gebhart/patrepeval huggingface dataset:
A COMPARISON OF PREPARATIONS OF HIGHLY PURIFIED HUMAN PITUITARY FOLLICLE-STIMULATING HORMONE: DIFFERENCES IN THE FOLLICLE-STIMULATING HORMONE POTENCIES AS DETERMINED BY IN-VIVO BIOASSAY, IN-VITRO BIOASSAY AND IMMUNOASSAY (1981)

The FSH potencies of 12 preparations of highly purified human pituitary FSH, originating from six different laboratories, were determined by in-vivo and in-vitro bioassays and by immunoassay in terms of the First International Reference Preparation of Human Pituitary Gonadotrophins (FSH and LH) for Bioassay (IRP; coded 69/104). The contamination of these FSH preparations with LH was also determined. Estimates of protein content were based on the absorbance at 280 nm of solutions of the preparations, assuming that A 1% 1 cm 280 = 10. The FSH potencies varied between different preparations from 827 i.u./mg to 13 100 i.u./mg by in-vivo bioassay; from 2930 to 14 600 i.u./mg by in-vitro bioassay and from 1680 to 5690 i.u./mg by immunoassay. The ratios of in-vivo biological activity relative to in-vitro biological activity and to immunoreactivity respectively varied between preparations from 0·06 to 2·3 and from 0·15 to 4·1, and there was a significant positive correlation between each of these ratios and the in-vivo biological potency of the preparations; such differences could be due to varying degrees of sialylation between preparations. On the other hand the ratios of in-vitro biological activity to immunoreactivity between preparations were fairly constant (approx. 2). The excess biological activity relative to immunoreactivity observed, in terms of the IRP, in all these materials is consistent with recent findings of some immunoreactive FSH in the IRP unassociated with biological activity. These data did not demonstrate any significant advantage, in terms of FSH in-vivo biological potency, from the use of fresh-frozen rather than acetone-dried pituitary glands for the isolation of FSH. Contamination of all these preparations with LH appeared to be less than 3% (w/w), as determined by in-vitro bioassay and by immunoassay. The results of this study are discussed in relation to the selection of material for an international reference preparation for immunoassay and attention is drawn to the value of high in-vivo biological FSH potency as a criterion of the identity of a preparation as well as of its freedom from contaminants without FSH biological activity.
Chronic opioid use is associated with increased DNA methylation correlating with increased clinical pain (2012)

Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics. A major epigenetic mechanism is methylation or demethylation at CpG-rich DNA islands. DNA methylation triggered by drugs has largely unexplored therapeutic consequences. Here we report increased methylation at a CpG rich island in the OPRM1 gene coding for μ-opioid receptors and at a global methylation site (LINE-1) in leukocytes of methadone-substituted former opiate addicts compared with matched healthy controls. Higher DNA methylation associated with chronic opioid exposure was reproduced in an independent cohort of opioid-treated as compared to non-opioid-treated pain patients. This suggests that opioids may stimulate DNA methylation. The OPRM1 methylation had no immediate effect on μ-opioid receptor transcription and was not associated with opioid dosing requirements. However, the global DNA methylation at LINE-1 was significantly correlated with increased chronic pain. This suggests inhibitory effects on the transcription of still unspecified nocifensive gene products. It further implies that opioids may be causally associated with increased genome-wide DNA methylation, although currently there is no direct evidence of this. This has phenotypic consequences for pain and may provide a new, epigenetics-associated mechanism of opioid-induced hyperalgesia. The results indicate a potential influence of opioid analgesics on the patients' epigenome. They emphasize the need for reliable and cost-effective screening tools and may imply that high-throughput screening for lead compounds in artificial expression systems may not provide the best tools for identifying new pain medications.
Studies on the expression of the beta nerve growth factor (NGF) gene in the central nervous system: level and regional distribution of NGF mRNA suggest that NGF functions as a trophic factor for several distinct populations of neurons. (1986)

