gebhart/patrepeval huggingface dataset:
Targeted mutagenesis using zinc-finger nucleases in Arabidopsis (2005)

Targeted mutagenesis is an essential tool of reverse genetics that could be used experimentally to investigate basic plant biology or modify crop plants for improvement of important agricultural traits. Although targeted mutagenesis is routine in several model organisms including yeast and mouse, efficient and widely usable methods to generate targeted modifications in plant genes are not currently available. In this study we investigated the efficacy of a targeted-mutagenesis approach based on zinc-finger nucleases (ZFNs). In this procedure, ZFNs are used to generate double-strand breaks at specific genomic sites, and subsequent repair produces mutations at the break site. To determine whether ZFNs can cleave and induce mutations at specific sites within higher plant genomes, we introduced a construct carrying both a ZFN gene, driven by a heat-shock promoter, and its target into the Arabidopsis genome. Induction of ZFN expression by heat shock during seedling development resulted in mutations at the ZFN recognition sequence at frequencies as high as 0.2 mutations per target. Of 106 ZFN-induced mutations characterized, 83 (78%) were simple deletions of 1-52 bp (median of 4 bp), 14 (13%) were simple insertions of 1-4 bp, and 9 (8%) were deletions accompanied by insertions. In 10% of induced individuals, mutants were present in the subsequent generation, thus demonstrating efficient transmission of the ZFN-induced mutations. These data indicate that ZFNs can form the basis of a highly efficient method for targeted mutagenesis of plant genes.
Alleviation of Both Binge Eating and Sexual Dysfunction With Naltrexone (2008)

Division of Psychosocial Oncology, and Palliative Care, Dana-Farber Cancer Institute, Boston, MA [email protected]
Regioisomers of 2 ,3 -dideoxynucleosides related to 2-(phosphonylmethoxy)ethyl nucleosides (1997)

Le 2,3-dideoxy-5-iodo-D-pentafuranoside de methyle a ete synthetise en quatre etapes a partir du 2-deoxy-D-ribose. Le nucleoside 5-phosphonate a ete synthetise par une reaction d'Arbuzov entre le 5-iodo sucre et le phosphite de triethyle, suivie d'une condensation avec la thymine et la N4-isobutyrylcytosine. Les regioisomeres du phosphonate en position 1' et les bases en position 5' sont synthetises par reaction de la base avec le sucre 5-tosyl suivie d'une reaction avec le phosphite de triethyle, en utilisant le TMSOTf comme catalyseur. Les phosphonates de diethyle sont ensuite liberes par utilisation du bromotrimethylsilane.
Argonaute of the archaeon Pyrococcus furiosus is a DNA-guided nuclease that targets cognate DNA (2015)

Functions of prokaryotic Argonautes (pAgo) have long remained elusive. Recently, Argonautes of the bacteria Rhodobacter sphaeroides and Thermus thermophilus were demonstrated to be involved in host defense. The Argonaute of the archaeon Pyrococcus furiosus (PfAgo) belongs to a different branch in the phylogenetic tree, which is most closely related to that of RNA interference-mediating eukaryotic Argonautes. Here we describe a functional and mechanistic characterization of PfAgo. Like the bacterial counterparts, archaeal PfAgo contributes to host defense by interfering with the uptake of plasmid DNA. PfAgo utilizes small 5'-phosphorylated DNA guides to cleave both single stranded and double stranded DNA targets, and does not utilize RNA as guide or target. Thus, with respect to function and specificity, the archaeal PfAgo resembles bacterial Argonautes much more than eukaryotic Argonautes. These findings demonstrate that the role of Argonautes is conserved through the bacterial and archaeal domains of life and suggests that eukaryotic Argonautes are derived from DNA-guided DNA-interfering host defense systems.
Shortest-path queries in static networks (2014)

