gebhart/patrepeval huggingface dataset:
A Debranching Enzyme Deficiency in Endosperms of the Sugary-1 Mutants of Maize (1984)

Many of the sugary-1 mutants of maize (Zea mays L.) have the highly branched water-soluble polysaccharide, phytoglycogen, in quantities equal to or greater than starch as an endosperm storage product in mature seeds. We find that all sugary mutants investigated are deficient in debranching enzyme [alpha-(1, 6)-glucosidase] activity in endosperm tissue 23 days postpollination and suggest that this deficiency is the primary biochemical lesion leading to phytoglycogen accumulation in sugary endosperms. This would indicate that the amylopectin component of starch depends on an equilibrium between the activities of branching enzymes introducing alpha-1,6 branch points into the linear alpha-1,4 glucans and debranching enzymes. The debranching enzyme activities from nonsugary endosperms can be separated into three peaks on a hydroxyapatite column. The sugary endosperm extracts lack one of these peaks of activity while the other two fractions have much reduced activity. The embryos of developing seeds (23 days after pollination) from both sugary and nonsugary genotypes have equivalent debranching activity. The debranching enzyme activity of developing endosperms is proportional to the number of copies (0 to 3) of the nonmutant (Su) allele present suggesting that the Su allele may be the structural gene for this debranching enzyme, although this is not definitive. This identification of debranching enzyme activity as being the biochemical lesion in sugary endosperms is consistent with several previous observations on the mutant.
QuickLib, a method for building fully synthetic plasmid libraries by seamless cloning of degenerate oligonucleotides (2017)

Incorporation of synthetic degenerate oligonucleotides into plasmids for building highly diverse genetic libraries requires efficient and quantitative DNA manipulation. We present a fast and seamless method for generating libraries of PCR-synthesized plasmids designed with a degenerate sequence and short overlapping ends. Our method called QuickLib should find many applications in synthetic biology; as an example, we easily prepared genetic libraries of Escherichia coli expressing billions of different backbone cyclic peptides.
Disorders of Tetrahydrobiopterin Metabolism and their Treatment (2002)

Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine metabolism in liver and neurotransmitters biosynthesis in brain. BH4 is the essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine triphosphate (GTP) catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase, and sepiapterin reductase (SPR), and in aromatic amino acids hydoxylating system is regenerated by pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR). To date, 4 enzyme deficiencies (GTPCH, PTPS, DHPR, PCD) have been reported and they all follow an autosomal recessive mode of inheritance. The incidence of BH4 deficiency is at 1 in 1,000,000, except that in Taiwanese (much higher than in Japanese and Caucasians). BH4 deficiency has been diagnosed in patients with hyperphenylalaninemia (HPA) by neonatal mass-screening based on BH4 oral loading tests, analysis of urinary or serum pteridines, and measurement of dihydropterindine reductase (DHPR) activity in blood from a Guthrie card. BH4 deficiency without treatment causes combined symptoms of HPA and neurotransmitter (dopamine, norepinephrine, epinephrine, and serotonin) deficiency, such as red hair, psychomotor retardation, and progressive neurological deterioration. Treatment of BH4 deficiencies consists of BH4 supplementation (2-20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precausers (L-dopa/CarbiDOPA and 5-hydroxytryptophan), and supplements of folinic acid in DHPR deficiency.
Nitric oxide inhalation and high frequency oscillatory ventilation for hypoxemic respiratory failure in infants. (2003)

Our results indicate that the combined treatment of HFOV and NO inhalation is superior to HFOV alone for improving oxygenation in a selected cohort of infants ventilated for a variety of lung diseases.
Generation of hepatocytes from oval cell precursors in culture. (1998)