Beta nerve growth factor (NGF), a target-derived protein necessary for survival and development of sympathetic and sensory neurons, can also affect subpopulations of neurons in the central nervous system (CNS). Using a blot hybridization assay capable of detecting 10 fg of mRNA, we measured the levels of NGF mRNA in the major brain regions, including those innervated by NGF-responsive neurons. NGF mRNA was detected unambiguously in each major region of the CNS. The levels were comparable to those in sympathetic effector organs. Discrete areas contained very different amounts of NGF mRNA. Up to 40-fold differences were seen, a range comparable to the differences between richly and sparsely innervated sympathetic effector organs. The highest concentrations of NGF mRNA were found in the cortex and hippocampus, which are the major targets of the NGF-responsive cholinergic neurons of the basal forebrain nuclei. Significant amounts of NGF mRNA were also found in areas that contain the central processes of NGF-responsive sensory neurons, such as the pons, medulla, and spinal cord. The presence of NGF mRNA in these areas suggests that brain NGF may act as a target-derived trophic factor for both populations of neurons. NGF mRNA was also found in the striatum, suggesting that locally derived NGF may act there as a trophic factor for a recently identified population of NGF-responsive cholinergic local circuit neurons. However, high levels of NGF mRNA were also found in some regions, such as the diencephalon, that have no relation to any identified population of NGF-responsive neurons. This suggests that there may be additional populations of NGF-responsive neurons in the CNS that have not yet been discovered.
Antisense Waxy Genes with Highly Active Promoters Effectively Suppress Waxy Gene Expression in Transgenic Rice (2000)

To regulate Waxy (Wx) gene expression by introducing antisense genes, we connected the 2.3 kb Wx cDNA having 450 bp of the Wx first intron in reverse orientation to rice Wx and maize alcohol dehydrogenase1 (Adh1) promoters and used these constructs to transform rice plants. Of 10 independent transgenic lines analysed, four lines showed various degrees of reduction in amylose and WAXY (WX) protein levels in the endosperm. In two transgenic lines, complete absence of amylose was observed which made the seeds opaque white like glutinous rice (amylose-deficient waxy (wx) mutant). In one of the transgenic lines, A1 line, the presence of the antisense Wx gene cosegregated with reduction of amylose content in the endosperm. In the same line, a reduction in the level of endogenous Wx mRNA was observed in immature endosperm. Interestingly, this reduction was observed only with mature spliced transcripts but not with unspliced transcripts. Reduced amylose synthesis was also observed in pollen grains of four transgenic lines. These results suggest that integrated antisense Wx gene caused a reduction in amylose synthesis in endosperms and pollen grains of transgenic rice carrying the antisense Wx cDNA. These results indicate that manipulation of starch and other carbohydrates in rice grain is possible using antisense genes.
Finding "It": Weakly-Supervised Reference-Aware Visual Grounding in Instructional Videos (2018)

Grounding textual phrases in visual content with standalone image-sentence pairs is a challenging task. When we consider grounding in instructional videos, this problem becomes profoundly more complex: the latent temporal structure of instructional videos breaks independence assumptions and necessitates contextual understanding for resolving ambiguous visual-linguistic cues. Furthermore, dense annotations and video data scale mean supervised approaches are prohibitively costly. In this work, we propose to tackle this new task with a weakly-supervised framework for reference-aware visual grounding in instructional videos, where only the temporal alignment between the transcription and the video segment are available for supervision. We introduce the visually grounded action graph, a structured representation capturing the latent dependency between grounding and references in video. For optimization, we propose a new reference-aware multiple instance learning (RA-MIL) objective for weak supervision of grounding in videos. We evaluate our approach over unconstrained videos from YouCookII and RoboWatch, augmented with new reference-grounding test set annotations. We demonstrate that our jointly optimized, reference-aware approach simultaneously improves visual grounding, reference-resolution, and generalization to unseen instructional video categories.
Secure locally repairable codes for distributed storage systems (2013)

This paper presents coding schemes for distributed storage systems (DSS) that are secure against eavesdroppers, while simultaneously enabling efficient node repair (regeneration). Towards this, novel upper bounds on secrecy capacity for minimum storage regenerating (MSR) codes and locally repairable codes (LRCs) are derived. The eavesdropper model considered in this paper incorporates the ability to listen in on data downloaded during ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> node repairs in addition to content stored on ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> nodes. Finally, this paper presents coding schemes, based on precoding using Gabidulin codes, that achieve the upper bounds on secrecy capacity and characterize the secrecy capacity of DSS for various settings of system parameters.
Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles (2002)

CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection.
[The level of autoantibodies to glutamate receptors in the blood serum of patients in the acute period of ischemic stroke]. (1996)

The level of autoantibodies (aAB) to main structural component of glutamate NMDA-receptors--phencyclidin-binding protein--was measured in blood serum of 70 patients during first 3, 6, 9, 12, 24 hours, and 3, 5 days after ischemic stroke development. 200 healthy individuals formed the control group. The elevation of titers of aAB to glutamate receptors was observed in all patients with severe or moderate disease from the very first hours of stroke. It was especially pronounced by 9-12 hours after stroke. The highest increase of aAB titers was found in severe cases. The tendency to normalization of aAB titers was observed by the end of the first twenty four hours. The degree of aAB elevation had the prognostic importance. The most favourable course of stroke with good restoration of damaged functions was predicted when stable normalization of the aAB level was observed by the third day of the disease development. Patients in stupor-coma condition did not show the phenomenon of aAB level's elevation during the first days of stroke, that reflected, probably, the development of immuno-deficient state. The decrease of aAB level down to subnormal values was extremely unfavourable prognostic sign proceeding patient's death as a rule.
Quantitative analysis of lymphocyte differentiation and proliferation in vitro using carboxyfluorescein diacetate succinimidyl ester (1999)

Mature T and B lymphocytes respond to receptor-delivered signals received during and following activation. These signals regulate the rates of cell death, growth, differentiation and migration that ultimately establish the behaviour patterns collectively referred to as immune regulation. We have been pursuing the philosophy that in vitro systems of lymphocyte stimulation, when analysed quantitatively, help reveal the logical attributes of lymphocyte behaviour. The development of carboxyfluorescein diacetate succinimidyl ester (CFSE) to track division has enabled the variable of division number to be incorporated into these quantitative analyses. Our studies with CFSE have established a fundamental link between differentiation and division number. Isotype switching, expression of T cell cytokines, surface receptor alterations and changes to intracellular signalling components all display independent patterns of change with division number. The stochastic aspects of these changes and the ability of external signals to independently regulate them argue for a probabilistic modelling framework for describing and understanding immune regulation.
Green Microwave Synthesis of MIL‐100(Al, Cr, Fe) Nanoparticles for Thin‐Film Elaboration (2012)

Abstract Nanoparticles of mesoporous MIL‐100(Al, Cr or Fe) metal–organic frameworks were synthesized by a microwave‐assisted solvothermal route with green solvents. The optimization of yield, crystallinity, and particle size was achieved through the control of synthetic parameters such as temperature, heating rate, and dwelling time. The particle size strongly depends on the metallic cation and the metal and linker precursors; nanoparticles smaller than 100 nm were obtained for iron and chromium based MIL‐100. Finally, stable colloidal solutions of iron and chromium MIL‐100 nanoparticles were used for thin layer dip‐coating deposition, which resulted in high optical quality thin films, the porosity of which was investigated by environmental ellipsometric porosimetry.
Purification and Characterization of a Porcine Liver Microsomal Triacylglycerol Hydrolase (1997)