We consider the point-to-point (approximate) shortest-path query problem , which is the following generalization of the classical single-source (SSSP) and all-pairs shortest-path (APSP) problems: we are first presented with a network (graph) . A so-called preprocessing algorithm may compute certain information (a data structure or index) to prepare for the next phase. After this preprocessing step, applications may ask shortest-path or distance queries, which should be answered as fast as possible. Due to its many applications in areas such as transportation, networking, and social science, this problem has been considered by researchers from various communities (sometimes under different names): algorithm engineers construct fast route planning methods; database and information systems researchers investigate materialization tradeoffs , query processing on spatial networks , and reachability queries ; and theoretical computer scientists analyze distance oracles and sparse spanners . Related problems are considered for compact routing and distance labeling schemes in networking and distributed computing and for metric embeddings in geometry as well. In this survey, we review selected approaches, algorithms, and results on shortest-path queries from these fields, with the main focus lying on the tradeoff between the index size and the query time. We survey methods for general graphs as well as specialized methods for restricted graph classes, in particular for those classes with arguable practical significance such as planar graphs and complex networks.
Adjuvanticity of Dimethyl Dioctadecyl Ammonium Bromide in Guinea Pigs (1982)

The effect of the adjuvant dimethyl dioctadecyl ammonium bromide (DDA) on the induction of cellular immunity in guinea pigs was studied. DDA, a surface-active lipid, was mixed with the antigen bovine serum albumin (BSA) or with a conjugate of BSA and dinitrophenol (DNP22--BSA) and injected into the footpads of guinea pigs. At varying intervals skin tests were performed to test the immediate and delayed hypersensitivity (DH) reactions. Optimal DH reactions to BSA were observed from 3 to 6 weeks after immunization with BSA in DDA. The hapten-specific response to DNP22--BSA had an optimum at 3 weeks and was highly specific for the homologous antigen. Histological examinations of skin test sites confirmed that the reaction was rather of the tuberculin type than of the cutaneous basophil hypersensitivity type. When guinea pigs were immunized with DNP22--BSA in Freund's complete adjuvant (FCA) a long-lasting DH to both carrier and hapten groups developed but the DH was always complicated by an Arthus reaction due to antibodies to the DNP hapten. In conclusion, DDA is superior to FCA as adjuvant for the induction of a state of pure DH in guinea pigs.
[Strong connection between malnutrition, inflammation and arteriosclerosis. Improved treatment of renal failure if underlying factors are attacked]. (1999)

Malnutrition, inflammation and atherosclerotic cardiovascular disease occur at high prevalence, and often concomitantly, in conjunction with chronic renal failure. Several features of malnutrition (e.g., increased oxidative stress, increased plasma levels of fibrinogen, Lp(a), and inflammation) may all, alone or in concert, increase the risk of cardiovascular disease. Recent findings suggest malnutrition and hypoalbuminaemia in chronic renal failure to be largely the consequence of such factors as heart failure, chronic infection and inflammation, that simultaneously trigger the development of atherosclerotic cardiovascular disease. Central to this scenario is the involvement of proinflammatory cytokines which may cause muscle wasting, hypoalbuminaemia, anorexia, and accelerated atherosclerosis. It is unlikely that the high mortality due to atherosclerotic disease among patients with chronic renal failure can be substantially reduced unless new treatment strategies are developed which address the complex relationships that exist between malnutrition, inflammation and cardiovascular disease.
HER2 RNA Aptamer‐ and Cell Penetrating Peptide‐Mediated Delivery of Multimeric Antisense Strands of siRNAs for Gene Silencing (2016)

In this study, we describe the development of a new siRNA delivery method for enhanced gene silencing, which is based on HER2 RNA aptamer‐ and cell penetrating peptide (CPP)‐mediated intracellular delivery of multimeric antisense strands of siRNAs . By making use of HER2 RNA aptamer or peptide nucleic acid‐linked CPP as delivery moiety for multimeric antisense strands of siRNAs , the multimeric siRNAs were observed to show significant gene silencing effects even without any delivery vehicles, in comparison with the conventional duplexed monomeric siRNAs mixed with lipofectamine. Our observations suggest that the introduction of RNA aptamer or CPP to multimeric siRNA as delivery moiety of siRNA delivery system can allow efficient target gene suppression with slow and steady but persistent intracellular uptake capacity.
Identification of N-Linked Glycosylation Sites in Human Testis Angiotensin-converting Enzyme and Expression of an Active Deglycosylated Form (1997)

