarkers in cohorts of sports-related concussion and AD subjects. Using Simoa, we have been able to detect changes in Abeta and total tau in blood in different neurodegenerative conditions. For example, a cohort of 28 hockey players, plasma tau was assessed pre-season and post-concussion with serial blood sampling. Plasma tau was significantly higher in post-concussion samples as compared with pre-season samples (P = 0.0011). The highest plasma tau levels were observed one hour post-concussion, with circulating tau dropping significantly after 12 hours (P = 0.0008). Additional results in neurodegeneration conditions (AD) will be reported. These data are the first to examine sports-related, post-concussion and neurodegenerative changes in Abeta and tau in blood. The results indicate that plasma tau for example is significantly elevated following mild to severe concussion, and returns to pre-season levels within six days post-concussion. Plasma tau measurement could have utility for determining fitness for return to play.
Mechanism of action of leflunomide in rheumatoid arthritis. (1998)

Leflunomide, a novel drug with proven efficacy in rheumatoid arthritis, is an isoxazol derivative structurally unrelated to other immunomodulatory drugs. Leflunomide is rapidly metabolized to its active form, A77 1726. Two mechanisms of action have been identified for A77 1726: inhibition of dihydroorotate dehydrogenase (DHODH) and inhibition of tyrosine kinases. DHODH inhibition occurs at lower concentrations of A77 1726 than that of tyrosine kinases and is currently considered the major mode of action. Stimulated lymphocytes must increase ribonucleotide levels from 8 to 16-fold before proceeding from the G1 into the S phase. Increased levels of ribonucleotides can only be met by de novo ribonucleotide synthesis. At low levels of ribonucleotides, p53, a "sensor" molecule, gets activated and prevents progression through the cell cycle. Therefore, an inhibitor of de novo uridine monophosphate synthesis would predictably arrest stimulated cells at the G1 phase. In support of this mechanism of action, in vitro mitogen stimulated human peripheral blood lymphocytes treated with A77 1726 undergo arrest at the G1 phase; this inhibition is reversed by uridine.
Endogenous morphine is produced in response to cardiopulmonary bypass in neonatal pigs (2000)

The CPB procedures elicits an endogenous morphine production in neonatal pigs. This morphine response is analogous to the previously demonstrated response in patients subjected to cardiac surgery and CPB.
Computing the stereo matching cost with a convolutional neural network (2015)

We present a method for extracting depth information from a rectified image pair. We train a convolutional neural network to predict how well two image patches match and use it to compute the stereo matching cost. The cost is refined by cross-based cost aggregation and semiglobal matching, followed by a left-right consistency check to eliminate errors in the occluded regions. Our stereo method achieves an error rate of 2.61% on the KITTI stereo dataset and is currently (August 2014) the top performing method on this dataset.
Abdominal ultrasonography as an adjunct to clinical examination 1. Small ruminants (2012)

Abdominal ultrasonography is a diagnostic technique that can be used in farm animal practice as a complementary adjunct to a thorough clinical examination. This article describes the ultrasonographic findings that can be visualised in the abdomen of small ruminants and outlines some of the common indications for ultrasonography. It illustrates how this modality can be readily incorporated into a clinical examination on farm to provide an accurate demonstration of underlying pathology. A second article, to be published in the February issue of In Practice , will discuss the use of abdominal ultrasonography in cattle.
Sampled-Data Control Systems. (1959)

ing equally well to pulsed linear filters and to the description of linear numerical processes.Sampled-data theory which is developed in this book serves as a common base for the analysis and synthesis of linear digital systems, pulsed continuous systems, and their combinations often found in practice.Contributions to the theory of sampled-data systems have been made by scientists, mathematicians, and engineers throughout the world.An examination of the list of references and bibliography in this book will reveal papers from many countries, including England, France, the U.S.S.R., and the United States.As in the case of all new fields, the PREFACE Vil feedback control, and the Laplace transformation, it is possible to use this book in a senior course.The material has also been used as the basis of a seminar in which literature study was the main element of the course.
Arylsulfonyltetrazoles, new coupling reagents and further improvements in the triester method for the synthesis of deoxyribooligonucleotides1 (1977)

The modified triester approach has been further improved and refined to the synthesis of defined sequences of deoxyribo-oligonucleotides. Improvements include arylsulfonyltetrazoles as faster and milder condensing agents, benzenesulfonic acid to avoid depurination during deblocking of trityl protecting groups and improved chromatographic procedures for purification of triester intermediates and purification of the final product containing 3'-5' phosphodiester linkages.
A Preclinical Evaluation of Minnelide as a Therapeutic Agent Against Pancreatic Cancer (2012)

