gebhart/patrepeval huggingface dataset:
Production of Recombinant β-Hexosaminidase A, a Potential Enzyme for Replacement Therapy for Tay-Sachs and Sandhoff Diseases, in the Methylotrophic Yeast Ogataea minuta (2007)

Human beta-hexosaminidase A (HexA) is a heterodimeric glycoprotein composed of alpha- and beta-subunits that degrades GM2 gangliosides in lysosomes. GM2 gangliosidosis is a lysosomal storage disease in which an inherited deficiency of HexA causes the accumulation of GM2 gangliosides. In order to prepare a large amount of HexA for a treatment based on enzyme replacement therapy (ERT), recombinant HexA was produced in the methylotrophic yeast Ogataea minuta instead of in mammalian cells, which are commonly used to produce recombinant enzymes for ERT. The problem of antigenicity due to differences in N-glycan structures between mammalian and yeast glycoproteins was potentially resolved by using alpha-1,6-mannosyltransferase-deficient (och1Delta) yeast as the host. Genes encoding the alpha- and beta-subunits of HexA were integrated into the yeast cell, and the heterodimer was expressed together with its isozymes HexS (alphaalpha) and HexB (betabeta). A total of 57 mg of beta-hexosaminidase isozymes, of which 13 mg was HexA (alphabeta), was produced per liter of medium. HexA was purified with immobilized metal affinity column for the His tag attached to the beta-subunit. The purified HexA was treated with alpha-mannosidase to expose mannose-6-phosphate (M6P) residues on the N-glycans. The specific activities of HexA and M6P-exposed HexA (M6PHexA) for the artificial substrate 4MU-GlcNAc were 1.2 +/- 0.1 and 1.7 +/- 0.3 mmol/h/mg, respectively. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern suggested a C-terminal truncation in the beta-subunit of the recombinant protein. M6PHexA was incorporated dose dependently into GM2 gangliosidosis patient-derived fibroblasts via M6P receptors on the cell surface, and degradation of accumulated GM2 ganglioside was observed.
Recruitment of American eels in the Richelieu River and Lake Champlain: Provision of upstream passage as a regional-scale solution to a large-scale problem (2002)

125-138
Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates (1987)

A method is described to synthesize small RNAs of defined length and sequence using T7 RNA polymerase and templates of synthetic DNA which contain the T7 promoter. Partially single stranded templates which are base paired only in the -17 to +1 promoter region are just as active in transcription as linear plasmid DNA. Runoff transcripts initiate at a unique, predictable position, but may have one nucleotide more or less on the 3' terminus. In addition to the full length products, the reactions also yield a large amount of smaller oligoribonucleotides in the range from 2 to 6 nucleotides which appear to be the result of abortive initiation events. Variants in the +1 to +6 region of the promoter are transcribed with reduced efficiency but increase the variety of RNAs which can be made. Transcription reaction conditions have been optimized to allow the synthesis of milligram amounts of virtually any RNA from 12 to 35 nucleotides in length.
Nucleotide sequence of a member of the napin storage protein family from Brassica napus. (1987)

We have begun the molecular characterization of genes encoding napin, the 1.7 S embryo-specific storage protein of Brassica napus. Genomic Southern blot analysis indicates that napin is encoded by a multigene family comprised of a minimum of 16 genes. Two DNA fragments containing single napin genes have been recovered from B. napus genomic libraries. We have determined the nucleotide sequence of one member of the napin gene family, gNa. The gene has a simple structure lacking introns and containing the canonical features expected for genes transcribed by RNA polymerase II. The site of the initiation of transcription was determined to be 37 base pairs upstream of the initiation codon by S1 and primer extension analyses. A gene-specific hybridization probe from the 3' non-translated portion of gNa was used to demonstrate transcription of gNa.
Telomerase activity in lesions of the thyroid: application to diagnosis of clinical samples including fine-needle aspirates. (1998)