The sites of glycosylation of Chinese hamster ovary cell expressed testicular angiotensin-converting enzyme (tACE) have been determined by matrix-assisted laser desorption ionization/time of flight/mass spectrometry of peptides generated by proteolytic and cyanogen bromide digestion. Two of the seven potential N-linked glycosylation sites, Asn90 and Asn109, were found to be fully glycosylated by analysis of peptides before and after treatment with a series of glycosidases and with endoproteinase Asp-N. The mass spectra of the glycopeptides exhibit characteristic clusters of peaks which indicate the N-linked glycans in tACE to be mostly of the biantennary, fucosylated complex type. This structural information was used to demonstrate that three other sites, Asn155, Asn337, and Asn586, are partially glycosylated, whereas Asn72 appears to be fully glycosylated. The only potential site that was not modified is Asn620. Sequence analysis of tryptic peptides obtained from somatic ACE (human kidney) identified six glycosylated and one unglycosylated Asn. Only one of these glycosylation sites had a counterpart in tACE. Comparison of the two proteins reveals a pattern in which amino-terminal N-linked sites are preferred. The functional significance of glycosylation was examined with a tACE mutant lacking the O-glycan-rich first amino-terminal 36 residues and truncated at Ser625. When expressed in the presence of the alpha-glucosidase I inhibitor N-butyldeoxynojirimycin and treated with endoglycosidase H to remove all but the terminal N-acetylglucosamine residues, it retained full enzymatic activity, was electrophoretically homogeneous, and is a good candidate for crystallographic studies.
Evaluation of the Magnitude and Rate of Nitric Oxide Production from Nitrite in Biological Systems (1998)

Recently it was shown that the formation of nitric oxide (NO) is increased in biological tissues during ischemia, and that there is an enzyme-independent pathway of NO generation due to reduction of tissue nitrite under the acidic conditions which occur. To investigate the quantitative importance of this mechanism of NO generation in biological systems where pH and nitrite concentrations vary, electron paramagnetic resonance and chemiluminescence studies were performed to characterize the kinetics and magnitude of the nitrite disproportionation process. The reaction process and the corresponding rate law of NO formation from nitrite were derived. The generation and accumulation of NO from typical nitrite concentrations found in biological tissues increased 100-fold when pH decreased from normal values of 7.4 to the acidic values found in ischemic tissues, such as the heart, where pH falls to 5.5. It was also observed that ischemic heart tissue contains reducing equivalents which reduce nitrite to NO, further increasing the rate of NO formation more than 40-fold. Under these conditions the magnitude of this enzyme-independent NO generation may exceed that which can be generated by tissue concentrations of nitric oxide synthase. Thus, in ischemic tissues nitrite can be primarily a source rather than a product of NO.
Influence of major histocompatibility complex class I and II antigens on survival in colorectal carcinoma. (1991)

HLA-A,B,C and HLA-D molecules present antigenic peptides to the antigen-specific receptor of autologous T-lymphocytes. T-cell-mediated host-versus-tumor response might therefore depend on the presence of these molecules on tumor cells, although the absence of HLA-A,B,C determinants on a cell has been shown to increase its susceptibility to lysis by natural killer cells. To investigate whether the presence or absence of HLA-A,B,C and/or HLA-DR in colorectal carcinoma influences relapse rate and time of tumor-related death, 152 patients who underwent putatively curative surgical treatment were surveyed for a maximum of 65 months (mean, 48 months). As determined by immunohistochemistry, aberrant reduction or loss of HLA-A,B,C/beta 2-microglobulin molecules was more frequent in tumors of the proximal colon than of the rectosigmoid (P = 0.032) and in mucinous carcinomas than in nonmucinous ones (P = 0.022). An abnormal induction of the HLA-D-associated invariant chain (Ii) was more frequent in Dukes' A and B than in stage C (P = 0.046). Reduction/loss of HLA-A,B,C/beta 2-microglobulin was correlated with the absence of HLA-DR (P = 0.024) and Ii (P = 0.005). In contrast to the prognostic role of tumor stage and grade, the presence versus the absence of HLA-A,B,C/beta 2-microglobulin and HLA-DR/Ii molecules was not correlated with recurrence rate or survival. We conclude that in spite of an increasing amount of experimental data suggesting the contrary, the status of HLA-A,B,C and HLA-DR expression in colorectal carcinoma seems to be irrelevant in vivo, regarding survival and growth of residual tumor cells after putatively curative resection of the initial tumor burden.
Scriptaid Corrects Gene Expression of a Few Aberrantly Reprogrammed Transcripts in Nuclear Transfer Pig Blastocyst Stage Embryos (2011)