Although there is experimental evidence supporting the involvement of hepatic stem cells in the pathogenesis of liver cancers, the detection and isolation of these cells remains elusive. A logical approach to detecting these cells would take advantage of their ability to differentiate (or to give rise to cells that differentiate) into hepatocytes. This approach requires an assay system that is conducive to hepatocytic differentiation. Here, we report the development of an in vitro system consisting of a three-dimensional collagen gel matrix and a fibroblast feeder layer that supports hepatocytic differentiation from precursor epithelial (oval) cell lines. The LE/2 and LE/6 oval cell lines used in this study are nontumorigenic cells that are derived from the livers of adult rats fed a choline-deficient diet containing 0.1% ethionine for 2 and 6 weeks, respectively. These lines consist of small cells that are phenotypically immature with few cytoplasmic organelles and a high nuclear-to-cytoplasmic ratio. After 4 weeks in the three-dimensional culture system, these cells acquired typical hepatocytic morphology. By electron microscopy, the cells formed canalicular structures that are typical of hepatocytes and were organelle rich, displaying peroxisomes, abundant mitochondria, and rough endoplasmic reticulum. The cells produced albumin and displayed a cytokeratin (CK) pattern typical of hepatocytes (CK 8 and CK 18-positive and CK 19-negative). The presence of a mesenchymal cell feeder layer was essential for supporting hepatocytic differentiation. Without a feeder layer but in the presence of hepatocyte growth factor and/or keratinocyte growth factor, the precursor cells formed ductal structures, suggestive of differentiation along the bile duct lineage. The three-dimensional system described provides direct proof of the lineage generation capacity of oval cells. It offers a model to study factors that may be important for hepatocytic differentiation from precursor cells and a means to assay cell populations for their ability to give rise to normal and transformed hepatocytes.
Skyline query processing over joins (2011)

This paper addresses the problem of efficiently computing the skyline set of a relational join. Existing techniques either require to access all tuples of the input relations or demand specialized multi-dimensional access methods to generate the skyline join result. To avoid these inefficiencies, we introduce the novel SFSJ algorithm that fuses the identification of skyline tuples with the computation of the join. SFSJ is able to compute the correct skyline set by accessing only a subset of the input tuples, i.e., it has the property of early termination. SFSJ employs standard access methods for reading the input tuples and is readily implementable in an existing database system. Moreover, it can be used in pipelined execution plans, as it generates the skyline tuples progressively. Additionally, we formally analyze the performance of SFSJ and propose a novel strategy for accessing the input tuples that is proven to be optimal for SFSJ. Finally, we present an extensive experimental study that validates the effectiveness of SFSJ and demonstrates its advantages over existing techniques.
Robust feature selection algorithms (2002)

Selecting a set of features which is optimal for a given task is a problem which plays an important role in wide variety of contexts including pattern recognition, adaptive control and machine learning. Experience with traditional feature selection algorithms in the domain of machine learning leads to an appreciation for their computational efficiency and a concern for their brittleness. The authors describe an alternative approach to feature selection which uses genetic algorithms as the primary search component. Results are presented which suggested that genetic algorithms can be used to increase the robustness of feature selection algorithms without a significant decrease in compuational efficiency.
Assay of anticancer drugs in tissue culture: comparison of a tetrazolium-based assay and a protein binding dye assay in short-term cultures derived from human malignant glioma. (1996)

Because of the methodological difficulties associated with the MTT assay in screening short-term cultures derived from human malignant glioma, a chemosensitivity assay based on the protein staining using sulforhodamine B (SRB) has been optimized for use with these cells. SRB at a fixed dye concentration achieved maximal staining density at 20 min for most cell lines and this intensity was not further increased by using dye concentrations above 0.2%. A delay in staining after fixation did not significantly decrease staining intensity, but delay in dye extraction after fixation and staining did. There was an excellent quantitative and qualitative linear relationship between cell number determined by either the SRB assay or by cell counting, but not with the MTT assay which consistently underestimated the number of cells in assay plates. The MTT assay appeared to be incapable of detecting less than about 150 cells/well, while these small numbers of cell were readily detectable by either cell counting or SRB staining. There was a close correlation between chemosensitivity values derived from the MTT and SRB assays for procarbazine, CCNU and vincristine when the endpoint is taken as either the ID25, ID50 or ID75. The results indicate that the SRB is capable of producing broadly similar results to the MTT assay, but is more sensitive in the detection of small numbers of cells with a linear relationship between cell number and SRB staining intensity over a wide range of cell numbers. It is capable of producing data from short-term cultures from malignant glioma and offers technical advantages over the MTT assay in that plates may safely be stored at certain points during the assay without the need for immediate processing. The SRB assay provides a useful alternative to the MTT assay for determining the sensitivity of short-term cultures of human glioma to cytotoxic drugs.
NK-cell activation and antibody-dependent cellular cytotoxicity induced by rituximab-coated target cells is inhibited by the C3b component of complement (2007)