We have purified an enzyme from porcine liver microsomes which catalyzes hydrolysis of triacylglycerols. The enzyme was solubilized from the membranes by the zwitterionic detergent 3-[(3- cholamidopropyl)dimethylammonio]-l-propansulfonate (CHAPS) and was purified to apparent homogeneity by sequential chromatography on Q-Sepharose, hydroxyapatite, Affi-Gel heparin, and Mono-Q. The purified hydrolase migrated in SDS-polyacrylamide gel electrophoresis (PAGE) as a single polypeptide band of an apparent molecular mass of 60 kDa. The enzyme hydrolyzed long-, medium-, and short-chain triacylglycerols, as well as a chromogenic lipase substrate, 1,2-O-dilauryl-rac-glycero-3-glutaric acid resorufin ester. The highest specific activity was obtained with tributyroylglycerol (240 mumol.min-1.mg-1). The reaction rate was maximal at pH 8.5. Sulfhydryl-directed reagents, such as N-ethylmaleimide (NEM), 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), and dodecyldithio-5-(2-nitrobenzoic acid) (C12-TNB) had no effect on the hydrolase activity; however, the enzyme was sensitive to HgCl2. Serine reagents, such as diethyl-p-nitrophenyl phosphate (E600) and diisopropyl fluorophosphate (DFP), used in 100-fold molar excess completely inhibited the activity, suggesting that it is a serine esterase. These results suggest that the enzyme may participate in the intracellular neutral lipid metabolism since the enzyme is located in the endoplasmic reticulum, an organelle where de novo triacylglycerol synthesis and assembly of lipoproteins take place.
A rapid genetic screening system for identifying gene-specific suppression constructs for use in human cells (2000)

We describe a rapid cell-based genetic screen using fission yeast for identifying efficient gene suppression constructs (GSCs) from large libraries (10(5)) for any target sequence for use in human cells. In this system, target sequences are fused to the 5' end of the lacZ reporter gene and expressed in yeast. Random fragment expression libraries derived from the target sequence are screened in the fusion gene-expressing strain using the lacZ gene-encoded colony color phenotype. We demonstrate the utility of this screening assay by identifying a range of different GSCs for the fission yeast ura4 gene and human c-myc and Chk1 sequences, including rare efficient suppressors. GSCs specific for c-myc were shown to regulate expression of both a c-myc-lacZ fusion gene and the endogenous c-myc gene in human cells.
Inhibitors and Breakers of Advanced Glycation Endproducts (AGEs): A Review (2002)

Advanced glycation end products (AGEs) are a complex, heterogeneous, sugar derived protein modification that have been implicated in the pathogenesis of diabetic complications, atherosclerosis, Alzheimers disease and in the process of normal aging. A large number of compounds as inhibitors of glycation and AGE-protein crosslink formation have been reported and currently being developed by us and others. We have previously reported two new classes of compounds; aryl-(and heterocyclic) ureido and aryl (and heterocyclic) carboxamido phenoxy isobutyric acids, and benzoic acid derivatives and related compounds as novel inhibitors of glycation and AGE formation. Additionally, investigation for selectively cleaving and breaking the existing AGEderived cross-links on tissue proteins by pharmacological strategies has been started. Most recently, we have developed several compounds with the ability of breaking AGE-protein cross-links that form in vitro with collagen and β-amyloid peptides, and in vivo with collagen and IgG on the surface of red blood cells of induced diabetic rats. Evidence is that both chelation of transition metals and trapping of reactive carbonyl or dicarbonyl intermediates are involved in the mechamisms of action of these novel AGE-inhibitors and breakers. Here we review the inhibitors of glycation and AGEbreakers published to date and describe a number of new inhibitors and AGE-cross-link-breakers not reported previously. These “AGE-inhibitors” and “AGE-breakers” may find therapeutic use in the treatment of diseases that AGE-formation and accumulation may be responsible for their pathogenesis such as diabetes, Alzheimers, rheumatoid arthritis and atherosclerosis.
A Reliable and Reproducible ELISA Method to Measure Ristocetin Cofactor Activity of von Willebrand Factor (2000)

The ristocetin induced binding of vWF to GPIb, which is routinely tested in a platelet agglutination assay, can be reproducibly studied in an ELISA where plasma vWF binds to a captured rGPIb alpha-fragment (His1-Val289) in the presence of ristocetin. This binding is specific since the vWF-GPIb interaction could (i) be blocked by inhibitory anti-GPIb or anti-(vWF A1 domain) monoclonal antibodies (mAbs) and (ii) be enhanced by an anti-vWF mAb that also facilitates ristocetin induced platelet agglutination. Further studies were undertaken to determine whether the test could be used to differentiate vWF from patients with different types of von Willebrand's disease. The median vWF:RiCof activity in controls (n = 24) was 0.75 U/ml, in type 1 vWD patients (n = 17) 0.28 U/ml, in type 2A (n = 18) 0.055 U/ml, in type 2B (n = 4) 0.094 U/ml and in type 3 (n = 3) <0.0005 U/ml. Moreover, the values correlated well with those obtained from the vWF:RiCof-agglutination assay (r = 0.873). The vWF:RiCof-ELISA has several advantages: the use of a recombinant fragment instead of donor platelets results in a more reproducible test with a low inter- and intra-assay variability (<14% CV), the test can further be readily automated and for a single determination, only minimal amounts of patient plasma are required (8 microl).
Macrocycles In New Drug Discovery (2012)