The telomerase enzyme is capable of replacing telomeric DNA sequences that are lost at each cell division. It has been suggested that the function of this enzyme is necessary for cells to become immortal, and in concordance with this hypothesis, telomerase activity has been detected in malignant tumor cells, whereas the enzyme is inactive in normal somatic cells. The measurement of this activity in human tissue samples may have diagnostic value, and in this study, we examined whether such a measurement may be useful for the detection of malignant cells within the thyroid. Telomerase activity was assayed using the telomeric repeat amplification protocol and related to the histological diagnosis of thyroid biopsy tissue samples and of cells obtained from the thyroid by fine-needle aspiration (FNA). Extracts from 9 of 11 (82%) carcinoma biopsy tissue samples contained telomerase activity, whereas enzyme activity was detected in only 2 of 14 (14%) benign tissue sample extracts. These two positive cases were subsequently diagnosed as Graves' disease with severe lymphocytic infiltration. Five of six (83.3%) histologically confirmed carcinoma FNA samples were identified by using the telomeric repeat amplification protocol assay, and two samples considered to be suspicious by FNA cytology were also positive. Conversely, only 4 of 48 (8.3%) benign FNA samples had telomerase. These promising data indicate that this sensitive assay could become a useful adjunct to microscopic cytopathology in the detection of cancer cells in small tissue biopsies and in fine-needle aspirates of the thyroid.
Adeno-associated virus vector for high-frequency integration, expression, and rescue of genes in mammalian cells. (1985)

We describe the construction of an adeno-associated virus (AAV) vector in which the coding sequence of the procaryotic gene neo is expressed under the control of the major AAV promoter p40. This AAV-neo vector allowed stable expression of neo as a dominant selective marker in mammalian cells by selection of cells which were resistant to the antibiotic geneticin (G418). When the vector was introduced into human (293 or HeLa) cell lines by a DNA transfection procedure, stable geneticin-resistant colonies were obtained. When the vector was first packaged into AAV particles and then introduced into cells via particle infection, geneticin-resistant cells were obtained at higher frequencies than those obtained by DNA transfection. In geneticin-resistant cells the AAV-neo vector was integrated at low copy number and could be rescued by subsequent infection with wild-type AAV and the helper adenovirus or, in some cases, by infection with adenovirus alone. The rescued AAV-neo vector could then be recovered as amplified unintegrated DNA from a Hirt lysate. These results demonstrate that AAV can be used as a transducing viral vector for stable integration and expression of a foreign gene in mammalian cells. The high frequency of integration and the ability to rescue the integrated vector suggest that this vector system may be useful for selecting genes from cDNA libraries. This vector may also be useful for introduction of genes into cells which are refractory to transfection in procedures such as those involving the use of CaPO4 or DEAE-dextran.
Design of Selective Peptidomimetic Agonists for the Human Orphan Receptor BRS-3 (2003)

New tool substances may help to unravel the physiological role of the human orphan receptor BRS-3 and its possible use as a drug target for the treatment of obesity and cancer. In continuation of our work on BRS-3, the solid- and solution-phase synthesis of a library of low molecular weight peptidomimetic agonists based on the recently developed short peptide agonist 4 is described. Functional potencies of the compounds were determined measuring calcium mobilization in a fluorometric imaging plate reader (FLIPR) assay. Focusing on the N-terminus, the d-Phe-Gln moiety of 4 was modified in a combinatorial SAR-oriented medicinal chemistry approach. With the incorporation of N-arylated glycine and alanine building blocks azaglycine, piperazine, or piperidine and the synthesis of semicarbazides and semicarbazones, a number of highly potent and selective compounds with a reduced number of peptide bonds were obtained, which also should have enhanced metabolic stability.
GDF11 Forms a Bone Morphogenetic Protein 1-Activated Latent Complex That Can Modulate Nerve Growth Factor-Induced Differentiation of PC12 Cells (2005)

All transforming growth factor beta (TGF-beta) superfamily members are synthesized as precursors with prodomain sequences that are proteolytically removed by subtilisin-like proprotein convertases (SPCs). For most superfamily members, this is believed sufficient for activation. Exceptions are TGF-betas 1 to 3 and growth differentiation factor 8 (GDF8), also known as myostatin, which form noncovalent, latent complexes with their SPC-cleaved prodomains. Sequence similarities between TGF-betas 1 to 3, myostatin, and superfamily member GDF11, also known as bone morphogenetic protein 11 (BMP11), prompted us to examine whether GDF11 might be capable of forming a latent complex with its cleaved prodomain. Here we demonstrate that GDF11 forms a noncovalent latent complex with its SPC-cleaved prodomain and that this latent complex is activated via cleavage at a single specific site by members of the developmentally important BMP1/Tolloid family of metalloproteinases. Evidence is provided for a molecular model whereby formation and activation of this complex may play a general role in modulating neural differentiation. In particular, mutant GDF11 prodomains impervious to cleavage by BMP1/Tolloid proteinases are shown to be potent stimulators of neurodifferentiation, with potential for therapeutic applications.
Serum levels of C‐reactive protein in Crohn's disease and ulcerative colitis (1982)