Antibody-dependent cellular cytotoxicity (ADCC) and complement fixation both appear to play a role in mediating antitumor effects of monoclonal antibodies (mAbs), including rituximab. We evaluated the relationship between rituximab-induced complement fixation, natural killer (NK)-cell activation, and NK cell-mediated ADCC. Down-modulation of NK- cell CD16 and NK-cell activation induced by rituximab-coated target cells was blocked by human serum but not heat-inactivated serum. This inhibition was also observed in the absence of viable target cells. C1q and C3 in the serum were required for these inhibitory effects, while C5 was not. An antibody that stabilizes C3b on the target cell surface enhanced the inhibition of NK-cell activation induced by rituximab-coated target cells. Binding of NK cells to rituximab-coated plates through CD16 was inhibited by the fixation of complement. C5-depleted serum blocked NK cell-mediated ADCC. These data suggest that C3b deposition induced by rituximab-coated target cells inhibits the interaction between the rituximab Fc and NK-cell CD16, thereby limiting the ability of rituximab-coated target cells to induce NK activation and ADCC. Further studies are needed to define in more detail the impact of complement fixation on ADCC, and whether mAbs that fail to fix complement will be more effective at mediating ADCC.
Selection of marker-free transgenic plants using the isopentenyl transferase gene (1997)

We have developed a new plant vector system for repeated transformation (called MAT for multi-auto-transformation) in which a chimeric ipt gene, inserted into the transposable element Ac, is used as a selectable marker for transformation. Selectable marker genes conferring antibiotic or herbicide resistance, used to introduce economically valuable genes into crop plants, have three major problems: (i) the selective agents have negative effects on proliferation and differentiation of plant cells; (ii) there is uncertainty regarding the environmental impact of many selectable marker genes; (iii) it is difficult to perform recurrent transformations using the same selectable marker to pyramid desirable genes. The MAT vector system containing the ipt gene and the Ac element is designed to overcome these difficulties. When tobacco leaf segments were transformed and selected, subsequent excision of the modified Ac produced marker-free transgenic tobacco plants without sexual crosses or seed production. In addition, the chimeric ipt gene could be visually used as a selectable marker for transformation of hybrid aspen (Populus sieboldii x Populus grandidentata). The chimeric ipt gene, therefore, is an attractive alternative to the most widely used selectable marker genes. The MAT vector system provides a promising way to shorten breeding time for genetically engineered crops. This method could be particularly valuable for fruit and forest trees, for which long generation times are a more significant barrier to breeding and genetic analysis.
Non-invasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma: Progress overview beyond predictive and personalized diagnosis (2011)

The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma allowed for the development of alternative methodologies that may facilitate safe non-invasive prenatal diagnosis (NIPD). The low concentration of cffDNA in maternal plasma, however, and the coexistence of maternal DNA limit its clinical application to the detection or exclusion of fetal targets that are not present in the mother, such as Y chromosome sequences, the RHD gene in a RhD-negative woman and genetic conditions inherited from the father. Strategies for NIPD of monogenic disorders and fetal chromosomal aneuploidies have also been achieved using next-generation sequencing and could be introduced to the clinics as soon as cost-effective and high throughput protocols are developed.
Gene Expression Profile and Angiogenic Markers Correlate with Response to Neoadjuvant Bevacizumab Followed by Bevacizumab plus Chemotherapy in Breast Cancer (2008)