Nuclear transfer efficiency in the pig is low and is thought to be caused by inadequate nuclear reprogramming. The objective of this study was to identify differentially represented transcripts in pig in vivo derived (BLIVV), in vitro fertilized (BLIVF), or nuclear transfer derived (NT, three different activation methods) blastocyst stage embryos and the donor cell line by microarray analysis, and to determine if treatment of reconstructed embryos with the histone deacetylase inhibitor, Scriptaid (NTS), for 14 h postactivation would correct gene expression in a subset of the identified aberrantly reprogrammed transcripts. There were 1481 differentially expressed transcripts when comparing all six treatment groups (p < 0.05). Transcripts that were different between BLIVV and NT (p < 0.20) and significantly different from donor cells (p < 0.05) were classified as being aberrantly reprogrammed (179 transcripts). Fourteen transcripts were chosen to determine the effect of Scriptaid treatment. After real-time PCR relative gene expression was compared among BLIVV, NT pool, cells, and NTS by the comparative Ct method, statistical analysis was performed in SAS 9.1 (p < 0.05). NTS embryos had three transcripts returning to the same level as BLIVV (H3F3A, CAPG, and SEPT7). Half of the transcripts (7/14) were not affected by NTS treatment, for example, SIRT1 and H1F0. Scriptaid treatment resulted high expression of COX5A and very low expression of GPD1L, EIF3E, and GSTA3. Scriptaid also reduced the number of 5-Methylcytidine-positive nuclei in blastocyst stage embryos (p < 0.0003). Scriptaid treatment significantly affected gene expression in 7 of the 14 transcripts evaluated and returned 3 genes to BLIVV levels.
N-Linked Protein Glycosylation in a Bacterial System (2009)

N-Linked protein glycosylation is conserved throughout the three domains of life and influences protein function, stability, and protein complex formation. N-Linked glycosylation is an essential process in Eukaryotes; however, although N-glycosylation affects multiple cellular processes in Archaea and Bacteria, it is not needed for cell survival. Methods for the analyses of N-glycosylation in eukaryotes are well established, but comparable techniques for the analyses of the pathways in Bacteria and Archaea are needed. In this chapter we describe new methods for the detection and analyses of N-linked, and the recently discovered free oligosaccharides (fOS), from whole cell lysates of Campylobacter jejuni using non-specific pronase E digestion and permethylation followed by mass spectrometry. We also describe the expression and immunodetection of the model N-glycoprotein, AcrA, fused to a hexa-histidine tag to follow protein glycosylation in C. jejuni. This chapter concludes with the recent demonstration that high-resolution magic angle spinning NMR of intact bacterial cells provides a rapid, non-invasive method for analyzing fOS in C. jejuni in vivo. This combination of techniques provides a powerful tool for the exploration, quantification, and structural analyses of N-linked and free oligosaccharides in the bacterial system.
The SCID Mouse Mutant: Definition, Characterization, and Potential Uses (1991)

Mice homozygous for the scid mutation (scid mice) are severely deficient in functional B and T lymphocytes. The mutation appears to impair the recombination of antigen receptor genes and thereby causes an arrest in the early development of B and T lineage-committed cells; other hematopoietic cell types appear to develop and function normally. The arrest in lymphocyte development is not absolute; some young adult scid mice are "leaky" and generate a few clones of functional B and T cells. By 10-14 months of age, virtually all scid mice are leaky. Scid mice readily support normal lymphocyte differentiation and can be reconstituted with normal lymphocytes from other mice and even partially reconstituted with human lymphocytes. They also support the growth of allogeneic and xenogeneic tumors. Thus, scid mice are of interest for studies of both normal and abnormal lymphocyte development and function. In addition, they can be used to study the function of nonlymphoid cell types in the absence of lymphocytes.
Highly Tunable Colloidal Perovskite Nanoplatelets through Variable Cation, Metal, and Halide Composition (2016)

