gebhart/patrepeval huggingface dataset:
Stoichiometric Inhibition of Reduced Xanthine Oxidase by Hydroxypyrazolo[3,4-d]pyrimidines (1970)

Abstract The inhibition of reduced bovine milk xanthine oxidase by 4-hydroxypyrazolo[3,4-d]pyrimidine (4-HPP) and 4,6-dihydroxypyrazolo[3,4-d]pyrimidine (4,6-diHPP) is stoichiometric or titrating in type, i.e. the inhibition is virtually complete (g90%) at concentrations of inhibitor equimolar with that of the enzyme. The dissociation constant of the reduced enzyme-4,6-diHPP complex, determined by the method of Easson and Stedman (Proc. Roy. Soc. Ser. B Biol. Sci., 121, 142 (1936)), is 5.4 x 10-10 m. No decrease in the fractional inhibition is detectable on increasing the substrate concentration from 0.04 to 0.33 mm, or on 10-fold dilution of the enzyme-inhibitor complex. The inhibitory properties of 4-HPP are virtually identical with those of 4,6-diHPP; this identity in behavior is the result of the conversion of 4-HPP to 4,6-diHPP by the enzyme. The rate of development of 4,6-diHPP inhibition is markedly temperature-dependent, more than 2 hours being required to reach maximal inhibition at 2°, but less than 1 min at 40°. The time required to reach maximal inhibition is not decreased by increasing the 4,6-diHPP level 100-fold, from 28 mµm to 2.8 µm; the inhibition appears, therefore, to be caused, not by the enzyme-inhibitor complex initially formed, but to a subsequent internal rearrangement of the latter to a less readily dissociable form.
Codon usage and secondary structure of MS2 phage RNA (1989)

MS2 is an RNA bacteriophage (3569 bases). The secondary structure of the RNA has been determined, and is known to play an important role in regulating translation. Paired regions of the genome have a higher G+C content than unpaired regions. It has been suggested that this reflects selection for high G+C content to encourage pairing, but a re-analysis of the data together with computer simulation suggest that it is an automatic consequence in any RNA sequence of the way it folds up to minimise its free energy. It has also been suggested that the three registers in which pairing can occur in a coding region are used differentially to optimise the use of the redundancy of the genetic code, but re-analysis of the data shows only weak statistical support for this hypothesis.
Normal Bacterial Populations of the Intestine and Their Relation to Intestinal Function (1964)

MalabsorptionThe Blind-Loop SyndromeAbnormal intestinal function has been observed in a number of conditions characterized by excessive proliferation of bacteria within the lumen of the small bowel. In this so-called "blind-loop syndrome" macrocytic anemia, vitamin B12 malabsorption and steatorrhea are associated with small-bowel abnormalities conducive to localized stasis of intestinal contents. The major clinical and pathological features of the syndrome were documented in 1939 by Barker and Hummel,180 and the subject has more recently been extensively reviewed from several points of view.105,133, 181 182 183 Surgical blind loops, strictures, enteroenterostomies, fistulas and diverticula involving the small intestine may all be associated . . .
Topographical Amino Acid Substitution in Position 10 of Glucagon Leads to Antagonists/Partial Agonists with Greater Binding Differences (1996)