Baseline CD31, PDGFR-beta, and GO classes for vascular endothelial growth factor receptor activity and mitosis were significantly associated with response to bevacizumab followed by bevacizumab plus chemotherapy.
Characterization of the Enzymatic Properties of the First and Second Domains of Metallocarboxypeptidase D (1999)

Carboxypeptidase D (CPD) contains three domains with homology to other metallocarboxypeptidases. To further characterize the various domains, we constructed a series of point mutants with a critical active site Glu of duck CPD converted to Gln. The proteins were expressed in the baculovirus system, purified to homogeneity, and characterized. Point mutations within both the first and second domains eliminated enzyme activity, indicating that the third domain is inactive toward dansyl-Phe-Ala-Arg. CPD removed only the C-terminal Lys or Arg from peptides, with the first domain more efficient toward Arg and the second domain more efficient toward Lys. Peptides containing Pro in the penultimate position were poorly cleaved by either domain. Cleavage of a peptide with Ala in the penultimate position was most efficient, with the relative order Ala >/= Met > Ser, Phe > Tyr > Trp > Thr >/= Gln, Asp, Leu, Gly >> Pro for CPD with both domains active. There were only minor differences between the first and the second domains regarding the influence of the penultimate amino acid. The first domain was optimally active at pH 6.3-7.5, whereas the second domain was optimally active at pH 5. 0-6.5. Thus, the first and second carboxypeptidase domains have complementary enzyme activities. Furthermore, the finding that CPD with both domains active shows a broad activity to a wide range of substrates is consistent with a role for this enzyme in the processing of many proteins that transit the secretory pathway.
A Complete Protocol for In Situ Hybridization of Messenger RNAs in Brain and Other Tissues With Radio-labeled Single-Stranded RNA Probes (1989)

We present a detailed protocol for In Situ hybridization of messenger RNA molecules in brain and other tissues, using 35S-labeled single-stranded RNA transcribed from commercially available plasmid vectors. These vectors contain promoter sequences for specific synthesis of RNA, and polylinker regions that will accept cDNA inserts for virtually any target molecule of interest. The protocol is optimized for studies that include concomitant irnmunohistochemical and cytoarchitectonic evaluations, and it is sufficiently detailed for the molecular biologist unfamiliar with histologic technique or the histologist inexperienced in molecular biological methods. We have used it with consistant results for In Situ hybridization studies using probes to more than twenty different mRNAs; and for several of those we have obtained results showing quantitative differences in experimentally altered mRNA levels. Included are details of perfusion fixation, tissue sectioning and preparation, probe synthesis, hybridization reaction, and signal detection. The introduction and annotated comments include rationale for basic procedures and the purpose of various specific steps in the hybridization histochemistry protocol. (The J HistotechnoL 12:169, 1989).
Synthesis and application of novel 4,5,6,7-tetrahydrobenzothiazole based azo disperse dyes (2005)

3,3,5-Trimethylcyclohexanone was subjected to Hantzsch synthesis by treating with iodine and thiourea to give an intermediate 2-Amino-5,5,7-trimethyl-4,5,6,7-tetrahydrobenzothiazole. This was then diazotized and coupled with various N,N-dialkylaniline derivatives to give a series of novel disperse dyes. These dyes were characterized by spectral studies. The dyeing performance of these dyes was assessed on polyester fabric.
The expanding role of biological agents in the treatment of inflammatory bowel disease – focus on selective adhesion molecule inhibition (2003)