Pancreatic cancer is one of the most lethal human malignancies with an all-stage 5-year survival frequency of <5%, which highlights the urgent need for more effective therapeutic strategies. We have previously shown that triptolide, a diterpenoid, is effective against pancreatic cancer cells in vitro as well as in vivo. However, triptolide is poorly soluble in water, limiting its clinical use. We therefore synthesized a water-soluble analog of triptolide, named Minnelide. The efficacy of Minnelide was tested both in vitro and in multiple independent yet complementary in vivo models of pancreatic cancer: an orthotopic model of pancreatic cancer using human pancreatic cancer cell lines in athymic nude mice, a xenograft model where human pancreatic tumors were transplanted into severe combined immunodeficient mice, and a spontaneous pancreatic cancer mouse model (KRas(G12D); Trp53(R172H); Pdx-1Cre). In these multiple complementary models of pancreatic cancer, Minnelide was highly effective in reducing pancreatic tumor growth and spread, and improving survival. Together, our results suggest that Minnelide shows promise as a potent chemotherapeutic agent against pancreatic cancer, and support the evaluation of Minnelide in clinical trials against this deadly disease.
Altered regulation of growth and expression of differentiation-associated keratins in benign mouse skin tumors (1991)

Alterations in the pattern of epidermal cell differentiation and proliferation in mouse skin and benign skin tumors were studied by two-color immunofluorescence using monospecific antibodies. Replicating cells were identified by 5-bromo-deoxyuridine (BrdU) pulse-labeling and differentiating cells by keratins K1 and K10. In normal mouse skin, pulse-chase experiments for 120 h revealed that replication was restricted to a single layer of basal cells. Replicating cells did not express K1 or K10, but these keratins were sequentially expressed in post-mitotic basal cells 18 and 24 h following DNA synthesis respectively, and cells expressing these keratins migrated into the suprabasal layers. In phorbol-ester- or cantharidin-stimulated hyperplastic skin, replicating cells were also confined to the basal cell compartment and suprabasal cells expressed keratins 1 and 10. In papillomas induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate, replication occurred predominantly in cells in an expanded basal cell compartment (two to four layers above the basement membrane). Cells in these basal layers did not express K1 or K10, but more superficial cells did. After a 1 h pulse of BrdU, replication was also identified in suprabasal cells expressing the differentiation-associated keratins. These and other results suggest that benign tumor cells escape the obligatory growth arrest associated with differentiation. Replication of K1- and K10-expressing suprabasal cells may represent an early alteration during mouse skin carcinogenesis.
BONE DISORDERS IN SICKLE CELL DISEASE (1996)

The bony skeleton of the patient with sickle cell disease is a frequent target of the consequences of sickling. Bone marrow necrosis, bone infarcts osteomyelitis, and aseptic necrosis are common complications in patients with sickle cell disease. An understanding of the pathogenesis, prevalence, diagnosis, and management of these conditions is therefore important for those involved in the care of such patients.
Speciation of Copper(II) Complexes in an Ionic Liquid Based on Choline Chloride and in Choline Chloride/Water Mixtures (2012)

A deep-eutectic solvent with the properties of an ionic liquid is formed when choline chloride is mixed with copper(II) chloride dihydrate in a 1:2 molar ratio. EXAFS and UV-vis-near-IR optical absorption spectroscopy have been used to compare the coordination sphere of the cupric ion in this ionic liquid with that of the cupric ion in solutions of 0.1 M of CuCl(2)·2H(2)O in solvents with varying molar ratios of choline chloride and water. The EXAFS data show that species with three chloride ions and one water molecule coordinated to the cupric ion as well as species with two chloride molecules and two water molecules coordinated to the cupric ion are present in the ionic liquid. On the other hand, a fully hydrated copper(II) ion is formed in an aqueous solution free of choline chloride, and the tetrachlorocuprate(II) complex forms in aqueous choline chloride solutions with more than 50 wt % of choline chloride. In solutions with between 0 and 50 wt % of choline chloride, mixed chloro-aquo complexes occur. Upon standing at room temperature, crystals of CuCl(2)·2H(2)O and of Cu(choline)Cl(3) formed in the ionic liquid. Cu(choline)Cl(3) is the first example of a choline cation coordinating to a transition-metal ion. Crystals of [choline](3)[CuCl(4)][Cl] and of [choline](4)[Cu(4)Cl(10)O] were also synthesized from molecular or ionic liquid solvents, and their crystal structures were determined.
Origin of Nerves Supplying the Posterior Portion of Lumbar Intervertebral Discs in Rats (1996)

The results showed that the posterior portion of lumbar intervertebral discs was innervated by the sympathetic nerves multisegmentally and bilaterally.
Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo (2001)

Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated Abeta42 levels and the varepsilon4 allele of the lipid-carrier apolipoprotein E are regarded as risk factors for sporadic and familial Alzheimer's disease. Here we demonstrate that the widely used cholesterol-lowering drugs simvastatin and lovastatin reduce intracellular and extracellular levels of Abeta42 and Abeta40 peptides in primary cultures of hippocampal neurons and mixed cortical neurons. Likewise, guinea pigs treated with high doses of simvastatin showed a strong and reversible reduction of cerebral Abeta42 and Abeta40 levels in the cerebrospinal fluid and brain homogenate. These results suggest that lipids are playing an important role in the development of Alzheimer's disease. Lowered levels of Abeta42 may provide the mechanism for the observed reduced incidence of dementia in statin-treated patients and may open up avenues for therapeutic interventions.