Prospective measurements were made of serum C-reactive protein levels and erythrocyte sedimentation rate in sixty-four patients with Crohn's disease and fifty with ulcerative colitis. The results were related to clinical assessment of disease activity. C-reactive protein levels were raised in both groups but were significantly higher in Crohn's disease than ulcerative colitis for all categories of disease severity: with mild disease the median and range of C-reactive protein concentration were 4, 0-65 mg/l in Crohn's disease v. 0, 0-15 mg/l in ulcerative colitis, P less than 0.01; in moderate disease the values were 15, 1-100 mg/l v. 3, 0-29 mg/l respectively, P less than 0.05 and in cases of severe disease, 85, 15-183 mg/l v. 12, 2-33 mg/l respectively, P less than 0.001. Erythrocyte sedimentation rate was also higher in Crohn's disease but did not closely reflect disease activity in individual patients. C-reactive protein levels corresponded closely with clinical and pathological indices of relapse, remission and response to therapy in patients with Crohn's disease. The precise assay of serum C-reactive protein provides an objective criterion of inflammatory activity, which may be useful in the assessment, management and study of Crohn's disease.
Association Between Iron Deficiency and A1C Levels Among Adults Without Diabetes in the National Health and Nutrition Examination Survey, 1999–2006 (2010)

Iron deficiency is common among women and is associated with shifts in A1C distribution from <5.5 to > or =5.5%. Further research is needed to examine whether iron deficiency is associated with shifts at higher A1C levels.
Electronic Communication by Deaf Teenagers (2005)

We present a qualitative, exploratory study to examine the space of electronic based communication (e.g. instant messaging, short message service, email) by Deaf teenagers in the greater Atlanta metro area. We answer the basic questions of who, what, where, when, and how to understand Deaf teenage use of electronic, mobile communication technologies. Our findings reveal that both Deaf and hearing teens share similar communication goals such as communicating quickly, effectively, and with a variety of people. Distinctions between the two populations emerge from language differences. The teenagers perspectives allow us to view electronic communication not from a technologist's point of view, but from the use-centric view of teenagers who are indifferent to the underlying infrastructure supporting this communication. This study suggests several unique features of the Deaf teens' communication as well as further research questions and directions for study.
Error driven word sense disambiguation (1998)

In this paper we describe a method for performing word sense disambiguation (WSD). The method relies on unsupervised learning and exploits functional relations among words as produced by a shallow parser. By exploiting an error driven rule learning algorithm (Brill 1997), the system is able to produce rules for WSD, which can be optionally edited by humans in order to increase the performance of the system.
Oligonucleotide therapy mitigates disease in spinocerebellar ataxia type 3 mice (2018)

This preclinical study established efficacy of ATXN3-targeted ASOs as a disease-modifying therapeutic strategy for SCA3. These results support further efforts to develop ASOs for human clinical trials in this polyglutamine disease as well as in other dominantly inherited disorders caused by toxic gain of function. Ann Neurol 2018;83:64-77.
Serum IL-6, TNFα and CRP levels in Greek colorectal cancer patients: Prognostic implications (2005)

Serum IL-6, TNFalpha and CRP levels definitely increase in CRC patients. Pre-operative serum elevation of IL-6 and CRP was thus found to be predictor of the prognosis of CRC patients. The clinical value of TNFalpha in CRC needs to be further investigated.
Inactivation of free and cell‐associated human immunodeficiency virus in platelet suspensions by aminomethyltrimethylpsoralen and ultraviolet light (1994)

These data suggest that AMT and UVA is an effective antiviral treatment for free and cell-associated HIV in platelet suspensions.
DNA TOPOISOMERASES (1996)