Inflammatory bowel disease presents in various forms. Its increasing incidence indicates that modern lifestyle triggers disease in genetically susceptible individuals. We present a model for inflammatory bowel disease pathophysiology and review the new biological therapies available. These biological agents have been developed to antagonise the processes of pathogenic inflammation, such as the reduction in T-lymphocyte apoptosis, increase in T-lymphocyte proliferation and increase in T-lymphocyte trafficking into the intestinal mucosa. Inhibitors of various inflammatory cytokines, including some antagonists to tumour necrosis factor, are effective therapies for inflammatory bowel disease. However, this class is associated with the risk of rare, but serious, side-effects, such as opportunistic infections and demyelinating diseases. The administration of anti-inflammatory cytokines, including interleukin-10 and interleukin-11, may theoretically be effective in reducing inflammation, although the clinical development of some of these therapies has been terminated. The selective inhibition of the adhesion molecules involved in T-lymphocyte trafficking can be effective in reducing gut inflammation. Of the selective adhesion molecule inhibitors under investigation, natalizumab has demonstrated efficacy in inflammatory bowel disease. The future of biological therapy for inflammatory bowel disease shows promise.
Diverse Temperate Bacteriophage Carriage in Clostridium difficile 027 Strains (2012)

A diverse set of temperate bacteriophages are associated with C. difficile 027. The observed correlation between phage carriage and the subtypes suggests that temperate bacteriophages contribute to the diversity of C. difficile 027 and may play a role in severity of disease associated with this ribotype. The capsid gene can be used as a tool to identify C. difficile myoviruses present within bacterial genomes.
Cell cycle and physiological characteristics of Synechococcus (WH7803) in chemostat culture (1999)

The marine cyanobacterium Synechococcus spp, is one of the most abundant picoplanktonic photoautotrophs in the world's oceans. When grown in nitrogen-limited chemostat culture under continuous light, Synechococcus strain WH7803 displays a bimodal DNA histogram. Consequently, the duration of each growth phase can be con~puted from the proportion of cells in each cell cycle phase. We measured cellular DNA distribution, carbon and nitrogen content, and pigment composit~on of Synechococcus WH7803 in a series of chemostat experiments with growth rate ranging from 0.1 to 0.9 d-'. Flow cytometric data showed that the duration of each cell cycle phase increased linearly with doubling time, and the fraction of cells in the S and G2 phases, fStG2, was relatively constant at growth rates of less than 1 doubling d-'. Cellular carbon and nitrogen contents were about 200 and 40 fg cell-'. respectively, but were much higher for slowly growing cells. The carbon to nitrogen ratio, the carbon to chlorophyll a ratio, and the ratio of zeaxanthin to chlorophyll a all decreased with increasing growth rate. These observed relationships are useful for applying cell cycle analysis to estimate growth rate, or for using cell abundance or pigment concentrations to estimate biomass and productivity of Synechococcus in the sea.
Autophagy, Bafilomycin and Cell Death: The “A-B-Cs” of Plecomacrolide-Induced Neuroprotection (2006)

Bafilomycin A1 (BafA1), which is a member of the plecomacrolide sub-class of macrolide antibiotics, has differential, concentration-dependent effects on neuronal cell viability. When used at high concentrations, BafA1 inhibits vacuolar ATPase (V-ATPase), promotes the accumulation of autophagic vacuoles and triggers Bax-dependent apoptosis. These effects are similar to those induced by the lysosomotropic agent chloroquine. Conversely, at concentrations below its reported ability to completely inhibit V-ATPase, BafA1 dramatically attenuates chloroquine-induced apoptosis. The protective effects of BafA1 appear to be independent of the chloroquine-induced accumulation of autophagosomes. Rather, BafA1 appears to inhibit events downstream of chloroquine-induced autophagosome accumulation, such as the loss of mitochondrial or lysosomal integrity. Our finding that BafA1 inhibits the death of neurons induced by autophagic stress/inhibition suggests a potentially novel mechanism of action apart from its ability to inhibit V-ATPase. Here we provide further evidence of neuroprotection against chloroquine-induced death by plecomacrolide antibiotics that are structurally similar to BafA1, including bafilomycin B1 and concanamycin A, and discuss potential mechanism(s) of neuroprotection against autophagic stress.