The use of drug-like macrocycles is emerging as an exciting area of medicinal chemistry, with several recent examples highlighting the favorable changes in biological and physicochemical properties that macrocyclization can afford. Natural product macrocycles and their synthetic derivatives have long been clinically useful and attention is now being focused on the wider use of macrocyclic scaffolds in medicinal chemistry in the search for new drugs for increasingly challenging targets. With the increasing awareness of concepts of drug-likeness and the dangers of 'molecular obesity', functionalized macrocyclic scaffolds could provide a way to generate ligand-efficient molecules with enhanced properties. In this review we will separately discuss the effects of macrocyclization upon potency, selectivity and physicochemical properties, concentrating on recent case histories in oncology drug discovery. Additionally, we will highlight selected advances in the synthesis of macrocycles and provide an outlook on the future use of macrocyclic scaffolds in medicinal chemistry.
Use of the KlADH4 Promoter for Ethanol-Dependent Production of Recombinant Human Serum Albumin in Kluyveromyces lactis (1999)

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity which is specifically induced by ethanol. The promoter of this gene was used for the expression of heterologous proteins in K. lactis, a very promising organism which can be used as an alternative host to Saccharomyces cerevisiae due to its good secretory properties. In this paper we report the ethanol-driven expression in K. lactis of the bacterial beta-glucuronidase and of the human serum albumin (HSA) genes under the control of the KlADH4 promoter. In particular, we studied the extracellular production of recombinant HSA (rHSA) with integrative and replicative vectors and obtained a significant increase in the amount of the protein with multicopy vectors, showing that no limitation of KlADH4 trans-acting factors occurred in the cells. By deletion analysis of the promoter, we identified an element (UASE) which is sufficient for the induction of KlADH4 by ethanol and, when inserted in the respective promoters, allows ethanol-dependent activation of other yeast genes, such as PGK and LAC4. We also analyzed the effect of medium composition on cell growth and protein secretion. A clear improvement in the production of the recombinant protein was achieved by shifting from batch cultures (0.3 g/liter) to fed-batch cultures (1 g/liter) with ethanol as the preferred carbon source.
Morphological abnormalities in the brains of estrogen receptor β knockout mice (2001)

Estrogen receptor beta (ERbeta) is expressed at high levels in both neurons and glial cells of the central nervous system. The development of ERbeta knockout (BERKO) mice has provided a model to study the function of this nuclear receptor in the brain. We have found that the brains of BERKO mice show several morphological abnormalities. There is a regional neuronal hypocellularity in the brain, with a severe neuronal deficit in the somatosensory cortex, especially layers II, III, IV, and V, and a remarkable proliferation of astroglial cells in the limbic system but not in the cortex. These abnormalities are evident as early as 2 mo of age in BERKO mice. As BERKO mice age, the neuronal deficit becomes more pronounced, and, by 2 yr of age, there is degeneration of neuronal cell bodies throughout the brain. This is particularly evident in the substantia nigra. We conclude that ERbeta is necessary for neuronal survival and speculate that this gene could have an important influence on the development of degenerative diseases of the central nervous system, such as Alzheimer's disease and Parkinson's disease, as well as those resulting from trauma and stroke in the brain.
Partial Chondrectomy and Subchondral Bone Drilling for Chondromalacia (1979)

Twenty-nine knees in 25 patients with chondromalacia patella resistant to conservative treatment were subjected to localized chondrectomy and subchondral bone plate drilling. Good or excellent results were achieved in most patients under the age of 30. The results in patients over the age of 30 were less satisfactory.