The role of position 10 in the beta-turn region of glucagon was investigated by substituting chiral constrained amino acids and other modifications in the N-terminal region. A series of glucagon analogues have been designed and synthesized by incorporating beta-methylphenylalanine isomers (2S,3S, 2S,3R, 2R,3R, and 2R,3S) at position 10 in order to explore the structural and topographical requirements of the glucagon receptor, and, in addition, utilizing previous studies which indicated that antagonism could be enhanced by modifications (des-His1, Glu9) and a bulky group at position 5. The structures of the new analogues are as follows: [des-His1,-Tyr5,Glu9]glucagon-NH2 (II), [des-His1,Tyr5,Glu9,Phe10]glucagon-NH2 (III), [des-His1,Tyr5,Glu9,-Ala10]glucagon-NH2 (IV), [des-His1,Tyr5,Glu9,(2S,3R)-beta-MePhe10]glucagon-NH2 (V), [des-His1,-Tyr5,Glu9,(2S,3S)-beta-MePhe10]glucagon-NH2 (VI), [des-His1,Tyr5,Glu9,D-Tyr10]glucagon-NH2 (VII), [des-His1,Tyr5,Glu9,D-Phe10]glucagon-NH2 (VIII), [des-His1,Tyr5,Glu9,D-Ala10]glucagon-NH2 (IX), [des-His1,Tyr5,Glu9,(2R,3R)-beta-MePhe10]glucagon-NH2 (X), and [des-His1,Tyr5,Glu9,(2R,3S)-beta-MePhe10]glucagon-NH2 (XI). These analogues led to dramatically different changes in in vitro binding affinities for glucagon receptors. Their receptor binding potencies IC50 values (nM) are 2.3 (II), 4.1 (III), 395.0 (IV), 10.0 (V), 170.0 (VI), 74.0 (VII), 34.5 (VIII), 510.0 (IX), 120.0 (X), and 180.0 (XI). Analogues II, III, V, VI, and XI were found to be weak partial agonists/partial antagonists with maximum stimulation between 5%-9%, while the other compounds (IV and VII-X) were antagonists unable to activate the adenylate cyclase system even at concentrations as high as 10(-5) M. In competition experiments, all of the analogues caused a right shift of the glucagon-stimulated adenylate cyclase dose-response curve. The pA2 values were 6.60 (II), 6.85 (III), 6.20 (IV), 6.20 (V), 6.10 (VI), 6.50 (VII), 6.20 (VIII), 5.85 (IX), 6.20 (X), and 6.00 (XI). Putative topographical requirements of the glucagon receptor for the aromatic side chain conformation in position 10 of glucagon antagonists are discussed.
AN INTRODUCTION TO HIDDEN MARKOV MODELS AND BAYESIAN NETWORKS (2001)

We provide a tutorial on learning and inference in hidden Markov models in the context of the recent literature on Bayesian networks. This perspective makes it possible to consider novel generalizations of hidden Markov models with multiple hidden state variables, multiscale representations, and mixed discrete and continuous variables. Although exact inference in these generalizations is usually intractable, one can use approximate inference algorithms such as Markov chain sampling and variational methods. We describe how such methods are applied to these generalized hidden Markov models. We conclude this review with a discussion of Bayesian methods for model selection in generalized HMMs.
GABAergic Cortical Neuron Chromatin as a Putative Target to Treat Schizophrenia Vulnerability (2003)

Inhibitory GABAergic interneurons of prefrontal cortex (PFC) appear to play an important role in the regulation of intermittent pyramidal neuron columnary firing and in the neuronal plasticity that mediate cognitive functions. In schizophrenia (SZ), cognitive defects and dysfunctions in pyramidal neuronal columnary firing appear to depend on abnormalities of GABAergic neurons. These abnormalities include a decrease of GAD67 and reelin expression, which result in a reduction of cortical inhibitory input to spine postsynaptic densities as a result of the decrease of GABA concentration at the synaptic cleft, and of neurotrophic stimuli as a result of the decrease of reelin secreted into the extracellular matrix. Our studies show that alterations in chromatin remodeling related to a selective upregulation of DNA-5-cytosine methyltransferase (DNMT) expression in GABAergic neurons of SZ PFC may induce a hypermethylation of reelin and GAD67 promoter CpG islands, which downregulates their expression. In addition, we report preliminary evidence suggesting that by targeting this chromatin-remodeling deficit with inhibitors of histone deacetylases (HDAC), it may be possible to reduce the DNMT upregulation via a covalent modification of nucleosomal histone tails, underscoring the possibility that by addressing a chromatin remodeling deficit, one may treat psychiatric disorders.
Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. (2007)

The higher levels of cytokines found in FM patients suggest the presence of an inflammatory response system (IRS) and highlight a parallel between the clinical symptoms and biochemical data. They support the hypothesis that cytokines may play a role in the clinical features of fibromyalgia. In addition, the similar cytokine patterns found in FM patients with different psychiatric profiles suggests that IRS impairment may play a specific role in the disease.
Untersuchungen zur Ausbildung des Hopfenaromas und technologische Maßnahmen zur Erzeugung hopfenaromatischer Biere (2000)