The various problems of disentangling DNA strands or duplexes in a cell are all rooted in the double-helical structure of DNA. Three distinct subfamilies of enzymes, known as the DNA topoisomerases, have evolved to solve these problems. This review focuses on work in the past decade on the mechanisms and cellular functions of these enzymes. Newly discovered members and recent biochemical and structural results are reviewed, and mechanistic implications of these results are summarized. The primary cellular functions of these enzymes, including their roles in replication, transcription, chromosome condensation, and the maintenance of genome stability, are then discussed. The review ends with a summary of the regulation of the cellular levels of these enzymes and a discussion of their association with other cellular proteins.
Tempol, a stable free radical, is a novel murine radiation protector. (1992)

Nitroxide compounds are stable free radicals which were previously investigated as hypoxic cell radiosensitizers. The stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) has recently been shown to protect aerated cells in culture against superoxide generated from hypoxanthine/xanthine oxidase, hydrogen peroxide, and radiation-induced cytotoxicity and to modestly sensitive hypoxic cultured cells. To extend these observations from the cellular level to the whole animal, the toxicity, pharmacology, and in vivo radioprotective effects of Tempol were studied in C3H mice. The maximum tolerated dose of Tempol administered i.p. was found to be 275 mg/kg, which resulted in maximal Tempol levels in whole blood 5-10 min after injection. Mice were exposed to whole-body radiation in the absence or presence of injected Tempol (275 mg/kg) 5-10 min after administration. Tempol treatment provided significant radioprotection (P less than 0.0001); the dose of radiation at which 50% of Tempol-treated mice die at 30 days was 9.97 Gy, versus 7.84 Gy for control mice. Tempol represents a new class of in vivo, non-sulfur-containing radiation protectors. Given the potential for hypoxic radiosensitization and aerobic cell radioprotection, Temporal or other analogues may have potential therapeutic application.
The vocabulary problem in human-system communication (1987)

In almost all computer applications, users must enter correct words for the desired objects or actions. For success without extensive training, or in first-tries for new targets, the system must recognize terms that will be chosen spontaneously. We studied spontaneous word choice for objects in five application-related domains, and found the variability to be surprisingly large. In every case two people favored the same term with probability &lt;0.20. Simulations show how this fundamental property of language limits the success of various design methodologies for vocabulary-driven interaction. For example, the popular approach in which access is via one designer's favorite single word will result in 80-90 percent failure rates in many common situations. An optimal strategy, unlimited aliasing, is derived and shown to be capable of several-fold improvements.
The Leptin-Deficient (ob/ob) Mouse (2006)

Whereas functional, metabolic, neurotrophic, and morphological abnormalities of peripheral diabetic neuropathy (PDN) have been extensively explored in streptozotocin-induced diabetic rats and mice (models of type 1 diabetes), insufficient information is available on manifestations and pathogenetic mechanisms of PDN in type 2 diabetic models. The latter could constitute a problem for clinical trial design because the vast majority of subjects with diabetes have type 2 (non-insulin dependent) diabetes. This study was aimed at characterization of PDN in leptin-deficient (ob/ob) mice, a model of type 2 diabetes with relatively mild hyperglycemia and obesity. ob/ob mice ( approximately 11 weeks old) clearly developed manifest sciatic motor nerve conduction velocity (MNCV) and hind-limb digital sensory nerve conduction velocity (SNCV) deficits, thermal hypoalgesia, tactile allodynia, and a remarkable ( approximately 78%) loss of intraepidermal nerve fibers. They also had increased sorbitol pathway activity in the sciatic nerve and increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in the sciatic nerve, spinal cord, and dorsal root ganglion (DRG). Aldose reductase inhibition with fidarestat (16 mg . kg(-1) . d(-1)), administered to ob/ob mice for 6 weeks starting from 5 weeks of age, was associated with preservation of normal MNCV and SNCV and alleviation of thermal hypoalgesia and intraepidermal nerve fiber loss but not tactile allodynia. Sciatic nerve nitrotyrosine immunofluorescence and the number of poly(ADP-ribose)-positive nuclei in sciatic nerve, spinal cord, and DRGs of fidarestat-treated ob/ob mice did not differ from those in nondiabetic controls. In conclusion, the leptin-deficient ob/ob mouse is a new animal model that develops both large motor and sensory fiber and small sensory fiber PDN and responds to pathogenetic treatment. The results support the role for increased aldose reductase activity in functional and structural changes of PDN in type 2 diabetes.
Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation (2010)