Colloidal perovskite nanoplatelets are a promising class of semiconductor nanomaterials-exhibiting bright luminescence, tunable and spectrally narrow absorption and emission features, strongly confined excitonic states, and facile colloidal synthesis. Here, we demonstrate the high degree of spectral tunability achievable through variation of the cation, metal, and halide composition as well as nanoplatelet thickness. We synthesize nanoplatelets of the form L2[ABX3]n-1BX4, where L is an organic ligand (octylammonium, butylammonium), A is a monovalent metal or organic molecular cation (cesium, methylammonium, formamidinium), B is a divalent metal cation (lead, tin), X is a halide anion (chloride, bromide, iodide), and n-1 is the number of unit cells in thickness. We show that variation of n, B, and X leads to large changes in the absorption and emission energy, while variation of the A cation leads to only subtle changes but can significantly impact the nanoplatelet stability and photoluminescence quantum yield (with values over 20%). Furthermore, mixed halide nanoplatelets exhibit continuous spectral tunability over a 1.5 eV spectral range, from 2.2 to 3.7 eV. The nanoplatelets have relatively large lateral dimensions (100 nm to 1 μm), which promote self-assembly into stacked superlattice structures-the periodicity of which can be adjusted based on the nanoplatelet surface ligand length. These results demonstrate the versatility of colloidal perovskite nanoplatelets as a material platform, with tunability extending from the deep-UV, across the visible, into the near-IR. In particular, the tin-containing nanoplatelets represent a significant addition to the small but increasingly important family of lead- and cadmium-free colloidal semiconductors.
Reactions of alkyl (halomethyl)furancarboxylates with hexamethylenetetramine (2006)

All isomers of (aminomethyl)furancarboxylic acids were prepared by the Delepine reaction from alkyl (halomethyl)furancarboxylates. Treatment of the initially formed quaternary salt with an ethanolic HCl solution yielded the salts of the corresponding unstable amino acid esters. A procedure for their purification to a high degree of purity was developed. Hydrolysis of the crude esters yielded stable amino acid salts.
A synthetic O2‐tolerant butanol pathway exploiting native fatty acid biosynthesis in Escherichia coli (2014)

Several synthetic metabolic pathways for butanol synthesis have been reported in Escherichia coli by modification of the native CoA-dependent pathway from selected Clostridium species. These pathways are all dependent on the O2 -sensitive AdhE2 enzyme from Clostridium acetobutylicum that catalyzes the sequential reduction of both butyryl-CoA and butyraldehyde. We constructed an O2 -tolerant butanol pathway based on the activities of an ACP-thioesterase, acting on butyryl-ACP in the native fatty acid biosynthesis pathway, and a promiscuous carboxylic acid reductase. The pathway was genetically optimized by screening a series of bacterial acyl-ACP thioesterases and also by modification of the physical growth parameters. In order to evaluate the potential of the pathway for butanol production, the ACP-dependent butanol pathway was compared with a previously established CoA-dependent pathway. The effect of (1) O2 -availability, (2) media, and (3) co-expression of aldehyde reductases was evaluated systematically demonstrating varying and contrasting functionality between the ACP- and CoA-dependent pathways. The yield of butanol from the ACP-dependent pathway was stimulated by enhanced O2 -availability, in contrast to the CoA-dependent pathway, which did not function well under aerobic conditions. Similarly, whilst the CoA-dependent pathway only performed well in complex media, the ACP-dependent pathway was not influenced by the choice of media except in the absence of O2 . A combination of a thioesterase from Bacteroides fragilis and the aldehyde reductase, ahr, from E. coli resulted in the greatest yield of butanol. A product titer of ~300 mg/L was obtained in 24 h under optimal batch growth conditions, in most cases exceeding the performance of the reference CoA-pathway when evaluated under equivalent conditions.
Peripheral Inflammatory Biomarkers and Risk of Parkinson's Disease (2007)

Experimental and postmortem evidence indicates a role of neuroinflammation in the pathogenesis of Parkinson's disease. The authors prospectively examined whether plasma concentrations of inflammatory biomarkers assessed before Parkinson's disease diagnosis were predictive of future risk of the disease in a nested case-control study in the United States (1993-2002), including 84 incident cases and 165 matched controls. Blood was collected from patients on average 4.3 years before the diagnosis. After adjustment for potential confounders, higher level of interleukin-6 was associated with a greater risk of Parkinson's disease. Compared with the lowest quintile, the odds ratios were 1.5 for the second, 1.6 for the third, 2.7 for the fourth, and 3.4 for the fifth quintiles (p for trend = 0.03). In contrast, concentrations of other inflammatory biomarkers including C-reactive protein, fibrinogen, and tumor necrosis factor-alpha receptors were not related to the risk. These data suggest that men with high plasma concentrations of interleukin-6 have an increased risk of developing Parkinson's disease. However, this finding should be interpreted with caution because of the small sample size and the lack of associations with other biomarkers of inflammation.