Der Schwerpunkt der Arbeit liegt zum einen in der Untersuchung zur Ausbildung des Hopfenaromas und zum anderen in der Ableitung technologischer Parameter zur Erzeugung hopfenaromatischer Biere. Die Anwendung spezieller Analysenmethoden und eines neu entwickelten Verkostungsschemas ermoglichen die Differenzierung der durchgefuhrten technologischen Versuche. Die Untersuchungen erstrecken sich vom eingesetzten Hopfenmaterial uber die Bedingungen im Sudhaus bis hin zum forciert gealterten Bier. Die Erarbeitung einer Sufenkontrolle uber den Linaloolgehalt ermoglicht die Kontrolle uber das zu erwartende Hopfenaroma im Bier.
Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes (2009)

Linagliptin is a new oral antidiabetic agent associated with minimal risk of hypoglycemia, which holds promise for treatment of type 2 diabetes.
14-3-3σ regulates B-cell homeostasis through stabilization of FOXO1 (2011)

14-3-3σ regulates cytokinesis and cell cycle arrest induced by DNA damage but its role in the immune system is unknown. Using gene-targeted 14-3-3σ-deficient (i.e., KO) mice, we studied the role of 14-3-3σ in B-cell functions. Total numbers of B cells were reduced by spontaneous apoptosis of peripheral B cells. Upon B-cell antigen receptor engagement in vitro, KO B cells did not proliferate properly or up-regulate CD86. In response to T cell-independent antigens, KO B cells showed poor secretion of antigen-specific IgM. This deficit led to increased lethality of KO mice after vesicular stomatitis virus infection. KO B cells showed elevated total FOXO transcriptional activity but also increased FOXO1 degradation. Coimmunoprecipitation revealed that endogenous 14-3-3σ protein formed a complex with FOXO1 protein. Our results suggest that 14-3-3σ maintains FOXO1 at a consistent level critical for normal B-cell antigen receptor signaling and B-cell survival.
Association between ABCB1 C3435T polymorphism and breast cancer risk: a Moroccan case-control study and meta-analysis (2016)

We have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.
Collection and Expansion of Single Cells and Colonies Released from a Micropallet Array (2007)

The ability to selectively grow out individual cells possessing unique characteristics from within a mixed population is of widespread importance for biomedical investigations. Generation of genetically engineered cell lines, transformation studies, cell-based assays, and stem cell studies are examples where single-cell cloning is of immense value. The vast majority of mammalian cells grow adherent to a surface; therefore, positive selection followed by cloning of cells while the cells remain adherent to their growth surface is an important goal. We recently demonstrated a microfabricated cell array combined with laser-based release of individual array elements for positive selection of single cells. In the current work, a strategy to collect single cells for clonal expansion is described. The system enabled cloning of individual cells with 80-90% efficiency. Single cells were selected and cloned from small populations of fewer than 10,000 cells. Strategies used by cells to migrate from the pallets to form colonies on the surface of the collection device were examined. Implementation of encoded array elements made it possible to follow specific cells throughout the selection, collection, and cloning procedure. Thus, a particular cell can be identified by any number of imaging techniques, isolated, and clonally expanded to generate a homogeneous cell line or a pure sample for genetic or biochemical analysis.
ANALYTICAL METHODS USED IN THE PRODUCTION AND FUEL QUALITY ASSESSMENT OF BIODIESEL (2001)

Biodiesel, an alternative diesel fuel derived from vegetable oil, animal fats, or waste vegetable oils, is obtainedby reacting the oil or fat with an alcohol (transesterification) in the presence of a basic catalyst to give the correspondingmonoalkyl esters. Two major categories of methods besides other miscellaneous ones have been reported in the literaturefor assessing biodiesel fuel quality and/or monitoring the transesterification reaction by which biodiesel is produced. Thetwo major categories comprise chromatographic and spectroscopic methods. This article considers the various methods ineach category, including advantages and drawbacks, and offers suggestions on selection of appropriate methods.
Design of DNA origami (2005)

The generation of arbitrary patterns and shapes at very small scales is at the heart of our effort to miniaturize circuits and is fundamental to the development of nanotechnology. Here I review a recently developed method for folding long single strands of DNA into arbitrary two-dimensional shapes using a raster fill technique - 'scaffolded DNA origami'. Shapes up to 100 nanometers in diameter can be approximated with a resolution of 6 nanometers and decorated with patterns of roughly 200 binary pixels at the same resolution. Experimentally verified by the creation of a dozen shapes and patterns, the method is easy, high yield, and lends itself well to automated design and manufacture. So far, CAD tools for scaffolded DNA origami are simple, require hand-design of the folding path, and are restricted to two dimensional designs. If the method gains wide acceptance, better CAD tools will be required.
Ras mediates translation initiation factor 4E-induced malignant transformation. (1992)

Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7 GpppN, where N is any nucleotide). eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras.
Synthesis of Ortho Substituted Arylboronic Esters by in Situ Trapping of Unstable Lithio Intermediates (2001)

[reaction: see text] Ortho lithiation-in situ boration using lithium 2,2,6,6-tetramethylpiperidide (LTMP) in combination with triisopropylborate (B(OiPr)(3)) is a highly efficient and experimentally straightforward process for the preparation of ortho substituted arylboronic esters. The mild reaction conditions allow the presence of functionalities such as ester or cyano groups or halogen substituents that are usually not compatible with the conditions used in directed ortho metalation of arenes. The arylboronic esters underwent Suzuki-type cross-coupling with a range of aryl halides, furnishing biaryls in 53-94% yield.
Identification of a Novel Tumor-Associated Antigen, Cadherin 3/P-Cadherin, as a Possible Target for Immunotherapy of Pancreatic, Gastric, and Colorectal Cancers (2008)

These results suggest that CDH3 is a novel TAA useful for immunotherapy against a broad spectrum of cancers, including pancreatic cancer.
New method to discriminate between cathepsin B and cathepsin L in crude extracts from fish muscle based on a simple acidification procedure (2006)

Summary A new and simple method to distinguish between cathepsin B and cathepsin L in crude extracts of herring ( Clupea harengus ) muscle has been established. An acid treatment of crude extracts (exposed to pH 3 for 5 min) activated a latent form of cathepsin L and inactivated cathepsin B. Furthermore, in neutral crude extract, the hydrolysis of benzyloxycarbonyl‐ l ‐phenylalanyl‐ l ‐arginyl‐4‐methylcoumarine (Z‐Phe‐Arg‐MCA) (cathepsin B and cathepsin L substrates) was between 0% and 15% of the hydrolysis of benzyloxycarbonyl‐ l ‐arginyl‐ l ‐arginyl‐7‐amino‐4‐methylcoumarine (Z‐Arg‐Arg‐MCA; cathepsin B substrate). Cathepsin B activity is measured in neutral extract using the specific cathepsin B substrate Z‐Arg‐Arg‐MCA and cathepsin L activity is measured in acid‐treated extract with Z‐Phe‐Arg‐MCA as substrate. The specific cathepsin B inhibitor, CA‐074, did not inhibit the Z‐Arg‐Arg‐MCA significantly without affecting the Z‐Phe‐Arg‐MCA activity. An acid treatment of the crude extract is therefore a more advantageous approach to discriminate between cathepsin B and cathepsin L activities.
Comparison of a Novel ET<sub>A </sub>Receptor Antagonist and Phosphoramidon in Renal Ischemia (1995)

Infusion (0.46 mumol/kg/min) of the endothelin (ET)-converting-enzyme inhibitor, phosphoramidon (P), protected function and structure after 30 min renal ischemia in rats more than treatment (5 mumol/kg/min) with the ETA receptor antagonist, BMS-182874 (B). The glomerular filtration rate (GFR; 0.7 +/- 0.12 ml/min) and renal plasma flow (RPF) decreased approximately 40% at 2 h reflow versus controls (C: 1.2 +/- 0.12). B weakly protected the GFR (0.8 +/- 0.07 ml/min); P restored it (1.1 +/- 0.05). Both compounds reduced tubular injury at 2 h reflow; P ameliorated glomerular changes. At 24 h the GFR (0.6 +/- 0.06 ml/min) and RPF decreased 67% versus C (1.8 +/- 0.08). B did not protect the GFR and RPF. P partially protected the GFR (0.9 +/- 0.07 ml/min) but not RPF, and reduced tubular injury. The results suggest that both ETA and non-ETA receptors mediate ET-induced changes in ischemic renal failure.
Machine learning in control of functional electrical stimulation systems for locomotion (1995)