Adhesive interactions of leukocytes and endothelial cells initiate leukocyte migration to inflamed tissue and are important for immune surveillance. Acute and chronic inflammatory diseases show a dysregulated immune response and result in a massive efflux of leukocytes that contributes to further tissue damage. Therefore, targeting leukocyte trafficking may provide a potent form of anti-inflammatory therapy. Leukocyte migration is initiated by interactions of the cell adhesion molecules E-, L-, and P-selectin and their corresponding carbohydrate ligands. Compounds that efficiently address these interactions are therefore of high therapeutic interest. Based on this rationale we investigated synthetic dendritic polyglycerol sulfates (dPGS) as macromolecular inhibitors that operate via a multivalent binding mechanism mimicking naturally occurring ligands. dPGS inhibited both leukocytic L-selectin and endothelial P-selectin with high efficacy. Size and degree of sulfation of the polymer core determined selectin binding affinity. Administration of dPGS in a contact dermatitis mouse model dampened leukocyte extravasation as effectively as glucocorticoids did and edema formation was significantly reduced. In addition, dPGS interacted with the complement factors C3 and C5 as was shown in vitro and reduced C5a levels in a mouse model of complement activation. Thus, dPGS represent an innovative class of a fully synthetic polymer therapeutics that may be used for the treatment of inflammatory diseases.
Expression of I-Sce I in Drosophila to Induce DNA Double-Strand Breaks (2003)

Generation of double-strand breaks (DSBs) in chromosomal DNA induces repair machinery of a cell, and is also a necessary step for recombination events. A system for the directed introduction of DSBs into a genome could substantially facilitate progress in understanding DSB repair mechanisms and could be used for efficient gene targeting. The most successful attempts toward this goal in Drosophila have utilized the P element transposition system. However, directed introduction of DSBs is still neither highly precise nor efficient, probably in part owing to the innate properties of the P element transposase, which although being a site-specific DNA binding protein, also has an affinity for nonspecific DNA sequences in vitro (). As a result, DSBs generated by P element transposase are distributed randomly in the Drosophila genome with the highest frequency close to or at the P element ends. Site-specific endonucleases with sufficiently long recognition sequences potentially could provide a solution to this problem. Among the most specific is the I-Sce I endonuclease. It recognizes an 18-bp nonpalindromic sequence (see Chaper 37) and has very low tolerance to nucleotide substitution. Theoretically, this recognition site should appear only once in every 6.87×1010 bp, which exceeds the size of the Drosophila genome by about 400 times.
Characterization of the Deposition of Organic Molecules at the Surface of Gold by the Electrochemical Reduction of Aryldiazonium Cations (2005)

The deposition of 4-X phenyl groups (X = NO2, COOH, N-(C2H5)2) on polycrystalline gold electrode was achieved by the electrochemical reduction of the corresponding 4-substituted phenyldiazonium tetrafluoroborate salts in anhydrous acetonitrile media. The electrochemical quartz crystal microbalance measurements evidenced a two-step deposition process: the first one is the deposition of close to a monolayer and the second one is the relatively slower growth of multilayers. In this second region, the deposition is less efficient than for the first one. The electrochemical behavior of the resulting modified gold electrode was investigated in the presence of an electroactive redox probe and these results, together with the electrochemical quartz crystal microbalance data, demonstrated significant differences in reactivity and in deposition efficiency between the diazonium salts. The characterization of the modified electrodes by cyclic voltammetry and electrochemical impedance spectroscopy, as well as X-ray photoelectron spectroscopy measurements, showed that the formation of multilayers is possible and that a significant fraction of the deposited material remained at the electrode surface, even following ultrasonic treatment. The X-ray photoelectron spectroscopy data indicate that the existence of Au-C and Au-N=N-C linkages (where C represents a carbon atom of the phenyl group) is uncertain. Nonetheless, the deposition of the aryl groups by electrochemical reduction of diazonium cations yielded a film that adheres well to the gold surface and the deposited organic film hindered gold oxides formation in acidic medium.