Two machine learning techniques were evaluated for automatic design of a rule-based control of functional electrical stimulation (FES) for locomotion of spinal cord injured humans. The task was to learn the invariant characteristics of the relationship between sensory information and the FES-control signal by using off-line supervised training. Sensory signals were recorded using pressure sensors installed in the insoles of a subject's shoes and goniometers attached across the joints of the affected leg. The FES-control consisted of pulses corresponding to time intervals when the subject pressed on the manual push-button to deliver the stimulation during FES-assisted ambulation. The machine learning techniques used were the adaptive logic network (ALN) [1] and the inductive learning algorithm (IL) [2]. Results to date suggest that, given the same training data, the IL learned faster than the ALN, while both performed the test rapidly. The generalization was estimated by measuring the test errors and it was better with an ALN, especially if past points were used to reflect the time dimension. Both techniques were able to predict future stimulation events. An advantage of the ALN over the IL was that ALN's can be retrained with new data without losing previously collected knowledge. The advantages of the IL over the ALN were that the IL produces small, explicit, comprehensible trees and that the relative importance of each sensory contribution can be quantified.
Role of fibronectin in collagen deposition: Fab' to the gelatin-binding domain of fibronectin inhibits both fibronectin and collagen organization in fibroblast extracellular matrix. (1982)

We report the effect of Fab' (anti-60k) to a 60,000 mol wt gelatin binding domain of fibronectin (1981, J. Biol. Chem. 256:5583) on diploid fibroblast (IMR-90) extracellular fibronectin and collagen organization. Anti-60k Fab' did not inhibit IMR-90 attachment or proliferation in fibronectin-depleted medium. Fibroblasts cultured with preimmune Fab' deposited a dense extracellular network of fibronectin and collagen detectable by immunofluorescence, while anti-60k Fab' prevented extracellular collagen and fibronectin fibril deposition. Matrix fibronectin and collagen deposition remained decreased in cultures containing anti-60k Fab' until cells became bilayered or more dense, when fibronectin and collagen began to appear in lower cell layers. Anti-60k Fab' added to confluent cultures 24 h before fixation and staining had no effect on matrix fibronectin or collagen, so anti-60k Fab' did not simply block immunostaining. Confluent cultures grown in anti-60k Fab' and labeled for 24 h with [3H]proline incorporated identical amounts of [3H]proline and [3H]hydroxyproline, but [3H]hydroxyproline deposition in the cell layer was significantly decreased by anti-60k Fab' (P less than 0.01). Extracellular matrix collagen does not appear to form a scaffold for fibronectin deposition, as neither gelatin nor a gelatin-binding fragment of plasma fibronectin inhibited deposition of matrix fibronectin. Our results suggest that interstitial collagens and fibronectin interact to form a fibrillar component of the extracellular matrix, and that fibronectin is required for normal collagen organization and deposition by fibroblasts in vitro. Domain-specific antibodies to fibronectin are powerful tools to study the biological role of fibronectin in extracellular matrix organization and other processes.
The cloning of two Arabidopsis genes belonging to a phosphate transporter family (1997)

Two genes, APT1 and APT2, with DNA sequences that exhibit significant sequence identity to yeast and fungal H+/orthophosphate co-transporters, have been isolated from Arabidopsis thaliana. These genes are genetically linked and map to chromosome 5 between markers g4028 and m435. The genes encode almost identical 524 amino acid polypeptides and are predicted to contain 12 membrane-spanning domains. Both APT1 and APT2 are predominantly expressed in A. thaliana root tissues. The level of expression of both genes in roots is regulated by the phosphorus status of the plant, being considerably enhanced when the plants were deprived of an external phosphate supply. The APT1 and APT2 polypeptides are likely to be associated with the membrane transport of phosphate within A. thaliana roots.
Immunological effects of native and polyethylene glycol-modified asparaginases from Vibrio succinogenes and Escherichia coli in normal and tumour-bearing mice. (1982)

The immunosuppressive effects of polyethylene glycol-modified asparaginases from Vibrio succinogenes (PEG-asparaginase VS) and Escherichia coli (PEG-asparaginase EC) have been investigated in mice. Measurements of the mitogen-induced blastogenic responses of splenocytes, harvested 5 days after in vivo administration of the PEG-enzymes, show that PEG-asparaginase VS is not immunosuppressive, whereas PEG-asparaginase EC does cause immunosuppression. Both enzymes cause the spleen to be smaller than the control mice. In mice carrying the L5178Y tumour and its associated LDH-elevating virus, which causes the circulation life of asparaginase VS to be comparable to that of PEG-asparaginase VS, tumour regression and its attendant immunological changes are identical in animals treated with either the native or the modified enzyme. The data presented in this paper, along with independent immunological evidence presented by other workers strongly suggest that PEG-asparaginase VS may be the enzyme of choice for clinical use.